[Prevention of cardiovascular disease by blocking the endocannabinoid system].
Risk factors for the development of cardiovascular disease, in particular myocardial infarction, are smoking, high body weight, sedentary lifestyle, unfavorable diet, high blood pressure, elevated fasting glucose or diabetes, and dyslipidemia (Tables 1 and 2). If the risk for cardiovascular mortality of 5% (using the SCORE Score) or for nonfatal cardiovascular events of 20% (PROCAM Score) within the next 10 years is exceeded or overt atherosclerosis or type 2 diabetes mellitus is present, the use of (poly)pharmacotherapy is indicated and lifestyle intervention (diet, physical activity) alone is not sufficient at that point (Figure 1). A new therapeutic option, able to modify a number of cardiovascular risk factors at a time, is the blockade of the so-called endocannabinoid system (Figure 2). For rimonabant not only a reduction of body weight and waist circumference was shown in clinical trials, its use was also accompanied by an increase of HDL cholesterol, a decrease in triglycerides, and a reduction in HbA1c and fasting blood glucose (Table 4). Together with preliminary data on the efficacy in smoking cessation, rimonabant has a therapeutic impact on four out of eight relevant risk factors in order to prevent myocardial infarction as promoted by the American College of Cardiology/American Heart Association. Currently, a large clinical study program is ongoing to further investigate the role of rimonabant in managing cardiovascular risk (Table 3). Published clinical trial results have revealed, that rimonabant is generally well tolerated (most frequent side effect: nausea) and the data are promising with regard to the potential future role of rimonabant in managing cardiovascular risk.
Bramlage
Peter
P
Institut für Klinische Pharmakologie, Medizinische Fakultät, TU Dresden, Dresden. bramlage@mailbox.tu-dresden.de
Schindler
Christoph
C
Thoenes
Martin
M
Bramlage
Carsten P
CP
Böcking
Wolfgang
W
Kirch
Wilhelm
W
D002186:Cannabinoids / Q000037:antagonists & inhibitors*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D006801:Humans; D010880:Piperidines / Q000627:therapeutic use*; D015995:Prevalence; D011720:Pyrazoles / Q000627:therapeutic use*; D000077285:Rimonabant; D016896:Treatment Outcome
D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D000077285:Rimonabant