Genotype-Guided P2Y(12) Inhibitor Monotherapy Within 7 Days of Percutaneous Coronary Intervention in High Bleeding Risk Patients: The CHAMP Trial - A Pilot Study and Safety Assessment.

To test the feasibility and safety of genotype guidance in the selection of P2Y12 monotherapy within 1 week of percutaneous coronary interventions (PCIs) among patients with high bleeding risk (HBR). The study was a single-center, open-label, pilot trial. Patients (n=100) with HBR (as defined by an academic research consortium) after successful PCI received dual antiplatelet therapy with clopidogrel and aspirin. Following availability of cytochrome P450 2C19 (CYP2C19) genotype results (mean, 2.9 days), aspirin was discontinued. Normal, rapid, or ultrarapid CYP2C19 metabolizers continued clopidogrel monotherapy for 90 days whereas loss-of-function allele carriers switched to prasugrel or ticagrelor monotherapy. The primary safety endpoints were a composite of post-dismissal cardiac death/spontaneous myocardial infarction less than 30 days or stent thrombosis <90 days of discharge. The subjects also underwent post-dismissal assessment for BARC (Bleeding Academic Research Consortium) type 3 or 5 bleeding, all-cause death, any MI, and/or repeat revascularization up to 90 days. There were 98 patients with complete data (median age, 76.5 years, 36% women; 49% acute coronary syndrome). Sixty-nine (70.4%) were normal, rapid, or ultrarapid metabolizers and continued clopidogrel monotherapy, and 29 (29.6%) were intermediate CYP2C19 metabolizers and received monotherapy with prasugrel (n=21) or ticagrelor (n=8). The mean duration of dual antiplatelet therapy was 5.1 days. During 90-day follow-up, no patient died, there was one possible stent thrombosis, and three patients on clopidogrel had Bleeding Academic Research Consortium type 3 bleeding events. Genotype-guided P2Y12 inhibitor monotherapy within a week of PCI is feasible and likely safe in patients with HBR (CHAMP [Clopidogrel With High Bleeding Risk and Adverse Events With Monotherapy in Patients Undergoing Percutaneous Coronary Interventions]; NCT05223335).

Ingraham BS ，Huxley SB ，Lane CM ，Gulati R ，Lewis BR ，Jaffe AS ，Bell MR ，Lerman A ，Pereira NL ，Moyer AM ，Baudhuin LM ，Rihal CS ，Singh M ... -  《-》

Aspirin versus Clopidogrel Monotherapy After Percutaneous Coronary Intervention: 1-Year Follow-up of the STOPDAPT-3 Trial.

Watanabe H ，Natsuaki M ，Morimoto T ，Yamamoto K ，Obayashi Y ，Nishikawa R ，Kimura T ，Ando K ，Domei T ，Suwa S ，Ogita M ，Isawa T ，Takenaka H ，Yamamoto T ，Ishikawa T ，Hisauchi I ，Wakabayashi K ，Onishi Y ，Hibi K ，Kawai K ，Yoshida R ，Suzuki H ，Nakazawa G ，Kusuyama T ，Morishima I ，Ono K ，Kimura T ... -  《-》

Short-Term Dual Antiplatelet Therapy After Drug-Eluting Stenting in Patients With Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis.

Carvalho PEP ，Gewehr DM ，Nascimento BR ，Melo L ，Burkhardt G ，Rivera A ，Braga MAP ，Guimarães PO ，Mehran R ，Windecker S ，Valgimigli M ，Angiolillo DJ ，Bhatt DL ，Sandoval Y ，Chen SL ，Stone GW ，Lopes RD ... -  《-》

CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

Tunehag KR ，Thomas CD ，Franchi F ，Rossi JS ，Keeley EC ，Anderson RD ，Beitelshees AL ，Duarte JD ，Gong Y ，Kerensky RA ，McDonough CW ，Nguyen AB ，Ortega-Paz L ，Venkatesh S ，Wang Y ，Johnson JA ，Winterstein AG ，Stouffer GA ，Angiolillo DJ ，Cavallari LH ，Lee CR ... -  《Journal of the American Heart Association》

Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y(12) Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study.

Chronic kidney disease (CKD) is a risk factor for ischemic and bleeding events with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Whether the presence of CYP2C19 loss of function (LOF) alleles modifies this risk, and whether a genotype-guided (GG) escalation of P2Y12 inhibitor therapy post PCI is safe in this population is unclear. This was a post hoc analysis of randomized patients in TAILOR PCI. Patients were divided into two groups based on estimated glomerular filtration rate (eGFR) threshold of < 60 ml/min/1.73 m2 for CKD (n = 539) and non-CKD (n = 4276). The aggregate of cardiovascular death, stroke, myocardial infarction, stent thrombosis, and severe recurrent coronary ischemia at 12-months post-PCI was assessed as the primary endpoint. Secondary endpoint was major or minor bleeding. Mean (standard deviation) eGFR among patients with CKD was 49.5 (8.4) ml/min/1.72 m2. Among all patients, there was no significant interaction between randomized strategy and CKD status for any endpoint. Among LOF carriers, the interaction between randomized strategy and CKD status on composite ischemic outcome was not significant (p = 0.2). GG strategy was not associated with an increased risk of bleeding in either CKD group. In this exploratory analysis, escalation of P2Y12 inhibitor therapy following a GG strategy did not reduce the primary outcome in CKD. However, P2Y12 inhibitor escalation following a GG strategy was not associated with increased bleeding risk in CKD. Larger studies in CKD are needed. https://clinicaltrials.gov/ct2/show/NCT01742117?term=TAILOR-PCI&draw=2&rank=1 . NCT01742117.

Mathew RO ，Sidhu MS ，Rihal CS ，Lennon R ，El-Hajjar M ，Yager N ，Lyubarova R ，Abdul-Nour K ，Weitz S ，O'Cochlain DF ，Murthy V ，Levisay J ，Marzo K ，Graham J ，Dzavik V ，So D ，Goodman S ，Rosenberg YD ，Pereira N ，Farkouh ME ... -  《-》