Hypertension-Obesity-Sibutramine - HOS
The goal of the trial was to evaluate the effect of different antihypertensive regimens on weight loss due to sibutramine therapy, a selective serotonin and norepinephrine reuptake inhibitor weight loss among obese hypertensive patients.
Patients Enrolled: 171
Mean Follow Up: 16 weeks
Mean Patient Age: Mean age, 52 years
BMI 27-45 kg/m2; ages 20-65 years; and essential hypertension (SBP 140-160 mm Hg, DBP 90-100 mm Hg) under pretreatment with a prespecified antihypertensive combination therapy
Secondary hypertension or obesity; a clinical history of coronary artery disease, myocardial infarction, or carditis; congestive heart failure; supraventricular/ventricular tachycardia; renal failure; liver failure; hyperthyroidism; uncontrolled diabetes mellitus; malignancies; chronic infectious disease; alcohol/drug abuse; epilepsy; psychosis; treatment with antidepressant/neuroleptic drugs; or pretreatment with sibutramine within the last 6 months
Weight loss at 16 weeks
Following a 2-week run-in period, patients receiving one of the three antihypertensive combination therapies (felodipine 5 mg/ramipril 5 mg, n = 57; verapamil 180 mg/trandolapril 2 mg, n = 55; or metoprolol succinate 95 mg/hydrochlorothiazide (HCT) 12.5 mg, n = 59) were randomized in a double-blind manner to sibutramine (15 mg, n = 87) or placebo (n = 84). Treatment was continued for 16 weeks.
At baseline, mean body mass index (BMI) was 35 kg/m2 and diabetes was present in 15% of patients. Compared with placebo, the sibutramine group had greater reductions in body weight reduction (5.7 vs. 1.5 kg; p < 0.0001), BMI (2.0 vs. 0.5 kg/m2; p < 0.0001), and waist circumference (5.0 vs. 0.8 cm; p < 0.0001). Reductions in body weight of >5% were more frequent in the sibutramine group than placebo group (54.7% vs. 14.5%; p < 0.001). Findings were consistent in the antihypertensive therapy cohorts, but were not as great in the metoprolol/HCT group.
Reductions in office systolic blood pressure (SBP)/diastolic blood pressure (DBP) were not different between the sibutramine and placebo groups (-5.9/-0.7 mm Hg vs. -4.8/-2.3 mm Hg, p = NS), nor changes in the 24-hour SBP. Heart rate increased in the sibutramine group compared with placebo (+4.5 bpm vs. -1.4 bpm, p < 0.0001), a finding that was consistent in all three antihypertensive therapy cohorts.
Fasting glucose levels were significantly lower in the sibutramine group (before treatment 5.7 mmol/L vs. after treatment 5.4 mmol/L, p = 0.04), but there was no effect in the placebo group. Results were similar for glucose tolerance at 60 minutes of the oral glucose tolerance test (sibutramine -1.1 mmol/L, p = 0.0003; placebo -0.4 mmol/L, p = 0.1297).
Among obese hypertensive patients, sibutramine therapy was associated with greater weight loss at 16 weeks compared with placebo, with an attenuation of weight loss in the metoprolol/HCT cohort.
Obesity-related hypertension has contributed to the overall increase in hypertension, and treatment recommendations do not differ for obese and nonobese hypertensive patients. Sibutramine has previously been shown to be effective for weight loss in obese patients. However, as the authors note, it is a monoamine reuptake inhibitor, which may cause increases in BP and thus offset any decrease in BP associated with the weight loss. Weight loss and reductions in waist circumference associated with sibutramine were reduced in the beta-blocker/diuretic cohort, possibly due to known increases in weight associated with beta-blocker use. One limitation of the study was the nonrandomized nature of the antihypertensive therapy cohorts.
Scholze J, Grimm E, Herrmann D, Unger T, Kintscher U. Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS). Circulation 2007;115:1991-8.
Keywords: Felodipine, Myocardial Ischemia, Follow-Up Studies, Weight Loss, Diuretics, Norepinephrine, Constriction, Pathologic, Heart Rate, Ramipril, Cyclobutanes, Waist Circumference, Body Mass Index, Glucose Tolerance Test, Indoles, Serotonin, Obesity, Verapamil, Hydrochlorothiazide, Metoprolol, Hypertension, Diabetes Mellitus
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