{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:25:42Z","timestamp":1790011542459,"version":"4.0.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Interventions"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      A genotype-guided de-escalation strategy\u2014switching from a potent P2Y\n                      <jats:sub>12<\/jats:sub>\n                      inhibitor to clopidogrel\u2014may reduce bleeding risk in patients with acute coronary syndrome. This analysis evaluated the safety and effectiveness of routine genetic testing to guide antiplatelet therapy in clinical practice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      In this investigator-initiated, prospective, multicenter implementation study, patients received either standard care, with antiplatelet therapy at the physician discretion, or genotype-guided therapy. In the genotype-guided group, physicians were recommended to switch to clopidogrel in noncarriers of\n                      <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                      loss-of-function alleles. The coprimary end points were major adverse cardiac events, a composite of cardiovascular death, myocardial infarction, or stroke, and major or nonmajor clinically relevant bleeding, at 1 year of follow-up. Hazard ratios were adjusted for baseline differences between cohorts using multivariable Cox regression. Net adverse cardiac events comprised all-cause death, myocardial infarction, stroke, stent thrombosis, and major bleeding. A Bonferroni-adjusted significance level of\n                      <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                      =0.025 was applied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      A total of 9907 patients were included in the analysis. Of these, 1208 (12%) were included in the genotype-guided cohort, whereas 8699 (88%) were assigned to the standard care cohort. Major adverse cardiac events occurred in 107 patients (8.9%) in the genotype-guided cohort and 897 patients (10.3%) in the standard care cohort (adjusted hazard ratio, 1.05 [95% CI, 0.85\u20131.29];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.64). Major or nonmajor clinically relevant bleeding was reported in 146 patients (12.1%) in the genotype-guided cohort compared with 1384 patients (15.9%) in the standard care cohort (adjusted hazard ratio, 0.79 [95% CI, 0.67\u20130.94];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01). There was no significant association with net adverse cardiac events (adjusted hazard ratio, 0.91 [95% CI, 0.76\u20131.09];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.31).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      In patients with acute coronary syndrome receiving antiplatelet therapy, implementation of a\n                      <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                      genotype-guided de-escalation strategy in clinical practice was associated with a significant reduction of major and nonmajor clinically relevant bleeding compared with standard care at 12 months, without increasing ischemic events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03823547.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circinterventions.125.016084","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:00:15Z","timestamp":1772100015000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Genotype-Guided P2Y\n                    <sub>12<\/sub>\n                    -Inhibitor De-Escalation Strategy in Acute Coronary Syndrome: Observational Evidence From the POPular-GUIDE PCI"],"prefix":"10.1161","volume":"19","clinical-trial-number":[{"clinical-trial-number":"nct03823547","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4083-9957","authenticated-orcid":true,"given":"Wout W.A.","family":"van den Broek","sequence":"first","affiliation":[{"name":"Department of Cardiology (W.W.A.v.d.B., J.A., Q.Y.F.v.d.P., D.R.P.P.C.P.Y., J.P., J.M.t.B.), St. Antonius Hospital, Nieuwegein, the Netherlands."},{"name":"Department of Cardiology, University Medical Center Maastricht, The Netherlands (W.W.A.v.d.B., J.M.t.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-0481","authenticated-orcid":true,"given":"Jaouad","family":"Azzahhafi","sequence":"additional","affiliation":[{"name":"Department of Cardiology (W.W.A.v.d.B., J.A., Q.Y.F.v.d.P., D.R.P.P.C.P.Y., J.P., J.M.t.B.), St. Antonius Hospital, Nieuwegein, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7051-986X","authenticated-orcid":true,"given":"Qiu Ying F.","family":"van de Pol","sequence":"additional","affiliation":[{"name":"Department of Cardiology (W.W.A.v.d.B., J.A., Q.Y.F.v.d.P., D.R.P.P.C.P.Y., J.P., J.M.t.B.), St. Antonius Hospital, Nieuwegein, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7741-205X","authenticated-orcid":true,"given":"Dean R.P.P.","family":"Chan Pin Yin","sequence":"additional","affiliation":[{"name":"Department of Cardiology (W.W.A.v.d.B., J.A., Q.Y.F.v.d.P., D.R.P.P.C.P.Y., J.P., J.M.t.B.), St. Antonius Hospital, Nieuwegein, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7661-9139","authenticated-orcid":true,"given":"Niels M.R.","family":"van der Sangen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, the Netherlands (N.M.R.v.d.S., S.S., J.P.S.H., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1534-7316","authenticated-orcid":true,"given":"Shabiga","family":"Sivanesan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, the Netherlands (N.M.R.v.d.S., S.S., J.P.S.H., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4008-1656","authenticated-orcid":true,"given":"J.","family":"Peper","sequence":"additional","affiliation":[{"name":"Department of Cardiology (W.W.A.v.d.B., J.A., Q.Y.F.v.d.P., D.R.P.P.C.P.Y., J.P., J.M.t.B.), St. Antonius Hospital, Nieuwegein, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3134-6608","authenticated-orcid":true,"given":"Ankie M.","family":"Harmsze","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy (A.M.H.), St. Antonius Hospital, Nieuwegein, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6156-3842","authenticated-orcid":true,"given":"Ronald J.","family":"Walhout","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Gelderse Vallei, Ede, the Netherlands (R.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9980-548X","authenticated-orcid":true,"given":"Melvyn","family":"Tjon Joe Gin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rijnstate Hospital, Arnhem, the Netherlands (M.T.J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoline J.","family":"Breet","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Gelre Hospitals, Apeldoorn, the Netherlands (N.J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorina","family":"Langerveld","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rivierenland Hospital, Tiel, the Netherlands (J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-7105","authenticated-orcid":true,"given":"Yolande","family":"Appelman","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, VU University, the Netherlands (Y.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1864-2151","authenticated-orcid":true,"given":"Ron H.N.","family":"van Schaik","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Erasmus MC\u2013University Medical Center, Rotterdam, the Netherlands (R.H.N.v.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-7929","authenticated-orcid":true,"given":"Jos\u00e9 P.S.","family":"Henriques","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, the Netherlands (N.M.R.v.d.S., S.S., J.P.S.H., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter J.","family":"Kikkert","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, the Netherlands (N.M.R.v.d.S., S.S., J.P.S.H., W.J.K.)."},{"name":"Department of Cardiology, Tergooi Hospital, Blaricum, the Netherlands 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