| Authors |
| Barter PJ, Caulfield M, Eriksson M,et al. |
| Title |
| Effects of torcetrapib in patients at high risk for coronary events |
| References |
| N Engl J Med. 2007 Nov 22;357(21):2109-22. |
| Background |
| Evidence supporting the proposition that high-density lipoprotein (HDL) cholesterol should be considered as a therapeutic target includes experimental models of atherosclerosis, an inverse relationship to the risk of cardiovascular disease in humans, clinical trials of drugs for which raising HDL cholesterol levels is a primary pharmacologic effect, and the residual risk of cardiovascular disease associated with a low HDL cholesterol level after effective statin therapy. |
| Purpose |
| To investigate the whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. |
| Design |
- Multicenter, randomized, double-blind trial
- 15,067 patients ages 45-75 years at high cardiovascular risk (hx of DM, MI, stroke, PVD or revascularization- within 30 days to 5 years prior to study)
|
| Exclusion Criteria |
- LDL <2.6mmol/L (if not on lipid lowering therapy)
- Cardiovascular event during run-in period
- Any serious medical condition that would limit life expectancy <5 years
- Uncontrolled hypertension (SBP >140mmHg; DBP >90mmHg)
|
| Follow-Up |
| 12 months |
| Treatment Regimen |
- 4-10 week run-in period with atorvastatin to achieve LDL <2.5mg/dL
- Patients who met LDL criteria were randomized to atorvastatin (at a dose established during the run-in period) plus 60 mg of torcetrapib or atorvastatin plus placebo
- Follow up visits 1, 3, 6, 9, and 12 months after randomization and then and then 6 months thereafter. Assessments included routine blood work and clinical interview
|
| Results |
|
Primary Endpoints
Atorvastatin only
n=7534 |
Torcetrapib + Atorvastatin
n=7533 |
Hazard Ratio |
p |
| Major CV event (cardiac death, non-fatal MI, hospitalization for unstable angina or any stroke) |
| 5.0% |
6.2% |
1.25 (1.09-1.44) |
0.001 |
Secondary Outcomes
(see study for complete list)
Atorvastatin only
n=7534 |
Torcetrapib + Atorvastatin
n=7533 |
Hazard Ratio |
p |
| Cardiac death |
| 0.4% |
0.5% |
1.21 (0.77–1.92) |
0.41 |
| Non-fatal MI |
| 1.6% |
1.9% |
1.21 (0.95–1.54) |
0.13 |
| Stroke |
| 0.5% |
0.6% |
1.08 (0.70–1.66) |
0.74 |
| Hospitalization for unstable angina |
| 2.7% |
3.6% |
1.35 (1.13–1.62) |
0.001 |
| Death from any cause |
| 0.8% |
1.2% |
1.58 (1.14–2.19) |
0.006 |
|
| Summary |
| The increased mortality associated with the use of torcetrapib included increased risks of death from both cardiovascular and noncardiovascular causes. There was also a significant increase in the risk of major cardiovascular events in the torcetrapib-treated group. |