ONCE DAILY PRASUGREL AND ROSUVASTATIN FDC

JUSTIFICATION RATIONALE
Obesity confers an elevated risk of acute coronary syndromes (ACS) in both
healthy and less healthy subgroups of lifestyle behaviors. The effect of obesity on
cholesterol levels is complex. Although obesity does not appear to be strongly
associated with overall cholesterol levels, among obese individuals triglyceride
levels are usually high while HDL (beneficial cholesterol) levels tend to be low,
both risk factors for heart disease. Obesity, in any case, has other effects
(hypertension, increase in inflammation) that pose major risks to the heart.

Acute coronary syndromes (ACS) are life-threatening manifestations of coronary

artery disease, occurring when a thrombus forms at the site of atherosclerotic
plaque rupture or fissuring. Acute coronary syndromes are an umbrella term
used to cover any group of clinical symptoms compatible with acute myocardial
ischemia. Acute myocardial ischemia is chest pain due to insufficient blood
supply to the heart muscle that results from coronary artery disease (also called
coronary heart disease).

Rosuvastatin is the best hypocholesterolemic drugs with superior efficacy and

safety, whereas Prasugrel Hydrochloride is a novel platelet inhibitor used for
acute coronary syndromes planned for percutaneous coronary intervention.

Clopidogrel is a pro-drug that needs to be metabolized in the liver and intestines

to form active metabolites. Prasugrel, a third generation thienopyridine, was
approved for use in Europe in February 2009, and is currently available in the
United Kingdom. On July 10, 2009, the US Food and Drug Administration
approved the use of prasugrel for the reduction of thrombotic cardiovascular
events (including stent thrombosis) in patients with acute coronary syndrome
who are to be managed with percutaneous coronary intervention. Compared with
clopidogrel, the newest thienopyridine, prasugrel, has a faster onset of platelet
inhibition and less variability of response. There was a consistent benefit of
Prasugrel over clopidogrel for reducing cardiovascular death, myocardial
infarction, or stroke in patients

Prasugrel improves circulation by preventing clot formation whereas

Rosuvastatin reduces LDL and triglyceride deposition by preventing lipid
synthesis. Rosuvastatin is one of the best statin available till now and so is the
prasugrel among its group.

There is no drug interaction between prasugrel and Rosuvastatin and thus it

paves the way to FDC formation.

Both the salts are having different mode of action but ultimately improve
circulation of coronary artery and prevent unwanted and untimely death.
Thus FDC of Prasugrel and Rosuvastatin is the need of the hour to prevent death
due to acute coronary syndrome. This could be a safeguard to protect life and
prevent the chances of untimely death.

Reference

• Med Sci Monit. 2009 Dec;15(12):MS24-30. Kowalczyk M, Banach M,

Mikhailidis DP, Hannam S, Rysz J.Department of Nephrology,
Hypertension and Family Medicine, Medical University of Łódź, Łódź,
Poland.
• J Clin Pharmacol. 2010 Apr 21.Small DS, Li YG, Ernest CS 2nd, April
JH, Farid NA, Payne CD, Winters KJ, Rohatagi S, Ni L.
• J Am Coll Cardiol. 2009 Aug 18;54(8):678-85. TIMI Study Group,
Brigham and Women's Hospital, Boston, MA 02115, USA. O'Donoghue M,
Antman EM, Braunwald E

MEHER PHARMA INTERNATIONAL

B-6/151, SECTOR-3, NEAR JAIPURE GOLDEN HOSPITAL, DELHI-85
DR.MOHD SHAHBAZ ALAM-9818131498, shahbaz@meherpharma.com
CAUSE & TREATMENT OF ACUTE CORONARY SYNDROME

Abnormal Lipid Profile Leads To Death

Lifestyle Mismanagement

Obesity

Increases LDL & TG

Coronary Syndrome

Complete Blockage

Cardiac Arrest

Death
 Medication for acute chronic syndrome

Prasugrel Rosuvastatin

Reduces Platelet Prevents LDL & TG

Aggregatopm

Reduces Coronary
Reduces Coronary
Congestion
Congestion

Improves Circulation
Improves Circulation

Saves Life
 OBESITY AND METABOLIC SYNDROME

Obesity is at epidemic levels in all age groups globally that is why it is termed as
globosity. The effect of obesity on cholesterol levels is complex. Although obesity
does not appear to be strongly associated with overall cholesterol levels, among
obese individuals triglyceride levels are usually high while HDL (beneficial
cholesterol) levels tend to be low, both risk factors for heart disease. Obesity, in
any case, has other effects (hypertension, increase in inflammation) that pose
major risks to the heart.

Obesity is a particularly hazardous when it is one of the components of the

metabolic syndrome. This syndrome is diagnosed when three of the following are
present: abdominal obesity, low HDL cholesterol, high triglyceride levels, high
blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic
condition that is significantly associated with heart disease and higher mortality
rates from all causes. A 2002 study estimated that 24% of the population now
has this condition.

Obesity is highly linked with type 2 diabetes, in any case. And diabetes itself
poses a significant risk for high cholesterol levels and heart disease. Obesity
confers an elevated risk of acute coronary syndromes (ACS) in both healthy and
less healthy subgroups of lifestyle behaviors.

Heart disease and stroke are the leading causes of death in people with
diabetes. People with diabetes are at risk for the following heart-risk conditions,
and the more of these conditions they have, the worse the outlook:

• High blood pressure (hypertension). Up to 75% of cardiovascular problems

in people with diabetes may be due to hypertension.
• Very unhealthy cholesterol and lipid balances (high triglyceride levels and
lower high density lipoprotein).
• Blood clotting problems.
• Impaired nerve function (neuropathy), which can also damage the heart. In
fact, some experts estimate that the mortality rates from neuropathy-related
heart conditions ranges from 15% to 53%.

Diabetics with heart disease may have a higher risk for silent ischemia, a
condition in which people have blocked arteries but do not experience the
angina, the chest pain that signals heart disease
Peripheral artery disease (PAD) occurs when atherosclerosis affects the
extremities, particularly the feet and legs. In fact, the major risk factors for heart
disease and stroke are also the most important risk factors for PAD. (The
combination of such conditions with PAD also produces more severe forms of
heart or circulatory disease.) Although signs of heart disease are detected in only
20% to 40% of patients with PAD after an initial diagnosis

The effects of mental stress on heart disease are controversial. Stress can
certainly influence the activity of the heart when it activates the sympathetic
nervous system (the automatic part of the nervous system that affects many
organs, including the heart). This effect may support the association between
acute stress and a higher risk for serious cardiac events, such as heart rhythm
abnormalities and heart attacks, in people with heart disease. Nevertheless, not
all studies report strong evidence that stress has any effect on the heart,
particularly in people without any history of heart disease.

Depression increases the severity of heart attack and may even impair a patient's
response to medication for heart disease. Although people with heart disease
may certainly become depressed, this does not explain entirely the link between
the two problems. The data are now suggesting that depression itself may be a
true risk factor for heart disease as well as its increased severity. A number of
studies have suggested that depression has biologic effects on the heart,
including blood clotting and heart rate.

A study in 2001, for example, reported an association between depression and a

greater risk for death from heart problems even in people without a history of
heart disease. A 2002 study reported a higher risk for heart failure in women--
although not in men--with depression. The more severe the depression, the more
dangerous to the health, although even mild depression, including feelings of
hopelessness, experienced over many years, may harm the heart, even in
people with no early signs of heart disease.

Reference

• Diabetologia. 2010 May 12A family history of type 2 diabetes increases

risk factors associated with overfeeding.Samocha-Bonet D, Campbell LV,
Viardot A, Freund J, Tam CS, Greenfield JR, Heilbronn LK.
• Rev Med Chil. 2010 Feb;138(2):181-7[Effect of counselling school
teachers on healthy lifestyle on the impact of a program to reduce
childhood obesity.]Kain J, Leyton B, Concha F, Salazar G, Lobos L, Vio F.
• Am J Med Sci. 2010 May 10. Metabolic Syndrome and Its Association
With Colorectal Cancer: A Review.Siddiqui AA.

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DR.MOHD SHAHBAZ ALAM-9818131498, shahbaz@meherpharma.com