PENDAHULUAN

High-density Lipoprotein (HDL) berperan penting dalam proses selular kolesterol

efflux, dan berefek tambahan didalam aterotrombosis. Hubungan antara tingginya kadar HDL

dengan kejadian Penyakit Jantung Koroner telah teruji dalam penelitian observasional dengan

menggunakan uji post hoc dan meta analisis terhadap terapi statin untuk pasien dengan factor

risiko tinggi penyakit jantung, penyakit jantung kronis atau sindrom koroner akut. Meskipun

begitu, masih belum jelas apakah naiknya kadar HDL akibat terapi farmakologi dapat

menurunkan resiko terjadinya penyakit jantung. Akan tetapi perubahan kadar HDL tidak

dapat merubah fungsi fisiologis HDL.

Kolesterol Ester Transfer Protein (CETP) dapat mentransfer kolesterol ester dari

kadar HDL menjadi partikel aterogenik lipoprotein yang berisi apolipoprotein B, seperti Low

Density Lipoprotein (LDL). Tetapi tidak semua analisis penelitian genetik polimorfis

memiliki hasil CETP berhubungan dengan tingginya kadar HDL kolesterol, rendahnya kadar

LDL kolesterol, dan rendahnya resiko kejadian penyakit jantung. Penelitian ini bertujuan

untuk mengetahui apakah inhibitor CETP dapat menurunkan resiko penyakit jantung

1. A. Was the assignment of patients to treatments randomised?

This paper: Yes No Unclear

Comment:

We randomly assigned 15,871 patients who had had a recent acute coronary

syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or

placebo, in addition to the best available evidence-based care. The primary efficacy

end point was a composite of death from coronary heart disease, nonfatal myocardial

infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation.

B. Were the groups similar at the start of the trial?This paper: Yes No Unclear

Comment:

The baseline characteristics of the two study groups (assessed at the time of

randomization) were well matched. Most patients in the two groups were treated with

aspirin, statins, thienopyridines, betablockers, and angiotensin-converting–enzyme

(ACE) inhibitors or angiotensin-receptor blockers (ARBs) and underwent a coronary

revascularization procedure between the time of the qualifying event and random

assignment. The mean baseline LDL cholesterol level was 76 mg per deciliter (2.0

mmol per liter) (with a level of 100 mg per deciliter or lower in 86% of the patients),

the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), the

mean apolipoprotein A1 level was 137 mg per deciliter, and the mean apolipoprotein

B level was 81 mg per deciliter.

2. A. Aside from the allocated treatment, were groups treated equally?This paper: Yes No Unclear

Comment:

After 4 to 12 weeks of run-in, and no later than 12 weeks after the index event,

qualifying patients were randomly assigned, 1:1 ratio, to receive dalcetrapib at a dose

of 600 mg daily or matching placebo.

B. Were all patients who entered the trial accounted for? – and were they analysed in the groups to which they were randomised?This paper: Yes No Unclear

Comment:

We randomly assigned 15,871 patients who had a recent acute coronary syndrome to

receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in

addition to the best available evidence-based care. From April 2008 through July

2010, a total of 15,871 patients were enrolled at 935 sites in 27 countries and were

included in the intention-totreat population

Patients 45 years of age or older who provided written informed consent were eligible

to participate if they had been hospitalized for an acute coronary syndrome

characterized by elevated cardiac biomarkers, with symptoms of acute myocardial

ischemia, ischemic electrocardiographic abnormalities that were new or presumed to

be new, or loss of viable myocardium on imaging. Patients without elevated cardiac

biomarkers were eligible to participate if symptoms of acute myocardial ischemia

were accompanied by electrocardiographic changes that were new or presumed to be

new and by additional evidence of obstructive coronary disease. Patients who had a

myocardial infarction associated with percutaneous coronary intervention were also

eligible.

There were no exclusions on the basis of the HDL cholesterol level; however, patients

with serum triglyceride levels of 400 mg per deciliter (4.5 mmol per liter) or higher

were excluded. Other exclusion criteria are listed in the Supplementary Appendix, available at NEJM.org.

3. Were measures objective or were the patients and clinicians kept “blind” to which treatment was being received?This paper: Yes No Unclear

Comment:

We entered patients who met the inclusion criteria into a single-blind, placebo run-in

period to assess adherence, ensure that no exclusion criteria were met, and allow time

for metabolic steady state to be achieved after the index acute coronary event. After 4

to 12 weeks of run-in, and no later than 12 weeks after the index event, qualifying

patients were randomly assigned, in a 1:1 ratio, to receive dalcetrapib at a dose of 600

mg daily or matching placebo, with randomization stratified according to country and

status with respect to cardiac biomarker levels (elevated or not elevated) at the time of

the index event.

The Result

1. How large was the treatment effect? RR (Relative Risk) = 0.028/0.029 = 0.96

RR < 1, the treatment decreases the risk of death.

ARR (Absolute Risk Reduction) = 0,029- 0,028 = 0,001

The absolute benefit of treatment is a 0,1% reduction in the death rate.

RRR (Relative Risk Reduction) = 0.001/0.029 = 0.034 or 3,4%

The treatment reduced the risk of death by 3,4% relative to that occurring in

the control group.

NNT (Number Needed to Treat) = inverse of the ARR and is calculated as 1 /

ARR.

1/ 0,001 = 1000

We would need to treat 1000 people for 3 years in order to prevent 1 death.

2. How precise was the estimate of the treatment effect?Dalcetrapib had no significant effect on the primary end point, which occurred in

8.3% of the patients in the dalcetrapib group and in 8.0% of the patients in the placebo

group (hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P =

0.52) (Fig. 2). Dalcetrapib also had no significant effect on the rate of any component

of the primary end point, on the rate of unanticipated coronary revascularization, or

on the rate of death from any cause.

Will the results help me in caring for my patient? (ExternalValidity/Applicability) Is my patient so different to those in the study that the results cannot apply?

Yes, it is

Is the treatment feasible in my setting?

Yes, it is

Will the potential benefits of treatment outweigh the potential harms of treatment for my

patient?

Yes, it will