Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial.
Lancet. 2010 Aug 14;376(9740):517-23
Authors: Topol EJ, Bousser MG, Fox KA, Creager MA, Despres JP, Easton JD, Hamm CW, Montalescot G, Steg PG, Pearson TA, Cohen E, Gaudin C, Job B, Murphy JH, Bhatt DL,
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. FUNDING: Sanofi-Aventis.
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– Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial.
An urgent matter-identifying your patients’ cardiovascular risk and improving their outcomes. Low-density lipoprotein cholesterol and coronary heart disease: the importance of reaching target goals with statin therapy.
J Fam Pract. 2009 Nov;58(11 Suppl Urgent):S32-40
Authors: Lewis SJ
While Managing Acute-Care Issues, family physicians are challenged daily to recognize and treat modifiable risk factors for coronary heart disease (CHD) and to educate patients on the importance of risk reduction. Time constraints and the imperatives of immediate issues make the challenge of identification and treatment of CHD risk difficult. A stunning number of family medicine patients present with 1 or more of the following CHD risk factors: low-density lipoprotein cholesterol (LDL-C) =130 mg/dL (33% of American adults), total cholesterol =200 mg/dL (45%), hypertension (33%), tobacco use (21%), sedentary lifestyle (69%), excessive body weight (body mass index =25; 67%), diabetes (8%), or pre-diabetes (26%). The objective of comprehensive therapeutic interventions in CHD, from diet and lifestyle changes, to smoking cessation, to medications, is to prevent new (primary prevention) or recurrent (secondary prevention) cardiovascular events, with the ultimate goal of preventing disability and death. Family physicians have the distinct advantage of seeing patients’ health status from a global perspective, giving them a greater opportunity to recognize risk and initiate preventive interventions. Although therapeutic efforts have been directed traditionally at patients with established CHD and asymptomatic patients at high risk for cardiac events, new data are emerging that suggest that earlier, more aggressive treatment increases clinical benefit. This article (1) reviews the importance of reaching target goals for LDL-C and other biomarkers of risk in the primary and secondary prevention of CHD, and (2) addresses dosing issues and other practical methods of identifying and treating family medicine patients who are at risk.
19891946
– An urgent matter-identifying your patients’ cardiovascular risk and improving their outcomes. Low-density lipoprotein…
Cost-effectiveness of fracture prevention in men who receive androgen deprivation therapy for localized prostate cancer.
Ann Intern Med. 2010 May 18;152(10):621-9
Authors: Ito K, Elkin EB, Girotra M, Morris MJ
BACKGROUND: Androgen deprivation therapy (ADT) increases the risk for fractures in patients with prostate cancer. Objective: To assess the cost-effectiveness of measuring bone mineral density (BMD) before initiating ADT followed by alendronate therapy in men with localized prostate cancer. DESIGN: Markov state-transition model simulating the progression of prostate cancer and the incidence of hip fracture. DATA SOURCES: Published literature. TARGET POPULATION: A hypothetical cohort of men aged 70 years with locally advanced or high-risk localized prostate cancer starting a 2-year course of ADT after radiation therapy. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: No BMD test or alendronate therapy, a BMD test followed by selective alendronate therapy for patients with osteoporosis, or universal alendronate therapy without a BMD test. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: The ICERs for the strategy of a BMD test and selective alendronate therapy for patients with osteoporosis and universal alendronate therapy without a BMD test were $66,800 per QALY gained and $178,700 per QALY gained, respectively. RESULTS OF SENSITIVITY ANALYSES: The ICER for universal alendronate therapy without a BMD test decreased to $100,000 per QALY gained, assuming older age, a history of fractures, lower mean BMD before ADT, or a lower cost of alendronate. LIMITATIONS: No evidence shows that alendronate reduces actual fracture rates in patients with prostate cancer who receive ADT. The model predicted fracture rates by using data on the surrogate BMD end point. CONCLUSION: In patients starting adjuvant ADT for locally advanced or high-risk localized prostate cancer, a BMD test followed by selective alendronate for those with osteoporosis is a cost-effective use of resources. Routine use of alendronate without a BMD test is justifiable in patients at higher risk for hip fractures.
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– Cost-effectiveness of fracture prevention in men who receive androgen deprivation therapy for localized prostate cancer.
