Protocol for a systematic review of the diagnostic and prognostic utility of tests currently available for the detection of aspirin resistance in patients with established cardiovascular or cerebrovascular disease

BACKGROUND: The benefits of aspirin as an anti-platelet agent are well established; however, there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function. In some patients, aspirin fails to inhibit platelets even where compliance has been verified, a phenomenon which has been termed "aspirin resistance". These patients may in turn be at a higher risk of future vascular events. The proportion of "resistant" patients identified depends on the type of platelet function test. Therefore, the aim of this systematic review is to determine which, if any, platelet function test has utility in terms of identifying patients with a high risk of vascular events. The review has been registered with PROSPERO (CRD42012002151). METHODS: Relevant studies will be sought from bibliographic databases. Trials registers will be searched for ongoing studies. Reference lists will be checked and subject experts contacted. There will be no date or language restrictions. Standard reviewing methodology to minimise bias will be employed. Any prospective studies in patients on aspirin therapy and assessing platelet function in relation to relevant clinical outcomes will be included, as will studies reporting prognostic models. Risk of bias assessment will be based on the Quality Assessment of Diagnostic Accuracy Studies guidelines, and suitable criteria for assessing quality of prognostic studies. Data on test accuracy measures, relative risks, odds or hazard ratios will be extracted and meta-analysed, where possible, using a random-effects model to account for between-study heterogeneity. Where appropriate, the causes of heterogeneity will be explored through meta-regression and sub-group or sensitivity analyses. If platelet function testing is demonstrated to have diagnostic/predictive utility in a specific population, the potential for a cost-effectiveness analysis will be considered and, if possible, an economic model constructed. This will be supported by a systematic review of existing economic evaluation studies. DISCUSSION: The results of the review could indicate if platelet function test(s) could lead to a reliable prediction of the risk of clinically important events in a defined population, and thus support investigations into adjustments to therapy in order to compensate for a predicted poor response to standard aspirin.