Dataset Information

Stroke Outcomes With Vorapaxar Versus Placebo in Patients With Acute Coronary Syndromes: Insights From the TRACER Trial.

ABSTRACT: Background Vorapaxar, a protease-activated receptor-1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage. Methods and Results TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ?1 stroke during the study period (median follow-up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ?1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan-Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22-6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58-1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71-1.24]). Conclusions Stroke occurred in <2% of patients. Vorapaxar-assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.

SUBMITTER: Ungar L

PROVIDER: S-EPMC6405615 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Stroke Outcomes With Vorapaxar Versus Placebo in Patients With Acute Coronary Syndromes: Insights From the TRACER Trial.

Ungar Leo L Clare Robert M RM Rodriguez Fatima F Kolls Bradley J BJ Armstrong Paul W PW Aylward Philip P Held Claes C Moliterno David J DJ Strony John J Van de Werf Frans F Wallentin Lars L White Harvey D HD Tricoci Pierluigi P Harrington Robert A RA Mahaffey Kenneth W KW Melloni Chiara C

Journal of the American Heart Association 20181201 24

Background Vorapaxar, a protease-activated receptor-1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage. Methods and Results TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the stu ...[more]

PMID: 30526198

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Project description:RATIONALE:Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE:We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. METHODS AND RESULTS:In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. CONCLUSIONS:CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.

Project description:Clinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER. TRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar did not reduce the first occurrence of the primary endpoint of CVD, MI, stroke, revascularization, or rehospitalization for recurrent ischemia, but reduced the secondary composite endpoint of CVD, MI, or stroke (14.7% vorapaxar vs. 16.4% placebo; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.02; number needed to treat [NNT], 81). Recurrent secondary events occurred in 2.7% of patients. Vorapaxar reduced overall occurrences of ischemic events, first and subsequent (HR, 0.88; 95% CI, 0.80 to 0.98; P=0.02; NNT, 51). Also, there was a trend indicating that vorapaxar reduced the expanded endpoint, including revascularization and rehospitalization for recurrent ischemia (HR, 0.92; 95% CI, 0.84 to 1.01; P=0.09). Vorapaxar increased overall occurrences of moderate and severe Global Use of Strategies to Open Occluded Coronary Arteries bleeding (HR, 1.42; 95% CI, 1.21 to 1.66; P<0.001) and Thrombolysis in Myocardial Infarction clinically significant bleeding (HR, 1.550; 95% CI, 1.403 to 1.713; P<0.001). Vorapaxar reduced overall occurrences of ischemic events, but increased bleeding. These exploratory findings broaden our understanding of vorapaxar's potential and expand our understanding of the value of capturing recurrent events. ClinicalTrials.gov. Unique identifier: NCT00527943.

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Project description:Background Atmospheric changes in pollen concentration may affect human health by triggering various allergic processes. We sought to assess if changes in pollen concentrations were associated with different acute coronary syndrome (ACS) subtype presentations and short-term clinical outcomes. Methods and Results We analyzed data in consecutive patients presenting with ACS (unstable angina, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction) treated with percutaneous coronary intervention between January 2014 and December 2017 and enrolled in the VCOR (Victorian Cardiac Outcomes Registry). Baseline characteristics were compared among patients exposed to different grass and total pollen concentrations. The primary outcome was occurrence of ACS subtypes and 30-day major adverse cardiac and cerebrovascular events (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or stroke). Of 15 379 patients, 7122 (46.3%) presented with ST-segment-elevation myocardial infarction, 6781 (44.1%) with non-ST-segment-elevation myocardial infarction, and 1476 (9.6%) with unstable angina. The mean age was 62.5 years, with men comprising 76% of patients. No association was observed between daily or seasonal grass and total pollen concentrations with the frequency of ACS subtype presentation. However, grass and total pollen concentrations in the preceding days (2-day average for grass pollen and 7-day average for total pollen) correlated with in-hospital mortality (odds ratio [OR], 2.17 [95% CI, 1.12-4.21]; P=0.021 and OR, 2.78 [95% CI, 1.00-7.74]; P=0.05), respectively, with a trend of 2-day grass pollen for 30-day major adverse cardiac and cerebrovascular events (OR, 1.50 [95% CI, 0.97-2.32]; P=0.066). Conclusions Increased pollen concentrations were not associated with differential ACS subtype presentation but were significantly related to in-hospital mortality following percutaneous coronary intervention, underscoring a potential biologic link between pollen exposure and clinical outcomes.

Dataset Information

Stroke Outcomes With Vorapaxar Versus Placebo in Patients With Acute Coronary Syndromes: Insights From the TRACER Trial.

Publications

Stroke Outcomes With Vorapaxar Versus Placebo in Patients With Acute Coronary Syndromes: Insights From the TRACER Trial.

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