1. Guided selection of antiplatelet therapy reduced rates of major adverse cardiovascular event rates compared to standard therapy.
2. Guided selection strategy was beneficial for both escalation and de-escalation of standard therapy, balancing patient-dependent ischemic and bleeding risks.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Patients who undergo percutaneous coronary intervention (PCI) are typically started on dual antiplatelet therapy consisting of aspirin and clopidogrel. However, patients can have persistently high platelet reactivity (HPR) on clopidogrel due to individual metabolic differences, which includes genetic polymorphisms of enzymes such as cytochrome P450 2C19 (CYP2C19). This systematic review and meta-analysis sought to aggregate randomized control trials and observational studies comparing outcomes in patients with acute or chronic coronary syndromes undergoing PCI, started on guided vs. standard antiplatelet therapies. Data from over 20,000 patients demonstrate that guided selection of antiplatelet therapies reduced risk of major adverse cardiovascular events including myocardial infarction, stent thrombosis, stroke, and minor bleeding compared to standard therapy. Additionally, both stepwise escalation and de-escalation of standard therapy, depending on clinical context, were associated with improved outcomes with regard to bleeding and ischemic events. According to study results, guided selection of antiplatelet therapy improves outcomes for patients undergoing PCI by accounting for individual genetic and risk profiles, especially when employed in a stepwise manner.
In-Depth [systematic review and meta-analysis]: After rigorous literature search and screening, 11 randomized control trials and 3 observational studies were included in this analysis, resulting in a total of 20 743 patients. Risk ratios and 95% CI were calculated for the primary outcome trial-defined major adverse cardiovascular events and primary safety outcome bleeding events; secondary outcomes including death, myocardial infarction, stroke, and stent thrombosis were assessed as well. A breadth of outcomes and risk ratios are reported in this study. Commonly used antiplatelet agents were clopidogrel, ticagrelor, and prasugrel at varying dosages. Major adverse cardiovascular events were reduced in guided antiplatelet selection compared to standard (RR 0.78, 95% CI [0.63–0.95], p=0.015). Risk of minor bleeding was reduced in with guided selection therapy, but no significant difference in overall bleeding was observed (p=0.069). Guided therapy improved all secondary outcomes when fixed-effect and random-effects models were applied. Both de-escalation and escalation strategies starting from standard therapy as a baseline favored guided therapy selection, with favorable risk ratios most notable in reducing major adverse cardiovascular events (RR 0.74, 95% CI [0.57-0.95]), stent thrombosis (RR 0.62, 95% CI [0.42-0.91]), and any bleed (RR 0.81, 95% CI [0.68-0.96]). The conclusions drawn by this review and meta-analysis are limited by heterogeneity among included studies and their patient cohorts, differences in interventional protocols, as well as altered medication choices. Despite these limitations, this study compiles a large volume of patient-outcomes regarding antiplatelet therapy selection in patients undergoing PCI, overall supporting guided selection of oral therapies to suit each patient’s genetic profile and risk factors.
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