{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:05:57Z","timestamp":1790139957697,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2025-463"],"award-info":[{"award-number":["075-15-2025-463"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: De-escalation of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) reduces bleeding risk; however, in carriers of loss-of-function CYP2C19 alleles, it may carry a risk of insufficient platelet inhibition. This study compared the safety and efficacy of CYP2C19 genotype-guided DAPT de-escalation with standard clinical practice in patients after ACS and PCI, and evaluated the cost implications of this approach. Methods: We conducted a prospective, randomized, open-label, parallel group trial (n = 75 genotype-guided group; n = 75 control group) with 12 months of follow-up. In the genotype-guided group, the de-escalation decision was based on the CYP2C19 genotype; in the control group, it followed standard practice at the treating physician\u2019s discretion. The primary safety endpoint was the cumulative incidence of clinically relevant bleeding (BARC \u22652); the secondary efficacy endpoint was a composite of ischemic events. The economic evaluation was performed as a cost\u2013consequence analysis (CCA), reporting drug and testing costs alongside the clinical outcomes described above, including a break-even threshold and one-way sensitivity analysis. Results: In the intention-to-treat population (n = 150), the 12-month cumulative incidence of BARC \u2265 2 bleeding was 10.7% in the genotype-guided group versus 12.0% in the control group (HR 0.88; 95% CI 0.34\u20132.28; p = 0.79). The cumulative incidence of the ischemic composite was 13.3% versus 14.7% (HR 0.91; 95% CI 0.38\u20132.13; p = 0.82), and neither difference was statistically significant. A per-protocol sensitivity analysis excluding eight patients who required non-protocol anticoagulant therapy yielded similar results for bleeding (9.7% vs. 11.4%; HR 0.84) and a numerically larger, though still non-significant, effect for the ischemic composite (11.1% vs. 15.7%; HR 0.69). Use of the genotype-guided strategy was associated with savings in drug and pharmacogenetic testing costs of RUB 1,036,340.21 for the cohort (RUB 15,278.16 per patient), a saving that remained positive across the full range of observed drug prices; the drug-and-testing-cost break-even price for testing was RUB 19,748.16 per patient. Conclusions: No statistically significant differences in bleeding or ischemic events were detected between genotype-guided de-escalation of DAPT based on CYP2C19 testing and standard practice in this trial, and the genotype-guided strategy was associated with a reduction in drug and testing costs. Confirmation of the clinical benefit of this approach requires further studies in larger cohorts.<\/jats:p>","DOI":"10.3390\/jcm15187261","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"7261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenetics-Guided De-Escalation of Dual Antiplatelet Therapy Based on CYP2C19 Testing in Patients After Acute Coronary Syndrome: Clinical Outcomes and Cost\u2013Consequence Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2343-4758","authenticated-orcid":false,"given":"Firuz Kh.","family":"Turaev","sequence":"first","affiliation":[{"name":"Egoryevsk Hospital of the Moscow Region, Egoryevsk 140301, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9001-1499","authenticated-orcid":false,"given":"Sherzod P.","family":"Abdullaev","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Center of Surgery, Moscow 119435, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Kirill I.","family":"Matrenin","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Center of Surgery, Moscow 119435, Russia"},{"name":"Center for Healthcare Quality Assessment and Control, Ministry of Health of the Russian Federation, Moscow 109028, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Furkatjon S.","family":"Gafurov","sequence":"additional","affiliation":[{"name":"Egoryevsk Hospital of the Moscow Region, Egoryevsk 140301, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2744-2752","authenticated-orcid":false,"given":"Svetlana N.","family":"Tuchkova","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Center of Surgery, Moscow 119435, Russia"},{"name":"Russian Medical Academy of Continuous Professional Education, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"David A.","family":"Gabrielyan","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Center of Surgery, Moscow 119435, Russia"},{"name":"Russian Medical Academy of Continuous Professional Education, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Karin B.","family":"Mirzaev","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Center of Surgery, Moscow 119435, Russia"},{"name":"Russian Medical Academy of Continuous Professional Education, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Dmitry A.","family":"Kaprin","sequence":"additional","affiliation":[{"name":"Egoryevsk Hospital of the Moscow Region, Egoryevsk 140301, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4496-3680","authenticated-orcid":false,"given":"Dmitry A.","family":"Sychev","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Center of Surgery, Moscow 119435, Russia"},{"name":"Russian Medical Academy of Continuous Professional Education, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update From the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. 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