Twenty studies (n=2,930) were included. The tables listed one randomised controlled trial (RCT; n=71), one case-control study (n=28), 17 prospective cohort studies (n=2542), and one prospective descriptive study (n=289). However, the text stated that no RCTs were included.
Most of the studies (17 out of 20) were graded A for quality. Three studies reported insufficient information to ascertain the risk of bias. However, the results of these 3 studies were consistent with the overall findings of the other 17 studies. Compliance with treatment was reported in 17 of the 20 studies.
Prevalence of aspirin resistance and characteristics of aspirin-resistant patients.
Overall, 28% of patients were classified as aspirin resistant (810 out of 2,930). Resistance was more prevalent in women (p<0.01) (n approximately 1,460) and in patients with renal impairment (p<0.03) (2 studies, n=268).
Clinical outcomes.
Aspirin-resistant patients were at a significantly higher risk of any cerebrovascular event (20 studies, n=2,930; OR 3.85, 95% CI: 3.08, 4.80, p<0.001), death (4 studies, n=728; OR 5.99, 95% CI: 2.28, 15.72, p<0.003), acute coronary syndrome (9 studies, n=1,275; OR 4.06, 95% CI: 2.96, 5.56, p<0.001), failure in vascular intervention (3 studies, n=420; OR 4.35, 95% CI: 2.26, 8.37, p<0.001) and new cerebrovascular event (4 studies, n=340; OR 3.78, 95% CI: 1.25, 11.41, p<0.02).
There was significant statistical heterogeneity associated with the outcome ‘any cerebrovascular event’ (I-squared 68.3%, p<0.001). Most of the heterogeneity (I-squared 50.3%) derived from the 8 studies that used the whole blood platelet function analyser, which defined 33% of patients as aspirin resistant, in contrast to the 7 studies that used the rich plasma aggregation assay, which defined 16% of patients as aspirin resistant and had relatively higher odds of a cerebrovascular event in this group (OR 3.85, 95% CI: 2.5, 5.88, p<0.001). There were insufficient data to assess the degree to which other platelet assays contributed to heterogeneity. Significant heterogeneity was also found for the analysis of acute coronary syndrome (I-squared 58.6%, no p-value reported).
Dose response.
There was no evidence of a dose-response relationship between aspirin resistance and any cardiovascular outcome, with or without secondary antiplatelet treatment.
Concomitant antiplatelet therapy.
Concomitant therapy with clopidogrel or tirofiban provided no benefit to patients identified as aspirin resistant. There was significant statistical heterogeneity associated with this analysis (I-squared 70.6%, p=0.004).
There was modest evidence of publication bias, with an absence of small studies that reported on a negative or no relation between aspirin resistance and adverse clinical outcomes.