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Does individualized guided selection of antiplatelet therapy improve outcomes after percutaneous coronary intervention? A systematic review and meta-analysis.

ABSTRACT:

Background

The potential benefits of individualized guided selection of antiplatelet therapy over standard antiplatelet therapy in improving outcomes in patients undergoing percutaneous coronary intervention (PCI) have not been established. Therefore, we pooled evidence from available clinical trials to assess the effectiveness by comparing the two regimens in patients undergoing PCI.

Methods

We queried two electronic databases, MEDLINE and Cochrane CENTRAL, from their inception to April 20, 2021 for published randomized controlled trials in any language that compared guided antiplatelet therapy, using either genetic testing or platelet function testing, versus standard antiplatelet therapy in patients undergoing PCI. The results from trials were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and were pooled using a random-effects model.

Results

Eleven eligible studies consisting of 18,465 patients undergoing PCI were included. Pooled results indicated that guided antiplatelet therapy, compared to standard therapy, was associated with a significant reduction in the incidence of MACE [RR 0·78, 95% CI (0·62-0·99), P = 0·04], MI [RR 0·73, 95% CI (0·56-0.96), P = 0·03], ST [RR 0·66, 95% CI (0·47-0.94), P = 0·02], stroke [RR 0·71, 95% CI (0·50-1.00), P = 0·05], and minor bleeding [RR 0·78, 95% CI (0·66-0.91), P = 0·003].

Conclusions

Individualized guided selection of antiplatelet therapy significantly reduced the incidence of MACE, MI, ST, stroke, and minor bleeding in adult patients when compared with standard antiplatelet therapy. Our findings support the implementation of genetic and platelet function testing to select the most beneficial antiplatelet agent.

SUBMITTER: Yamani N

PROVIDER: S-EPMC9289299 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND:CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS:After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS:Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS:These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Project description:Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across cytochrome P450 2C19 isozyme (CYP2C19) metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%), and ultrarapid metabolizers (80.6%) (P = 0.360). Clopidogrel-treated normal metabolizers (20.4 events/100 patient-years; adjusted hazard ratio (HR) 1.00, 95% confidence interval (CI), 0.75-1.33, P = 0.993) and clopidogrel-treated rapid or ultrarapid metabolizers (19.1 events/100 patient-years; adjusted HR 0.95, 95% CI, 0.69-1.30, P = 0.734) exhibited no difference in major atherothrombotic events compared with patients treated with prasugrel or ticagrelor (17.6 events/100 patient-years). In contrast, clopidogrel-treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared with prasugrel/ticagrelor-treated patients (adjusted HR 1.56, 95% CI, 1.12-2.16, P = 0.008). When comparing clopidogrel-treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI, 0.73-1.29, P = 0.808) or bleeding events (adjusted HR 1.34, 95% CI, 0.83-2.17, P = 0.224) were observed. In a real-world setting of genotype-guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post-PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI.

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