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Effects of body size and hypertension treatments on cardiovascular event rates: Amlodipine-based therapy is equally effective across BMI subgroups

In previous clinical trials in high-risk hypertensive patients, paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals.
As a prespecified analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension ( ACCOMPLISH ) trial, researchers have aimed to evaluate whether the type of hypertension treatment affects patients' cardiovascular outcomes according to their body size.

On the basis of body-mass index ( BMI ), investigators have divided the full ACCOMPLISH cohort into obese ( BMI greater than or equal to 30, n=5709 ), overweight ( greater than or equal to 25 to less than 30, n=4157 ), or normal weight ( less than 25, n=1616 ) categories.
The ACCOMPLISH cohort had already been randomised to treatment with single-pill combinations of either Benazepril and Hydrochlorothiazide ( Lotensin HCT ) or Benazepril and Amlodipine ( Lotrel ).

Researchers have compared event rates ( adjusted for age, sex, diabetes, previous cardiovascular events, stroke, or chronic kidney disease ) for the primary endpoint of cardiovascular death or non-fatal myocardial infarction or stroke.
The analysis was by intention to treat.

In patients allocated Benazepril and Hydrochlorothiazide, the primary endpoint ( per 1000 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; p=0.0369 ) and those of normal weight ( HR=0.57; p=0.0037 ).

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 non-obese hypertension. ( Xagena )

Weber MA et al, The Lancet 2013: 381: 537-545