Effect of rimonabant on blood pressure in overweight/obese patients with/without co-morbidities: analysis of pooled RIO study results.

@article{citeulike:2675322, abstract = {OBJECTIVE: Rimonabant, the first selective cannabinoid type 1 (CB1) receptor blocker, has been shown to improve multiple cardiometabolic risk factors in overweight/obese patients. This analysis assessed the impact of rimonabant on blood pressure in the pooled population from four large trials with similar design - the Rimonabant-In-Obesity (RIO) programme. METHODS: RIO-Europe (n = 1507) and RIO-North America (n = 3040) recruited overweight/obese patients, and RIO-Lipids (n = 1033) and RIO-Diabetes (n = 1045) recruited overweight/obese patients with untreated dyslipidaemia or type 2 diabetes, respectively. At study entry (screening), 37.2\% (n = 2463) of patients had hypertension, 71.4\% (n = 1757) of whom were taking an antihypertensive treatment. RESULTS: After 1 year of treatment, mean change in systolic blood pressure (SBP) from baseline was -0.8 mmHg for rimonabant 20 mg versus +0.3 mmHg for placebo (P = 0.007); diastolic blood pressure (DBP) decreased by -0.8 versus -0.3 mmHg (P = 0.029) respectively. In the subgroup of patients with high blood pressure at baseline, SBP change was -7.5 mmHg for rimonabant 20 mg versus -4.7 mmHg for placebo (P = 0.005); DBP change was -5.2 versus -3.0 mmHg (P < 0.001). Reductions were more pronounced in patients with dyslipidaemia and type 2 diabetes. There was no effect of rimonabant 20 mg on blood pressure beyond that expected from weight loss alone. Overall, there was a similar incidence of adverse events (AEs) at 1 year in the placebo (81.8\%) and rimonabant 20 mg (86.0\%). The most common AEs occurring with rimonabant were nausea, dizziness, arthralgia and diarrhoea. A slightly higher proportion of patients in the rimonabant 20 mg group discontinued as a result of AEs (13.8\%) versus placebo (7.2\%). CONCLUSIONS: Rimonabant 20 mg led to modest, but significant SBP and DBP reductions in overweight/obese patients. The effect of rimonabant on blood pressure appears to be mediated by weight loss.}, address = {Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain.}, author = {Ruilope, L. M. and Despr\'{e}s, J. P. and Scheen, A. and Pi-Sunyer, X. and Mancia, G. and Zanchetti, A. and Van Gaal, L. }, citeulike-article-id = {2675322}, comment = {Rimonabant, still unapproved in the U.S., is nevertheless widely known because of its potential as a CB1 receptor blocker, thereby inhibiting the endocannabinoid system. The drug has been shown to have favorable diverse effects including cigarette smoking cessation as well as promoting weight loss With regard to the latter, sustained weight loss has been shown in several studies to be accompanied by reductions in blood pressure. The question addressed in this analysis is to what extent does the weight loss account for the observed blood pressure changes. Pooled data from four studies consisted of 1,602 and 2,505 patients randomized to placebo and rimonabant 20 mg, respectively. There was an impressive difference in weight loss between the groups at 12 months (6.6 kg) and a significant difference in SBP and DBP particularly in the hypertensive sub-group. The blood pressure reduction was also greater in those with diabetes or dyslipidemia at baseline. Regression lines of blood pressure change vs. weight change were similar for the two groups with no residual treatment effect, suggesting that the effects of rimonabant on blood pressure were secondary to weight loss without an independent effect. The four to six month lag time for blood pressure differences to emerge was also consistent with this mechanism of action. As expected there were favorable differences reported between the two groups in HgA1C fasting plasma glucose, insulin levels, HDL-c and triglycerides. Although the analysis is not provided, it is likely that these changes also are explained by the weight loss difference between the groups. These findings underscore the importance of weight loss in controlling these CV risk factors, and until long term safety of drug therapy is shown, we must redouble our efforts at helping patients lose weight the old fashioned way - diet and exercise. Jerome D. Cohen, M.D. }, doi = {10.1097/HJH.0b013e3282f2d625}, issn = {0263-6352}, journal = {Journal of hypertension}, keywords = {hta, insulinresistance, obesity, rct}, month = {February}, number = {2}, pages = {357--367}, posted-at = {2008-04-15 21:32:03}, priority = {2}, title = {Effect of rimonabant on blood pressure in overweight/obese patients with/without co-morbidities: analysis of pooled RIO study results.}, url = {http://dx.doi.org/10.1097/HJH.0b013e3282f2d625}, volume = {26}, year = {2008} }

TY - JOUR ID - citeulike:2675322 L3 - citeulike-article-id:2675322 TI - Effect of rimonabant on blood pressure in overweight/obese patients with/without co-morbidities: analysis of pooled RIO study results. JF - Journal of hypertension VL - 26 IS - 2 SP - 357 EP - 367 AD - Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain. SN - 0263-6352 N2 - OBJECTIVE: Rimonabant, the first selective cannabinoid type 1 (CB1) receptor blocker, has been shown to improve multiple cardiometabolic risk factors in overweight/obese patients. This analysis assessed the impact of rimonabant on blood pressure in the pooled population from four large trials with similar design - the Rimonabant-In-Obesity (RIO) programme. METHODS: RIO-Europe (n = 1507) and RIO-North America (n = 3040) recruited overweight/obese patients, and RIO-Lipids (n = 1033) and RIO-Diabetes (n = 1045) recruited overweight/obese patients with untreated dyslipidaemia or type 2 diabetes, respectively. At study entry (screening), 37.2% (n = 2463) of patients had hypertension, 71.4% (n = 1757) of whom were taking an antihypertensive treatment. RESULTS: After 1 year of treatment, mean change in systolic blood pressure (SBP) from baseline was -0.8 mmHg for rimonabant 20 mg versus +0.3 mmHg for placebo (P = 0.007); diastolic blood pressure (DBP) decreased by -0.8 versus -0.3 mmHg (P = 0.029) respectively. In the subgroup of patients with high blood pressure at baseline, SBP change was -7.5 mmHg for rimonabant 20 mg versus -4.7 mmHg for placebo (P = 0.005); DBP change was -5.2 versus -3.0 mmHg (P < 0.001). Reductions were more pronounced in patients with dyslipidaemia and type 2 diabetes. There was no effect of rimonabant 20 mg on blood pressure beyond that expected from weight loss alone. Overall, there was a similar incidence of adverse events (AEs) at 1 year in the placebo (81.8%) and rimonabant 20 mg (86.0%). The most common AEs occurring with rimonabant were nausea, dizziness, arthralgia and diarrhoea. A slightly higher proportion of patients in the rimonabant 20 mg group discontinued as a result of AEs (13.8%) versus placebo (7.2%). CONCLUSIONS: Rimonabant 20 mg led to modest, but significant SBP and DBP reductions in overweight/obese patients. The effect of rimonabant on blood pressure appears to be mediated by weight loss. KW - hta KW - insulinresistance KW - obesity KW - rct N1 - Rimonabant, still unapproved in the U.S., is nevertheless widely known because of its potential as a CB1 receptor blocker, thereby inhibiting the endocannabinoid system. The drug has been shown to have favorable diverse effects including cigarette smoking cessation as well as promoting weight loss With regard to the latter, sustained weight loss has been shown in several studies to be accompanied by reductions in blood pressure. The question addressed in this analysis is to what extent does the weight loss account for the observed blood pressure changes. Pooled data from four studies consisted of 1,602 and 2,505 patients randomized to placebo and rimonabant 20 mg, respectively. There was an impressive difference in weight loss between the groups at 12 months (6.6 kg) and a significant difference in SBP and DBP particularly in the hypertensive sub-group. The blood pressure reduction was also greater in those with diabetes or dyslipidemia at baseline. Regression lines of blood pressure change vs. weight change were similar for the two groups with no residual treatment effect, suggesting that the effects of rimonabant on blood pressure were secondary to weight loss without an independent effect. The four to six month lag time for blood pressure differences to emerge was also consistent with this mechanism of action. As expected there were favorable differences reported between the two groups in HgA1C fasting plasma glucose, insulin levels, HDL-c and triglycerides. Although the analysis is not provided, it is likely that these changes also are explained by the weight loss difference between the groups. These findings underscore the importance of weight loss in controlling these CV risk factors, and until long term safety of drug therapy is shown, we must redouble our efforts at helping patients lose weight the old fashioned way - diet and exercise. Jerome D. Cohen, M.D. AU - Ruilope, LM AU - Després, JP AU - Scheen, A AU - Pi-Sunyer, X AU - Mancia, G AU - Zanchetti, A AU - Van Gaal, L PY - 2008/02// UR - http://dx.doi.org/10.1097/HJH.0b013e3282f2d625 ER -