Relationship between changes in platelet reactivity and ischemicevents following percutaneous coronary intervention: Ameta-regression analysis of 30 randomized trials

Objective: High on-treatment platelet reactivity (HPR) is a well-known risk factor for adverse events in patients undergoing percutaneous coronary intervention (PCI). However, whether reducing platelet reactivity can lead to a lower incidence of ischemic events after PCI is still controversial. Therefore, we sought to investigate this issue by a meta-regression analysis of randomized trials. Methods: We collected randomized trials reporting HPR rates in patients receiving different antiplatelet therapies. δHPR was defined as the difference between HPR rates achieved in control vs. experimental arms, and the relationship between δHPR and clinical outcomes was evaluated. Results: Thirty trials totalling 6683 patients with a mean follow-up of 3-month were included. Reducing platelet reactivity was associated to a decreased risk of major adverse cardiac events (MACE), with a linear relationship between δHPR and MACE (change in tau²=-2.50; p=0.023). Particularly, achieving a 10% difference in HPR rates resulted in a parallel risk reduction in MACE of about 11% (Exp^(b)=0.98; 95% CI, 0.97-0.99).Changes in HPR predict the risk of ischemic events in patients with acute coronary syndrome (change in tau²=-2.52; Exp^(b)=0.98; 95% CI, 0.97-0.99; p=0.03), but not in patients with poor response to clopidogrel (change in tau²=-1.44; Exp^(b)=0.98; 95% CI, 0.96-1.01; p=0.19) or stable coronary artery disease (change in tau²=-0.14; Exp^(b)=0.99; 95% CI, 0.94-1.05; p=0.89). Conclusion: Reducing HPR occurrence decreases the risk of ischemic events in patients with acute coronary syndrome undergoing PCI, whereas a strategy of reducing platelet reactivity does not improve clinical outcomes in patients with poor response to clopidogrel or stable coronary artery disease.