title: Effects of body size and hypertension treatments on cardiovascular event rates: subanalysis of the ACCOMPLISH randomised controlled trial.
abstract: BACKGROUND
  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, we aimed to investigate whether the type of hypertension treatment affects patients' cardiovascular outcomes according to their body size.
  
  
  METHODS
  On the basis of body-mass index (BMI), we divided the full ACCOMPLISH cohort into obese (BMI ≥30, n=5709), overweight (≥25 to <30, n=4157), or normal weight (<25, n=1616) categories. The ACCOMPLISH cohort had already been randomised to treatment with single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine. We 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. This trial is registered with ClinicalTrials.gov, number NCT00170950.
  
  
  RESULTS
  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 0·76, 95% CI 0·59-0·94; p=0·0369) and those of normal weight (0·57, 0·39-0·84; p=0·0037).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Novartis Pharmaceuticals.
authors.affiliation: State University of New York, Downstate College of Medicine, Brooklyn, NY 11203, USA. michaelwebermd@cs.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weber
authors.forename: Kenneth
authors.initials: K
authors.lastname: Jamerson
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
authors.forename: Dion
authors.initials: D
authors.lastname: Zappe
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bjorn
authors.initials: B
authors.lastname: Dahlof
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Velazquez
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015992:Body Mass Index; D049628:Body Size / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy
chemical_list: D000959:Antihypertensive Agents; D001552:Benzazepines; D004338:Drug Combinations; D006852:Hydrochlorothiazide; D017311:Amlodipine; C044946:benazepril