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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171 Citations (Scopus)


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 <60 ml/min/1.73 m2 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 <60, 45 to 59, and <45 ml/min/1.73 m2, 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 <45 ml/min/1.73 m2 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
Issue number12
Publication statusPublished - 14 Sept 2010
Externally publishedYes


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


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