Towards tailored antiplatelet therapy in vascular disease

Abstract

Inhibition of platelet activation, aggregation and consequent thrombus formation is an essential target in primary and secondary prevention for secondary cardiovascular events (CVE). Although stronger platelet inhibitory therapy has been developed, there are still individual patients who develop a second CVE, such as stroke and myocardial infarction, while other patients develop bleeding events with the same dose of platelet inhibitors. This argues for tailored treatment strategies. Several platelet reactivity tests have been used to identify patients with high on treatment platelet reactivity, and therefore increased risk for CVE, however adjusting antiplatelet therapy based on these measurement has not yet been proven effective in large cardiology trials. Possible explanations for the lack of benefit of tailored compared to standard antiplatelet therapy may be the following: 1. The large variety of utilized platelet reactivity tests, 2. The currently available tests are not standardized and hold a poor correlation. This makes the diagnosis of ‘’high on treatment platelet reactivity " dependent of the utilized platelet reactivity test and cut-off values, 3. The present platelet reactivity tests measure the overall capacity of the platelet to form a thrombus but do not provide information about the different platelet activation pathways and -markers. 4. Potentially there is an intra-individual variability in platelet reactivity over time. The decision to continue platelet inhibitors, adjust the dosage or switch to a different antiplatelet therapy is made based on a single measurement. The optimal timing for testing should therefore be investigated. 5. Research on platelet reactivity involves mostly patients undergoing percutaneous coronary intervention (PCI). The cut-off values of high- and low platelet reactivity per test are determined on measurements of patients undergoing PCI. It remains questionable if these cut-off values can be extrapolated to patients undergoing vascular surgery. 6. Optimal antiplatelet treatment strategies are not known for all forms of vascular disease and should be investigated prior the implementation of tailored antiplatelet therapy. Overall, although the concept of ‘’tailored antiplatelet therapy " is promising, largescale clinical trials investigating this concept in vascular surgery patients are warranted.