Aspirin is beneficial in hypertensive patients with chronic kidney disease: A post-hoc subgroup analysis of a randomized controlled trial

Meg J. Jardine, Toshiharu Ninomiya, Vlado Perkovic, Alan Cass, Fiona Turnbull, Martin P. Gallagher, Sophia Zoungas, Hiddo J. Lambers Heerspink, John Chalmers, Alberto Zanchetti

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Abstract

Objectives The purpose of this study was to determine the benefit and risk associated with antiplatelet therapy in the chronic kidney disease (CKD) population. Background Cardiovascular and possibly bleeding risks are elevated in patients with CKD. The balance of benefit and harm associated with antiplatelet therapy remains uncertain. Methods The HOT (Hypertension Optimal Treatment) study randomly assigned participants with diastolic hypertension to aspirin (75 mg) or placebo. Study treatment effects were calculated using univariate proportional hazards regression models stratified by baseline estimated glomerular filtration rate (eGFR) with trends tested by adding interaction terms. End points included major cardiovascular events, total mortality, and major bleeding. Results The study included 18,597 participants treated for 3.8 years. Baseline eGFR was 2 in 3,619 participants. Major cardiovascular events were reduced by 9% (95% confidence interval [CI]: -9% to 24%), 15% (95% CI: -17% to 39%), and 66% (95% CI: 33% to 83%) for patients with baseline eGFR of 2, respectively (p trend = 0.03). Total mortality was reduced by 0% (95% CI: -20% to 17%), 11% (95% CI: -31% to 40%), and 49% (95% CI: 6% to 73%), respectively (p trend = 0.04). Major bleeding events were nonsignificantly greater with lower eGFR (hazard ratio [HR]: 1.52 [95% CI: 1.11 to 2.08], HR: 1.70 [95% CI: 0.74 to 3.88], and HR: 2.81 [95% CI: 0.92 to 8.84], respectively; p trend = 0.30). Among every 1,000 persons with eGFR 2 treated for 3.8 years, 76 major cardiovascular events and 54 all-cause deaths will be prevented while 27 excess major bleeds will occur. Conclusions Aspirin therapy produces greater absolute reduction in major cardiovascular events and mortality in hypertensive patients with CKD than with normal kidney function. An increased risk of major bleeding appears to be outweighed by the substantial benefits.

Original languageEnglish
Pages (from-to)956-965
Number of pages10
JournalJournal of the American College of Cardiology
Volume56
Issue number12
DOIs
Publication statusPublished - Sep 14 2010

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Chronic Renal Insufficiency
Aspirin
Randomized Controlled Trials
Confidence Intervals
Glomerular Filtration Rate
Hemorrhage
Mortality
Hypertension
Therapeutics
Proportional Hazards Models
Cause of Death
Placebos
Kidney
Population

Keywords

  • aspirin
  • bleeding
  • cardiovascular risk
  • chronic kidney disease
  • mortality
  • primary prevention
  • risk-benefit analysis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Aspirin is beneficial in hypertensive patients with chronic kidney disease : A post-hoc subgroup analysis of a randomized controlled trial. / Jardine, Meg J.; Ninomiya, Toshiharu; Perkovic, Vlado; Cass, Alan; Turnbull, Fiona; Gallagher, Martin P.; Zoungas, Sophia; Lambers Heerspink, Hiddo J.; Chalmers, John; Zanchetti, Alberto.

In: Journal of the American College of Cardiology, Vol. 56, No. 12, 14.09.2010, p. 956-965.

Research output: Contribution to journalArticle

Jardine, MJ, Ninomiya, T, Perkovic, V, Cass, A, Turnbull, F, Gallagher, MP, Zoungas, S, Lambers Heerspink, HJ, Chalmers, J & Zanchetti, A 2010, 'Aspirin is beneficial in hypertensive patients with chronic kidney disease: A post-hoc subgroup analysis of a randomized controlled trial', Journal of the American College of Cardiology, vol. 56, no. 12, pp. 956-965. https://doi.org/10.1016/j.jacc.2010.02.068
Jardine, Meg J. ; Ninomiya, Toshiharu ; Perkovic, Vlado ; Cass, Alan ; Turnbull, Fiona ; Gallagher, Martin P. ; Zoungas, Sophia ; Lambers Heerspink, Hiddo J. ; Chalmers, John ; Zanchetti, Alberto. / Aspirin is beneficial in hypertensive patients with chronic kidney disease : A post-hoc subgroup analysis of a randomized controlled trial. In: Journal of the American College of Cardiology. 2010 ; Vol. 56, No. 12. pp. 956-965.
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AU - Perkovic, Vlado

AU - Cass, Alan

AU - Turnbull, Fiona

AU - Gallagher, Martin P.

AU - Zoungas, Sophia

AU - Lambers Heerspink, Hiddo J.

AU - Chalmers, John

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N2 - Objectives The purpose of this study was to determine the benefit and risk associated with antiplatelet therapy in the chronic kidney disease (CKD) population. Background Cardiovascular and possibly bleeding risks are elevated in patients with CKD. The balance of benefit and harm associated with antiplatelet therapy remains uncertain. Methods The HOT (Hypertension Optimal Treatment) study randomly assigned participants with diastolic hypertension to aspirin (75 mg) or placebo. Study treatment effects were calculated using univariate proportional hazards regression models stratified by baseline estimated glomerular filtration rate (eGFR) with trends tested by adding interaction terms. End points included major cardiovascular events, total mortality, and major bleeding. Results The study included 18,597 participants treated for 3.8 years. Baseline eGFR was 2 in 3,619 participants. Major cardiovascular events were reduced by 9% (95% confidence interval [CI]: -9% to 24%), 15% (95% CI: -17% to 39%), and 66% (95% CI: 33% to 83%) for patients with baseline eGFR of 2, respectively (p trend = 0.03). Total mortality was reduced by 0% (95% CI: -20% to 17%), 11% (95% CI: -31% to 40%), and 49% (95% CI: 6% to 73%), respectively (p trend = 0.04). Major bleeding events were nonsignificantly greater with lower eGFR (hazard ratio [HR]: 1.52 [95% CI: 1.11 to 2.08], HR: 1.70 [95% CI: 0.74 to 3.88], and HR: 2.81 [95% CI: 0.92 to 8.84], respectively; p trend = 0.30). Among every 1,000 persons with eGFR 2 treated for 3.8 years, 76 major cardiovascular events and 54 all-cause deaths will be prevented while 27 excess major bleeds will occur. Conclusions Aspirin therapy produces greater absolute reduction in major cardiovascular events and mortality in hypertensive patients with CKD than with normal kidney function. An increased risk of major bleeding appears to be outweighed by the substantial benefits.

AB - Objectives The purpose of this study was to determine the benefit and risk associated with antiplatelet therapy in the chronic kidney disease (CKD) population. Background Cardiovascular and possibly bleeding risks are elevated in patients with CKD. The balance of benefit and harm associated with antiplatelet therapy remains uncertain. Methods The HOT (Hypertension Optimal Treatment) study randomly assigned participants with diastolic hypertension to aspirin (75 mg) or placebo. Study treatment effects were calculated using univariate proportional hazards regression models stratified by baseline estimated glomerular filtration rate (eGFR) with trends tested by adding interaction terms. End points included major cardiovascular events, total mortality, and major bleeding. Results The study included 18,597 participants treated for 3.8 years. Baseline eGFR was 2 in 3,619 participants. Major cardiovascular events were reduced by 9% (95% confidence interval [CI]: -9% to 24%), 15% (95% CI: -17% to 39%), and 66% (95% CI: 33% to 83%) for patients with baseline eGFR of 2, respectively (p trend = 0.03). Total mortality was reduced by 0% (95% CI: -20% to 17%), 11% (95% CI: -31% to 40%), and 49% (95% CI: 6% to 73%), respectively (p trend = 0.04). Major bleeding events were nonsignificantly greater with lower eGFR (hazard ratio [HR]: 1.52 [95% CI: 1.11 to 2.08], HR: 1.70 [95% CI: 0.74 to 3.88], and HR: 2.81 [95% CI: 0.92 to 8.84], respectively; p trend = 0.30). Among every 1,000 persons with eGFR 2 treated for 3.8 years, 76 major cardiovascular events and 54 all-cause deaths will be prevented while 27 excess major bleeds will occur. Conclusions Aspirin therapy produces greater absolute reduction in major cardiovascular events and mortality in hypertensive patients with CKD than with normal kidney function. An increased risk of major bleeding appears to be outweighed by the substantial benefits.

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