Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. Academic Article uri icon

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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.).

authors

  • Lonn, Eva
  • Bosch, Jackie
  • López-Jaramillo, Patricio
  • Zhu, Jun
  • Liu, Lisheng
  • Pais, Prem
  • Diaz, Rafael
  • Xavier, Denis
  • Sliwa, Karen
  • Dans, Antonio
  • Avezum, Alvaro
  • Piegas, Leopoldo S
  • Keltai, Katalin
  • Keltai, Matyas
  • Chazova, Irina
  • Peters, Ron JG
  • Held, Claes
  • Yusoff, Khalid
  • Lewis, Basil S
  • Jansky, Petr
  • Parkhomenko, Alexander
  • Khunti, Kamlesh
  • Toff, William D
  • Reid, Christopher M
  • Varigos, John
  • Leiter, Lawrence A
  • Molina, Dora I
  • McKelvie, Robert
  • Pogue, Janice
  • Wilkinson, Joanne
  • Jung, Hyejung
  • Dagenais, Gilles
  • Yusuf, Salim
  • HOPE-3 Investigators

publication date

  • May 26, 2016