Clopidogrel is the most commonly used anti-P2Y12 drug in DAPT. Impaired pharmacological response and antithrombotic efficacy associated with cytochrome-P450 and/or ABCB1 gene mutations is observed in about 1/3 of treated patients. To circumvent this problem, guided therapy has been tested, based on either identification of predisposing gene mutations or results of platelet function tests (PFTs). Patients with with predisposing gene mutations or high platelet reactivity on clopidogrel (HPR) were treated with alternative, potentially more effective regimens: higher clopidogrel doses, prasugrel, ticagrelor, or additional cylostazol. In this meta-analysis, we tested the efficacy and safety of these two different strategies of guided therapy separately.
We searched relevant articles published in English until October 1th 2022 on MEDLINE, Embase and Central. Articles included all RCTs comparing standard anti-P2Y12 therapy (ST) versus genotype-guided or PFTs-guided anti-P2Y12 therapy in patients with acute coronary syndromes (ACS) or chronic coronary artery disease (CCAD) undergoing PCI. Two reviewers independently assessed study eligibility and risk of bias, and extracted data. Hazard ratios with 95% CI were calculated based on fixed effects models. Efficacy outcomes comprised major adverse cardiovascular events (MACE) as defined in each study. Main safety outcome included major bleedings (MB) according to BARC. Different sub-analyses were also performed based on type of anti-P2Y12 drug in ST, type of alternative drug, type of PFT, patients’ ethnicity, prevalence of ACS.
We retrieved 6 RCTs testing genotype-guided anti-P2Y12 therapy on 10443 patients and 14 RCTs testing PFTs-guided anti-P2Y12 therapy on 11596 patients. MACE were lower in genotype-guided therapy than in ST, RR 0.68 (95% CI, 0.49-0.94) while MB did not significantly differ between the two groups, RR 0.88 (95% CI, 0.63-1.23). MACE and MB did not significantly differ between PFTs-guided anti-P2Y12 therapy and ST: RR 0.83 (95% CI, 0.58-1.18) and 1.24 (95% CI, 1.00-1.53), respectively. Sub-analyses revealed that MACE were lower in PFTs-guided anti-P2Y12 therapy compared to ST in patients of Asian descent.
In conclusion, gentotype-guided anti-P2Y12 therapy reduced the incidence of MACE without increasing MB, compared with ST, in patients with ACS or CCAD undergoing PCI; in contrast, PFTs-guided anti-P2Y12 therapy did not affect the incidence of MACE or MB in these patients.