Randomized controlled trials comparing the effects of
aspirin for primary prevention of CVD versus control and including at least 1000 patients were eligible for this meta-analysis. The primary efficacy outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (
MACE),
myocardial infarction,
ischemic stroke, and net clinical benefit. The primary safety outcome was major
bleeding. Subgroup analyses involving sex, concomitant
statin treatment, diabetes, and smoking were performed.
RESULTS: Thirteen randomized controlled trials comprising 164,225 patients were included. The risk of all-cause and cardiovascular mortality was similar for
aspirin and control groups (RR 0.98; 95% CI, 0.93-1.02; RR 0.99; 95% CI, 0.90-1.08; respectively).
Aspirin reduced the relative risk (RRR) of major adverse cardiovascular events (
MACE) by 9% (RR 0.91; 95% CI, 0.86-0.95),
myocardial infarction by 14% (RR 0.86; 95% CI, 0.77-0.95), and
ischemic stroke by 10% (RR 0.90; 95% CI, 0.82-0.99), but was associated with a 46% relative risk increase of major
bleeding events (RR 1.46; 95% CI, 1.30-1.64) compared with controls.
Aspirin use did not translate into a net clinical benefit adjusted for event-associated mortality risk (mean 0.034%; 95% CI, - 0.18 to 0.25%). There was an interaction for
aspirin effect in three patient subgroups: (i) in patients under
statin treatment,
aspirin was associated with a 12% RRR of
MACE (RR 0.88; 95% CI, 0.80-0.96), and this effect was lacking in the no-
statin group; (ii) in non-smokers,
aspirin was associated with
a 10% RRR of
MACE (RR 0.90; 95% CI, 0.82-0.99), and this effect was not present in smokers; and (iii) in males,
aspirin use resulted in a 11% RRR of
MACE (RR 0.89; 95% CI, 0.83-0.95), with a non-significant effect in females.
CONCLUSIONS:
Aspirin use does not reduce all-cause or cardiovascular mortality and results in an insufficient benefit-risk ratio for CVD primary prevention. Non-smokers, patients treated with
statins, and males had the greatest risk reduction of
MACE across subgroups.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118474.