uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial.
Show others and affiliations
2010 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 376, no 9740, 517-23 p.Article in journal (Refereed) Published
Abstract [en]

Background: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival.

Methods: This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18 695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042.

Findings: At a mean follow-up of 13.8, months (95% CI 13.6-14.0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3.9%) patients assigned to rimonabant and 375 (4.0%) assigned to placebo (hazard ratio 0.97, 95% CI 0.84-1.12, p=0.68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2.5%] vs 120 [1.3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide.

Interpretation: The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated.

Place, publisher, year, edition, pages
2010. Vol. 376, no 9740, 517-23 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-151864DOI: 10.1016/S0140-6736(10)60935-XPubMedID: 20709233OAI: oai:DiVA.org:uu-151864DiVA: diva2:411519
Group Author(s): CRESCENDO Investigators. Claes Held, UCR-Uppsala Clinical Research center Available from: 2011-04-18 Created: 2011-04-18 Last updated: 2011-04-29Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
In the same journal
The Lancet
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 124 hits
ReferencesLink to record
Permanent link

Direct link