Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease

N Engl J Med. 2016 May 26;374(21):2009-20. doi: 10.1056/NEJMoa1600175. Epub 2016 Apr 2.

Abstract

Background: Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear.

Methods: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.

Results: The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes).

Conclusions: Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Benzimidazoles / administration & dosage*
  • Biphenyl Compounds
  • Blood Pressure
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydrochlorothiazide / administration & dosage*
  • Hypertension / drug therapy*
  • Hypotension / chemically induced
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Risk Factors
  • Tetrazoles / administration & dosage*

Substances

  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • Hydrochlorothiazide
  • candesartan

Associated data

  • ClinicalTrials.gov/NCT00468923