Authors
Schwartz GG, Olsson AG, Abt M, et al.
Title
Effects of dalcetrapib in patients with a recent acute coronary syndrome
References
N Engl J Med. 2012 Nov 29;367(22):2089-99.
Background
In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain.
Purpose
To evaluate the effects of dalcetrapib on cardiovascular risk among patients with a recent acute coronary syndrome.
Design
  • Multicenter, randomized, double-blind trial
  • 15,871 patients age >45 years with recent ACS
  • All patients on appropriate statin therapy ideally to LDL <1.8mmol/L; (<2.6mmol/L allowed). No specific statin recommended
Exclusion Criteria
  • Triglycerides >4.5 mmol/L
  • Women of childbearing potential
  • Severe anemia Hb <100 g/L
  • ACS from uncontrolled HTN
  • HbA1c >10%
  • Severe liver disease and/or ALT >1.5x ULN
  • CK > 3x ULN
  • Creatinine >195umol/L
  • Concomitant treatment with other lipid controlling agents
  • Malignancy during past 3 years and/or any serious life threatening condition
Follow-Up
Median 31 months
Treatment Regimen
  • 4-12 week placebo run-in period to assess adherence
  • After qualifying, patients randomized to dalcetrapib 600mg/day or placebo
Results

Primary Endpoint

HDL increased by 31-40% in dalcetrapib group and 4-11% in placebo group

Placebo
n=7933
Event rate at 3 yr		 Dalcetrapib
n=7938
Event rate at 3 yr		Hazard Ratiop
Major CV event (cardiac death, non-fatal MI, hospitalization for unstable angina, cardiac arrest or any stroke)
9.1%9.2%1.04 (0.93–1.16)0.52

Secondary Outcomes

(see study for complete list)

Placebo
n=7933
Event rate at 3 yr		 Dalcetrapib
n=7938
Event rate at 3 yr		Hazard Ratiop
Cardiac death
1.8%1.6%0.94 (0.73–1.21)0.66
Non-fatal MI
6.0%5.9%1.02 (0.89–1.17)0.80
Stroke
1.0%1.4%1.25 (0.92–1.70)0.16
Hospitalization for unstable angina
1.3%1.3%0.91 (0.68–1.22)0.54
Death from any cause
3.4%3.1%0.99 (0.82–1.19)0.90
Summary
In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events.