DRUG PRESENTATION

PRESENTER: Dr. Md. Abdur Rashid D-card Student NICVD

MODERATOR : DR. MOHSIN AHMED Assistant Professor Cardiology, NICVD.

HDL RAISING DRUGS

INTRODUCTION
HDL-C level is a strong inverse predictor of cardiovascular events. Low HDL level is an independent risk factor for coronary artery disease even when LDL is low.

INTRODUCTION (cont )

An increase of HDL by 1 mg/dl can be expected to reduce the risk of major cardiovascular events by 1-3%.

INTRODUCTION (cont )
HDL-C level more than 60 mg/dl actually protects people from coronary heart disease, thats why researchers have been looking for the way to increase HDL level.

How we can increase HDL?

Aerobic exercise : 5% Ethanol (1-2 drinks/day) : 12% Tobacco cessation: 10% Weight loss : .35mg/dl/kg lost

Nicotinic Acid: 10-30 %

Drugs that increase HDL level

Statins Fibrates

Niacin
CETP inhibitors
Torcetrapib Anacetrapib

Statins
Current therapies with conventional statins raise

HDL-C by only 5-10%.

Fibrates
The prime action of Fibrates is to decrease TG.

It increases HDL 10- 20% by

reverse cholesterol transport mechanism.

Fibrates ( cont..)
It increases the production of apoA-I and apoA-II in liver. It

also converts small, dense

LDL-C to normal size LDL-C

molecule.

Niacin
Niacin strongly inhibit lipolysis in adipose tissue. It increases HDL level by 1030% but side effects of flushing

and dyspepsia are problematic

CETP Inhibitors
Cholesteryl Ester Transfer Proteins (CETP) inhibitors are:

Torcetrapib
Anacetrapib

Torcetrapib
Torcetrapib increases HDL level by 40- 150 % Torcetrapib was developed by Pfizer in 2006. Significant side effect like increase BP was observed.

Anacetrapib
Anacetrapib not only able to increase HDL but also

decrease LDL-C level.

Reduce LDL by 39.8% than placebo.

Anacetrapib (cont..)
Increase HDL by 138.1% than placebo. Orally active, potent, selective CETP inhibitor. Does not raise BP like Torcetrapib

Anacetrapib (cont..)
Developed by Merck Research Laboratory in 2010. Still no FDA recommendation and not available in market

Background: CETP inhibition

LDL / VLDL

LDL-R

CE
SR-B1
FC

CETP

X inhibition
HDL
Free Cholesterol (FC) in Extrahepatic tissues

CE
LCAT Bile

FC

TRIAL ON ANACETRAPIB

Study Objectives and Endpoints

Randomized, double-blind placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patient with CHD or CHD risk equivalent disease.

Cont..
The primary objective of this study was to evaluate safety

to allow decision making for

large outcomes study.

Study Design
Randomization 1:1 Ratio

Age: 18-80 years LDL-C @ NCEP ATPIII goal < 100 mg/dL Statin other lipid modifying therapy

Anacetrapib 100 mg n=750

Study drug stopped if LDL-C<25mg/dL during treatment

12 week follow-up

Placebo n=750

Stable dose-regimen of lipid-modifying therapy

Week -2 0 6 12 18 24 30 38 46 54 62 70 76 80 84 88

Visit

3 4 5 6 7 8 9 10 11 12

13 14

15

16 18

Placebo Screening Run-in Treatment Phase

Reversibility Phase

Conclusion

Anacetrapib treatment had robust

effects on HDL-C, LDL-C, with

sustained effects over 18 months.

Cannon CP et al. N Engl J Med 2010;363 (19) online 11/17/2010

Conclusion

(cont..)

Anacetrapib had an acceptable side-effect profile with no effects on blood pressure. The long term safety and efficacy of anacetrapib will now be tested in a large clinical outcomes trial.

Thank You