Comprehensive Rimonabant Evaluation Study of Cardiovascular Endpoints and Outcomes - CRESCENDO


The goal of the trial was to evaluate treatment with the endocannabinoid receptor rimonabant compared with placebo in patients with overt vascular disease or increased risk for vascular disease.


Rimonabant has been shown to reduce obesity and have favorable effects on several cardiovascular risk factors. The hypothesis was that rimonabant would in turn be effective in preventing cardiovascular death, myocardial infarction, or stroke.

Study Design

  • Placebo Controlled
  • Blinded
  • Randomized
  • Parallel
  • Stratified

Patient Populations:

  • Patients at least 55 years of age with abdominal obesity, defined as waist circumference >88 cm (35 inches) in women and >102 cm (40 inches) in men
  • Documented vascular disease in the last 3 years (coronary, cerebrovascular, or peripheral arterial disease) or two or more cardiovascular disease risk factors (type 2 diabetes, renal artery disease, advanced age, asymptomatic cerebrovascular or peripheral arterial disease, or elevated high-sensitivity C-reactive protein)


Number of enrollees: 18,695

Duration of follow-up: mean 13.8 months

Age: mean 64 years

Percentage female: 36%


  • Obesity due to endocrine disorder
  • Pregnancy
  • Surgical procedure for weight loss or a very low calorie diet in the last 6 months
  • Previous suicide attempt
  • Limited life span

Primary Endpoints:

  • Cardiovascular death, myocardial infarction, or stroke

Secondary Endpoints:

  • Adverse events

Drug/Procedures Used:

Patients with abdominal obesity, ages 55 or older, with overt vascular disease or increased risk for vascular disease were randomized to rimonabant 20 mg (n = 9,381) versus placebo (n = 9,314).

Concomitant Medications:

Antiplatelet and lipid-lowering therapy were used in 81% and 82%, respectively, and were balanced in the two groups.

Principal Findings:

Overall, 18,695 patients were randomized. In the rimonabant group, the mean age was 64 years, 36% were women, 12% were current smokers, mean body mass index was 33 kg/m2, 61% had diabetes, 88% had hypertension, 36% had prior myocardial infarction, 17% had prior stroke, and 7.6% had prior transient ischemic attack. The mean exposure to study drug was 13.8 months.

The primary outcome, cardiovascular death, myocardial infarction, or stroke, occurred in 3.9% of the rimonabant group versus 4.0% of the placebo group (p = 0.68). The primary outcome was similar between treatment groups among those with overt vascular disease or with just cardiovascular risk factors. All-cause mortality occurred in 2.1% versus 2.2% (p = 0.96), cardiovascular mortality in 1.3% versus 1.3% (p = 0.95), myocardial infarction in 1.5% versus 1.5% (p = 0.72), and stroke in 1.4% versus 1.6% (p = 0.50), respectively.

Gastrointestinal side effects occurred in 33% versus 22% (p < 0.05) in the rimonabant versus placebo groups, respectively; neuropsychiatric side effects in 32% versus 21% (p < 0.0001); serious psychiatric side effects in 2.5% versus 1.3% (p < 0.0001); and suicide in four patients versus one patient.


Among patients with abdominal obesity, rimonabant was not effective at reducing the primary outcome of cardiovascular death, myocardial infarction, or stroke at 13.8 months of follow-up either for primary or secondary prevention. Rimonabant increased gastrointestinal, neuropsychiatric, and serious psychiatric side effects.

Four patients committed suicide in the rimonabant group compared with one in the placebo group. These excess side effects led regulatory authorities to terminate the CRESCENDO trial prematurely. The drug was not approved for use in the United States, and the drug was withdrawn from the market worldwide. Safe and effective weight loss agents are urgently needed.


Topol EJ, Bousser MG, Fox KA, et al., on behalf of the CRESCENDO Investigators. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomized, multicentre, placebo-controlled trial. Lancet 2010;376:517-23.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Heart Failure and Cardiac Biomarkers, Hypertension

Keywords: Obesity, Abdominal, Myocardial Infarction, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Diabetes Mellitus, Type 2, Peripheral Arterial Disease, Pyrazoles, Risk Factors, Waist Circumference, C-Reactive Protein, Piperidines, Renal Artery, Body Mass Index, Cannabinoid Receptor Antagonists, Anti-Obesity Agents, Hypertension, Suicide, Endocannabinoids

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