Beruflich Dokumente
Kultur Dokumente
Highlights from
ASCO 2017 & ADA 2017
How to manage
vertebral compression
fractures
CONTENTS
MIMS DOCTOR - YOUR TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA CEO
Yasunobu Sakai
Senior Editor
Saras Ramiya
Associate Editor
Pank Jit Sin
JULY ISSUE
Contributing Editors
Malaysia Focus Christina Lau, Jackey Suen, Joseph Ro-
bles (Hong Kong), Dr. Joslyn Ngu, Rachel
6 Back pain in young people possibly due to AS Soon (Malaysia), Elvira Manzano, Audrey
Abella, Roshini Claire Anthony, Pearl Toh
(Singapore), Dr. Mel Beluan (Philippines)
8 Metabolism a promising biomarker of embryo viability
Designers
10 More screening awareness required to reduce thalassaemia Razli Rahman, Tina Ng, Peggy Tio, Sam
Shum
Indonesia
Ruth Theresia
Tel: (62 21) 729 2662
Email: enquiry.id@mims.com
6 10
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MIMS DOCTOR - YOUR TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA India
Monica Bhatia
Tel: (9180) 2349 4644
Email: enquiry.in@mims.com
Korea
Choe Eun Young
Tel: (822) 3019 9350
Email: inquiry@kimsonline.co.kr
JULY ISSUE
Malaysia
Tiffany Collar, Sumitra Pakry,
24 SGLT-2 inhibitors may lower HF, death rates in T2D patients regardless of CVD Sharon Ong, Wong Wen Dee
status Tel: (603) 7623 8000
Email: enquiry.my@mims.com
25 REMOVAL: Metformin may slow atherosclerosis progression in adults with T1D Philippines
Gracia Cruz, Rowena Belgica,
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26 DEVOTE: Degludec as safe as glargine for the heart, with less severe hypoglycae- Malicsi, Cliford Patrick
mia Tel: (632) 886 0333
Email: enquiry.ph@mims.com
Singapore
Conference Coverage Rayne Lee, Josephine Cheong,
Ronald Ho, Kelvin Sor, Elaine Teo
2017 American Society of Clinical Oncology (ASCO) Annual Meeting, Chica- Tel: (65) 6290 7400
27 go, Illinois, US Email: enquiry.sg@mims.com
High-dose vitamin D boosts PFS in metastatic colorectal cancer
Thailand
Nawiya Witayarithipakorn
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Newsbites Email: enquiry.th@mims.com
HOW TO CONTACT US
To subscribe:
25 27 enquiry.my@mims.com
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28 31
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DOCTOR | JULY ISSUE
CONTENTS
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MALAYSIA FOCUS
L–R: Dr. Amir Azlan Zain, Nawfal Johnson, AS Fighter; Associate Professor Dr. Sargunan Sockalingam, Bernice Chan, franchise head for immunology
and dermatology, neuroscience of Novartis Malaysia.
SARAS RAMIYA has to be not only amongst the mem- higher chance of dying compared
F
bers of the public but also members with the general population. [Arthri-
urther investigation of back within the medical community as well tis Rheum 2011;63:1182–1189, Ann
pain in the below 30 age group including family physicians, ortho- Rheum Dis 2011;70:1921–1925]
may lead to early diagnosis of paedic surgeons and professionals
ankylosing spondylitis (AS), says an who also evaluate people with back AS is an autoimmune disease
expert. pain on a regular basis,” said Amir. whereby the immune system has
been switched on via trigger and
“Ankylosing spondylitis is a AS is in a group of conditions the immune cells—mostly white
chronic condition that causes back which is typified by long-term inflam- blood cells (WBC)—are activated
pain because of inflammation of lig- mation. If the inflammation is left un- and produce inflammatory substanc-
aments between the vertebra and checked, it can lead to progressive es. These inflammatory substances
inflammation of the tendons and lig- stiffening of the areas involved. In the drive the inflammation in the spine
aments,” said Dr. Amir Azlan Zain, case of the intervertebral ligaments, it and cause the eventual stiffening of
consultant physician and rheuma- causes a stiffening of the spine. This the spine. The HLA-B27 is a genetic
tologist, at a media briefing on AS in process is irreversible. [Spondylitis marker found in most of the human
Kuala Lumpur. Association of America. Available at: cells and 90% of people with AS have
www.spondylitis.org Accessed on it although it is a fairly common ge-
The inflammatory back pain ex- 30 May] netic marker in general.
perienced by patients with AS is the
opposite of mechanical back pain. It Other comorbidities associated The prevalence of AS is much
improves when they move and wors- with AS include cardiovascular com- higher in North America (3,190 per
ens with rest. The early morning stiff- plications, osteoporosis, reduced million) and Europe (2,380 per mil-
ness usually lasts for hours. These pulmonary function, chronic pain, lion) but there is a fair number in
two symptoms are cardinal in inflam- depression and gastrointestinal prob- Asia (1,670 per million). [Rheuma-
matory back pain. “Awareness of AS lems. Patients with AS are also at a tology (Oxford) 2014;53:650–657]
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DOCTOR | JULY ISSUE
MALAYSIA FOCUS
AS affects young people and is di- In terms of treatment, only alingam, consultant rheumatologist,
agnosed when patients are at the anti-inflammatory tablets and physio- University Malaya Specialist Centre,
most productive age in terms of work therapy were available until about 18 said, “AFM was founded in 1994 and
productivity. [Curr Opin Rheumatol years ago. The emergence of tumour an organization for people involved in
2000;12:239–247] As a result, 30% necrosis factor (TNF) inhibitors—so- the care of arthritis patients and also
of patients with AS have to quit their called biologic medicines—have of people living with arthritis.”
job because they are unable to sus- changed the treatment landscape
tain the job in the long term. [Curr for patients with AS. There are five AFM is a support group for peo-
Rheumatol Rep 2010;12(5):325–331] anti-TNF medicines that are licensed ple with rheumatoid arthritis, psoriatic
for use in Malaysia, he said. arthritis, osteoarthritis and, more re-
Diagnosing AS is fairly straight- cently, AS. AFM organizes fundrais-
forward and involves firstly, the rec- The newly available secukinum- ing activities in terms of public fo-
ognition that back pain is inflamma- ab (Cosentyx®) targets a completely rums, support group platforms with
tory and secondly, through specific novel pathway ie, IL-17A. Inflamma- meetings and activities and weekly
physical examination especially of the tory substances produced by WBC exercise sessions. The Arthritis Fund,
spine. Tests for inflammation and include TNF and IL-17A. Blocking which was established sometime in
HLA-B27 are recognized as standard these molecules has been effective in 1995, provides partial or full finan-
tests for inflammatory back pain. controlling AS, said Amir. cial support for joint replacements
X-ray or magnetic resonance imaging and plans to include biologics. AFM
(MRI) changes are now important in Speaking on Arthritis Foundation, held a fundraising run in May for the
classification of AS, said Amir. Malaysia (AFM), its president Asso- Arthritis Fund. For further information
ciate Professor Dr. Sargunan Sock- on AFM, go to www.afm.org.my
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MALAYSIA FOCUS
M
Australia. requirements during its development
etabolism plays an important and differentiation. If the changes did
role in the development of an In IVF, better identification and se- not occur, development will be com-
embryo, particularly during lection of viable embryos for transfer promised. In day 1 to 3 of life, embry-
the pre-implantation period, and may will lead to a reduction in the number os utilize pyruvate, lactate and amino
have a role to play in the selection of of embryos that need to be trans- acids to generate energy. In day 4,
embryos in in vitro fertilization (IVF), ferred and improve the efficiency of embryos switch to a glucose-based
says an expert. single embryo transfer. This will play a metabolism, he explained.
role in reducing the frequency of mul-
According to a study, glucose up- tiple gestations and increasing the It is difficult to quantify the met-
take by the embryo was shown to be efficiency of IVF. abolic functions of an embryo in
associated with pregnancy outcome. cultures as it can be influenced by
The findings showed that glucose Conventionally, the embryo’s factors such as oxygen concentra-
consumption by embryos which re- morphology is used to determine tion, gender and composition of the
sulted in a pregnancy was higher on embryo selection. However, mor- culture medium. Continuous technol-
day 4 and 5, compared to embryos phology alone is not an accurate indi- ogy advancements will enable future
that failed to develop post-transfer. cator of the embryo’s physiology and research to further explore the link
[Hum Reprod 2011;26(8):1981– not indicative of its viability. In animal between said factors and metabolic
1986] As such, glucose metabolism studies, metabolism has been shown functions, leading to the development
in embryos may be useful as a fac- to be a useful marker of viability after of metabolism algorithms for embryo
tor in the selection of embryos for transfer and the same may be true for selection. Gardner was speaking at
transfer in IVF, said Professor David humans, said Gardner. the 7th Congress of the Asia Pacific
K. Gardner, of the School of Biosci- Initiative on Reproduction (ASPIRE
ences, University of Melbourne and The embryo’s metabolism chang- 2017), held in Kuala Lumpur recently.
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DOCTOR | JULY ISSUE
MALAYSIA FOCUS
G
reater awareness of once-
in-a-lifetime screening for
thalassaemia among Malay-
sian adults is necessary to mitigate a
growing healthcare burden, accord-
ing to government statistics.
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MALAYSIA FOCUS
young adults, partners planning to “Transfusions are lifesaving for “On average, 2,000 bags of
have children, and pregnant mothers thalassaemia, but with every trans- blood are needed every day in MOH
especially so that prenatal diagnosis fusion, iron buildup occurs,” said Ja- hospitals throughout the country… in
can be offered and termination of meela. “One bag of blood contains the Klang Valley alone, the National
pregnancy suggested if necessary. 200 mg of iron. A young adult weigh- Blood Center is required to provide
ing 50 kg requires three bags of blood more than 500 bags a day to meet
As part of the MOH’s national transfused per month… by the end of MOH hospital requirements and
thalassaemia programme, a nation- the year they have about 7 g of iron, some supplies to the private hos-
wide targeted screening initiative for and the human body has no mecha- pitals,” said Azman. “It is estimated
students 16 years of age (Form 4) nism for getting rid of this excess iron about 17% to 20% of the [national]
was launched in November 2016. [beyond] what we shed through our blood supply goes to TDT patients
Jameela and Azman also encour- skin, mucosa, and—in women—the annually.”
aged the public to take advantage of menstrual blood. Iron accumulation
voluntary screening services provid- in the pancreas can cause diabetes, Azman added that in 2016,
ed at public healthcare centres, the while accumulation in the thyroid can 693,982 bags of blood in total were
list of which can be found at www. cause hypothyroidism.” collected nationwide, amounting to
mytalasemia.net.my/. around 1,900 bags per day. Given
Jameela added that even with that regular blood donors can only
The hidden hereditary regular blood transfusions and iron donate every 3 to 4 months a year,
link chelation therapy, some patients with concerted and continuous efforts are
Thalassaemia refers to a group of thalassaemia are unable to achieve needed to recruit new donors and re-
autosomal recessive genetic blood normal growth rates, often resulting tain existing ones, he said.
disorders which result in insufficient in additional psychosocial issues as
haemoglobin production from birth. they attain school-going age. “Overall, the total number of [Ma-
Characteristic symptoms include laysians] who become regular blood
anaemia (comprising pale complex- “Those born with thalassaemia donors is still low compared to other
ion, fatigue, shortness of breath), re- live a life full of injections, tied to developed countries,” said Azman.
current fevers, spleen enlargement, the hospital,” said Jameela. “Every “At the moment, our percentage
dark urine production and overall 3 weeks a blood transfusion, every is about 2% [of the population] … I
stunted development. night parents who must make sure hope we can attract more people to
they get their medication.” donate and achieve 3% to 5%.”
Apart from bone marrow trans-
plantation—and only 25% of patients Shortfalls in blood sup- Jameela encouraged more men
have suitable sibling donors—no ply to donate blood, as women were
known cure is available for the dis- According to the 2014 guidelines for more likely to be iron deficient; in ad-
ease. Severe thalassaemias (eg, beta TDT management by the Thalassae- dition, women who had undergone
thalassaemia major) require the pa- mia International Federation, patients one or more pregnancies were more
tient to receive regular blood transfu- with TDT require transfusions every 2 likely to have foetal antigens which
sions to prolong life, but this brings to 5 weeks, with each patient requir- could result in adverse reactions in
its own host of problems, Jameela ing between 7.5 to 24 ml of blood per the patient recipient.
noted. kg of body weight.
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DOCTOR | JULY ISSUE
MALAYSIA FOCUS
L
concern amongst health-
iver Update is a series of inter- care professionals and pol-
national scientific meetings or- icy makers. Mohd Ismail
ganized by the Malaysian Liver said: “Now we have a real-
Foundation. It is meant to keep our istic possibility of a cure for
healthcare professionals (HCPs) up- patients with chronic hepa-
dated on current developments and titis C, a major public health
new advances in the management problem globally.” Howev-
of liver diseases. Usually held around er, on the other end of the
mid to late July, the conference is a spectrum, the increasing
must-go for hepatologists, GPs and incidence of non-alcoholic
allied health professionals alike. fatty liver disease (NAFLD)
which is associated with
MIMS Doctor got in touch with obesity, diabetes mellitus,
Tan Sri Dato’ Seri Dr Haji Mohd Is- hyperlipidaemia, the meta-
mail Merican, founder and president bolic syndrome and lifestyle
of the Malaysian Liver Foundation, diseases is a great concern
to get his views about the upcoming to all of us.
event. He said: “It is imperative that The event will see lec-
our HCPs keep themselves updated tures from local and overseas ‘su- • Dato Dr Christopher Lee
on current advances in the approach perstars’ in hepatology. Overseas • Professor Dato’ Dr Nor Shahidah
and management of common liver speakers include the following: Khairullah
disorders found in this country so • Professor Dr Edward Gane from • Professor Dato’ Dr Ravindran Je-
that their patients will be given the New Zealand gasothy
right information and advice.” • Professor Dr Henry Chan from • Dato’ Dr Robert Ding
Hong Kong • Dato‘ Dr Nik Ritza Kosai Nik Mah-
Mohd Ismail said patients are • Dr Thomas Leung from Hong mud
nowadays actively searching for infor- Kong • Dr Tan Soek Siam
mation on the World Wide Web and • Professor Dr Mohamad Rela • Dr Haniza Omar
it is therefore imperative that HCPs from India • Dato’ Dr Mazlam Mohd Zawawi
know more about liver diseases • Dr Richard Guan from Singapore
than their patients. Also, information • Dr Rohit Agarwal from Singapore When asked which particular
on the internet may be misleading, • Dr Chow Wan Cheng from Singa- sessions he deem as ‘must-attend’
which requires a well-informed and pore sessions, Mohd Ismail said all ses-
up-to-date HCP to put the patient • Professor Dr Laurentius Lesmana sions are important, it just depends
back on track. “This is in fact part from Indonesia on the interest of the delegate. “If I
of continuing professional develop- • Professor Dr Teerha Piratvisuth can make a suggestion, sessions
ment and is an important factor in the from Thailand on chronic hepatitis C and fatty liver
practice of medicine, as information should be attractive to participants in
is ever evolving, even as we speak, Meanwhile the local speakers list view of recent developments.”
and none of our HCPs should be left comprises:
behind clinging to outdated knowl- • Datuk (Mr) Harjit Singh- Malaysia The conference will be looking at
edge.” • Datuk Dr Ryan Ponnudurai more than 300 participants with more
This year’s Liver Update has • Mr Krishnan Raman slated to register on the spot. Spe-
been organized with great effort to • Datin Dr Sharmila Sachithanan- cialists, doctors and allied healthcare
bring world renowned experts to dan professionals including pharmacists,
share their experiences and knowl- • Dr Manisekhar Subramaniam assistant medical officers and nurses
edge with our HCPs. Recent devel- • Datuk Dr Shahnaz Murad should make their way to the event.
opments pertaining to liver diseases • Dr L. Sanker
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DOCTOR | JULY ISSUE
MALAYSIA FOCUS
D
Speaking at a recent MMA con- 2:52–62]
espite declining incidence of ference in Kota Kinabalu, Jayaram
hepatitis C virus (HCV) infec- added that an estimated 30% of “Treatment with pegylated inter-
tions in Malaysia, the impact individuals with chronic infection re- feron-α and ribavirin was the gold
of existing untreated cases will con- tain normal liver enzyme function, al- standard up to 4 years ago, but that
tinue to be felt for years to come, though silent damage to the liver may is no longer the case,” said Jayaram.
says an expert. yet be progressing. “Genotype 1 only had a 40 to 50%
chance of treatment success with
“[Many] who were infected 30 “All patients with risk factors for PEG-IFN/RBV, while genotype 3 had
to 60 years ago are now dying from hepatitis C should have a serological about 60 to 70%.”
HCV-related cirrhosis and hepato- screening test for anti-hepatitis C an-
cellular carcinoma (HCC),” said Da- tibodies,” said Jayaram. “A positive At present, three classes ofdi-
tuk Dr. Jayaram Menon, head of the screening test should be followed by rect-acting antivirals (DAAs) are avail-
department of medicine at Queen a test for hepatitis C RNA to confirm able; most recommended DAA treat-
Elizabeth Hospital, Kota Kinaba- the diagnosis.” ment regimens span 8 to 24 weeks,
lu. “In the absence of interventions, which Jayaram highlighted as an
HCV-related mortality and morbidity Current recognized risk factors improvement from PEG-IFN and rib-
will double over the next 15 years ... for HCV infection include recipients avarin, which can involve up to 1 year
the increasing number of deaths re- of blood transfusions prior to 1992 or of treatment.
flects the high incidence of hepatitis clotting factor concentrates prior to
C in the mid-20th century due to ex- 1990; transfusions from donors later “Combinations of two or three
panded use of parenteral injections found to be HCV+; organ transplants of these DAAs can cure HCV infec-
and drug use.” before the 1990s; maternal HCV+; tion—with ‘cure’ defined as a sus-
current or past intravenous drug use; tained virologic response (SVR) at 12
Jayaram noted that according invasive medical procedures done weeks post-treatment—in over 90%
to estimates from the Global Burden prior to the 90s; haemodialysis; HIV of patients, including populations
of Disease studies, worldwide mor- infection; healthcare workers, es- that have been difficult to treat in the
tality from hepatitis C complications pecially after needle/sharp injury or past,” said Jayaram.
increased from 333,000 in 1990 exposure to HCV+ blood; high-risk
to 499,000 in 2010, followed by sexual behaviours; incarceration; However, he noted that issues of
704,000 in 2013. Current prevalence intravenous illicit drug use; and un- pricing remain a barrier to the wider
of infection among Malaysians is es- regulated tattoos. [J Fam Pract use of DAAs for treatment compared
timated to be around 2.5%. [Lancet 2017;66(3):136–144] to more cost-effective options such
Gastroenterol Hepatol 2017;2:52– as PEG-IFN/RBV. In addition, a re-
62] Considering treatment cently published Cochrane review
options of 138 randomized clinical trials for
Chronic HCV infections—which Jayaram noted that at present, six DAAs on the market found little long-
produce detectable HCV RNA only key HCV genotypes have been iden- term evidence available to support
after 6 months post-infection—ac- tified globally; while HCV-1 is the DAA impact on hepatitis C-related
count for 75 to 80% of all cases of most common on an international morbidity or all-cause mortality (OR
HCV, and often prove challenging for scale, a recently published study of 3.72, 95% CI 0.53 to 26.18, P =
primary care physicians to diagnose HCV prevalence in the Asia-Pacific 0.19, I² = 0%, 2,996 participants, 11
without blood tests. Common ear- region found that 62.3% of Malaysian trials), and warned that all trials and
ly symptoms (if they manifest at all) cases involved HCV-3, while 35.8% outcome results were at high risk
such as fatigue, muscle ache, and involved HCV-1. The same study of bias. [Cochrane Database Syst
nausea may be passed off as those also noted that overall prevalence Rev 2017; doi:10.1002/14651858.
of a flu-like viral infection, or another of infection in Malaysia was 2.5%. CD012143.pub2]
14
DOCTOR | JULY ISSUE
MALAYSIA FOCUS
PANK JIT SIN Dolutegravir is indicated in the treat- specialist to manage the patient.
D
ment of HIV-1 in combinations with While the initial launch was car-
olutegravir (Tivicay®), a HIV-1 other antiretroviral medications. ried out towards the end of 2014, the
integrase strand transfer in- drug grappled with accessibility and
hibitor (INSTI) is now part of In the government setting, do- affordability issues. With its accep-
the MOH medicine formulary. lutegravir will be prescribed as a cat- tance into the government’s medicine
egory ‘A’ drug, meaning it can only formulary, the drug should see wider
The drug was recently relaunched be prescribed by specialists in the use among persons with HIV.
after being accepted into the medi- field of infectious disease. In the pri-
cine formulary. Respondng to ques- vate setting, there are no restrictions Dolutegravir is an integrase inhib-
tions from MIMS Doctor, Steve on prescriber category or purchaser itor. Integrase is required by the HIV
Yoong, associate marketing and ie., GP or specialist. However, this virus as part of its replication process.
sales manager, HIV Business Unit, is still a specialized medicine for HIV By binding to the integrase and thus
GSK, said the drug will now feature treatment and will require prescription blocking viral replication, dolutegravir
more prominently in the treatment of and monitoring by a trained special- slows down the reproduction of HIV-
HIV in Malaysia. Beyond better ac- ist. GPs will normally refer patients to 1 virus particles. However, it should
cessibility, a pricing restructure prac- an infectious disease centre or ideally be used in combination with other
tice will also make it more affordable. together with an infectious disease antiretroviral therapy.
15
DOCTOR | JULY ISSUE
MALAYSIA FOCUS
I
ntellectual Property (IP) rights play
a key role in strengthening the
pharmaceutical industry, which can
contribute to improving Malaysia’s
economy and general health out-
comes, experts say.
16
DOCTOR | JULY ISSUE
COVER STORY
Is lower
better?
Blood
pressure
target:
PEARL TOH
A
“[T]here were linear associations The researchers observed that the
chieving a systolic blood pres- between mean achieved SBP and risk higher the levels of achieved SBP, the
sure (SBP) below the currently of CVD and mortality, with the lowest greater the risk for major CVD: in in-
recommended targets signifi- risk at 120 to 124 mmHg,” said the re- dividuals who achieved a mean SBP
cantly decreases the risk of cardiovas- searchers. “Our findings do not support between 120–124 mmHg, the risk of
cular disease (CVD) and death from the existence of a J-shaped association major CVD was 29% lower vs the 130–
any cause, according to a network me- between achieved SBP and the risk of 134 mmHg group, 42% lower vs the
ta-analysis of 42 randomized trials. CVD and all-cause mortality.” 140–44 mmHg group, 54 percent low-
18
DOCTOR | JULY ISSUE
COVER STORY
er vs the 150–154 mmHg group, and remains controversial … There were Approaches to BP control
64% lower vs the ≥160 mmHg group too few studies of treatment below 120 Several considerations to managing
(hazard ratio [HR], 0.71, 0.58, 0.46, and mmHg to comment on,” said Adjunct hypertension, according to Yancy and
0.36 for each increasing SBP stratum Associate Professor Tan Ru San, a se- Bonow, include: confirm diagnosis with
respectively). nior consultant at the Department of multiple BP recordings, determine the
Cardiology at the National Heart Cen- patient’s overall risk of CVD, and remain
Similarly, individuals who achieved tre, Singapore, noting that there were aware of the risks of intensive treatment
an SBP of 120–124 mmHg were in- only three trials in the meta-analysis and polypharmacy.
creasingly less likely to die from any with achieved SBP of <120 mmHg.
cause compared with individuals A target SBP of <130 mmHg might
with progressively higher SBP: HRs The network meta-analysis includ- be applicable to high-risk patients (eg,
for all-cause mortality were 0.73 vs ed 42 randomized trials comprising diabetic with hypertension), while non-
the 130–134 mmHg group, 0.59 vs 144,220 hypertensive participants pharmacological intervention should
the 140–44 mmHg group, 0.51 vs with diverse comorbidities (30 trials be the first step for low-risk patients
the 150–154 mmHg group, and 0.47 with type 2 diabetes patients). They who cannot tolerate antihypertensive
vs the ≥160 mmHg group. [JAMA were followed for an average of 3.6 therapy, with a treatment goal of <150
Cardiol 2017;doi:10.1001/jamacar- years (range, 6 months to beyond 8 mmHg (the lower the better), they sug-
dio.2017.1421] years) and categorized into 10 groups gested.
of achieved SBP range, from <120 to
“The lowest risks for major CVD, >160 mmHg. “In addition, analysis of mean
coronary heart disease, all-cause mor- achieved SBP does not guide treat-
tality, and CVD mortality were at a mean The finding that intensive SBP low- ment decisions regarding diastolic BP,”
achieved SBP of 120–124 mmHg, ering to 120–124 mmHg is associated reminded researchers of the meta-anal-
whereas the lowest risk for stroke with the lowest risk for CVD and mor- ysis.
was at a mean achieved SBP of <120 tality corroborates with the SPRINT
mmHg,” the researchers observed. study, but contradicts with some stud- “Medicine is practised on a pa-
ies which suggest a J-shaped relation- tient-level basis, and individualized
“These findings support more in- ship between SBP and CV outcomes. treatments based on a shared deci-
tensive SBP control among adults with One such study is the pooled analysis sion-making model should drive pa-
hypertension and suggest the need for from ONTARGET and TRANSCEND tri- tient-level interventions; this is especial-
revising the current clinical guidelines als, which showed that achieved SBP ly the case for those at higher risk for
for management of hypertension,” they of 130 mmHg was associated with the CVD and for those who are most vul-
contended. lowest risk for composite CV events nerable,” said Yancy and Bonow.
and all-cause mortality, while intensive
Intensive treatment lowering to <120 mmHg was associat- A common risk of intensive SBP
remains controversial ed with increased risk of CV outcomes. management, postural hypotension,
“[The study provides] provocative evi- [Lancet 2017;389:2226–2237] can lead to falls and fractures especially
dence that lower is better and likely so among the elderly, cautioned Tan.
in all cohorts with hypertension,” wrote Commenting on the conflicting re-
Drs Clyde Yancy and Robert Bonow sults, Tan said the J-shaped associa- “Whatever SBP target one choos-
from the Feinberg School of Medicine, tion may not be conclusively confirmed es, the medications should be intro-
Northwestern University in Chicago, Illi- or refuted by the current network me- duced gradually with adequate moni-
nois, US, in a separate editorial. “These ta-analysis, simply because there were toring,” he said.
are nontrivial findings. We should not few data below this threshold.
ignore the potential for harm attribut-
ed to lowering blood pressure too ag- “Another point to consider is that
gressively, particularly in the elderly, but the ONTARGET and TRANSCEND
those harms have not yet emerged to populations comprised patients with
be more important than the benefits.” existing CVD, a higher-risk subgroup
[JAMA Cardiol 2017;doi:10.1001/ja- compared to the JAMA study which
macardio.2017] included hypertensive patients with a
broader range of risks. Thus, the in-
“Recommendation for more ag- ferences may not [be] directly transfer-
gressive lowering below 120 mmHg able,” explained Tan.
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77th Scientific Sessions of the American Diabetes Association (ADA) • June 9-13 • San Diego, California, US
T
he sodium-glucose cotransport- The incidence of the primary out-
er 2 (SGLT2) inhibitor canagli- come (composite of CV death, nonfatal
flozin was associated with better myocardial infarction, or nonfatal stroke)
cardiovascular (CV) outcomes com- was lower among patients on canagli-
pared with placebo in individuals with flozin vs those on placebo (26.9 vs 31.5
type 2 diabetes (T2D) and high CV risk, participants per 1,000 patient-years,
though it was also linked to an elevated hazard ratio [HR], 0.86, 95% confidence
risk of amputation, according to find- interval [CI], 0.75–0.97; p<0.001 for
ings from the CANVAS* Program. noninferiority and p=0.0158 for superi-
ority). [N Engl J Med 2017;doi:10.1056/
“The CANVAS Program met its pri- NEJMoa1611925]
mary objective of demonstrating [CV]
safety, and also showed efficacy of Patients on canagliflozin also had
canagliflozin for the prevention of CV a lower incidence of hospitalization
events,” said study investigator Pro- for heart failure (HR, 0.67, 95% CI,
fessor Bruce Neal from The George 0.52–0.87) and CV death or hospital-
Institute of Global Health, New South ization for heart failure (HR, 0.78, 95%
Wales, Australia, who presented the CI, 0.67–0.91) compared with those on Professor Bruce Neal
findings. placebo.
would be 23 fewer deaths from CV
“The primary adverse effect that we There was a 40 percent reduction in disease, nonfatal heart attacks, or non-
observed that was unanticipated was the composite of estimated glomerular fatal strokes, 17 fewer hospitalizations
amputations. There was an approx- filtration rate, end-stage renal disease, for heart failure, and 16 fewer serious
imate doubling of the risk of amputa- or renal-related death (5.5 vs 9.0 par- declines in renal function, but 15 more
tions in the participants treated with ticipants per 1,000 patient-years, HR, amputations, said Neal.
canagliflozin compared to placebo and 0.60, 95 percent CI, 0.47–0.77), though
about two-thirds of these were ampu- these findings were not significant. “These data suggest net overall
tations of the toe or forefoot and about benefit of canagliflozin for most patients
one-third were amputations above the While the incidence of serious ad- with type 2 diabetes and high CV risk,”
level of the ankle,” he said. verse events was less frequent among he said, and recommended that physi-
patients on canagliflozin compared cians take into account the amputation
Participants in the CANVAS Pro- with placebo (104.3 vs 120.0 partic- risk when planning diabetes care for
gram which comprised the CANVAS ipants per 1,000 person-years, HR, their patients.
and CANVAS-R** studies were 9,734 0.93, 95% CI, 0.87–1.00), patients on
individuals with T2D (mean age 63.3 canagliflozin had an elevated risk of
years, 35.8% female, mean diabetes lower extremity amputations compared
duration 13.5 years) from 667 centres with those on placebo (6.3 vs 3.4 par-
in 30 countries. About 66% of partic- ticipants per 1,000 person-years, HR,
ipants had a history of CV disease. 1.97, 95% CI, 1.41–2.75), 71 percent
Participants were randomized to daily of which involved the toe or metatarsal
doses of canagliflozin (100 mg or 300 and 29% above-ankle amputations.
mg in the CANVAS study or 100 mg * CANVAS: CANagliflozin cardioVascular
with the option to increase to 300 mg To estimate the risks vs benefits of Assessment Study
** CANVAS-R: Effects of canagliflozin on renal
at week 13 in the CANVAS-R study) or canagliflozin, in an estimate of 1,000 endpoints in adult participants with type 2
placebo and followed up for a mean of patients treated for 5 years, there diabetes mellitus
20
DOCTOR | JULY ISSUE
CONFERENCE COVERAGE
77th Scientific Sessions of the American Diabetes Association (ADA) • June 9-13 • San Diego, California, US
T
requiring treatment with an intravitreal
he higher rate of diabetic retinop- agent or photocoagulation) were signifi-
athy seen in patients taking the cantly increased with semaglutide (haz-
glucagon-like peptide 1 (GLP-1) ard ratio, [HR], 1.76; p=0.02). [N Engl J
receptor agonist semaglutide vs place- Med 2016;375:1834–1844]
bo is likely a result of the rapid lowering
of HbA1c, a new analysis of data from Further analysis of the data showed
the SUSTAIN-6* trial suggests. that the 79 patients who had retinop-
athy had a longer duration of diabetes
“Patients who had retinopathy (17.7 years vs 13.9 for the overall study
complications had a rapid and steep population) and higher mean HbA1c (9.4
decrease of approximately 2.5% in vs 8.7% for the entire cohort). [ADA
HbA1c level,” said investigator Dr. Tina 2017, presentation 1-AC-SY09]
Vilsbøll, clinical manager at the Steno
Diabetes Center in Copenhagen, Den- Almost 65% of patients who expe-
mark. “Rapid improvement in glycae- rienced retinopathy were taking insulin Dr. Tina Vilsbøll
mic control is a risk factor for retinopa- compared with 58% of the total study
thy complications.” population. In addition, 83.5% of those dard care regimen.
in the retinopathy group had a history
Semaglutide cut the primary com- of diabetic retinopathy at baseline, 29 Vilsbøll said the data at hand sug-
posite outcome of cardiovascular (CV) percent had a history of proliferative gest that compared with the full study
death, nonfatal MI, or nonfatal stroke retinopathy, and 17.7% had a laser or population, patients with retinopa-
in SUSTAIN-6, an outcome that estab- injection therapy for proliferative reti- thy complications had worse control
lished its noninferiority to placebo, with nopathy. of their HbA1c and are more likely to
a safety profile that was comparable to have pre-existing retinopathy at base-
other GLP-1 agonists for type 2 diabe- “When we split the patients into line. Considering that patients with
tes (T2D). Rates of new or worsening those without retinopathy at baseline the greater treatment effect in terms
nephropathy were lower with sema- and patients with retinopathy, patients of HbA1c were the ones most at risk,
glutide vs placebo. However, rates of who did not have any history of retinop- clinically this means clinicians should
retinopathy complications (vitreous athy [had] no signals with semaglutide exercise caution when using potent
—it was exactly the same as placebo,” glucose-lowering agents in this popu-
said Vilsbøll. lation.
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77th Scientific Sessions of the American Diabetes Association (ADA) • June 9-13 • San Diego, California, US
T
reatment with bacillus Calmette-
Guérin (BCG) appears to reverse
advanced type 1 diabetes (T1D)
in patients after repeat vaccination, ac-
cording to a phase II study.
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CONFERENCE COVERAGE
77th Scientific Sessions of the American Diabetes Association (ADA) • June 9-13 • San Diego, California, US
G
lycaemic control is no better
in diabetic patients who moni-
tor their blood glucose than in
those who do not, the open label ran-
domized MONITOR trial has shown.
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CONFERENCE COVERAGE
77th Scientific Sessions of the American Diabetes Association (ADA) • June 9-13 • San Diego, California, US
S
odium-glucose transporter-2
inhibitors (SGLT-2i) were associ-
ated with a significant reduction
in the rates of death and hospitaliza-
tion due to heart failure (HF) in patients
with type 2 diabetes (T2D) regardless
of pre-existing cardiovascular disease
(CVD), according to a new analysis of
the CVD-REAL* study.
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DOCTOR | JULY ISSUE
CONFERENCE COVERAGE
77th Scientific Sessions of the American Diabetes Association (ADA) • June 9-13 • San Diego, California, US
A
dults with type 1 diabetes (T1D)
who were prescribed metformin
experience reductions in athero-
sclerosis progression and low density
lipoprotein-cholesterol (LDL-c), accord-
ing to results of the REMOVAL* study.
However, the impact of metformin on
glycaemic control in these patients is
limited.
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DOCTOR | JULY ISSUE
CONFERENCE COVERAGE
77th Scientific Sessions of the American Diabetes Association (ADA) • June 9-13 • San Diego, California, US
I
nsulin degludec had comparable car-
diovascular safety and reduced the
risk of severe hypoglycaemia com-
pared with insulin glargine U100 in
patients with type 2 diabetes and high
cardiovascular risk, according to results
of the DEVOTE* study.
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DOCTOR | JULY ISSUE
CONFERENCE COVERAGE
2017 American Society of Clinical Oncology (ASCO) Annual Meeting • June 2-6 • Chicago, Illinois, US
S
upplementation with high doses
of vitamin D slows down disease
progression in patients with col-
orectal cancer, the phase II SUNSHINE
trial has shown.
27
DOCTOR | JULY ISSUE
NEWSBITES
A
lcohol intake, even in moder-
ation, is a risk factor for multi-
ple markers of abnormal brain
structure and cognitive function, includ-
ing hippocampal atrophy, a recent UK
study has found.
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DOCTOR | JULY ISSUE
NEWSBITES
P
or fibrate, ≥3 other cardiovascular risk
atients are more likely to report factors but no history of myocardial in- All the other reported AEs were not
muscle-related adverse effects farction and not undergoing treatment significantly different between the two
(AEs) when they know they are on for angina. During the double-blind ran- groups, except for renal and urinary
statins, but not when they have no idea domized phase, the participants were AEs, which were more common among
whether they are given statin or place- assigned to either atorvastatin 10 mg patients taking atorvastatin than place-
bo in a blinded trial, the ASCOT-LLA* daily (n=5,101) or placebo (n=5,079) bo (1.87 vs 1.51%, HR, 1.23; p=0.002).
study found, suggesting that clinicians and followed up for a median of 2.3
should be aware of potential nocebo years. All the patients were then offered In the open-label phase, no signif-
effects when prescribing statins. atorvastatin in the open-label extension icant differences were seen between
phase, of which 6,409 chose atorvas- statin users and nonusers for the oth-
“These results will help assure both tatin and 3,490 preferred not to take er AEs except for blood and lymphatic
physicians and patients that most AEs the drug. system disorders (0.88 vs 0.64%, HR,
associated with statins are not causally 1.40; p=0.03) and musculoskeletal and
related to use of the drug and should connective tissue disorders (8.69 vs
help counter the AE on public health of 7.45%, HR, 1.17; p=0.001).
exaggerated claims about statin-relat-
ed side-effects,” said the researchers. Due to widespread claims about
the side effects of statins, particular-
During the blinded randomized ly muscle pain and weakness, which
phase of the study, there was no ex- were mainly based on observational
cess of muscle-related AEs among studies, the researchers noted that “up
atorvastatin-treated patients vs the to one fifth of patients … at high risk of
placebo group (incidence rate, 2.03 vs major vascular events with established
2.0%, hazard ratio [HR], 1.03; p=0.72). cardiovascular disease [stopped] their
[Lancet 2017;doi:10.1016/ S0140- statin therapy.”
6736(17)31075-9]
“Clinicians should be fully informed
However, the same patients report- about potential nocebo effects, includ-
ed a significantly higher rate of mus- ing patients’ previous knowledge or
cle-related AEs when they were aware perceptions of statin therapy, and dis-
that they were treated with atorvastatin cuss the evidence for [statin-associated
compared with nonusers of atorvas- muscle symptoms] with patients,” ad-
tatin during the open-label extension vised Drs Juan Pedro-Botet and Juan
phase of the study (incidence rate, 1.26 Rubiés-Prat of Universitat Autònoma de
vs 1.00%, HR, 1.41; p=0.006). Barcelona, Barcelona, Spain, in a sep-
arate commentary, as they noted that
“These analyses illustrate the so- poor understanding of warnings about
called nocebo effect, with an excess Besides muscle-related AEs, erec- the side effects related to statins can lead
rate of muscle-related AE reports only tile dysfunction also occurred at sim- to poor adherence or discontinuation of
when patients and their doctors were ilar rates in the statin and placebo treatment. [Lancet 2017;doi:10.1016/
aware that statin therapy was being groups during the blinded phase (1.86 S0140-6736(17)31163-7]
used and not when its use was blind- vs 2.14%, HR, 0.88; p=0.13). Sleep
ed,” explained the researchers. disturbance rate was significantly low-
er with statin than with placebo (1.00
The trial included 10,180 hyperten- vs 1.46%, HR, 0.69; p=0.0005), while
sive patients (aged 40–79 years) who cognitive impairment occurred too rare- * ASCOT-LLA: Anglo-Scandinavian Cardiac
had fasting total cholesterol of ≤6.5 ly to be reliably assessed statistically Outcomes Trial—Lipid-Lowering Arm
30
DOCTOR | JULY ISSUE
NEWSBITES
L
ong-term metformin was associ-
ated with a significantly lower cor-
onary artery calcium (CAC) than
placebo or lifestyle modification in men,
but not in women, with prediabetes,
according to data from the DPP* and
DPPOS** cohort.
31
DOCTOR | JULY ISSUE
NEWSBITES
O
nly one-in-five children with
painless rectal bleeding, the
most common symptom of
rectal polyps, presents with a fleshy
growth on the lining of the rectum at
endoscopy, a study finds.
32
DOCTOR | JULY ISSUE
NEWSBITES
T
he prevalence of cerebral small
vessel disease (SVD) is high in
Asian populations, particularly
in the elderly, a new population-based
study reveals. Moreover, SVD is cor-
related with poorer cognitive function
and may be caused by environmental,
cultural, and genetic risk factors.
34
DOCTOR | JULY ISSUE
NEWSBITES
R
esults of recent studies present-
ed at the American Psychiatric
Association 2017 Annual Meet-
ing showed that electroconvulsive ther-
apy (ECT) is effective for treatment of
depression, psychosis, and self-harm
among patients aged 16 to 25 years
and those with severe long-lasting de-
pression refractory to treatment.
Diagnoses of patients in the study “The study, however, is not a ran- twice per week was associated with an
included depressive disorder (61.7%) domized trial. A lot more research is overall response rate of 92 percent and
and psychotic disorder (16.5%). Around needed in this very unstudied popula- a remission rate of 44 percent. [Del-
60% of the patients screened positive tion,” commented Dr. Nicole Benson ,of monte D, et al, APA Annual Meeting
for substance use disorder based on the Massachusetts General Hospital– 2017]
AUDIT-C, a single-item screening tool McLean Hospital, Boston, Massachu-
derived from the Drug Abuse Screening setts, US, one of the study authors who Relapse rates during the follow-up
Test (DAST)-10. presented the results at the meeting. period were 5.5% in the first month, 3.7
% within the third month, 16.6% within
The researchers also found signifi- ECT has been shown to be effica- the sixth month and 14.8% within 12
cantly greater improvements in patients cious and safe for treatment of depres- months.
with co-existent substance use disor- sive and psychotic disorders in adults,
der vs those who tested negative for but studies in the younger population Around 60% of the patients exhib-
substance use (depression, p=0.008; are still lacking. ited improved well-being at the end of
interpersonal relationships, p=0.037; the follow-up period.
emotional lability, p=0.042) Another study presented at the
meeting showed the efficacy of ECT in ECT involves a brief electrical stim-
In the study, BASIS-24 (Behaviour patients with severe depression refrac- ulation of the brain while the patient
and Symptom Identification Scale-24) tory to conventional treatment. is under anaesthesia. The treatment
was used to assess outcomes based is administered by a team of medical
on six domains, namely depression/ In this study of 54 patients (female, professionals including a psychiatrist,
functioning, interpersonal relationships, 61 percent; mean age, 59.1 years) hos- an anaesthesiologist, and a nurse or
psychosis, emotional lability, self-harm, pitalized in 2005–2015 for bipolar dis- a physician assistant. [https://www.
and substance abuse. order (74 percent) or major depressive psychiatry.org/patients-families/
disorder (26 percent), bitemporal ECT ect]
35
DOCTOR | JULY ISSUE
NEWSBITES
ELAINE SOLIVEN ly pregnancy (mean gestational age, between clarithromycin use in early
T
14.1 weeks). Penicillins were the most pregnancy and the risk of spontaneous
he use of antibiotics such as commonly used antibiotics (n=6,073), abortion. [PLoS One 2013;8:e53327]
quinolones, tetracyclines, met- followed by macrolides (n=1,789),
ronidazole, sulfonamides, and quinolones (n=689), cephalosporins A subgroup analysis on pregnant
macrolides (excluding erythromycin) (n=682), metronidazole (n=344), tet- women who had urinary tract infection
may increase the risk of spontaneous racyclines (n=315), and sulfonamides showed that the use of quinolone was
abortion in early pregnancy, according (n=169). also associated with an increased risk
to a recent study. of spontaneous abortion compared
Compared with no antibiotic use, with the use of penicillin (adjOR, 8.73,
“Our findings may be of use to pol- the risk of spontaneous abortion 95%t CI, 3.08–24.77).
icy-makers to update guidelines for the was increased with the use of quino-
treatment of infections during pregnan- lones (adjusted odds ratio [adjOR], Given the overlapping indications of
cy,” said the researchers. 2.72, 95% confidence interval [CI], penicillins or cephalosporins with other
2.27–3.27), tetracyclines (adjOR, 2.59, antibiotics, confounding by indication
The researchers gathered data 95%CI, 1.97–3.41), metronidazole (ad- was considered a potential limitation,
from the Quebec Pregnancy Cohort jOR, 1.70, 95% CI, 1.27–2.26), and said the researchers.
and conducted a nested case-con- sulfonamides (adjOR, 2.01, 95% CI,
trol study involving 95,722 pregnant 1.36–2.97) after adjusting for potential “Many classes of antibiotics were
women, of which 8,702 had sponta- confounders. associated with increased risk of spon-
neous abortion (defined as pregnancy taneous abortion ... [However,] we in-
termination at <20 weeks of gestation The risk of spontaneous abortion cluded only pregnant women who were
[cases]) and 87,020 were matched also increased with the use of mac- insured by the province’s Prescription
controls. [CMAJ 2017;doi:10.1503/ rolides such as clarithromycin (adjOR, Drug Insurance programme. Therefore,
cmaj.161020] 2.35, 95% CI, 1.90–2.91) and azith- our results may not be generalizable
romycin (adjOR, 1.65, 95% CI, 1.34– to those with private drug insurance,”
Among all the participants, 12,446 2.02), and this was consistent with a they added.
were exposed to antibiotics during ear- previous study revealing an association
36
DOCTOR | JUNE ISSUE
NEWSBITES
A
flexible extended regimen of
ethinylestradiol plus drospire-
none decreased the number of
days with dysmenorrhoea compared
with the standard 28-day cyclic regi-
men of ethinylestradiol plus drospire-
none, according to a Japanese study.
Participants either had primary dys- minogen levels were the most common Soc Sci Med 1989;29:163–169]
menorrhoea (n=148, most common treatment-emergent adverse events in
form with unknown aetiology) or sec- both the flexible extended and standard “[R]educing the number of days
ondary dysmenorrhoea (n=64, asso- groups. with [dysmenorrhoea] even by 1 day
ciated with pelvic pathologies such as can substantially alleviate the burden …
endometriosis or uterine fibroids, and Overall, the findings suggest that on both patients and society,” said the
occurs mostly in older women). at an annual rate, the number of days researchers.
with dysmenorrhoea is estimated to be
Compared with participants in the 31 days shorter in the flexible extended The ethinylestradiol+drospirenone
standard group, women in the flexi- group vs 40 days shorter in the stan- combination has a well-characterized
ble extended group had fewer days dard group. “[This suggests] that the safety profile as an oral contraceptive,
with dysmenorrhoea over the 140-day number of days with [dysmenorrhoea] with previous evidence revealing its ef-
evaluation period (mean -3.4 days, is 9 days shorter per year in the flexible ficacy in reducing the severity of symp-
95% confidence interval [CI], -6.5 to extended group than in the 28-day cy- toms associated with dysmenorrhoea.
-0.3; p=0.03). [Int J Womens Health cle group,” said the researchers. [Aust Fam Physician 2016;45:59–64;
2017;9:295–305] Contraception 2014;89:253–263; Con-
There was also a significant reduc- traception 2016;93:378–385; Obstet
In the subgroup analysis, the num- tion in the need for analgesics in the Gynecol 2010;77:977–988]
ber of days with dysmenorrhoea was flexible extended vs standard group
also fewer in the flexible extended vs (mean -2.6 days, 95% CI, -5.2 to 0.1). The findings were not generalizable
standard group (11.0 vs 14.3 days for to the full study population as a major-
women with primary dysmenorrhoea Due to the pain severity associat- ity of the participants had primary dys-
and 13.8 vs 17.8 days for those with ed with dysmenorrhoea, about 52% of menorrhoea, noted the researchers,
secondary dysmenorrhoea). Japanese women reported medication who called for further trials in women
use for pain management, while approx- with secondary dysmenorrhoea.
Genital haemorrhage, headache, imately 28% reported absenteeism. [Int
nasophar
yngitis, and increased plas- J Gynaecol Obstet 2008;100:13-17;
38
DOCTOR | JULY ISSUE
NEWSBITES
P
sion end). from one patient who discontinued the
ostmenopausal women with os- study (long-term group) and one who
teoporosis had a low incidence Over the extension period, five and withdrew consent (crossover group), all
of fracture and a continuous in- four subtrochanteric or diaphyseal fem- other cases were resolved. None of the
crease in bone mineral density (BMD) oral fractures occurred in the long-term participants developed neutralizing an-
after 7 to 10 years of denosumab and crossover groups, respectively, tibodies to denosumab.
treatment, according to results of the with one in each group determined as
open-label, 7-year extension of the atypical. However, the prescribing informa-
phase III FREEDOM* trial. tion for denosumab was revised to sug-
The annual incidence of new ver- gest a possible increase in incidence of
“These findings suggest a con- tebral and nonvertebral fractures in the osteonecrosis of the jaw with longer
tinued favourable balance between long-term group was low (0.90–1.86% exposure, said the researchers.
benefit and risk through 10 years of and 0.84–2.55%, respectively) during
treatment with denosumab,” said the the extension period and comparable “Given the need for long-term treat-
researchers. “Fracture rates remained to that of the initial FREEDOM trial, ment in many people with osteoporo-
consistently low throughout the study, while in the crossover group, incidence sis, this evidence that the safety pro-
similar to rates observed in the active of new fractures was comparable to file of denosumab remains stable over
treatment group during FREEDOM and that in the first 7 years of denosumab many years in an ageing population is
lower than in a virtual long-term place- treatment in the long-term group. important,” said Professor Juliet Comp-
bo cohort. Our results support the skel- ston from the University of Cambridge,
etal safety of long-term treatment with BMD increased over time in both UK, in a commentary. [Lancet Diabetes
denosumab,” they said. [Lancet Dia- the long-term and crossover groups Endocrinol 2017;doi:10.1016/S2213-
betes Endocrinol 2017;doi:10.1016/ (increase of 21.7 and 16.5% at the lum- 8587(17)30178-X]
S2213-8587(17)30138-9] bar spine, 9.2 and 7.4% at total hip, 9.0
and 7.1% at femoral neck, and 2.7 and “The results of our study support
Participants in the 3-year FREE- 2.3% at the one-third radius; p<0.05 for the use of denosumab as primary
DOM trial were 7,808 postmenopausal all, based on FREEDOM and extension long-term therapy in patients with post-
women aged 60 to 90 years with os- baseline, respectively). menopausal osteoporosis similar to our
teoporosis who were randomized to study population. [However], routine
receive subcutaneous denosumab (60 “Closing of the remodelling space interruption of treatment is not recom-
mg) or placebo every 6 months for 3 and increases in secondary mineraliza- mended,” said the researchers.
years. tion of bone matrix”, “modelling-based
bone formation”, and “reductions in cor- “[Cessation] of denosumab is fol-
Women who completed the trial tical porosity” were among the potential lowed by rapid bone loss and an in-
without treatment discontinuation or mechanisms behind the improvement crease in the rate of vertebral fractures;
missing more than one dose of inves- in BMD, said the researchers. therefore, if treatment is discontinued,
tigational drug were enrolled in the ex- patients should be switched to an alter-
tension trial where all participants were Over the 10-year treatment period, native therapy,” cautioned Compston.
given subcutaneous denosumab (60 yearly incidence of adverse events re-
mg) every 6 months and asked to take duced from 165.3 to 95.9 per 100 par-
calcium (≥1.0 g) and vitamin D (≥400 ticipant-years among all individuals on
IU) daily. denosumab, while the incidence of se-
rious adverse events ranged from 11.5
A total of 2,626 women completed to 14.4 per 100 participant-years.
the extension study (1,343 and 1,283
were given denosumab [long-term Incidence of osteonecrosis of the
* FREEDOM extension: Extension study to evaluate
group] and placebo [crossover group] jaw was comparable between groups the long term safety and efficacy of denosumab
in the initial FREEDOM study, respec- (seven and six in the long-term and in the treatment of osteoporosis
39
DOCTOR | JULY ISSUE
NEWSBITES
A
n increase in body mass index
(BMI) is independently associat-
ed with an elevated risk of devel-
oping end-stage renal disease (ESRD),
according to a Singapore study.
40
DOCTOR | JULY ISSUE
ASIAN PACIFIC
DIGESTIVE WEEK
23 – 26 SEP TEMBER 20 1 7
H O N G KO N G
W W W. A P D W 2 0 1 7. O R G
NAMED LECTURESHIPS
R
there may be slightly better outcomes
obotic-assisted percutane- with the radial approach,” observed
ous coronary intervention (PCI) Mahmud.
showed high clinical and tech-
nical success rates across multiple “[However], after conducting a pro-
sites in patients with lesions, according pensity score matched analysis, no dif-
to data from the PRECISION* registry ferences were observed between the
presented at the Society for Cardiovas- two approaches. Although, there was
cular Angiography and Interventions a slightly superior clinical success with
(SCAI) 2017 Scientific Sessions held in radial access, it was likely the result of
New Orleans, Louisiana, US. patient selection,” he added, noting that
several baseline demographic and an-
“This is the first time we are demon- giographic characteristics were signifi-
strating that the robotic system can be cantly different between the two groups
used, with either a radial or femoral ap- of patients. In general, patients in the
proach, with high clinical and technical transfemoral group were older (mean
success in multiple sites with multiple age, 68.9 vs 65.1 years; p<0.001) and
operators,” said lead author Dr. Ehtish- had lower BMIs (mean, 29.1 vs 31.1;
am Mahmud, director of the Sulpizio p<0.001) with a higher prevalence of di-
Cardiovascular Center at the University abetes (49.8 vs 32.2%; p<0.001) than
of California, San Diego School of Med- the transradial group.
icine in La Jolla, California, US.
They were also more likely to have
The multicentre PRECISION reg- more complex lesion, as assessed by
istry (16 US sites) included data from the ACC/AHA lesion classification (le-
754 robotic PCI procedures performed sion type C, 44.3 vs 27.7%) compared
on 949 lesions using the first FDA-ap- with patients undergoing transradial
proved robotic system for PCI, CorPath robotic PCI. There were 18 serious ad-
200. Two-thirds of the procedures were verse events in total, with 1.99% occur-
conducted using transradial access ring in the transradial group vs 3.02%
(n=452) and the remaining cases with a in the transfemoral group (p=0.47), of
transfemoral approach (n=298). which six were MACE in the transfemo-
”
ral group. All were adjudicated to be not
Clinical success—as determined by related to the robotic system.
“This is the first time procedural success (residual stenosis
of <30% and TIMI 3 flow) without any The CorPath 200 allows coronary
we are demonstrating major adverse cardiovascular event guidewires and stents to be remotely
that the robotic (MACE; comprising cardiac death, controlled for PCI patients. The newer
system can be used, myocardial infarction, or urgent need for CorPath GRX system, which enables
with either a radial target vessel revascularization)—was robotic control of the guide catheter,
reported in 99% of transradial and 95% would be expected to further reduce
or femoral approach, of transfemoral procedures (p=0.0012). the rates of manual assistance or con-
with high clinical and version, according to Mahmud.
technical success In addition, technical success—
in multiple sites with which refers to clinical success without
manual assistance—was also high with
multiple operators” both the transradial and transfemoral * PRECISION: Post-market CorPath Registry on the
approaches (88.6 vs 82.4%; p=0.017). CorPath 200 System in percutaneous coronary
42
DOCTOR | JULY ISSUE
CLINICAL INSIGHTS | IN PRACTICE
Managing vertebral
compression fractures
in primary care
V
ertebral compression fractures, Underdiagnosis of fragility fractures
or fragility fractures, are preva- is a primary concern. Evidence shows
Dr Benjamin Tow lent in the elderly and character- that majority of high-risk individuals are
ized by severe back pain. If left untreat- neither diagnosed nor treated, with
ed, this condition may result in loss of only about one-third seeking medical
height, deformity, immobility, increased attention, and other cases are being
number of bed days, and reduced left unrecognized during a routine tho-
pulmonary function, which can further racolumbar radiographic assessment.
lead to low self-esteem and even de-
pression. An X-ray of the spine is mandato-
ry to assess the presence and severity
Osteoporosis is a significant factor of the fracture. However, fracture age
in the aetiology of fragility fractures. To- might not be accurately evaluated as
gether with menopause and increased X-rays are unable to detect microscop-
age, the weakened bone structure due ic bone cracks.
to the gradual loss of minerals in oste-
oporosis increases an individual’s frac- A magnetic resonance imaging
ture risk. (MRI) scan is therefore recommended
for diagnosing fracture age and occult
Other contributing factors are phys- fractures missed by X-rays. This can
ical inactivity and sedentary lifestyle as also better distinguish the presence
these impair neuromuscular function of spinal cord compression and risk
Vertebral compression
(gait, balance, and muscle strength), of paralysis, as well as rule out other
fractures can lead prolonged corticosteroid use, and low conditions such as tumours and/or in-
to serious pain and body weight/weight loss. Long-term fections.
disability that can use of proton pump inhibitors (PPIs)
significantly affect may also increase the risk of osteo- Bone mineral density (BMD) test
quality of life and porosis-related fractures because PPI is an important tool that can assess
decreases calcium absorption, subse- the degree of osteoporosis and risk
activities of daily living.
quently leading to a lower bone mass. of developing a fragility fracture. Addi-
It comes with significant tionally, the FRAX tool may be able to
economic drawbacks Diagnosing vertebral estimate the likelihood of sustaining a
due to the high risk compression fractures fragility fracture.
of refracture and The back pain could range from mini-
rehospitalization. mal pain with normal activities (eg, sit- The pain associated with vertebral
ting, lying at rest) to excruciating pain compression fractures is far worse than
MIMS Doctor spoke
even with slight movements (eg, get- the usual arthritic aches and pains.
with Dr. Benjamin Tow, ting up from a chair). Such mechanical However, in other cases, the pain may
orthopaedic surgeon pain with light motion signals a defect not be severe enough to warrant at-
at the Orthopaedic and in the spine, which signifies that it is tention and might be misconstrued as
Spine Clinic at Mount unable to support the patient’s load. arthritic back pain.
Elizabeth Medical
The compromised support eventu- It is therefore important to acknowl-
Centre, Singapore,
ally leads to serious pain and immobil- edge the onset and severity of pain,
on how GPs can best ity and may further progress to spinal and take note of the patient’s history
manage this preventable cord and nerve compression with pa- of fragility fractures and other recent
condition. ralysis. injuries that may have contributed to
43
DOCTOR | JULY ISSUE
CLINICAL INSIGHTS | IN PRACTICE
44
DOCTOR | JULY ISSUE
Singapore Prevention & Cardiac
Rehabilitation Symposium 2017
FRIDAY – SATURDAY
20 – 21 OCTOBER 2017
8:00AM – 5:00PM
OBJEC TIVE
NOVOTEL SINGAPORE The SPCRS 2017 aims to provide the latest information and connect them
CLARKE QUAY under an overarching theme, Advances in Cardiac Rehabilitation for
Improved Health. The conference will feature a series of prominent
international and national speakers, and serve as a platform to promote
knowledge exchange, networking and drive strategic alliances for
collaborative research.
46
42
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CLINICAL INSIGHTS | INDUSTRY UPDATE
Pharmacological Ranolazine has signifi cant an- nebivolol have a favourable effect on
management of stable CAD tianginal actions in a clinical trial da- endothelial function and show much
“There is some discordance be- tabase of almost 10, 000 subjects. It promise.”
tween the level of evidence and rec- is an effective antianginal when com-
ommendations made for the treat- pared to placebo and in addition to Central BP elevation can also be
ment of stable CAD in international standard antianginal therapy such successfully treated with vasodilatory
guidelines,” noted Professor Peter as beta-blockers, calcium channel beta-blockers. Dr Antonia Anna Lukito
Collins from Imperial College and the blockers, and nitrates. It also has a of Pelita Harapan University, Tangerang,
Royal Brompton Hospital, London, signifi cant antianginal action in di- Indonesia, reviewed study data showing
UK. abetic subjects and in patients with that nebivolol, which modulates nitric
acute coronary syndromes. It has oxide release, effectively reduces
Beta-blockers and calcium channel also been shown to improve diabet- central BP and aortic stiffness without
blockers are recommended for first-line ic control by reducing HbA1c and has any of the limitations associated with
therapy (class IA evidence in the ESC antiarrythmic properties, reducing traditional beta-blockers. Nebivolol
guidelines). However, US guidelines rate atrial fi brillation and supraventricular also has favourable effects on lipids
the level of evidence for these therapies and ventricular tachyarrythmias. and glucose control in patients with
as class IB. The rating for ranolazine, a hypertension.
novel anti-angina therapy that inhibits Professor Jong-Won Ha from the
the ischaemia-induced sodium influx Yonsei University College of Medicine, Revascularization
that occurs in cardiac myocytes, also Seoul, South Korea, emphasized the “Revascularization procedures
differs (IIaA in the US guidelines and importance of distinguishing between should only be considered for
IIaB in the ESC guidelines). older and newer-generation beta- patients who have symptoms that
blockers when treating hypertension. are not satisfactorily controlled with
“The US guidelines are probably “Older generation beta-blockers optimal medical therapy,” said Collins.
correct,” said Collins. “Ranolazine, for such as atenolol have been shown He reported data from the Clinical
example, is the only novel anti-angina to be inferior to angiotensin receptor Outcomes Utilizing Revascularization
therapy recommended for clinical use in blockers [ARBs] for uncomplicated and Aggressive Drug Evaluation
the US in the past 20 years. Uniquely, it hypertension, suggesting that they are (COURAGE) trial, which indicated that
does not have any significant effects on no longer suitable for first-line therapy,” coronary interventions had a neutral
heart rate or BP and is a highly effective he said. “However, third-generation effect on patient outcomes. [N Engl J
second-line and add-on therapy.” vasodilating beta-blockers such as Med 2007;356:1503-1516]
The esteemed international faculty comprises 22 European and Asian key opinion leaders.
47
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CLINICAL INSIGHTS | INDUSTRY UPDATE
Group Captain Krisada Sastravaha, bypass grafting (CABG) or PCI. [Lancet future CV events, not for ischaemic
Bhumibol Adulyadej Hospital, Thailand, 2013;381:629-638] Although the control.
agreed that revascularization is researchers found fewer adverse events
not suitable for most patients with following CABG, outcomes were similar “There is compelling evidence
stable CAD. However, he noted between the two interventions when that optimal medical therapy reduces
that in the NUCLEAR substudy of patients had a SYNTAX score <22. postrevascularization mortality rates
the COURAGE trial, percutaneous “CABG remains the standard of care and should be initiated in all patients
coronary intervention (PCI) was found for patients with complex, multivessel following revascularization unless
to improve outcomes in patients with disease but in less complex cases, such there are any contraindications,” said
significant ischaemia. [J Nucl Cardiol as patients who have left main disease Collins. Analyses of the 5-year clinical
2006;13:685] “PCI is a mechanical with low or intermediate SYNTAX outcomes from the SYNTAX trial have
revascularization procedure aimed scores or triple vessel disease with a shown that postrevascularization
at relieving acute ischaemia. Optimal low SYNTAX score, PCI is a reasonable OMT signifi cantly reduces the risk
medical therapy is clearly the best alternative treatment,” said Dr Kai Hang of death (hazard ratio [HR], 0.64,
first-line option for most patients with Yiu from the University of Hong Kong 95 percent confi dence interval [CI],
stable CAD, but medical therapy is and the Queen Mary Hospital, Hong 0.48–0.85; p=0.002) (Figure 1) as
insufficient in certain patients, such as Kong. well as the composite endpoint of
those with left ventricular dysfunction,” death, myocardial infarction (MI),
he said. Optimal medical therapy and stroke (HR, 0.73, 95 percent
after revascularization CI, 0.58–0.92; p=0.007) (Figure 2).
The type of intervention selected Optimal medical therapy (OMT) [Lancet 2013;381:629-638]
also requires careful targeting. In the is defined as a combination therapy
Synergy Between Percutaneous Co- with at least one antiplatelet drug, “However, changes in clinical
ronary Intervention with TAXUS and such as aspirin (or thienopyridine practice have been modest despite
Cardiac Surgery (SYNTAX) trial, clinical after PCI), and a beta-blocker, statin, the publication of such findings and
outcomes were compared among and angiotensin converting enzyme further work is required to determine
patients with complex CAD randomized (ACE) inhibitor or ARB. The regimen how best to incorporate OMT into
to revascularization with coronary artery is aggressive and is used to prevent interventional strategies and to improve
48
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CLINICAL INSIGHTS | INDUSTRY UPDATE
the translation of clinical evidence into the importance of viewing HF-PEF cite concerns regarding possible
practice,” concluded Collins. as a real HF and not a collection angioedema and cognitive adverse
of comorbidities. Although there events. The use of beta-blockers in
Management of HF is at present no specific treatment HF patients with atrial fibrillation is also
“China is facing an epidemic of for HF-PEF that improves survival, controversial given that they do not
HF, and the prevalence is only likely LCZ696 was shown in the phase II seem to significantly reduce mortality
to increase given that a significant PARAMOUNT trial to significantly risk in this population.
proportion of the population is classified reduce N-terminal pro-B-type natriuretic
as high risk,” said Dr Jiefu Yang, peptide (NT-proBNP) levels after 12 Future directions
Beijing Hospital, China. Hypertension weeks compared with valsartan. Professor Panos Vardas from the
and CAD are the leading causes of HF [Lancet 2012;380:1387-1395] HF-PEF Heraklion University Hospital, Greece,
in the region, and diuretics, digitalis, and is now thought to result from systemic highlighted promising developments
nitrates the primary therapies. However, endothelial activation and inflammation, expected to impact CV medicine
the use of digitalis is declining and and drugs such as LCZ696, an in the next two decades. PCSK9
that of beta-blockers, ACE inhibitors, angiotensin receptor neprilysin inhibitor, inhibitors, monoclonal antibodies,
ARBs, and aldosterone antagonists may be beneficial by addressing this and novel antithrombotic and anti-
are increasing. The number of patients endothelial dysfunction. A phase III arrhythmic drugs are all expected
reaching the target doses of these agents PARAGON trial of LCZ696 is currently to alter medical therapy, while
remains quite low and they are more underway. Professor Imran Zainal technological advances are expected
frequently used for HF-reduced ejection Abidin from the University of Malaya, to lead to the miniaturization of
fraction (REF) rather than HF-preserved Kuala Lumpur, Malaysia noted that pacemakers, the advent of leadless
ejection fraction (PEF) patients. there is currently some controversy and batteryless devices, increased
regarding whether or not LCZ696 use of multisensors, high-quality
Professor Carolyn Lam, National should be recommended as first-line imaging, and increasing use of
Heart Centre, Singapore, noted therapy. Those advocating caution regenerative biology.
Figure 2. Optimal medical therapy significantly reduces the risk of the composite endpoint of death, MI, and stroke
following revascularization
Drug Group Death/MI/CVA HR (95% CI) P-value
49
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Sponsored Symposium Highlights
Oral or nasal nonsedative H1-antihistamines are the Bilastine has a good safety profile
recommended pharmacotherapy to alleviate the symptoms and In general, bilastine is well tolerated and has a good safety
discomfort associated with the acute phase reaction of AR.2,3 profile. In terms of long-term safety, bilastine was shown to be
According to Assoc Prof Tiongco-Recto, first-generation H1- well tolerated over a treatment period of 1 year.12,13 Bilastine
antihistamine are not recommended mainly due to its adverse confers good central nervous system (CNS) safety due to its
effects such as, somnolence, sedation, dry mouth, palpitation limited passage through the blood-brain barrier.14 Furthermore,
in certain patients, urinary retention in the elderly, weight positron emission tomography investigations indicated that
gain and effects on the QTc interval of the heart’s electrical bilastine has minimal H1-receptor occupancy in the brain.15 The
cycle. Second-generation oral H1-antihistamines, in particular, limitation of bilastine across the blood-brain barrier coupled
are recommended by the ARIA guidelines for use in patients with its minimal H1-receptor brain occupancy contributes to
with mild intermittent, moderate-to-severe intermittent, mild its nonsedative effects and overall CNS safety. Safety studies
persistent and moderate-to-severe persistent AR due to their also concluded that bilastine does not potentiate the effects of
nonsedative properties and higher anti-inflammatory effect.4 CNS depressants such as alcohol and lorazepam.14
this study further accentuates the nonsedative effect of
Figure 1. Bilastine reduced the total NSS within 1 hour bilastine whereby it does not impact psychomotor and driving
(A) with persistent activity beyond 24 hours (B)11 performance. Bilastine is associated with good cardiac safety,
Treatment
whereby a multiple-dose, triple-dummy, crossover study
(A) 10 concluded that bilastine did not cause any significant change
9 Day 1 experiment on the QTc interval of healthy subjects at therapeutic and
8 supratherapeutic doses.12,17
7
6 * Figure 2. Bilastine exhibited no effects towards driving
Total NSS
SDLP (cm)
21
0
20
-2 -1 0 1 2 3 4
19
Allergen exposure time (hours)
18
17
(B) 10
Day 2 experiment 16
9
15
8 Placebo Bilastine Bilastine Hydroxyzine
20 mg 40 mg
7
° † Treatment
6
Total NSS
References: 1. Mello Junior JF. Braz J Otorhinolaryngol 2016;82:621–622. 2. Brozek JL, et al. J Allergy Clin Immunol 2010;126:466–476. 3. Okubo K, et al. Allergol Int
2017;66:97–105. 4. Bousquet J, et al. Allergy 2008;63:8–160. 5. Bousquet J, et al. Curr Med Res Opin 2012;28:131–139. 6. Bilaxten® (product information). Italy: A.
Menarini Manufacturing Logistics and Services; 2014. 7. Corcóstegui R, et al. Drugs R D 2005;6:371–384. 8. Sadaba B, et al. Ther Clin Risk Manag 2013;9:197–205.
9. Kuna P, et al. Clin Exp Allergy 2009;39:1338–1347. 10. Bachert C, et al. Allergy 2009;64:158–165. 11. Horak F, et al. Inflamm Res 2010;59:391–398. 12. Tyl B, et al.
J Clin Pharmacol 2012;52:893–903. 13. Bachert C, et al. Allergy 2010;65:1–13. 14. Church MK. Expert Opin Drug Saf 2011;10:779–793. 15. Farŕe M, et al. Br J Clin
Pharmacol 2014;78:970–980. 16. Conen S, et al. J Psychopharmacol 2011;25:1517–1523. 17. Sastre J, et al. Curr Med Res Opin 2012;28:121–130. 18. Lasseter KC, et
al. Clin Drug Investig 2013;33:665–673. 19. Kalliokoski A, et al. Br J Pharmacol 2009;158:693–705.
O
ften described as pain that is akin to a tight underlying organic diseases as the cause of the
band placed around the head, TTH is a form headache. 5
of mild-to-moderate pain that occasionally
radiates down the neck.1 Globally, TTH accounts for
42% of the adult population with an active headache Box. Red flags in the evaluation of acute
disorder.2 In the United States, 9.2% of people who headaches in adults4
experienced headaches during work were reported to ● Sudden onset of headache
be associated with more than 50% reduction in work
● Headaches increasing in frequency and severity
productivity.3 In addition, the lost of work days due
to headaches was 40 days in a year, equivalent to 3 ● Headache with signs of systemic illnesses (fever,
years in one’s working life (assuming one works from stiff neck and rash)
ages 25–65).4 ● New-onset headache in high-risk patients
● Papilloedema
According to Ms McSwan, TTH can be divided into ● Headache subsequent to head trauma
episodic or chronic TTH. Episodic TTH occurs in ● Headache beginning after 50 years of age
attack-like episodes that last no more than a few
hours but can persist for several days. On the other
hand, chronic TTH occurs for 15 or more days in a TTH is mediated by both central and
month; and is also less common compared with peripheral pathways
episodic TTH.1
Evidence suggests that TTH is associated with an
increased number of active trigger points in the
Differentiating primary from secondary pericranial muscles, leading to increased myofascial
headache disorders pain sensitivity.7 This increase in myofascial pain
sensitivity in TTH is thought to be due to peripheral
TTH is a type of primary headache disorder. Primary
sensitization as well as central factors such as
headaches are usually recurrent and are not
sensitization of various neurons in the brain.7 In view
attributable to underlying organic diseases. The other
of this, Ms McSwan emphasized that nonsteroidal
two common primary headache disorders are migraine
anti-inflammatory drugs (NSAIDs) are favourable for
and cluster headache.5 Causative and exacerbating
management of acute TTH as these agents target
factors of TTH include stress/tension, irregular meal
both central and peripheral pathways of TTH.
time, fatigue and lack of sleep.6
On the other hand, secondary headache disorders are Ibuprofen: A first-line treatment for TTH
caused by underlying organic diseases, ranging from
with favourable side-effect profile
sinusitis to subarachnoid hemorrhage.5
According to the European Federation of Neurology
To differentiate TTH from secondary headache Societies (EFNS), mild-to-moderate, episodic TTH
disorders, healthcare professionals should look can be easily managed with simple analgesics
out for “red flags” (Box) that might suggest (paracetamol and aspirin) or NSAIDs. However,
Sponsored Symposium Highlights
simple analgesics are usually ineffective in chronic Figure 2. The efficacy of ibuprofen is optimized in
TTH since their efficacy tend to decrease with fasted state12
increasing frequency of the headaches.8 Ms McSwan
suggested that a NSAID with good bioavailability 30
1.9
3.9
2.0 2.3
3.2
2.5 2.9 3.2 ulcer, severe heart failure, severe liver disease or
1
1.4
who are taking low-dose aspirin as treatment for
cardiovascular disease should seek advice from a
healthcare professional prior to using ibuprofen.13
0.1
ro LD
c HD
co LD
D
HD
In fena D
In eta D
Na tac D
Na xen D
o LD
D
LD
xi HD
xic LD
HD
fe b H
fe b L
m cH
m in L
pr in H
to n H
Ce oxib
cl ac
Pi cam
Ib ofen
xib
ro n
am
Ce fen
Ke xe
Pi fe
c
Ro xi
n
co
o
o
e
c
r
pr
of
p
e
pr
up
le
up
le
ro
cl
to
do
Ib
do
Di
Di
NSAIDs
GI, gastrointestinal; HD, high dose; LD, low dose; NSAIDs, nonsteroidal anti-inflammatory drugs Benckiser): Relieves pain twice as fast
Ibuprofen lysine is an improved formulation of
A study was conducted to evalute the absorption ibuprofen and has been shown to absorb faster than
of ibuprofen and paracetamol given as a fixed-dose standard ibuprofen. In a study to compare the time
combination tablet in fed and fasted patients.12 It was to reach the maximum plasma concentration (Cmax) of
found that absorption for both drugs was delayed standard ibuprofen (TmaxRef) for various formulations
in fed patients compared with patients who fasted of ibuprofen, Sancak et al noted that ibuprofen lysine
(p>0.05 for ibuprofen and p<0.001 for paracetamol, can be absorbed up to 5.75 times faster than the
respectively) (Figure 2). In view of this, Ms McSwan standard ibuprofen (Table).14 Furthermore, 100% of
Table. Ibuprofen lysine has faster absorption and rapid onset of action14
Cmax, mean (SD), [µg/mL] 29.1 (7.60) 42.3 (10.50) 39.6 (9.37) 37.8 (10.78)
Tmax, median, [min] 150 36 40 37
TCmaxRef, Ref to test GLSM 5.75 (4.53–7.29) 4.51 (3.62–5.64) 3.66 (2.71–4.95)
ratios (95% CI), [%]
Tlag, GM (95% CI), [min] 10.1 (8.7–11.5) 3.1 (2.8–3.4) 4.8 (4.3–5.4) 6.1 (5.5–6.7)
Subjects with Tlag ≤5 min 12 (0–23) 100 (100–100) 64 (48–80) 32 (17–48)
(95% CI), [%]
Cmax, maximum plasma concentration; CI, confidence interval; GLSM, geometric least squares mean; GM, geometric mean; Ref, reference; SD, standard
deviation; TCmaxRef, time to reach Cmax of ibuprofen acid; Tlag, time between drug administration and start of drug absorption; Tmax, time to maximum plasma
concentration
Sponsored Symposium Highlights
subjects in the ibuprofen lysine group achieved less ► A Appropriate use of NSAIDs for those who can
than 5 minutes onset of action (Tlag ≤5 minutes).14 take them
Nurofen® Express should be consumed with water ► D Duration of use is for no more than 3 days per
for best result and to further enhance the benefits of week to avoid medication-overuse headache
ibuprofen in fasted and fed states.
► S Symptoms that are red flagged that you should
be aware of or refer to the pharmacist
Non-drug approaches: Equally important
Self-care should be the preferable way to
for management of TTH manage in the long-term.
Nonpharmacologic interventions play important
roles in the management of TTH.15 Active (relaxation Summary
training, yoga) and passive (acupuncture, spinal
manipulative therapies, massage) modalities are Even though TTH is regarded as a form of mild-
examples of nonpharmacologic therapies effective to-moderate pain, it has adverse impact on work
in managing TTH. Although studies have shown that
productivity, highlighting the need for effective
pharmacologic intervention is typically more quick
and effective, over time, however, nonpharmacologic management of TTH. Ibuprofen is a first-line
intervention is equally as effective.15 Therefore, both treatment for TTH and the novel formulation
pharmacologic and nonpharmacologic therapies of ibuprofen lysine is associated with faster
are equally important and work synergistically in the absorption and rapid onset of action for effective
management of TTH. pain relief. To achieve maximal and effective
treatment outcomes, it is important for healthcare
Optimizing care in TTH: Tips for healthcare professionals to consider using both drug and
professionals non-drug approaches in managing TTH.
Editorial development by MIMS Medica. The opinions expressed in this publication are not
necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or
Reckitt Benckiser (Malaysia) Sdn Bhd
NRF/000640/A
damage howsoever arising is hereby disclaimed. ©2017 MIMS Medica. All rights reserved.
Level 5, Menara UAC, No. 12, Jalan PJU 7/5, Mutiara Damansara, No part of this publication may be reproduced by any process in any language without
47800 Petaling Jaya, Selangor Darul Ehsan, Malaysia. the written permission of the publisher. Enquiries: MIMS Medica Sdn Bhd (891450-U),
2nd Floor, West Wing, Quattro West, No. 4, Lorong Persiaran Barat, 46200 Petaling Jaya,
Tel: +603 7719 1000 Fax: +603 7719 1193 Selangor, Malaysia. Tel: (603) 7623 8000 Fax: (603) 7623 8188 Email: enquiry.my@mims.com
www.reckittbenckiser.com Website: www.mims.com MY-REC-066
Sponsored Symposium Highlights
H
ypertension (blood pressure [BP] ≥140/90 It is noteworthy that the overall reduction of BP is
mmHg) is one of the leading causes of death key in reducing the rate of premature morbidity and
worldwide.1 At present, about 1.5 billion of the mortality in the general hypertensive population.
adult population suffer from hypertension, and this
number is projected to increase in the coming years, The role of CCBs in hypertension
emphasized Professor Agabiti Rosei. Studies have management
shown that BP levels are strongly correlated to the
relative risks of stroke, heart failure, coronary heart CCBs are medications that inhibit the movement
disease (CHD) and renal disease.2,3 of calcium ions into cardiac and vascular smooth
muscle cells via calcium channels. 6 The main
Investigations of the cause of hypertension are typically effect of CCBs is vasodilation, which decreases
inconclusive as most parameters would be, on average, peripheral resistance. The three major classes
normal (eg, sympathetic activity, plasma renin activity). of CCBs – dihydropyridines (eg, lercanidipine),
There is only one parameter that is consistently phenylalkylamines and benzothiazepines – have
abnormal, ie, increased peripheral resistance.4 The a similar mechanism of action, but they differ in
increased peripheral resistance is generally due to selectivity and reactivity at tissue sites.6 For instance,
structural remodelling of small resistance vessels dihydropyridines predominantly affect vascular
(consisting of the small arteries and arterioles) that smooth muscle cells.
can also lead to a reduction in blood flow at maximal
vasodilatation. The structural alteration in the vascular Based on a meta-analysis of 10 randomized controlled
wall of small arteries may have a strong prognostic trials in which active treatment was based on a CCB
significance in patients with hypertension, particularly (dihydropyridine), a –6/–3.4 mmHg systolic BP/
on the risk of cardiovascular events.5 Therefore, the diastolic BP difference between CCB therapy and
correction of small artery remodelling should be a goal placebo was accompanied by a significant relative
of antihypertensive therapy. Evidence have shown risk reduction of all outcomes, including CHD and
that different classes of antihypertensive agents (ie, heart failure (Table).7
CCBs, angiotensin-converting enzyme inhibitors,
angiotensin receptor blockers, beta-blockers, The 2013 guidelines on hypertension of the European
diuretics and direct renin inhibitors) have different Society of Hypertension (ESH) and the European
effects on reversing abnormal vascular structure in Society of Cardiology (ESC) recommend the use
patients with hypertension with beta-blockers and of CCBs in hypertension associated with several
diuretics being less effective in this respect.5 clinical conditions, ie, left ventricular hypertrophy,
Sponsored Symposium Highlights
Table. Relative and absolute risk reduction of various outcomes in BP lowering by CCBs trials in
hypertensive patients with no or minimal baseline therapy7
Sensitivity analysis
Stroke 4 7.8 -6.5/-3.7 306/9532 466/9348 0.63 (0.53–0.76) 0.25 -26 (-31, -17) 39 (32,58)
CHD 3 2.9 -6.3/-3.5 113/8492 151/8308 0.74 (0.58–0.94) 0.26 -7 (-11, -2) 143 (94, 579)
HF 3 1.9 -6.3/-3.5 59/8492 84/8308 0.68 (0.49–0.95) 0.77 -5 (-7, -1) 194 (135,1091)
Stroke + 3 10.3 -6.3/-3.5 382/8492 528/8308 0.71 (0.62–0.81) 0.36 -27(-34, -18) 37 (29, 55)
CHD
Stroke + 3 12.3 -6.3/-3.5 463/8492 612/8308 0.74 (0.66–0.83) 0.64 -29 (-37, -20) 34 (27,51)
CHD + HF
CV death 3 4.6 -6.3/-3.5 162/8492 221/8308 0.71 (0.58–0.87) 0.87 -12 (-16, -6) 84 (62,176)
All-cause 4 7.7 -6.5/-3.7 344/9532 432/9348 0.77 (0.67–0.89) 0.68 -16 (-23, -8) 61 (144,123)
death
BP: blood pressure; CCBs: calcium channel blockers; CHD: coronary heart disease; CI: confidence interval; CV: cardiovascular; DBP; diastolic blood pressure; HF: heart failure; n: number; NNT: number
(and 95% CI) of patients needed to treat for 5 years to prevent one event; pts: patients; P (Heterogen): P for the heterogeneity test χ2Q; RR: Mantel–Haenszel risk ratios; SBP: systolic blood pressure.
asymptomatic atherosclerosis, angina pectoris, ► It does not cause significant reflex tachycardia or
atrial fibrillation for ventricular rate control, other signs of sympathetic activation in the long
peripheral artery disease and isolated systolic term when given at therapeutic doses.16
hypertension. 8 Additionally, findings from the
► At a dose of 10 mg, it has a significant and durable
Valsartan Antihypertensive Long-Term Use Evaluation
antihypertensive effect over 24 hours.17
(VALUE) and Avoiding Cardiovascular Events
through Combination Therapy in Patients Living ► It helps in the regression of left ventricular
with Systolic Hypertension (ACCOMPLISH) studies hypertrophy in patients with hypertension.18
showed that CCBs may be recommended as part ► It displays a particular activity on small-sized
of the first-line regimen for hypertensive patients at intraparenchymal brain arteries and this might
high cardiovascular risk.9,10 CCBs have also been represent an interesting property for the treatment
found to reduce carotid intima-media thickening – of hypertensive brain damage with concomitant
a mechanism that might confer protection against ischaemia.19
stroke.11
Various comparative studies between lercanidipine
Clinical efficacy of lercanidipine and other dihydropyridines have been conducted. In a
(Zanidip®) double-blind, crossover study, lercanidipine was found
to be as effective as amlodipine (24-hour efficacy) in
Lercanidipine is a third-generation lipophilic
lowering systolic and diastolic BP in patients with mild-
dihydropyridine CCB with a long half-life.12 It is
to-moderate essential hypertension (Figure 1).20 Both
characterized by a high vasoselectivity and a
prolonged interaction with L-type calcium channel in agents are known to exhibit consistent BP control;
human cardiovascular tissue.13 The following are the however, lercanidipine is associated with a better
main clinical benefits of lercanidipine: tolerability profile and lesser vasodilation-related
adverse reactions (eg, peripheral oedema, swelling,
► It consistently decreases matrix metalloproteinase-9 flushing and headache) than amlodipine, either used
activity and reduces oxidative stress in patients as a single agent or as initial therapy combined with
with hypertension.14 other classes of antihypertensive agents.21.22
► It improves flow-mediated dilatation in brachial
arteries in patients with coronary vasospasm, and Besides providing effective BP control, lercanidipine
this process is accompanied by an improvement of also exerts favourable effects on the renal vasculature,
chest pain and stress-induced ischaemic changes.15 thus conferring renal protection in patients with
Figure 1. Consistency of BP control (24-hour Figure 2. Preservation of small-sized renal
efficacy) between lercanidipine and amlodipine20 artery lumen by llercanidipine in spontaneously
hypertensive rats24
Placebo
Amlodipine 10 mg
Systolic Lercanidipine 20 mg
160 Normal rat SHR
Blood Pressure (mmHg)
140
120
Diastolic
100
SHR + SHR +
Lercanidipine Manidipine
80
60
9 am 12 3 pm 6 pm 9 pm 12 3 am 6 am
noon midnight
Time of day L: lumen; M: media; A: adventitia; SHR: spontaneously hypertensive rats
hypertension.23 A preclinical study by Sabbatini et al good tolerability profile and provides renoprotective
showed that lercanidipine administration prevented effects in patients with hypertension.
wall thickening and luminal narrowing in small-sized
References: 1. American Heart Association. What is High Blood
arteries and glomerular arterioles (Figure 2). 24,25 Pressure? Available at: https://www.heart.org/idc/groups/heart-public/@
Moreover, lercanidipine exerted antiproteinuric effects wcm/@hcm/documents/downloadable/ucm_300310.pdf. Accessed 7
April 2017. 2. Thomopoulos C, et al. J Hypertens 2014;32:2285–2295.
to a greater extent than other calcium antagonists, 3. World Health Organization. A Global Brief on Hypertension.Available
by inducing vasodilatation of glomerular afferent and at:http://ish-world.com/downloads/pdf/global_brief_hypertension.pdf.
efferent arterioles in patients with hypertension.26 Accessed 7 April 2017. 4. Mulvany MJ. News Physiol Sci 2002;17:105–
109. 5. Agabiti-Rosei E, et al. J Hypertens 2009;27:1107–1114. 6. Parmley
Findings from the REnal Disease: LErcanidipine WW. Clin Cardiol 1992;15:235–242. 7. Thomopoulos C, et al. J Hypertens
Valuable Effect on urine protein Losses (RED LEVEL) 2015;33:195–211. 8. Mancia G, et al. J Hypertens 2013;31:1281–1357.
9. Julius S, et al. Lancet 2004;363:2022–2231. 10. Weber MA, et al. Blood
study also showed that lercanidipine provides Press 2007;16:13–19. 11. Wang JG, et al. Stroke 2006;37:1933–1940.
long-term renoprotective effects in patients with 12. Borghi C. Vasc Health Risk Manag 2005;1:173–182. 13. Brixius K,
et al. Clin Exp Pharmacol Physiol 2005;32:708–713. 14. Martinez ML, et
hypertension, a benefit not seen with the use of al. J Cardiovasc Pharmacol 2006;47:117–122. 15. Janaviciene S, et al.
amlodipine.27 Seminars in Cardiology 2005;11:15–23. 16. Grassi G, et al. Hypertension
2003;41:558–562. 17. Omboni S, Zanchetti A. J Hypertens 1998;16:1831–
1838. 18. Fogari R, et al. J Hypertens 2000;18:s65. 19. Sabbatini M, et
Take-home message al. Mech Ageing Dev 2001;122:795–809. 20. De Giorgio L, et al. Current
Therapeutic Research 1999;60:511–520. 21. Zanchetti A. Clin Cardiol
2003;26:II17–II20. 22. Barrios V, et al. Int J Clin Pract 2008;62:723–728.
Lercanidipine is a third-generation dihydropyridine 23. Burnier M. Curr Med Res Opin 2013;29:1727–1735. 24. Sabbatini M,
CCB with high lipophilicity and high vascular et al. J Cardiovasc Pharmacol 2000;39:39–48. 25. Rosenthal T, et al. J
Cardiovasc Pharmacol Ther 2007;12:145–152. 26. Robles NR, et al.
selectivity, which confers a gradual and prolonged Renal Failure 2010;32:192–197. 27. Robles NR, et al. Curr Med Res Opin
antihypertensive effect throughout 24 hours. It has a 2016;32:29–34.
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