Background Clopidogrel is recommended after acute myocardial infarction (AMI) but has variable efficacy and safety, in part related to the effect of cytochrome P450 (CYP) polymorphisms on its metabolism. The effect of CYP polymorphisms on cardiovascular events among clopidogrel-treated patients after AMI remains controversial, and no studies to date have investigated the association of CYP variants with outcomes in African American patients. Methods and Results 2732 subjects (2062 Caucasians; 670 African Americans) hospitalized with AMI enrolled in the prospective, multicenter TRIUMPH study were genotyped for CYP polymorphisms. The majority of Caucasians (79%) and African Americans (64.4%) were discharged on clopidogrel. Among Caucasians, carriers of the loss-of-function CYP2C19*2 allele had significantly increased 1-year mortality (adjusted HR: 1.70; CI: 1.01 to 2.86; p=0.046), and a trend toward increased rate of recurrent MI (adjusted HR: 2.10; CI 0.95 to 4.63; p= 0.066). Among African Americans, increased 1-year mortality was associated with the gain of function CYP2C19*17 allele (adjusted HR for *1/*17 vs. *1/*1: 2.02; CI: 0.92 to 4.44; *17/*17 vs. *1/*1: 8.97; CI: 3.34 to 24.10; p< 0.0001) and the CYP1A2*1C allele (adjusted HR for *1/*1C vs. *1/*1: 1.89; CI: 0.85 to 4.22; *1C/*1C vs. *1/*1: 4.96; CI: 1.69 to 14.56; p= 0.014). Bleeding events were significantly more common among African American carriers of CYP2C19*17 or CYP1A2*1C. Conclusions Both loss of function and gain of function CYP polymorphisms affecting clopidogrel metabolism are associated with increased mortality among clopidogrel treated patients following AMI; the specific polymorphism and the putative mechanism vary according to race.

Background and Purpose-Antiplatelet therapy nonresponse is associated with worse clinical outcomes. We studied the clinical outcomes associated with platelet function-guided modifications in antiplatelet therapy in patients with ischemic stroke or transient ischemic attack. Methods-From January 2005 to August 2007, 324 patients with ischemic stroke underwent platelet function testing using platelet aggregometry. Aspirin nonresponse was defined as a mean platelet aggregation Ն20% with 0.5 mg/mL arachidonic acid and/or Ն70% with 5 mol/L adenosine diphosphate. Clopidogrel nonresponse was defined as a mean platelet aggregation Ն40% with 5 mol/L adenosine diphosphate. A modification was any increase in antiplatelet therapy occurring after testing. Clinical outcomes were compared between patients with and without platelet function-guided antiplatelet therapy modifications using univariate and propensity score-adjusted analyses. Results-In patients with ischemic stroke or transient ischemic attack, 43% (nϭ128) and 35% (nϭ54) were nonresponders to aspirin and clopidogrel, respectively. After platelet function testing, antiplatelet therapy was increased in 23% of patients (nϭ73). After propensity score matching (nϭ61 in each group), antiplatelet therapy modification was associated with significantly increased rates of death, ischemic events, or bleeding (hazard ratio, 2.24; 95% CI, 1.12-4.47; Pϭ0.02) compared with no modification in antiplatelet therapy and a trend toward increased bleeding (hazard ratio, 3.56; 95% CI, Pϭ0.05). No differences in ischemic events were observed. Conclusions-Platelet function-guided modification in antiplatelet therapy after an ischemic stroke or transient ischemic attack was associated with significantly higher rates of adverse clinical outcomes.

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Provisional stenting of complex coronary bifurcation lesions using a JBT is associated with a high procedural success rate, improved SB patency, and a low rate of immediate cardiac events. Further study is warranted to evaluate the role of JBT in improving long-term clinical outcomes in PCI of complex bifurcation lesions.

The US Food and Drug Administration has issued a warning that omeprazole (Prilosec) reduces the antiplatelet activity of clopidogrel (Plavix) by about 50%. However, the warning is based largely on ex vivo data. Preliminary results from a randomized clinical trial revealed no effect on cardiovascular outcomes when omeprazole was given with clopidogrel. We recommend that physicians continue to prescribe a proton pump inhibitor for patients receiving dual antiplatelet therapy who are at risk of gastrointestinal bleeding or have an indication for use of a proton pump inhibitor.

We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19-2.19; p = 0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26-3.33; p = 0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95-2.99; P=0.07) while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization.

Background: As the use of left atrial appendage closure (LAAC) becomes more widespread, improvements in resource utilization and cost-effectiveness are necessary. Currently, there are limited data on same-day discharge (SDD) after LAAC. We aimed to evaluate the safety and feasibility of SDD versus non-SDD in patients with nonvalvular atrial fibrillation who underwent LAAC. Methods: We retrospectively studied 211 patients who underwent the WATCHMAN procedure in a tertiary hospital (June 2016 to June 2019). The primary safety outcome was the composite of stroke, systemic embolism, major bleeding requiring transfusion, vascular complications requiring endovascular intervention, or death through 7 days (periprocedural) and 45 days post-procedure. The secondary outcomes were the individual components of the primary outcome and all-cause readmission. We compared the clinical outcomes of patients who had SDD and non-SDD post-procedure. Results: Patients with procedure-related complications on the day of LAAC and patients who were admitted for acute clinical events before LAAC were excluded. One hundred ninety patients were included in the final analysis. Seventy-two of 190 (38%) patients had SDD, and 118 of 190 (62%) had non-SDD. There were no statistically significant differences in the primary safety outcome through 7 days (1.4% versus 5.9%; P =0.26) and 45 days post-procedure (2.8% versus 9.3%; P =0.14) between the two groups. The secondary outcomes were similar in both groups. No patients had device-related thrombus on transesophageal echocardiography at 45 days. Only 1 patient from the non-SDD group had clinically significant peri-device flow (>5 mm) at 45 days. Conclusions: In a selected cohort of patients who underwent successful elective LAAC with WATCHMAN without same-day procedure-related complications, the primary safety outcome and secondary outcomes through 7 and 45 days post-procedure were similar in the SDD and non-SDD groups. Our findings are hypothesis generating and warrant further investigation in prospective trials.

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