Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease
New England Journal of Medicine, April 2016
Eva M. Lonn, Jackie Bosch, Patricio López-Jaramillo, Jun Zhu, Lisheng Liu, Prem Pais, Rafael Diaz, Denis Xavier, Karen Sliwa, Antonio Dans, Alvaro Avezum, Leopoldo S. Piegas, Katalin Keltai, Matyas Keltai, Irina Chazova, Ron J.G. Peters, Claes Held, Khalid Yusoff, Basil S. Lewis, Petr Jansky, Alexander Parkhomenko, Kamlesh Khunti, William D. Toff, Christopher M. Reid, John Varigos, Lawrence A. Leiter, Dora I. Molina, Robert McKelvie, Janice Pogue, Joanne Wilkinson, Hyejung Jung, Gilles Dagenais, Salim Yusuf, Lonn, Eva M, 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 J G, 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, , , Lonn, Eva M., Lonn, E. M.
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 .).
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