Long-term effects of weight-reducing drugs in hypertensive patients.

BACKGROUND: All major guidelines for antihypertensive therapy recommend weight loss; anti-obesity drugs might be a helpful option. PRIMARY OBJECTIVES: To assess the long-term effects of pharmacologically induced reduction in body weight with orlistat, sibutramine or rimonabant on:- all cause mortality - cardiovascular morbidity - adverse events SECONDARY OBJECTIVES: - changes in systolic and/or diastolic blood pressure - body weight reduction SEARCH STRATEGY: Studies were obtained from computerised searches of Ovid MEDLINE, EMBASE, CENTRAL and from hand searches in reference lists and systematic reviews. SELECTION CRITERIA: Randomized controlled trials in adult hypertensive patients with a study duration of at least 24 weeks comparing pharmacologic interventions (orlistat, sibutramine, rimonabant) for weight loss with placebo. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias and extracted data. Studies were pooled using fixed-effect meta-analysis in the absence of significant heterogeneity between studies (p>0.1). Otherwise, we used the random effects method and investigated the cause of heterogeneity. MAIN RESULTS: Eight studies comparing orlistat or sibutramine to placebo fulfilled our inclusion criteria. No relevant studies investigating rimonabant for weight loss were identified. No study included mortality and cardiovascular morbidity as a pre-defined outcome. Incidence of gastrointestinal side effects was consistently higher in orlistat treated vs. placebo treated patients. Most frequent side effects with sibutramine were dry mouth, constipation and headache. Patients assigned to weight loss diets, orlistat or sibutramine reduced their body weight more effectively than patients in the usual care/placebo groups. Blood pressure reduction in patients treated with orlistat was for systolic blood pressure (SBP): weighted mean difference (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and for diastolic blood pressure (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg. Meta-analysis showed DBP increase under therapy with sibutramine: WMD +3.2 mm Hg; 95%CI +1.4 to +4.9 mm Hg. AUTHORS' CONCLUSIONS: In patients with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree. In the same trials, orlistat reduced blood pressure and sibutramine increased blood pressure. No trials investigating rimonabant in people with elevated blood pressure could be included. Long-term trials assessing the effect of orlistat, sibutramine and rimonabant on mortality and morbidity are needed.

Long-term effects of weight-reducing interventions in hypertensive patients: systematic review and meta-analysis.

Weight loss is recommended in all major guidelines for antihypertensive therapy. We searched for randomized controlled trials investigating the effects of weight-reducing diets, pharmacologic substances, and invasive interventions for weight reduction on patient-relevant end points and blood pressure (BP) in patients with essential hypertension. No information on the effects on patient-relevant end points was available. Patients assigned to weight loss diets, orlistat, or sibutramine reduced their body weight more effectively than did patients in the usual care/placebo groups. Reduction of BP was higher in patients treated with weight loss diets (systolic BP [SBP]: weighted mean difference [WMD], -6.3 mm Hg; diastolic BP [DBP]: WMD, -3.4 mm Hg) or orlistat (SBP: WMD, -2.5 mm Hg; DBP: WMD, -2.0 mm Hg). Systolic BP increased with sibutramine treatment (WMD, 3.2 mm Hg). In patients with essential hypertension, therapy with a weight loss diet or orlistat resulted in reductions in body weight and BP. Although sibutramine treatment reduced body weight, it did not lower BP.