Updated Management of

Hypertriglyceridaemia
Rio Herdyanto, MD, FIHA
DR. R. Sosodoro Djatikoesoemo General Hospital
Bojonegoro
 Introduction
• To date, treatment of hyperlipidaemia has centered on the
management of plasma total and low-density lipoprotein (LDL)
cholesterol levels.
• Although there is robust evidence for an association between LDL
cholesterol levels and cardiovascular disease (CVD), there has been
more uncertainty regarding the meaning of the association
between triglyceride levels and CVD.
Classification of Triglyceride Levels
According to The Guideline

J Chronic Dis Manag 2(2): 1012 (2017)

 Statements about Triglycerides
(305 respondents participated in the survey, 305 (156 cardiologist & 149 CV Team members)

Amarin Beyond LDL: Focused Insights High Triglycerides, Very High Triglycerides and
CV Residual Risks

December 2017
Q15: Below are some statements made about Triglycerides. Please select the statements with which you agree. 5
 What is Non-HDL-C ?
BAD ALL ATHEROGENIC LIPOPROTEIN
LDL Chylomicron
IDL VLDL
remnant

APOA-1 APOB APOB APOB APOB 48

Non-HDL
The Possible Mechanism of TRLs Atherogenicity

Penget al. Lipids in Health and Disease (2017) 16:233

Optimizing LDL-Cholesterol still :
most important
 Decrease in LDL-C levels reduces the rate of coronary events

30 CHD event rates against LDL-C levels in primary & secondary prevention trials
4S - Placebo
25
Secondary
20
4S - Rx Prevention
LIPID - Placebo
15
CARE - Placebo
LIPID - Rx
CARE - Rx
Primary
10
TNT – ATV80
HPS - Rx TNT – ATV10
PROVE-IT - PRA
HPS - Placebo
Prevention
WOSCOPS – Placebo
PROVE-IT – ATV AFCAPS - Placebo
5 AFCAPS - Rx 46
WOSCOPS - Rx
ASCOT - Placebo
ASCOT - Rx

40 60 80 100 120 140 160 180 200

(1.0) (1.6) 2.1) (2.6) (3.1) (3.6) (4.1) (4.7) (5.2)
LDL-C achieved mg/dL (mmol/L)
1. Rosenson RS. Exp Opin Emerg Drugs 2004; 9 (2):269-279
2. LaRosa JC, et al. NEJM 2005; 352:1425-1435
Lowering LDL-C alone insufficient
to address patients with high risk of CV events
 Many CHD Events Still Occur in Statin-Treated Patients
Residual CVD Risk in Statin vs Placebo Trials
40

25-40% CVD Reduction Leaves High Residual Risk

Major CHD Events, %
Patients Experiencing

30 28.0 Placebo
Statin
19.4
20
15.9
12.3 13.2
10.2 11.8 10.9
10 8.7 7.9
5.5 6.8

0
4S1 LIPID2 CARE3 HPS4 WOSCOPS5 AFCAPS/TexCAPS6
N 4S
4444 LIPID
9014 CARE
4159 HPS
20 536 WOS
6595 AFCAPS
6605 /
 LDL -35% -25% -28% -29% -26% -25%
TexCAPS
Secondary High Risk Primary
14S 4HPS Collaborative Group. Lancet. 2002;360:7-22.
Group. Lancet. 1994;344:1383-1389.
2LIPID Study Group. N Engl J Med. 1998;339:1349-1357. 5Shepherd J et al. N Engl J Med. 1995;333:1301-1307.

3Sacks FM et al. N Engl J Med. 1996;335:1001-1009. 6 Downs JR et al. JAMA. 1998;279:1615-1622.

 Even When LDL-C Is < 70 mg/dL, Low HDL-C & High TG levels
Are Predictive For CV Events
TNT study PROVE IT-TIMI 22 study

30-day risk of death, MI or recurrent

5-yr risk of major CV events (%)

10 25
9
8 +39% 20 20.3
7
+56%
p=0.03
6 15 p=0.001

ACS (%)
5 13.5
4 10
3
2 5
1
0 0
Q1 Q2 Q3 Q4 Q5
(<37) (37 to <42) (42 to <47) (47 to <55) (≥55)
≥200 <200
(n=603) (n=2,796)
Quintile of HDL-C Level (mg/dL) On-treatment TG (mg/dl)
in pts who achieved LDL-C <70 mg/dL in patients who achieved LDL-C <70 mg/dL
on statin therapy on statin therapy
Barter P et al. N Engl J Med. 2007; 357:1301-10. Miller M et al. J Am Coll Cardiol. 2008;51:724-30.
 Thinking & acting beyond LDL
For further reduction of residual CV risk, attention should be
paid to modifiable risk factors .
 While LDL-C Levels Are Improving,
The Problem Of Elevated TG & Low HDL-C May Be Worsening
In the past 3 decades in the US, while the prevalence of normal LDL-C levels has increased, the prevalence of
combined abnormal TG & HDL-C has more than doubled1,2

NHANES
Abnormal TG & HDL-C
Proportion with optimal or

80%
Optimal or near optimal LDL-C (<130 6%
(TG >150 mg/dL & HDL-C <40 mg/dL)
near optimal LDL-C

mg/dL)
70% 5%

abnormal TG and
abnormal HDL-C
Proportion with
60%
64% 4.8%
50% 24% 4% 2.3-fold
40% 3%

30%
40%
2%
20%
2.1%
1%
10%

0% 0%
1976-1980 1999-2006 1976-1980 1999-2006

1. Cohen JD et al. Am J Cardiol. 2010;106:969-75.

2. Cohen JD et al. Circulation. 2008;118(18Suppl):S1081-82. (Abstract).
 Elevated TG & Low HDL-C Represent
An Even Greater Risk For Patients With T2DM
Proportion with event (%) ACCORD Lipid
18
16
18.1%
17.3% +70%
14
12
10
8 10.1%
6
Mean LDL-C:
4
2 80 mg/dL
0
Elevated TG (≥204 mg/dL) Previous CVD All others
+ low HDL-C (≤34 mg/dL) (n=1,008) (n=2,284)
(40.5% of pts with
(n=456) elevated TG/low HDL-C)

In pts. with T2DM, elevated TG & low HDL-C is associated with:

▪ Almost as high CVD risk* as that of pts with previous CVD +1,2
▪ 70% higher residual CV risk* despite achievement of LDL-C goal with a statin
*Major CV events defined as CV death, nonfatal MI & nonfatal stroke (primary endpoint)
1. ACCORD Study Group. N Engl J Med. 2010;362:1563-74; 2. Elam MB et al. AHA 2010. Presentation 19724.
MIRACL Trial dal-OUTCOMES Trial
Treatment Targets & Goals for CVD prevention
 2016 ESC/EAS Guidelines For
The Management Of Dyslipidaemias
Recommendations Class Level
LDL-C is recommended as the I A
primary target for treatment.
TC should be considered as a IIa A
treatment target if other analyses
are not available.
Non-HDL-C should be considered IIa B
as a secondary treatment target.
Apo-B should be considered as a IIa B
secondary treatment target, when
available.

Catapano A, et al. European Heart Journal (2016)37, 2999–3058

 Lipids LDL-C is The Primary Target
Very high-risk:
LDL-C <70 mg/dL or a reduction of at least 50% if the baseline b is between 70 and 135 mg/dL.

High-risk:
LDL-C <100 mg/dL or a reduction of at least 50% if the baseline b is between 100 and 200
mg/dL).
Low to moderate risk:
LDL-C <115 mg/dL.
Non-HDL-C secondary targets are <100, 130 and 145 mg/dL for very high-, high- and moderate-
risk subjects, respectively.
HDL-C: no target, but >40 mg/dL in men and >48 mg/dL in women indicates lower risk.

TG: no target but <150 mg/dL indicates lower risk and higher levels indicate a need to look for
other risk factors.

b The term “baseline LDL-C“ refers to the level in a subject not taking any lipid lowering medication.

Catapano A, et al. European Heart Journal (2016)37, 2999–3058

 2016 ESC/EAS Guidelines
The Management Of Dyslipidaemias:
Recommendations for drug treatment of hypertriglyceridaemia

Recommendations Class Level

Drug treatment should be considered in high risk patients with IIa B
TG> 200mg/dL.
Statin treatment may be considered as the first drug of choice IIb B
for reducing CVD risk in high risk individuals with
hypertriglyceridaemia
In high risk patients with TG>200mg/dL despite statin IIb C
treatment, fenofibrate may be considered in combination with
statins

Catapano A, et al. European Heart Journal 2016,

 CONCLUSION
• The remnant cholesterol in TGRL not TG itself has a relation for
atherosclerosis.
• It is well known that the CV risk is increased if TG >150mg/dl even in
patients with statin treatment.
• The TG lowering therapy is beneficial especially in high CVD risk
patients with HTG and low HDL.
• We have to keep our treatment goals tight for both LDL and non-HDL
levels especially in high risk patients.
Thank You
 Strategies for Management of Elevated Triglycerides
Triglyceride Actions Follow-up
Level

150 to • Check to see if LDL-C is at target. 6 to 12

199 • Evaluate and treat secondary causes. months
mg/dL • Evaluate CVD risk factors and metabolic syndrome
criteria.
• Lifestyle measures.
200 to • Check LDL-C and non-HDL-C. 3 to 6
499 • Evaluate and treat secondary causes. months
mg/dL • Evaluate CVD risk factors and metabolic syndrome
criteria.
• If LDL-C and non-HDL-C not at target, consider
pharmacologic therapy with statins (or intensify current
statin treatment).
• In patients who still have high non-HDL levels on
statins, consider adding a fibrate or omega-3 fatty acid,
(although there is no evidence for clinical benefit).
Triglyceride Level Actions Follow-
up
500 to 999 •Check non-HDL-C. 4 to 8
mg/dL •Evaluate and treat secondary causes. weeks
•Evaluate CVD risk factors and metabolic syndrome
criteria.
•Check for family history of dyslipidemia.
•Intensify lifestyle measures.
•Institute/intensify pharmacological treatment to avoid
pancreatitis and to achieve TG levels < 500 mg/dL
as well as LDL-C and non-HDL-C goals (Statins-without
history of pancreatitis, Fibrate, Omega-3 FA & Niacin).
>1000 mg/dL • Evaluate and treat secondary causes. 4 to 8
• Evaluate for primary genetic causes. weeks
• Intensify dietary measures with very low fat diet (<15%
of calories) and avoidance of alcohol.
• Simultaneously start pharmacological treatment to avoid
pancreatitis (Fibrate, Omega-3 FA and Niacin).
• After triglycerides fall < 500 mg/dL, assess LDL-C &
non-HDL-C and risk of cardiovascular disease, and treat
appropriately.