Association of Laboratory-Defined Aspirin Resistance With a Higher Risk of Recurrent Cardiovascular Events

Abstract

Background: The risk of recurrence of cardiovascular events among patients using aspirin (acetylsalicylic acid) for secondary prevention of such events remains high. Persistent platelet reactivity despite aspirin therapy, a laboratory-defined phenomenon called aspirin resistance (hereinafter, laboratory aspirin resistance), might explain this in part, but its actual contribution to the risk remains unclear. The objective of this study was to systematically review all available evidence on whether laboratory aspirin resistance is related to a higher risk of cardiovascular recurrent events. Methods: Using a predefined search strategy, we searched electronic databases. To be included in our analysis, articles had to report on patients who used aspirin for secondary cardiovascular prevention, had to contain a clear description of a method to establish the effects of aspirin on platelet reactivity, and had to report recurrence rates of cardiovascular events. Odds ratios of cardiovas-cular outcome of eligible studies were pooled in a randomeffects model. Results: We included 15 full-text articles and 1 meeting abstract. Fifteen of these studies revealed an adverse association between laboratory aspirin resistance and occurrence of cardiovascular events. The pooled odds ratio of all cardiovascular outcomes was 3.8 (95% confidence interval, 2.3-6.1) for laboratory aspirin resistance. Conclusion: This systematic review and meta-analysis shows that patients biochemically identified as having laboratory aspirin resistance are more likely to also have "clinical resistance" to aspirin because they exhibit significantly higher risks of recurrent cardiovascular events compared with patients who are identified as (laboratory) aspirin sensitive.

Residual platelet reactivity on aspirin therapy and recurrent cardiovascular events — A meta-analysis

“…In the present meta-analysis we confirm the data recently published by Snoep et al [7], by systematically analysing all the published clinical studies that evaluated platelet function among patients with CHD on ASA therapy. This in order to give further insights on this matter that is arousing increasing clinical interest among physicians and researchers.…”

“…In a recent systematic review of all the clinical trials that evaluated persistent platelet reactivity in patients under ASA therapy, the mean prevalence of RPR was nearly 25% [3]. Some clinical prospective studies reported a significant association between RPR and the occurrence of secondary cardiovascular events [4][5][6], and a recent meta-analysis by Snoep et al [7] reported a significant role for the laboratory-defined aspirin resistance on the risk of clinical cardiovascular recurrences.…”

“…The question whether this phenomenon has a significant clinical implication on the occurrence of atherothrombotic events has not been, to date, definitely answered. Some studies evaluating the occurrence of clinical events during follow-up in patients with RPR have been conducted [4][5][6], and a recent meta-analysis by Snoep et al, evidenced an association between a laboratory-defined aspirin resistance and a higher risk of recurrent cardiovascular events [7]. The aim of this study is to systematically review all the available studies that prospectively investigated the possible association between RPR on ASA therapy and the occurrence of major adverse cardiovascular events in patients with CHD.…”

How I use laboratory monitoring of antiplatelet therapy

“…39 However, if "resistance" is defined in pharmacological terms as the failure of aspirin intake to fully inactivate its target, platelet COX-1, as evidenced by lack of inhibition of thromboxane B 2 generation, then aspirin resistance is either a very rare phenomenon [40][41][42] or does not exist. 17 Based on this pharmacologic definition, a study of 400 healthy volunteers failed to identify a single case of aspirin resistance.…”

Assessment of platelets and the endothelium in patients presenting with acute coronary syndromes – is there a future?

“…Several studies report a link between CT and occurrence of ischaemic events. Meta-analyses comparing patients who are responsive to aspirin treatment and patients with persistent platelet activity despite aspirin therapy suggest that the latter group faces a significantly (Krasopoulos et al: nearly 4-fold) greater risk of adverse CV events (35,(43)(44)(45). Another meta-analysis, based only on prospective studies, shows that high residual platelet reactivity in aspirin-treated CV patients evaluated by the PFA-100 is associated with recurrent ischaemic events (46).…”