title: Aspirin is beneficial in hypertensive patients with chronic kidney disease: a post-hoc subgroup analysis of a randomized controlled trial.
abstract: OBJECTIVE
  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 m(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 ≥ 60, 45 to 59, and < 45 ml/min/1.73 m(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 < 45 ml/min/1.73 m(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.
authors.affiliation: The George Institute for Global Health, Sydney, Australia; Concord Repatriation General Hospital, Sydney, Australia.
authors.forename: Meg J
authors.initials: MJ
authors.lastname: Jardine
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.forename: Fiona
authors.initials: F
authors.lastname: Turnbull
authors.forename: Martin P
authors.initials: MP
authors.lastname: Gallagher
authors.forename: Sophia
authors.initials: S
authors.lastname: Zoungas
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.forename: Alberto
authors.initials: A
authors.lastname: Zanchetti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006470:Hemorrhage / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000150:complications*; D007674:Kidney Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011322:Primary Prevention; D018570:Risk Assessment
chemical_list: D010975:Platelet Aggregation Inhibitors; D003404:Creatinine; D001241:Aspirin