Genotype‐guided antiplatelet treatment versus conventional therapy: A systematic review and meta‐analysis

Abstract

This meta-analysis was carried out to explore if a personalized antiplatelet strategy based on genotyping is superior to conventional therapy.Methods: PubMed, Web of Science, EMBASE and the Cochrane Library were searched from the inception of each database to 5 May 2020. Studies reporting endpoints in genotype-guided treatment group and conventional treatment group were included. The endpoint results were presented as the risk ratio (RR), with 95% confidence interval (CI).Results: A total of 10 561 patients from 16 studies (eight randomized controlled trials [RCT] and eight cohort studies) were included in the meta-analysis. The rates of major adverse cardiovascular events (MACE), stent thrombosis and myocardial infarction (MI) were significantly lower in the genotype-guided group than in the conventional treatment group (RR 0.56, 95% CI 0.44-0.73, P < .0001; RR 0.40, 95% CI 0.24-0.67, P = .0005; RR 0.45, 95% CI 0.35-0.58, P < .00001, respectively).A significant difference was found between the two groups in major bleeding (RR 0.73, 95% CI 0.55-0.98, P = .04), which was not robust after sensitivity analysis. Conclusion:Genotype-guided antiplatelet treatment could decrease the risk of MACE, stent thrombosis and MI in patients with coronary artery disease or undergoing percutaneous coronary intervention, without increasing the risk of bleeding over a long follow-up period. The decreased risk of efficacy outcomes was more obvious in cohort studies. Well-organized RCTs and clinical trials are required to verify the benefit of genotype-guided therapy.

Genetic variation in activating clopidogrel: longer-term outcomes in a large community cohort

“…Our results are consistent with previous studies of clopidogrel efficacy in CYP2C19 LoF genotype carriers, although the previous evidence was predominantly from high-risk acutely hospitalized patient groups (24–27), with limited follow-up periods (rarely over 12 months). Some studies reported that the effect of CYP2C19 genotype on reducing clopidogrel efficacy was limited to the short-term (1-6 months) only (28,29), but in our community based longer term follow-up we found no evidence for deviation from the proportional hazards assumptions, with survival analysis results suggesting sustained effects over the follow-up period.…”

“…A recent meta-analysis of 16 studies (8 RCTs and 8 cohorts) concluded that genotype-guided antiplatelet treatment (primarily based on CYP2C19 LoF alleles) improved patient outcomes for major cardiovascular events (e.g. Relative Risk for MI 0.45: 95% CI 0.35 to 0.58, p<0.00001), with decreased risk of major bleeding (27). Treatment strategy in the different metabolizer groups varied between individual studies, but included use of higher doses of clopidogrel (150 mg/d instead of the usual 75 mg/d), or prescribing of prasugrel or ticagrelor, or a combination.…”

“…A recent meta-analysis of 16 studies (8 RCTs and 8 cohorts) concluded that genotype-guided antiplatelet treatment (primarily based on CYP2C19 LoF alleles) improved patient outcomes for major cardiovascular events (e.g. Relative Risk for MI 0.45: 95% CI 0.35 to 0.58, p<0.00001), with decreased risk of major bleeding (27).…”

Analysis ofCYP2C19genetic variants with ischaemic events in UK patients prescribed clopidogrel in primary care: a retrospective cohort study

“…Our results are consistent with previous studies of clopidogrel efficacy in CYP2C19 LoF genotype carriers, although the previous evidence was predominantly from high-risk acutely hospitalised patient groups, [26][27][28][29] with limited follow-up periods (rarely over 12 months). Some studies reported that the effect of CYP2C19 genotype on reducing clopidogrel efficacy was limited to the short term (1-6 months) only, 30 31 but in our community based longer term follow-up we found no evidence for deviation from the proportional hazards assumptions, with survival analysis results suggesting sustained effects over the follow-up period.…”

Clinical Outcomes after Percutaneous Coronary Intervention Over Time on the Basis of CYP2C19 Polymorphisms: Evidence from a Chinese Cohort

“…Although multiple lines of evidence support the association between CYP2C19 LOF (*2 and *3) alleles and ischemic events in patients treated with clopidogrel, homozygous carriers of LOF alleles are at higher risk than heterozygous carriers [7,30,31]. Conclusions from recent RCTs and meta-analyses, nevertheless, have not yet reached agreement on the clinical e cacy of gene-guided antiplatelet therapy [19,29,32]. Due to the lack of su cient evidence, the current guidelines and consensus state that routine genetic testing is not recommended for tailoring DAPT [11,33,34].…”