Aspirin is beneficial in hypertensive patients with chronic kidney disease: a post-hoc subgroup analysis of a randomized controlled trial.
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.
Jardine
Meg J
MJ
The George Institute for Global Health, Sydney, Australia; Concord Repatriation General Hospital, Sydney, Australia.
Ninomiya
Toshiharu
T
Perkovic
Vlado
V
Cass
Alan
A
Turnbull
Fiona
F
Gallagher
Martin P
MP
Zoungas
Sophia
S
Lambers Heerspink
Hiddo J
HJ
Chalmers
John
J
Zanchetti
Alberto
A
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
D010975:Platelet Aggregation Inhibitors; D003404:Creatinine; D001241:Aspirin