Blood-pressure lowering in intermediate-risk persons without cardiovascular disease

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 JanskyChristopher M. Reid, John Varigos

Research output: Contribution to journalArticleResearchpeer-review

343 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2009-2020
Number of pages12
JournalThe New England Journal of Medicine
Volume374
Issue number21
DOIs
Publication statusPublished - 26 May 2016

Cite this

Lonn, E. M., Bosch, J., López-Jaramillo, P., Zhu, J., Liu, L., Pais, P., Diaz, R., Xavier, D., Sliwa, K., Dans, A., Avezum, A., Piegas, L. S., Keltai, K., Keltai, M., Chazova, I., Peters, R. J. G., Held, C., Yusoff, K., Lewis, B. S., ... Varigos, J. (2016). Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. The New England Journal of Medicine, 374(21), 2009-2020. https://doi.org/10.1056/NEJMoa1600175