Impact of prasugrel pretreatment and timing of coronary artery bypass grafting on clinical outcomes of patients with non-ST-segment elevation myocardial infarction: From the A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST-Elevation Myocardial Infarction (ACCOAST) study.

OBJECTIVES: We evaluated impact of timing of coronary artery bypass grafting (CABG) and prasugrel pretreatment in patients with non-ST-segment elevation myocardial infarction undergoing CABG in the ACCOAST study. METHODS: Of 4033 enrolled patients, 314 (7.8%) underwent isolated CABG through 30 days. Primary efficacy end point for this analysis was any cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor bailout through 30 days. RESULTS: More CABG versus percutaneous coronary intervention or medically managed patients were men, diabetic, or had peripheral arterial disease. Per randomization, 157 of 314 patients received a 30-mg prasugrel loading dose before CABG, and 157 of 314 received placebo. Patients were stratified by tertile of time from randomization to CABG: <2.98 days (n = 104), ≥2.98 and <6.95 days (n = 106), and ≥6.95 days (n = 104). Primary end point occurred in 12.5%, 4.7%, and 4.8%, respectively (<2.98 days vs other tertiles, hazard ratio [HR] = 2.80; P = .011). Similarly, the rate of all TIMI major bleeding was highest in the lowest tertile (26.0% vs 10.4% and 4.8%; P < .001), but no difference in all-cause death was observed through 30 days (3.9% vs 1.9% and 1.9%; P = .30). Time from randomization to CABG (HR = 0.84 for each day delay), left main disease (HR = 1.76), region of enrollment (Non-Eastern Europe vs Eastern Europe; HR = 3.83), but not prasugrel pretreatment and baseline troponin ≥3× upper limit of normal, were independent predictors of combined 30-day end point of all-cause death/myocardial infarction/stroke/TIMI major bleeding. CONCLUSIONS: In ACCOAST, early (<2.98 days) surgical revascularization carried increased risk of bleeding and ischemic complications without affecting all-cause mortality through 30 days. Baseline troponin and prasugrel pretreatment did not impact ischemic clinical outcomes.

Impact of Access Site on Bleeding and Ischemic Events in Patients With Non-ST-Segment Elevation Myocardial Infarction Treated With Prasugrel: The ACCOAST Access Substudy.

OBJECTIVES: This study assessed whether the choice of vascular access site influenced outcomes among non-ST-segment elevation myocardial infarction (NSTEMI) patients enrolled in the ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction NCT01015287). BACKGROUND: Transfemoral access (TFA) has been associated with the risk of bleeding and increased mortality that is elevated compared to transradial access (TRA) in acute coronary syndromes, although less consistently in NSTE acute coronary syndrome (NSTE-ACS) than in STE-ACS. METHODS: The ACCOAST study evaluated a prasugrel loading dose of 60 mg given at the start of percutaneous coronary intervention (PCI) versus a split loading dose of 30 mg given at the time of diagnosis of NSTE-ACS (prior to coronary angiography), followed by 30 mg given at the start of PCI. In the study, choice of access site was at the investigator's discretion. We compared ischemic and bleeding outcomes with TFA versus those with TRA, using propensity score correction. RESULTS: Of 4,033 patients, 1,711 (42%) underwent TRA. Use of TRA varied widely by country. TFA was not associated with significant increases in noncoronary bypass graft (CABG)-related thrombolysis in myocardial infarction (TIMI) (hazard ratio [HR] for TFA = 1.46; 95% confidence interval [CI]: 0.59 to 3.62; p = 0.42), nor in GUSTO (Global Utilization Of Streptokinase and Tpa for Occluded arteries) or STEEPLE (Safety and Efficacy of Enoxaparin in PCI) major bleeding after propensity score correction. TFA, however, increased combined non-CABG TIMI major or minor bleeding (HR for TFA = 2.34; 95% CI: 1.17 to 4.69; p = 0.017). Primary ischemic outcomes did not differ by access site, albeit individual endpoint analysis suggested an association between TFA with an increase in urgent revascularizations and reduced risk of procedure-related stroke. CONCLUSIONS: In the ACCOAST trial, TFA did not significantly increase TIMI major bleeding, although TRA was associated with a reduction in TIMI major or minor bleeding. Further study is needed to determine whether wider application of radial approach to NSTE-ACS patients at high risk for bleeding improves overall outcomes. (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction [ACCOAST]; NCT01015287).

Predictors of bleeding in patients with acute coronary syndromes treated with prasugrel.

BACKGROUND: When considering antiplatelet therapy for acute coronary syndrome (ACS), it is essential to balance benefits (less thrombotic/ischaemic events) versus bleeding risks related to intense platelet inhibition via antagonism of P2Y12 receptors. This analysis aimed to identify predictors of bleeding events among A Comparison of Prasugrel at the Time of PCI or as Pretreatment at the Time of Diagnosis in Patients with NSTEACS (ACCOAST) study population. METHODS AND RESULTS: The ACCOAST study randomised 4033 patients with non-ST-segment elevation myocardial infarction (NSTEMI) to (A) a 30 mg prasugrel loading dose (LD) followed by coronary angiography with an additional 30 mg prasugrel at the time of percutaneous coronary intervention (PCI) or (B) a placebo LD followed by a 60 mg prasugrel at the time of PCI. Patients received standard of care, including use of aspirin. Independent predictors of Thrombolysis in Myocardial Infarction (TIMI) major bleeding not related to coronary artery bypass grafting (CABG) within 7 days were assessed using stepwise Cox proportional model for time to first occurrence of the event. Non-CABG-related TIMI major or minor bleeding was similarly analysed. Non-CABG-related TIMI major bleeding occurred in 36 (0.9%) patients, and TIMI major or minor bleeding occurred in 81 (2.0%) patients. Independent predictors for TIMI major bleeding alone were pretreatment with prasugrel LD (HR 3.02; 95% CI 1.42 to 6.43), femoral access (HR 2.45; 95% CI 1.11 to 5.38), female sex (HR 2.57; 95% CI 1.32 to 5.00), placement of >1 stent (HR 2.50; 95% CI 1.26 to 4.95) and age (HR 1.05; 95% CI 1.02 to 1.09). Pretreatment with prasugrel LD (HR 3.05; 95% CI 1.84 to 5.07), femoral access (HR 3.06; 95% CI 1.74 to 5.38), female sex (HR 2.62; 95% CI 1.67 to 4.12), performed PCI (HR 2.21; 95% CI 1.23 to 3.99), therapy with glycoprotein IIb/IIIa inhibitors (HR 1.88; 95% CI 1.06 to 3.33) and age (increased bleed per year of age HR 1.04; 95% CI 1.02 to 1.06) were independent predictors of TIMI major or minor bleeding through 7 days. CONCLUSIONS: Pretreatment, age, gender and procedural variables predicted bleeding risk in patients with NSTEMI. CLINICAL REGISTRATION NO: NCT01015287.

Effect of prasugrel pre-treatment strategy in patients undergoing percutaneous coronary intervention for NSTEMI: the ACCOAST-PCI study.

BACKGROUND: After percutaneous coronary intervention (PCI) for non-ST-segment elevation myocardial infarction (NSTEMI), treatment with a P2Y12 antagonist with aspirin is recommended for 1 year. OBJECTIVES: The oral P2Y12 antagonists ticagrelor and prasugrel have higher recommendations than clopidogrel, but it is unknown if administration before the start of PCI is beneficial. METHODS: In the randomized, double-blind ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction) trial, 4,033 patients were diagnosed with NSTEMI and 68.7% underwent PCI; 1,394 received pre-treatment with prasugrel (30-mg loading dose), and 1,376 received placebo. At the time of PCI, patients who received pre-treatment with prasugrel received an additional 30-mg dose of prasugrel, and those who received placebo received a 60-mg loading dose of prasugrel. Primary efficacy was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout through 7 days from randomization. Investigators captured the presence of thrombus on initial angiography and during PCI. RESULTS: The incidence of the primary endpoint through 7 days from randomization in the pre-treatment group versus the no pre-treatment group was 13.1% versus 13.1% (p = 0.93). Pre-treatment with prasugrel was not associated with decreases in any ischemic event, including total mortality. Patients with thrombus on angiography had a 3-fold higher incidence of the primary endpoint than patients without thrombus. There was no impact of pre-treatment with prasugrel on the presence of thrombus before PCI or on occurrence of stent thrombosis after PCI. There was a 3-fold increase in all non-coronary artery bypass graft Thrombolysis In Myocardial Infarction (TIMI) major bleeding and a 6-fold increase in non-coronary artery bypass graft life-threatening bleeding with pre-treatment with prasugrel; the same trends persisted in patients who had radial or femoral access even with use of a closure device. CONCLUSIONS: These findings support deferring treatment with prasugrel until a decision is made about revascularization in patients with NSTEMI undergoing angiography within 48 h of admission. (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction [ACCOAST]; NCT01015287).

Factors associated with statin selection among privately insured commercial and Medicare patients.

OBJECTIVES: Given the availability of several statins in the United States, it is important to understand patient characteristics associated with their initiation. We analyzed demographic and clinical factors associated with statin selection among new statin users. METHODS: This retrospective cohort study examined factors associated with statin selection among patients newly initiated on therapy between 1/1/2007 and 12/31/2007. Commercial and Medicare patient cohorts were evaluated separately and comparisons were made between pravastatin (PS) and other statins including simvastatin (SS), atorvastatin (AS), or rosuvastatin (RS). Multiple logistic regression models were employed to assess factors associated with PS initiation versus other statins. RESULTS: In commercially insured patients, patients initiating PS were more likely to be older, female, and have diabetes mellitus, liver dysfunction, human immunodeficiency virus (HIV) infection, or hypertension and use calcium channel blockers, protease inhibitors, or additional lipid-modifying agents (p < 0.01 for each comparison). In Medicare-age patients, a higher percentage of PS initiators were aged 75-85, female, had atrial fibrillation, and were prescribed warfarin or triazole antifungals (p < 0.01 for each comparison). Presence of atrial fibrillation or HIV infection, or use of calcium channel blockers or additional lipid-modifying agents was associated with PS initiation compared with AS and SS. Use of warfarin was significantly associated with initiating PS compared with SS, AS, and RS in Medicare-age patients. CONCLUSION: Older age and female gender were associated with PS initiation. In addition, selected comorbidities and use of certain medications including warfarin or protease inhibitors were associated with PS initiation, which may reflect the tolerability of PS and its reduced risk of significant drug-drug interactions for certain patients. Because this study is a retrospective analysis of US healthcare claims, the findings are limited to only those factors captured within claims data and may not be generalizable to all patient populations in which statin therapy is initiated.

Transfusion outcomes in patients undergoing coronary artery bypass grafting treated with prasugrel or clopidogrel: TRITON-TIMI 38 retrospective data analysis.

OBJECTIVE: Coronary artery bypass grafting-related bleeding and associated transfusion is a concern with dual antiplatelet therapy in patients with acute coronary syndromes. The objective of the present study was to characterize a potential risk-adjusted difference in transfusion requirements between prasugrel and clopidogrel cohorts. METHODS: The data from 422 patients undergoing isolated coronary artery bypass grafting from the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 were analyzed retrospectively. RESULTS: We found no difference in baseline transfusion risk scores between cohorts. As predicted, the number of units of red blood cells transfused perioperatively correlated with the transfusion risk score (P < .0001). Overall, the 12-hour chest tube drainage volumes and platelet transfusion rates in the prasugrel cohort were significantly greater. However, no statistically significant differences were found in the number of red blood cell transfusions, total hemostatic components transfused, or total blood donor exposure. A significantly greater number of platelet units were transfused postoperatively in the prasugrel patients who underwent surgery within 5 days or less after withdrawal of drug. In an analysis adjusted for the predicted risk of mortality, total donor exposure was not associated with increased mortality. CONCLUSIONS: The use of prasugrel compared with clopidogrel was associated with greater 12-hour chest tube drainage volumes and platelet transfusion rates but without any significant differences in red blood cell transfusions, total hemostatic components transfused, or total blood donor exposure.

Mortality benefit with prasugrel in the TRITON-TIMI 38 coronary artery bypass grafting cohort: risk-adjusted retrospective data analysis.

OBJECTIVES: The objective of this study was to characterize the bleeding, transfusion, and other outcomes of patients related to the timing of prasugrel or clopidogrel withdrawal before coronary artery bypass grafting (CABG). BACKGROUND: There is little evidence to guide clinical decision making regarding the use of prasugrel in patients who may need urgent or emergency CABG. Experience with performing CABG in the presence of clopidogrel has raised concern about perioperative bleeding complications that are unresolved. METHODS: A subset of the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38), in which patients with acute coronary syndrome were randomized to treatment with aspirin and either clopidogrel or prasugrel, underwent isolated CABG (N = 346). A supplemental case report form was designed and administered, and the data combined with the existing TRITON-TIMI 38 database. Baseline imbalances were corrected for using elements of the European System for Cardiac Operative Risk Evaluation and The Society of Thoracic Surgeons predictive algorithm. RESULTS: A significantly higher mean 12-h chest tube blood loss (655 ± 580 ml vs. 503 ± 378 ml; p = 0.050) was observed with prasugrel compared with clopidogrel, without significant differences in red blood cell transfusion (2.1 U vs. 1.7 U; p = 0.442) or the total donor exposure (4.4 U vs. 3.0 U; p = 0.463). All-cause mortality was significantly reduced with prasugrel (2.31%) compared with 8.67% with clopidogrel (adjusted odds ratio: 0.26; p = 0.025). CONCLUSIONS: Despite an increase in observed bleeding, platelet transfusion, and surgical re-exploration for bleeding, prasugrel was associated with a lower rate of death after CABG compared with clopidogrel.

Factors associated with clopidogrel use, adherence, and persistence in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

OBJECTIVE: Recent guidelines recommend use of aspirin and either clopidogrel or prasugrel for at least 12 months following use of drug-eluting or bare metal stents in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). This study evaluated factors associated with clopidogrel use and adherence in ACS patients following PCI. RESEARCH DESIGN AND METHODS: The US employer-based MarketScan commercial claims database was used to examine factors associated with clopidogrel use and adherence. Adherence was defined as a medication possession ratio of 80% or higher. Multivariate logistic regression analyses were conducted to identify factors associated with clopidogrel use and adherence and included patient demographics, comorbidities, and prior beta-blocker, statin, and angiotensin converting enzyme inhibitor (BSI) use as factors. RESULTS: A total of 10,465 patients aged 18-65 years who met inclusion criteria were hospitalized for ACS and underwent PCI between 01/01/2005 and 12/31/2006. Overall, the rate of clopidogrel use was 92.8% for ACS-PCI patients and 66.8% of the clopidogrel users were adherent. Receiving PCI without stenting (Odds Ratio [OR] = 3.28), comorbid hypertension (OR = 1.50), diabetes (OR = 1.49), and atrial fibrillation (OR = 1.91) were associated with decreased filled prescriptions for clopidogrel. Younger age (OR = 0.83) and prior use of clopidogrel (OR = 0.54) or other BSI medications (OR = 0.44) were associated with increased use of clopidogrel (all p values < 0.05). Factors significantly associated with non-adherence of clopidogrel were prior use of clopidogrel (OR = 1.40), prior hospitalization (OR = 1.34), chronic pulmonary disease (OR = 1.31), PCI without stenting (OR = 1.32), diabetes (OR = 1.17), and younger age (OR = 1.29). Prior use of BSI medications (OR = 0.82) increased adherence to clopidogrel. CONCLUSIONS: Prior use of clopidogrel, comorbid conditions such as diabetes and chronic pulmonary disease, prior hospitalization, PCI without stenting, and younger age had a negative impact on clopidogrel adherence. These findings may assist programs to improve thienopyridine compliance through a better understanding of patients' disease profiles and concomitant medication use.

Resource utilization and healthcare costs for acute coronary syndrome patients with and without diabetes mellitus.

OBJECTIVE: This study compared differences in healthcare costs and resource utilization for acute coronary syndrome (ACS) patients with and without diabetes mellitus (DM). METHODS: A retrospective cohort study of a large, US employer-based claims database identified adults hospitalized for ACS between 01/01/2005 and 12/31/2006 and categorized them based on DM status. Resource utilization and costs during the index hospitalization and in the 12-month follow-up period were compared for ACS patients with and without DM using the propensity score stratification bootstrapping method, adjusting for differences in demographic and clinical characteristics. RESULTS: Of 12,502 patients who met selection criteria, 3,040 (24%) had a history of DM and 9,462 (76%) did not. Patients with DM were older, female, and had higher rates of previous cardiovascular and renal diseases. After the propensity score stratification, patients with DM incurred higher index hospitalization costs ($32,577 vs. $29,150, p < 0.01) as well as higher total follow-up healthcare costs ($35,400 vs. $24,080, p < 0.01), including higher inpatient ($17,278 vs. $11,247, p < 0.01), outpatient ($12,357 vs. $8,853, p < 0.01), and pharmacy costs ($5,765 vs. $3,980, p < 0.01). LIMITATIONS: General limitations exist with any retrospective claims database analysis including potential diagnostic or procedural coding inaccuracies. Additionally, the patient population was representative of a working-age population with employer-sponsored health insurance and results may not be generalizable to other patient populations. CONCLUSIONS: DM is significantly associated with increased healthcare resource utilization and costs for ACS patients.

Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial.

OBJECTIVES: This trial examined the relative clinical efficacy, angiographic outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a phosphorylcholine polymer versus sirolimus-eluting stents (SES). BACKGROUND: Whether a cobalt-based alloy stent coated with the novel antiproliferative agent, zotarolimus, and a phosphorylcholine polymer may provide similar angiographic and clinical benefit compared with SES is undetermined. METHODS: A prospective, multicenter, 3:1 randomized trial was conducted to evaluate the safety and efficacy of ZES (n = 323) relative to SES (n = 113) in 436 patients undergoing elective percutaneous revascularization of de novo native coronary lesions with reference vessel diameters between 2.5 mm and 3.5 mm and lesion length > or =14 mm and < or =27 mm. The primary end point was 8-month angiographic in-segment late lumen loss. RESULTS: Angiographic in-segment late lumen loss was significantly higher among patients treated with ZES compared with SES (0.34 +/- 0.44 mm vs. 0.13 +/- 0.32 mm, respectively; p < 0.001). In-hospital major adverse cardiac events were significantly lower among patients treated with ZES (0.6% vs. 3.5%, p = 0.04). In-segment binary angiographic restenosis was also higher in the ZES cohort (11.7% vs. 4.3%, p = 0.04). Total (clinically and non-clinically driven) target lesion revascularization rates at 9 months were 9.8% and 3.5% for the ZES and SES groups, respectively (p = 0.04). However, neither clinically driven target lesion revascularization (6.3% zotarolimus vs. 3.5% sirolimus, p = 0.34) nor target vessel failure (12.0% zotarolimus vs. 11.5% sirolimus, p = 1.0) differed significantly. CONCLUSIONS: Compared with SES, treatment with a phosphorylcholine polymer-based ZES is associated with significantly higher late lumen loss and binary restenosis at 8-month angiographic follow-up. (The Endeavor III CR; http://clinicaltrials.gov/ct/show/NCT00265668?order=1?).