Effects of Body Size and Hypertension Treatments on Cardiovascular Event Rates: Subanalysis of the ACCOMPLISH Randomised Controlled Trial

Study Questions:

In high-risk hypertensive patients, paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals. A prespecified analysis of the ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension) trial was conducted to determine whether the type of hypertension treatment affects patients’ cardiovascular outcomes according to their body mass index (BMI = kg/m2).


On the basis of BMI, patients were divided into obese (BMI ≥30, n = 5,709), overweight (≥25 to <30, n = 4,157), or normal weight (<25, n = 1,616) categories. The ACCOMPLISH cohort had already been randomized to treatment with single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine. Event rates were compared (adjusted for age, sex, diabetes, previous cardiovascular events, stroke, or chronic kidney disease) for the primary endpoint of cardiovascular death or nonfatal myocardial infarction or stroke. The analysis was by intention to treat.


In patients allocated benazepril and hydrochlorothiazide, the primary endpoint (per 1,000 patient-years) was 30.7 in normal weight, 21.9 in overweight, and 18.2 in obese patients (overall p = 0.0034). However, in those allocated benazepril and amlodipine, the primary endpoint did not differ between the three BMI groups (18.2, 16.9, and 16.5, respectively; overall p = 0.9721). In obese individuals, primary event rates were similar with both benazepril and hydrochlorothiazide and benazepril and amlodipine, but rates were significantly lower with benazepril and amlodipine in overweight patients (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.59-0.94; p = 0.0369) and those of normal weight (HR, 0.57; 95% CI, 0.39-0.84; p = 0.0037).


The authors concluded that hypertension in normal weight and obese patients might be mediated by different mechanisms. Thiazide-based treatment gives less cardiovascular protection in normal weight than obese patients, but amlodipine-based therapy is equally effective across BMI subgroups and thus offers superior cardiovascular protection in those with nonobese hypertension.


In the initial analysis of ACCOMPLISH, the benazepril + amlodipine combination had a 20% lower cardiovascular event rate than did benazepril + hydrochlorothiazide. A 43% difference in cardiovascular events between these regimens was found in lean patients, a 24% difference in overweight individuals, and an 11% nonsignificant difference in obese people. The findings support using combination benazepril + hydrochlorothiazide in obese persons who have edema associated with amlodipine. The relative value of amlodipine over hydrochlorothiazide in lean and overweight persons may be related to the adverse effects of hydrochlorothiazide on the neuroendocrine systems involved in nonobese hypertension.

Keywords: Myocardial Infarction, Neurosecretory Systems, Overweight, Benzazepines, Thiazides, Renal Insufficiency, Body Mass Index, Cardiology, Cardiovascular Diseases, Obesity, Body Size, Hypertension

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