Blood-pressure and cholesterol lowering in persons without cardiovascular disease

Salim Yusuf, Eva Lonn, Prem Pais, Jackie Bosch, Patricio López-Jaramillo, Jun Zhu, Denis Xavier, Alvaro Avezum, Lawrence A. Leiter, Leopoldo S. Piegas, Alexander Parkhomenko, M. Keltai, Katalin Keltai, Karen Sliwa, Irina Chazova, Ron J G Peters, Claes Held, Khalid Yusoff, Basil S. Lewis, Petr JanskyKamlesh Khunti, William D. Toff, Christopher M. Reid, John Varigos, Jose L. Accini, Robert McKelvie, Janice Pogue, Hyejung Jung, Lisheng Liu, Rafael Diaz, Antonio Dans, Gilles Dagenais

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

BACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P = 0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P = 0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease.

Original languageEnglish
Pages (from-to)2032-2043
Number of pages12
JournalNew England Journal of Medicine
Volume374
Issue number21
DOIs
Publication statusPublished - May 26 2016

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Cardiovascular Diseases
Cholesterol
Placebos
Blood Pressure
Group Psychotherapy
Hydrochlorothiazide
LDL Cholesterol
Confidence Intervals
Muscle Weakness
Dizziness
Heart Arrest
Antihypertensive Agents
Cause of Death
Heart Failure
Stroke
Myocardial Infarction
Therapeutics
Rosuvastatin Calcium

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yusuf, S., Lonn, E., Pais, P., Bosch, J., López-Jaramillo, P., Zhu, J., ... Dagenais, G. (2016). Blood-pressure and cholesterol lowering in persons without cardiovascular disease. New England Journal of Medicine, 374(21), 2032-2043. https://doi.org/10.1056/NEJMoa1600177

Blood-pressure and cholesterol lowering in persons without cardiovascular disease. / Yusuf, Salim; Lonn, Eva; Pais, Prem; Bosch, Jackie; López-Jaramillo, Patricio; Zhu, Jun; Xavier, Denis; Avezum, Alvaro; Leiter, Lawrence A.; Piegas, Leopoldo S.; Parkhomenko, Alexander; Keltai, M.; Keltai, Katalin; Sliwa, Karen; Chazova, Irina; Peters, Ron J G; Held, Claes; Yusoff, Khalid; Lewis, Basil S.; Jansky, Petr; Khunti, Kamlesh; Toff, William D.; Reid, Christopher M.; Varigos, John; Accini, Jose L.; McKelvie, Robert; Pogue, Janice; Jung, Hyejung; Liu, Lisheng; Diaz, Rafael; Dans, Antonio; Dagenais, Gilles.

In: New England Journal of Medicine, Vol. 374, No. 21, 26.05.2016, p. 2032-2043.

Research output: Contribution to journalArticle

Yusuf, S, Lonn, E, Pais, P, Bosch, J, López-Jaramillo, P, Zhu, J, Xavier, D, Avezum, A, Leiter, LA, Piegas, LS, Parkhomenko, A, Keltai, M, Keltai, K, Sliwa, K, Chazova, I, Peters, RJG, Held, C, Yusoff, K, Lewis, BS, Jansky, P, Khunti, K, Toff, WD, Reid, CM, Varigos, J, Accini, JL, McKelvie, R, Pogue, J, Jung, H, Liu, L, Diaz, R, Dans, A & Dagenais, G 2016, 'Blood-pressure and cholesterol lowering in persons without cardiovascular disease', New England Journal of Medicine, vol. 374, no. 21, pp. 2032-2043. https://doi.org/10.1056/NEJMoa1600177
Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. New England Journal of Medicine. 2016 May 26;374(21):2032-2043. https://doi.org/10.1056/NEJMoa1600177
Yusuf, Salim ; Lonn, Eva ; Pais, Prem ; Bosch, Jackie ; López-Jaramillo, Patricio ; Zhu, Jun ; Xavier, Denis ; Avezum, Alvaro ; Leiter, Lawrence A. ; Piegas, Leopoldo S. ; Parkhomenko, Alexander ; Keltai, M. ; Keltai, Katalin ; Sliwa, Karen ; Chazova, Irina ; Peters, Ron J G ; Held, Claes ; Yusoff, Khalid ; Lewis, Basil S. ; Jansky, Petr ; Khunti, Kamlesh ; Toff, William D. ; Reid, Christopher M. ; Varigos, John ; Accini, Jose L. ; McKelvie, Robert ; Pogue, Janice ; Jung, Hyejung ; Liu, Lisheng ; Diaz, Rafael ; Dans, Antonio ; Dagenais, Gilles. / Blood-pressure and cholesterol lowering in persons without cardiovascular disease. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 21. pp. 2032-2043.
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abstract = "BACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6{\%}) in the combined-therapy group and in 157 (5.0{\%}) in the dual-placebo group (hazard ratio, 0.71; 95{\%} confidence interval [CI], 0.56 to 0.90; P = 0.005). The second coprimary outcome occurred in 136 participants (4.3{\%}) and 187 participants (5.9{\%}), respectively (hazard ratio, 0.72; 95{\%} CI, 0.57 to 0.89; P = 0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease.",
author = "Salim Yusuf and Eva Lonn and Prem Pais and Jackie Bosch and Patricio L{\'o}pez-Jaramillo and Jun Zhu and Denis Xavier and Alvaro Avezum and Leiter, {Lawrence A.} and Piegas, {Leopoldo S.} and Alexander Parkhomenko and M. Keltai and Katalin Keltai and Karen Sliwa and Irina Chazova and Peters, {Ron J G} and Claes Held and Khalid Yusoff and Lewis, {Basil S.} and Petr Jansky and Kamlesh Khunti and Toff, {William D.} and Reid, {Christopher M.} and John Varigos and Accini, {Jose L.} and Robert McKelvie and Janice Pogue and Hyejung Jung and Lisheng Liu and Rafael Diaz and Antonio Dans and Gilles Dagenais",
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T1 - Blood-pressure and cholesterol lowering in persons without cardiovascular disease

AU - Yusuf, Salim

AU - Lonn, Eva

AU - Pais, Prem

AU - Bosch, Jackie

AU - López-Jaramillo, Patricio

AU - Zhu, Jun

AU - Xavier, Denis

AU - Avezum, Alvaro

AU - Leiter, Lawrence A.

AU - Piegas, Leopoldo S.

AU - Parkhomenko, Alexander

AU - Keltai, M.

AU - Keltai, Katalin

AU - Sliwa, Karen

AU - Chazova, Irina

AU - Peters, Ron J G

AU - Held, Claes

AU - Yusoff, Khalid

AU - Lewis, Basil S.

AU - Jansky, Petr

AU - Khunti, Kamlesh

AU - Toff, William D.

AU - Reid, Christopher M.

AU - Varigos, John

AU - Accini, Jose L.

AU - McKelvie, Robert

AU - Pogue, Janice

AU - Jung, Hyejung

AU - Liu, Lisheng

AU - Diaz, Rafael

AU - Dans, Antonio

AU - Dagenais, Gilles

PY - 2016/5/26

Y1 - 2016/5/26

N2 - BACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P = 0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P = 0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease.

AB - BACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P = 0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P = 0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease.

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