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, M. Keltai, Irina Chazova, Ron J G Peters, Claes Held, Khalid Yusoff, Basil S. Lewis, Petr JanskyAlexander 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

Research output: Contribution to journalArticle

305 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
JournalNew England Journal of Medicine
Volume374
Issue number21
DOIs
Publication statusPublished - May 26 2016

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Cardiovascular Diseases
Blood Pressure
Placebos
Hydrochlorothiazide
Confidence Intervals
Therapeutics
Heart Arrest
Antihypertensive Agents
Cause of Death
Heart Failure
Stroke
Myocardial Infarction
candesartan

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lonn, E. M., Bosch, J., López-Jaramillo, P., Zhu, J., Liu, L., Pais, P., ... Yusuf, S. (2016). Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. New England Journal of Medicine, 374(21), 2009-2020. https://doi.org/10.1056/NEJMoa1600175

Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. / 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, M.; 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.

In: New England Journal of Medicine, Vol. 374, No. 21, 26.05.2016, p. 2009-2020.

Research output: Contribution to journalArticle

Lonn, EM, Bosch, J, López-Jaramillo, P, Zhu, J, Liu, L, Pais, P, Diaz, R, Xavier, D, Sliwa, K, Dans, A, Avezum, A, Piegas, LS, Keltai, K, Keltai, M, Chazova, I, Peters, RJG, Held, C, Yusoff, K, Lewis, BS, Jansky, P, Parkhomenko, A, Khunti, K, Toff, WD, Reid, CM, Varigos, J, Leiter, LA, Molina, DI, McKelvie, R, Pogue, J, Wilkinson, J, Jung, H, Dagenais, G & Yusuf, S 2016, 'Blood-pressure lowering in intermediate-risk persons without cardiovascular disease', New England Journal of Medicine, vol. 374, no. 21, pp. 2009-2020. https://doi.org/10.1056/NEJMoa1600175
Lonn EM, Bosch J, López-Jaramillo P, Zhu J, Liu L, Pais P et al. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. New England Journal of Medicine. 2016 May 26;374(21):2009-2020. https://doi.org/10.1056/NEJMoa1600175
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, M. ; 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. / Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 21. pp. 2009-2020.
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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.",
author = "Lonn, {Eva M.} and Jackie Bosch and Patricio L{\'o}pez-Jaramillo and Jun Zhu and Lisheng Liu and Prem Pais and Rafael Diaz and Denis Xavier and Karen Sliwa and Antonio Dans and Alvaro Avezum and Piegas, {Leopoldo S.} and Katalin Keltai and M. Keltai and Irina Chazova and Peters, {Ron J G} and Claes Held and Khalid Yusoff and Lewis, {Basil S.} and Petr Jansky and Alexander Parkhomenko and Kamlesh Khunti and Toff, {William D.} and Reid, {Christopher M.} and John Varigos and Leiter, {Lawrence A.} and Molina, {Dora I.} and Robert McKelvie and Janice Pogue and Joanne Wilkinson and Hyejung Jung and Gilles Dagenais and Salim Yusuf",
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T1 - Blood-pressure lowering in intermediate-risk persons without cardiovascular disease

AU - Lonn, Eva M.

AU - Bosch, Jackie

AU - López-Jaramillo, Patricio

AU - Zhu, Jun

AU - Liu, Lisheng

AU - Pais, Prem

AU - Diaz, Rafael

AU - Xavier, Denis

AU - Sliwa, Karen

AU - Dans, Antonio

AU - Avezum, Alvaro

AU - Piegas, Leopoldo S.

AU - Keltai, Katalin

AU - Keltai, M.

AU - Chazova, Irina

AU - Peters, Ron J G

AU - Held, Claes

AU - Yusoff, Khalid

AU - Lewis, Basil S.

AU - Jansky, Petr

AU - Parkhomenko, Alexander

AU - Khunti, Kamlesh

AU - Toff, William D.

AU - Reid, Christopher M.

AU - Varigos, John

AU - Leiter, Lawrence A.

AU - Molina, Dora I.

AU - McKelvie, Robert

AU - Pogue, Janice

AU - Wilkinson, Joanne

AU - Jung, Hyejung

AU - Dagenais, Gilles

AU - Yusuf, Salim

PY - 2016/5/26

Y1 - 2016/5/26

N2 - 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.

AB - 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.

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