Antiplatelet Therapy Changes for Patients With Myocardial Infarction With Recurrent Ischemic Events: Insights Into Contemporary Practice From the TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) Study

BACKGROUND: Guidelines recommend P2Y12 inhibitor therapy for 1 year after myocardial infarction (MI), yet little guidance is provided on antiplatelet management for patients with recurrent ischemic events during that year. We describe changes in P2Y12 inhibitor type among patients with recurrent ischemic events in the first year after MI. METHODS AND RESULTS: The TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study enrolled 12 365 patients with MI treated with percutaneous coronary intervention. We examined whether P2Y12 inhibitor choice changed among patients with recurrent MI, stent thrombosis, and/or unplanned revascularization during the first year after MI, and modeled factors associated with P2Y12 inhibitor intensification (changing clopidogrel to prasugrel or ticagrelor). In the first year after MI, 1414 patients (11%) had a total of 1740 recurrent ischemic events (771 recurrent MIs, 969 unplanned revascularizations, and 165 stent thromboses). Median time to the first recurrent ischemic event was 154 days (25th-75th percentiles, 55-287 days). Of those with recurrent ischemic events, 101 of 1092 (9.3%) occurring in clopidogrel-treated patients led to P2Y12 inhibitor intensification. Recurrent events involving stent thrombosis or MI were the strongest factors associated with P2Y12 inhibitor intensification, yet only 40% of patients with stent thrombosis and 14% of patients with recurrent MI had P2Y12 inhibitor intensification. Increasing age and longer time from the index MI were associated with lower likelihood for intensification. CONCLUSIONS: Few patients after MI with a recurrent ischemic event who were taking clopidogrel switched to a more potent P2Y12 inhibitor, even after stent thrombosis events. Specific guidance is needed for patients who have recurrent ischemic events, particularly when closely spaced. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503

Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

BACKGROUND: Potent P2Y12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. METHODS: PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. RESULTS: The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). CONCLUSIONS: Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction

Treating Patients With 'Wake-Up' Stroke The Experience of the AbESTT-II Trial

Background and Purpose-Approximately 10% to 20% of patients with a new stroke have symptoms present on awakening (wake-up stroke), but these persons are not treated with interventions to restore perfusion because the time of onset is not known. We elected to test the safety and possible efficacy of abciximab in treatment of enrolled subjects with wake-up stroke.Methods-Abciximab in Emergency Stroke Treatment Trial-II (AbESTT-II) tested the usefulness of abciximab in improving outcomes after acute ischemic stroke and it prospectively tested an intervention in subjects that awakened with their stroke. We compared the outcomes among the subjects in the wake-up group with the other subjects in the trial.Results-Of the 801 subjects randomized in the trial, 43 (22 abciximab and 21 placebo) had wake-up strokes. Those with wake-up strokes had similar baseline characteristics as the other subjects except for a higher rate of a new stroke found on CT. Recruitment of patients into the wake-up group was halted early because of the rate of bleeding with abciximab exceeded the prespecified safety margins (3 of 22 [13.6%]) within 5 days or at discharge versus 15 of 375 (4.0%) for the nonwake-up group (P=0.07). Favorable outcomes at 3 months, as defined by scores on the modified Rankin Scale, among the wake-up group (4 of 43 [9.3%]) were worse than the nonwake-up group (221 of 758 [ 29.2%]; P=0.005).Conclusions-Although the baseline characteristics of the wake- up group of subjects were similar to those of persons enrolled in the nonwake-up group, their outcomes were much poorer. Patients with wake- up stroke may not tolerate reperfusion therapies even when started within a short time of awakening. (Stroke. 2008;39:3277-3282.

Adherence and persistence with prasugrel following acute coronary syndrome with percutaneous coronary intervention

Purpose: To measure the adherence and persistence of patients with acute coronary syndrome (ACS) initiating prasugrel after percutaneous coronary intervention (PCI). Methods: Using the Thomson Reuters MarketScan Commercial and Medicare Supplemental database, a retrospective cohort study identified patients initiating prasugrel following ACS-PCI hospitalization in 2009-2011. Prasugrel adherence over 12 months was measured using the medication possession ratio (MPR); predictors of adherence were identified using a logistic regression model. Persistence was defined as time on continuous therapy; a Cox model identified predictors of prasugrel discontinuation. Results: Among 1,340 patients, the mean age was 57 years; 79.5 % were male. Median prasugrel MPR was 93.2 %; 69.0 % of patients had an MPR >= 80 %. Predictors of adherence < 80 % included prior PCI [odds ratio (OR) 0.60; 95 % confidence interval (CI) 0.40-0.90], prior depression (OR 0.37; 95 % CI 0.16-0.84), prior bleeding (OR 0.41; 95 % CI 0.19-0.86), and baseline anticoagulant use (OR 0.13; 95 % CI 0.03-0.55). Baseline statin use predicted higher adherence (OR 1.56; 95 % CI 1.21-2.02). The median duration of prasugrel therapy was 259 days. Predictors of discontinuation included prior anemia [hazard ratio (HR) 1.63; 95 % CI 1.21-2.21], prior cardiomyopathy (HR 2.72; 95 % CI 1.44-5.13), and prior ischemic heart disease (HR 1.15; 95 % CI 1.00-1.32); baseline statin use predicted reduced risk of discontinuation (HR 0.85; 95 % CI 0.75-0.97). Conclusions: Although adherence to prasugrel was generally high, the duration of therapy was frequently below recommendations. An awareness of risk factors for low adherence or early discontinuation can point to appropriate targets for intervention

Glycoprotein IIb/IIIa inhibitor use in patients with acute myocardial infarction undergoing PCI: insights from the TRANSLATE ACS study

Introduction: Concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and P2Y inhibitors increases bleeding risk. How GPIs are being used with faster onset, higher potency P2Y inhibitors are unclear. Methods and results: We studied 11,781 myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI) at 233 hospitals in the TRANSLATE ACS study (2010–2012). We used propensity matching to compare 6-week major adverse cardiac events (MACE: death, recurrent MI, stroke, or unplanned revascularization) and BARC 2+ bleeding events between patients who did and did not receive planned GPI. Planned and bailout GPI were used in 4,983 (42.2%) and 229 (4.4%) MI patients undergoing PCI, respectively. Patients receiving planned GPI were younger (58 vs. 61 years), more likely to present with STEMI (62.6% vs. 45.4%) or have stent thrombosis (4.2% vs. 2.1%, all P 6 hr prior to PCI versus earlier (27.8% vs. 44.4%, both P < 0.01). After propensity matching, planned GPI use was not associated with any difference in MACE (6.4% vs. 5.5% OR 1.18; 95% CI: 0.99–1.57), however, the risk of BARC 2+ bleeding was higher in patients who received planned GPI (11.3% vs. 8.7%; OR 1.34; 95% CI: 1.13–1.59). Conclusion: Planned GPI use as reported by practicing physicians was prevalent between 2010 and 2012 and was associated with increased risk of bleeding but not lower MACE

Impact of bleeding on quality of life in patients on DAPT: insights from TRANSLATE-ACS

BACKGROUND Prolonged dual antiplatelet therapy (DAPT) is recommended after an acute myocardial infarction (AMI) to reduce ischemic events but is associated with increased rates of major and minor bleeding.OBJECTIVES This study sought to determine the incidence of post-percutaneous coronary intervention (PCI) bleeding that occurs on contemporary DAPT and its impact on quality of life (QOL).METHODS We studied 9,290 AMI patients treated with PCI and discharged alive between April 2010 and September 2012. Post-discharge bleeding was categorized according to the Bleeding Academic Research Consortium (BARC) definition. The primary outcome was the 6-month Euro QOL-5 Dimension (EQ-5D) index score (a measure of health utility); a secondary outcome was the EQ-5D visual analog scale (VAS) at 6 months.RESULTS Of the 9,290 patients with AMI, bleeding events occurred as follows: any BARC bleeding: 24.2%; BARC 1: 9.1%; BARC 2: 13.8%; BARC 3: 1.1%; BARC 4: 0.03%; and BARC 5: 0%. Those who experienced any BARC bleeding had lower scores across all 5 EQ-5D domains (mobility, self-care, usual activities, pain, and anxiety), as well as lower EQ-5D VAS and EQ-5D index scores. After clinical risk adjustment, any BARC bleeding was independently associated with 6-month EQ-5D index score (p < 0.0001) and lower QOL (p < 0.001). Both the EQ-5D index and the VAS score declined in a stepwise fashion with increasing BARC severity.CONCLUSIONS Among patients undergoing PCI for AMI, bleeding during follow-up was associated with worse 6-month utility and QOL. Although even minor bleeding was associated with impaired health status and QOL, the degree of impairment increased in a stepwise fashion with bleeding severity. (C) 2016 by the American College of Cardiology Foundation