JACC. Cardiovascular interventions · 2026
Genotype-Guided vs Conventional Oral P2Y12 Inhibitors in Acute Coronary Syndrome: A Combined Analysis of TAILOR-PCI and POPular Genetics.
СтатьяМетаанализПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Galli Mattia, Pereira Naveen L, Lennon Ryan J, van den Broek Wout W A, Claassens Daniel M F, Bergmeijer Thomas O, Rosenberg Yves, Fazzini Luca, Deneer Vera H M, Murad M Hassan, Farkouh Michael E, Rihal Charanjit, Ten Berg Jurrien, Angiolillo Dominick J
Аннотация
BACKGROUND: Genotype-guided P2Y12 inhibitor selection may improve outcomes in acute coronary syndrome (ACS) or percutaneous coronary interventions (PCI) patients.
OBJECTIVES: This study sought to assess the impact of guided therapy escalation or de-escalation vs conventional therapy.
METHODS: Randomized controlled trials comparing guided therapy using CYP2C19 genetic testing vs conventional therapy among patients with ACS undergoing PCI were searched and individual participant-level data obtained. The primary safety endpoint was time-to-first type 2, 3, or 5 Bleeding Academic Research Consortium (BARC) bleeding at 12 months. The primary efficacy endpoint was time-to-first major adverse cardiovascular event (MACE) at 12 months.
RESULTS: A total of 6,734 participants from 2 randomized controlled trials were available for analysis. After 1 year, there were no differences in the primary safety or efficacy endpoints with overall guided therapy vs conventional therapy. However, guided therapy reduced myocardial infarction (0.68; 95% CI: 0.48-0.97) and net adverse cardiovascular events (NACE) (0.85; 95% CI: 0.73-1.00) compared with conventional therapy. Guided therapy de-escalation reduced the primary safety endpoint (0.77; 95% CI: 0.62-0.97) and NACE (0.77; 95% CI: 0.62-0.94) with no significant difference in MACE, compared with conventional therapy. The primary safety and efficacy endpoints were similar between patients undergoing guided therapy escalation and conventional therapy groups. Time-dependent covariate analyses showed that overall guided therapy and de-escalation strategies reduced bleeding and NACE before 90 days, compared with conventional therapy.
CONCLUSIONS: These findings support evaluating genotype-guided therapy by separately analyzing de-escalation and escalation. In ACS patients undergoing PCI, genotype-guided de-escalation reduces bleeding and NACE without increasing MACE, with the greatest benefit in the first 3 months post-PCI. (Genotype-Guided versus Conventional Oral P2Y12 Inhibitors in Acute Coronary Syndrome: An Individual Patient Data Meta-analysis of Randomized Controlled Trials; PROSPERO CRD42024580431).
OBJECTIVES: This study sought to assess the impact of guided therapy escalation or de-escalation vs conventional therapy.
METHODS: Randomized controlled trials comparing guided therapy using CYP2C19 genetic testing vs conventional therapy among patients with ACS undergoing PCI were searched and individual participant-level data obtained. The primary safety endpoint was time-to-first type 2, 3, or 5 Bleeding Academic Research Consortium (BARC) bleeding at 12 months. The primary efficacy endpoint was time-to-first major adverse cardiovascular event (MACE) at 12 months.
RESULTS: A total of 6,734 participants from 2 randomized controlled trials were available for analysis. After 1 year, there were no differences in the primary safety or efficacy endpoints with overall guided therapy vs conventional therapy. However, guided therapy reduced myocardial infarction (0.68; 95% CI: 0.48-0.97) and net adverse cardiovascular events (NACE) (0.85; 95% CI: 0.73-1.00) compared with conventional therapy. Guided therapy de-escalation reduced the primary safety endpoint (0.77; 95% CI: 0.62-0.97) and NACE (0.77; 95% CI: 0.62-0.94) with no significant difference in MACE, compared with conventional therapy. The primary safety and efficacy endpoints were similar between patients undergoing guided therapy escalation and conventional therapy groups. Time-dependent covariate analyses showed that overall guided therapy and de-escalation strategies reduced bleeding and NACE before 90 days, compared with conventional therapy.
CONCLUSIONS: These findings support evaluating genotype-guided therapy by separately analyzing de-escalation and escalation. In ACS patients undergoing PCI, genotype-guided de-escalation reduces bleeding and NACE without increasing MACE, with the greatest benefit in the first 3 months post-PCI. (Genotype-Guided versus Conventional Oral P2Y12 Inhibitors in Acute Coronary Syndrome: An Individual Patient Data Meta-analysis of Randomized Controlled Trials; PROSPERO CRD42024580431).
Предметные рубрики MeSH
HumansAcute Coronary SyndromePercutaneous Coronary InterventionTreatment OutcomeCytochrome P-450 CYP2C19Time FactorsRisk FactorsPurinergic P2Y Receptor AntagonistsFemalePharmacogenomic VariantsAdministration, OralHemorrhagePhenotypeAgedPharmacogenomic TestingRandomized Controlled Trials as TopicMaleRisk AssessmentMiddle AgedPredictive Value of TestsClinical Decision-MakingReceptors, Purinergic P2Y12Platelet Aggregation InhibitorsPrecision Medicine