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Harvey D White - One of the best experts on this subject based on the ideXlab platform.

  • use of thienopyridine prior to presentation with non st segment elevation acute coronary syndrome and association with safety and efficacy of vorapaxar insights from the tracer trial
    European heart journal. Acute cardiovascular care, 2017
    Co-Authors: Ralf E Harskamp, Philip E Aylward, Yuliya Lokhnygina, David J Moliterno, Claes Held, Robert Clare, Harvey D White, Paul W Armstrong, Giuseppe Ambrosio, Kenneth W Mahaffey
    Abstract:

    Background:Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We hypothesized that patients with NSTE ACS already receiving thienopyridine prior to the ACS event may show differential efficacy/safety effects with vorapaxar vs. placebo added to their standard care.Methods:We studied 12,944 patients from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial with respect to thienopyridine use before admission for the index NSTE ACS event. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, rehospitalization for ischemia, and urgent revascularization. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Safety endpoints were bleeding complications.Results:Only 1513 patients (11.7%) were re...

  • high sensitivity troponin i in stable patients with atherosclerotic disease in the tra 2 p timi 50 trial
    Clinical Chemistry, 2017
    Co-Authors: Alon Eisen, Benjamin M Scirica, Marc P. Bonaca, Harvey D White, Mikael Dellborg, João Morais, Michal Tendera, Jose C Nicolau, Petr Jarolim, Keith A A Fox
    Abstract:

    BACKGROUND: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined. METHODS: We measured hs-TnI (Abbott ARCHITECT) in 15833 patients with prior MI, ischemic stroke, or peripheral arterial disease from the placebo-controlled Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)–Thrombolysis in Myocardial Infarction (TIMI) 50 trial of the platelet inhibitor vorapaxar, excluding patients with recent MI (<30 days). hs-TnI was categorized into 5 groups based on the detection limit (1.9 ng/L), 99th percentile reference limit (26 ng/L), and tertiles in between (1.9–26 ng/L), as well as sex-specific reference limits. RESULTS: Higher hs-TnI concentration was associated with older age, male sex, and increased atherosclerosis burden. hs-TnI identified a graded 3-year risk of cardiovascular death, MI, or stroke from 5.0% to 18.6% ( P 26 ng/L vs 26 ng/L vs 0.3% with hs-TnI <1.9 ng/L; P interaction = 0.82). CONCLUSIONS: In stable patients with established atherosclerosis, hs-TnI concentrations effectively stratified the risk of new or recurrent cardiovascular (CV) events, in particular CV death and MI. High-risk patients with prior MI identified by increased hs-TnI had a substantial absolute improvement in net clinical outcome with vorapaxar.

  • trade off of myocardial infarction vs bleeding types on mortality after acute coronary syndrome lessons from the Thrombin Receptor Antagonist for clinical event reduction in acute coronary syndrome tracer randomized trial
    European Heart Journal, 2016
    Co-Authors: Yuliya Lokhnygina, David J Moliterno, Robert Clare, Paul W Armstrong, Lars Wallentin, Marco Valgimigli, F Costa, Harvey D White
    Abstract:

    Aims Dual antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome (ACS) but increases bleeding to a similar extent. We sought to determine the prognostic impact of myocardial infarction (MI) vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after ACS. Methods and results In 12 944 patients with non-ST-segment elevation ACS from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, we investigated the relative impact of MI and bleeding occurring >30 days post-ACS and subsequent all-cause mortality. Bleeding was graded according to Bleeding Academic Research Consortium (BARC) criteria. MI was associated with a five-fold increase in mortality. BARC type 2 and 3, but not type 1, bleeding had a significant impact on mortality. MI was associated with a greater risk of mortality compared with BARC 2 [relative risk (RR) 3.5; 95% confidence interval (CI) 2.08-4.77; P Conclusion In patients treated with antiplatelet therapy after ACS, both MI and bleeding significantly impacted mortality with similar time-dependency. Although BARC 2 and 3a bleeding were less prognostic for death than MI, the risk of mortality was equivalent between BARC 3b bleeding and MI, and was higher following BARC 3c bleeding.

  • effect of age on efficacy and safety of vorapaxar in patients with non st segment elevation acute coronary syndrome insights from the Thrombin Receptor Antagonist for clinical event reduction in acute coronary syndrome tracer trial
    American Heart Journal, 2016
    Co-Authors: Luciana Armaganijan, Philip E Aylward, Claes Held, Harvey D White, Paul W Armstrong, Pierluigi Tricoci, Zhen Huang, Frans Van De Werf, Karen P Alexander, David J Moliterno
    Abstract:

    Background Antithrombotic therapy plays an important role in the treatment of non–ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. Methods Efficacy and safety of vorapaxar (a protease-activated Receptor 1 Antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. Results The median age of the population was 64years (25th, 75th percentiles=58, 71). Also, 1,791 patients (13.8%) were ≤54years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively ( P value for interaction=.435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively ( P value for interaction=.574). Conclusion Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.

  • universal classification system type of incident myocardial infarction in patients with stable atherosclerosis observations from Thrombin Receptor Antagonist in secondary prevention of atherothrombotic ischemic events tra 2 p timi 50
    Journal of the American Heart Association, 2016
    Co-Authors: Stephen Kidd, Benjamin M Scirica, Marc P. Bonaca, Sabina A Murphy, Harvey D White, Eugene Braunwald, Gaetano M De Ferrari, Basil S Lewis, Piera Angelica Merlini, David A Morrow
    Abstract:

    Background Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first‐in‐class platelet protease‐activated Receptor ‐1 Antagonist, on new or recurrent MI. Methods and Results We analyzed data from TRA 2°P‐TIMI 50, a multinational, randomized, double‐blind, placebo‐controlled trial of vorapaxar. This analysis included 20 770 patients with previous MI or peripheral arterial disease without a history of transient ischemic attack or stroke. Each new or recurrent MI after randomization that met the trial end point definition was further categorized according to the European Society of Cardiology, American College of Cardiology, American Heart Association, World Heart Federation Universal Definition classification of type and size. Of 1095 incident MIs, 77% were spontaneous (Type 1), with a smaller number (9.8%) of secondary MIs (Type 2). Vorapaxar reduced Type 1 MI (hazard ratio [HR] 0.84, CI 0.73–0.98, P =0.024), with a similar pattern for Type 2 MI (HR 0.74, CI 0.49–1.10, P =0.13). Notably, vorapaxar showed a consistent pattern of reduction across size of MIs, including MIs in the highest Universal MI size class (≥10× upper reference limit, HR 0.83, CI 0.70–0.98, P =0.025). As such, there was a significant reduction in larger, spontaneous MIs (Type 1, ≥10× upper reference limit, HR 0.81, CI 0.67–0.99, P =0.036), and a consistent pattern with respect to fatal MI (HR 0.66, CI 0.39–1.11, P =0.12). Conclusions Among stable patients with established atherosclerosis, the most common type of incident MI is spontaneous MI, and the reduction in MI with vorapaxar was consistent across MIs of varying type and size, including spontaneous infarctions ≥10× upper reference limit. Clinical Trial Registration URL: . Unique identifier: NCT00526474.

David A Morrow - One of the best experts on this subject based on the ideXlab platform.

  • universal classification system type of incident myocardial infarction in patients with stable atherosclerosis observations from Thrombin Receptor Antagonist in secondary prevention of atherothrombotic ischemic events tra 2 p timi 50
    Journal of the American Heart Association, 2016
    Co-Authors: Stephen Kidd, Benjamin M Scirica, Marc P. Bonaca, Sabina A Murphy, Harvey D White, Eugene Braunwald, Gaetano M De Ferrari, Basil S Lewis, Piera Angelica Merlini, David A Morrow
    Abstract:

    Background Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first‐in‐class platelet protease‐activated Receptor ‐1 Antagonist, on new or recurrent MI. Methods and Results We analyzed data from TRA 2°P‐TIMI 50, a multinational, randomized, double‐blind, placebo‐controlled trial of vorapaxar. This analysis included 20 770 patients with previous MI or peripheral arterial disease without a history of transient ischemic attack or stroke. Each new or recurrent MI after randomization that met the trial end point definition was further categorized according to the European Society of Cardiology, American College of Cardiology, American Heart Association, World Heart Federation Universal Definition classification of type and size. Of 1095 incident MIs, 77% were spontaneous (Type 1), with a smaller number (9.8%) of secondary MIs (Type 2). Vorapaxar reduced Type 1 MI (hazard ratio [HR] 0.84, CI 0.73–0.98, P =0.024), with a similar pattern for Type 2 MI (HR 0.74, CI 0.49–1.10, P =0.13). Notably, vorapaxar showed a consistent pattern of reduction across size of MIs, including MIs in the highest Universal MI size class (≥10× upper reference limit, HR 0.83, CI 0.70–0.98, P =0.025). As such, there was a significant reduction in larger, spontaneous MIs (Type 1, ≥10× upper reference limit, HR 0.81, CI 0.67–0.99, P =0.036), and a consistent pattern with respect to fatal MI (HR 0.66, CI 0.39–1.11, P =0.12). Conclusions Among stable patients with established atherosclerosis, the most common type of incident MI is spontaneous MI, and the reduction in MI with vorapaxar was consistent across MIs of varying type and size, including spontaneous infarctions ≥10× upper reference limit. Clinical Trial Registration URL: . Unique identifier: NCT00526474.

  • universal classification system type of incident myocardial infarction in patients with stable atherosclerosis observations from Thrombin Receptor Antagonist in secondary prevention of atherothrombotic ischemic events tra 2 p timi 50
    Journal of the American Heart Association, 2016
    Co-Authors: Stephen Kidd, Benjamin M Scirica, Marc P. Bonaca, Sabina A Murphy, Harvey D White, Eugene Braunwald, Gaetano M De Ferrari, Basil S Lewis, Piera Angelica Merlini, David A Morrow
    Abstract:

    Background Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first‐in‐class platelet protease‐activated Receptor ‐1 Antagonist, on new or recurrent MI. Methods and Results We analyzed data from TRA 2°P‐TIMI 50, a multinational, randomized, double‐blind, placebo‐controlled trial of vorapaxar. This analysis included 20 770 patients with previous MI or peripheral arterial disease without a history of transient ischemic attack or stroke. Each new or recurrent MI after randomization that met the trial end point definition was further categorized according to the European Society of Cardiology, American College of Cardiology, American Heart Association, World Heart Federation Universal Definition classification of type and size. Of 1095 incident MIs, 77% were spontaneous (Type 1), with a smaller number (9.8%) of secondary MIs (Type 2). Vorapaxar reduced Type 1 MI (hazard ratio [HR] 0.84, CI 0.73–0.98, P =0.024), with a similar pattern for Type 2 MI (HR 0.74, CI 0.49–1.10, P =0.13). Notably, vorapaxar showed a consistent pattern of reduction across size of MIs, including MIs in the highest Universal MI size class (≥10× upper reference limit, HR 0.83, CI 0.70–0.98, P =0.025). As such, there was a significant reduction in larger, spontaneous MIs (Type 1, ≥10× upper reference limit, HR 0.81, CI 0.67–0.99, P =0.036), and a consistent pattern with respect to fatal MI (HR 0.66, CI 0.39–1.11, P =0.12). Conclusions Among stable patients with established atherosclerosis, the most common type of incident MI is spontaneous MI, and the reduction in MI with vorapaxar was consistent across MIs of varying type and size, including spontaneous infarctions ≥10× upper reference limit. Clinical Trial Registration URL: . Unique identifier: NCT00526474.

  • efficacy and safety of vorapaxar with and without a thienopyridine for secondary prevention in patients with previous myocardial infarction and no history of stroke or transient ischemic attack results from tra 2 p timi 50
    Circulation, 2015
    Co-Authors: Erin A. Bohula, Philip E Aylward, Benjamin M Scirica, Ramón Corbalán, Marc P. Bonaca, Sabina A Murphy, Harvey D White, Robert Gabor Kiss, Eugene Braunwald, David A Morrow
    Abstract:

    Background—Vorapaxar antagonizes protease-activated Receptor 1, the primary Receptor for Thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use. Methods and Results—The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26 449 patients with previous atherothrombosis. This prespecified analysis included 16 897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or transient ischemic attack given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization...

  • coronary stent thrombosis with vorapaxar versus placebo results from the tra 2 p timi 50 trial
    Journal of the American College of Cardiology, 2014
    Co-Authors: Marc P. Bonaca, Benjamin M Scirica, Sabina A Murphy, Eugene Braunwald, Stephen D Wiviott, Michelle L Odonoghue, David A Morrow
    Abstract:

    Abstract Background Vorapaxar, a novel Thrombin Receptor Antagonist, reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy in patients with stable atherosclerotic vascular disease. Objectives The goal of this study was to test the hypothesis that treatment with vorapaxar reduces the rate of coronary stent thrombosis (ST) in stable patients with a history of coronary stenting. Methods TRA 2°P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) was a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar in stable patients with prior myocardial infarction, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria. Results A total of 26,449 patients were randomized, with 14,042 (53%) having a history of a coronary stent implantation before randomization, and an additional 449 patients receiving a coronary stent during the trial (total 14,491). During follow-up (median 2.5 years), there were 152 definite ST events, with the majority (92%) occurring late or very late. Vorapaxar reduced ARC definite ST (1.1% vs. 1.4%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.51 to 0.98; p = 0.037). The reduction was consistent, regardless of time from percutaneous coronary intervention, history of diabetes, use of drug-eluting stents, and use of dual antiplatelet therapy (DAPT) at randomization. Vorapaxar increased GUSTO moderate/severe bleeding (HR: 1.57, 95% CI: 1.26 to 1.94; p  Conclusions The rate of ARC definite ST in stable patients, the majority of whom were receiving DAPT, was approximately 1.4% at 3 years. In stable patients with coronary stenting receiving standard antiplatelet therapy, vorapaxar administered for long-term secondary prevention significantly reduced ARC definite ST, including very late ST. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Patients With Atherosclerosis [TRA 2°P-TIMI 50] [P04737]; NCT00526474 )

  • evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease design and rationale for the Thrombin Receptor Antagonist in secondary prevention of atherothrombotic ischemic events tra 2 p timi
    American Heart Journal, 2009
    Co-Authors: David A Morrow, Benjamin M Scirica, Marc P. Bonaca, Enrico P Veltri, John Strony, Gail Berman, Polly Fish, Carolyn H Mccabe, Eugene Braunwald
    Abstract:

    Background Thrombin potently activates platelets via interaction with the protease-activated Receptor 1. SCH 530348 is a novel antiplatelet agent that selectively inhibits the cellular actions of Thrombin via antagonism of the protease-activated Receptor 1. Because SCH 530348 does not interfere with other pathways for hemostasis, it is possible that SCH 530348 reduces thrombosis with less increase in bleeding than do other potent antiplatelet agents. Study design TRA 2°P-TIMI 50 is a phase III, randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of SCH 530348 during long-term treatment of patients with established atherosclerotic disease receiving standard therapy (up to 27,000). Eligible patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease are randomized 1:1 to SCH 530348 2.5 mg daily or matched placebo until the end of study. Randomization is stratified by the qualifying disease and planned use of a thienopyridine. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization. The major secondary end point is the composite of cardiovascular death, myocardial infarction, or stroke. The evaluation of long-term safety includes bleeding defined by the GUSTO and TIMI criteria. Recruitment began in September 2007. The trial will continue until 2,279 primary end points and 1,400 secondary end points are recorded with expected completion in 36 to 44 months from first enrollment. Conclusions TRA 2°P-TIMI 50 is evaluating whether a new approach to platelet inhibition via interruption of Thrombin-mediated platelet activation reduces major cardiovascular events with a favorable safety profile in patients with established atherosclerosis.

Paul W Armstrong - One of the best experts on this subject based on the ideXlab platform.

  • clinical features and outcomes of patients with type 2 myocardial infarction insights from the Thrombin Receptor Antagonist for clinical event reduction in acute coronary syndrome tracer trial
    American Heart Journal, 2018
    Co-Authors: Patricia O Guimaraes, Philip E Aylward, David J Moliterno, Claes Held, Robert A Harrington, Lars Wallentin, Zhen Huang, Sergio Leonardi, Frans Van De Werf, Paul W Armstrong
    Abstract:

    Background Type 2 myocardial infarction (MI) is characterized by an imbalance between myocardial blood supply and demand, leading to myocardial ischemia without coronary plaque rupture, but its diagnosis is challenging. Methods In the TRACER trial, patients with non–ST-segment elevation acute coronary syndromes were included. We aimed to describe provoking factors, cardiac biomarker profiles, treatment patterns, and clinical outcomes of patients with type 2 MIs. MI events during trial follow-up were adjudicated by an independent clinical events classification committee (CEC) and were classified according to the Third Universal Definition of MI. Using available source documents retrieved as part of the CEC process, we performed a retrospective chart abstraction to collect details on the type 2 MIs. Cox regression models were used to explore the association between MI type (type 1 or type 2) and cardiovascular death. Results Overall, 10.3% (n = 1327) of TRACER participants had a total of 1579 adjudicated MIs during a median follow-up of 502 days (25th and 75th percentiles [IQR] 349-667). Of all MIs, 5.2% (n = 82) were CEC-adjudicated type 2 MIs, occurring in 76 patients. The incidence of type 2 MI was higher in the first month following randomization, after which the distribution became more scattered. The most frequent potential provoking factors for type 2 MIs were tachyarrhythmias (38.2%), anemia/bleeding (21.1%), hypotension/shock (14.5%), and hypertensive emergencies (11.8%). Overall, 36.3% had a troponin increase >10× the upper limit of normal. Coronary angiography was performed in 22.4% (n = 17) of patients during hospitalizations due to type 2 MIs. The hazard of cardiovascular death was numerically higher following type 2 MI (vs. no MI, adj. HR 11.82, 95% CI 5.71-24.46; P  Conclusions Type 2 MIs were more prevalent in the first month after ACS, were characterized by the presence of triggers and infrequent use of an invasive strategy, and were associated with a high risk of death. Further efforts are needed to better define the role and implications of type 2 MI in both clinical practice and research.

  • use of thienopyridine prior to presentation with non st segment elevation acute coronary syndrome and association with safety and efficacy of vorapaxar insights from the tracer trial
    European heart journal. Acute cardiovascular care, 2017
    Co-Authors: Ralf E Harskamp, Philip E Aylward, Yuliya Lokhnygina, David J Moliterno, Claes Held, Robert Clare, Harvey D White, Paul W Armstrong, Giuseppe Ambrosio, Kenneth W Mahaffey
    Abstract:

    Background:Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We hypothesized that patients with NSTE ACS already receiving thienopyridine prior to the ACS event may show differential efficacy/safety effects with vorapaxar vs. placebo added to their standard care.Methods:We studied 12,944 patients from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial with respect to thienopyridine use before admission for the index NSTE ACS event. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, rehospitalization for ischemia, and urgent revascularization. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Safety endpoints were bleeding complications.Results:Only 1513 patients (11.7%) were re...

  • trade off of myocardial infarction vs bleeding types on mortality after acute coronary syndrome lessons from the Thrombin Receptor Antagonist for clinical event reduction in acute coronary syndrome tracer randomized trial
    European Heart Journal, 2016
    Co-Authors: Yuliya Lokhnygina, David J Moliterno, Robert Clare, Paul W Armstrong, Lars Wallentin, Marco Valgimigli, F Costa, Harvey D White
    Abstract:

    Aims Dual antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome (ACS) but increases bleeding to a similar extent. We sought to determine the prognostic impact of myocardial infarction (MI) vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after ACS. Methods and results In 12 944 patients with non-ST-segment elevation ACS from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, we investigated the relative impact of MI and bleeding occurring >30 days post-ACS and subsequent all-cause mortality. Bleeding was graded according to Bleeding Academic Research Consortium (BARC) criteria. MI was associated with a five-fold increase in mortality. BARC type 2 and 3, but not type 1, bleeding had a significant impact on mortality. MI was associated with a greater risk of mortality compared with BARC 2 [relative risk (RR) 3.5; 95% confidence interval (CI) 2.08-4.77; P Conclusion In patients treated with antiplatelet therapy after ACS, both MI and bleeding significantly impacted mortality with similar time-dependency. Although BARC 2 and 3a bleeding were less prognostic for death than MI, the risk of mortality was equivalent between BARC 3b bleeding and MI, and was higher following BARC 3c bleeding.

  • effect of age on efficacy and safety of vorapaxar in patients with non st segment elevation acute coronary syndrome insights from the Thrombin Receptor Antagonist for clinical event reduction in acute coronary syndrome tracer trial
    American Heart Journal, 2016
    Co-Authors: Luciana Armaganijan, Philip E Aylward, Claes Held, Harvey D White, Paul W Armstrong, Pierluigi Tricoci, Zhen Huang, Frans Van De Werf, Karen P Alexander, David J Moliterno
    Abstract:

    Background Antithrombotic therapy plays an important role in the treatment of non–ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. Methods Efficacy and safety of vorapaxar (a protease-activated Receptor 1 Antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. Results The median age of the population was 64years (25th, 75th percentiles=58, 71). Also, 1,791 patients (13.8%) were ≤54years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively ( P value for interaction=.435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively ( P value for interaction=.574). Conclusion Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.

  • glycoprotein iib iiia Receptor inhibitors in combination with vorapaxar a platelet Thrombin Receptor Antagonist among patients with non st segment elevation acute coronary syndromes from the tracer trial
    American Journal of Cardiology, 2015
    Co-Authors: Jan H Cornel, Philip E Aylward, Yuliya Lokhnygina, David J Moliterno, Robert Clare, Paul W Armstrong, Lars Wallentin, Pierluigi Tricoci, Edmond Chen, Sergio Leonardi
    Abstract:

    We evaluated the interaction between protease-activated Receptor-1 Antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa Receptor inhibitors in patients with non–ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non–ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa Receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa Receptor inhibitors modified vorapaxar's effect on non–coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non–CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa Receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa Receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIb/IIIa group; adjusted HR 1.34, 95% CI 0.44 to 4.07 in the no–GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa Receptor inhibitor use plus dual antiplatelet therapy in a population with non–ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa Receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

Philip E Aylward - One of the best experts on this subject based on the ideXlab platform.

  • clinical features and outcomes of patients with type 2 myocardial infarction insights from the Thrombin Receptor Antagonist for clinical event reduction in acute coronary syndrome tracer trial
    American Heart Journal, 2018
    Co-Authors: Patricia O Guimaraes, Philip E Aylward, David J Moliterno, Claes Held, Robert A Harrington, Lars Wallentin, Zhen Huang, Sergio Leonardi, Frans Van De Werf, Paul W Armstrong
    Abstract:

    Background Type 2 myocardial infarction (MI) is characterized by an imbalance between myocardial blood supply and demand, leading to myocardial ischemia without coronary plaque rupture, but its diagnosis is challenging. Methods In the TRACER trial, patients with non–ST-segment elevation acute coronary syndromes were included. We aimed to describe provoking factors, cardiac biomarker profiles, treatment patterns, and clinical outcomes of patients with type 2 MIs. MI events during trial follow-up were adjudicated by an independent clinical events classification committee (CEC) and were classified according to the Third Universal Definition of MI. Using available source documents retrieved as part of the CEC process, we performed a retrospective chart abstraction to collect details on the type 2 MIs. Cox regression models were used to explore the association between MI type (type 1 or type 2) and cardiovascular death. Results Overall, 10.3% (n = 1327) of TRACER participants had a total of 1579 adjudicated MIs during a median follow-up of 502 days (25th and 75th percentiles [IQR] 349-667). Of all MIs, 5.2% (n = 82) were CEC-adjudicated type 2 MIs, occurring in 76 patients. The incidence of type 2 MI was higher in the first month following randomization, after which the distribution became more scattered. The most frequent potential provoking factors for type 2 MIs were tachyarrhythmias (38.2%), anemia/bleeding (21.1%), hypotension/shock (14.5%), and hypertensive emergencies (11.8%). Overall, 36.3% had a troponin increase >10× the upper limit of normal. Coronary angiography was performed in 22.4% (n = 17) of patients during hospitalizations due to type 2 MIs. The hazard of cardiovascular death was numerically higher following type 2 MI (vs. no MI, adj. HR 11.82, 95% CI 5.71-24.46; P  Conclusions Type 2 MIs were more prevalent in the first month after ACS, were characterized by the presence of triggers and infrequent use of an invasive strategy, and were associated with a high risk of death. Further efforts are needed to better define the role and implications of type 2 MI in both clinical practice and research.

  • use of thienopyridine prior to presentation with non st segment elevation acute coronary syndrome and association with safety and efficacy of vorapaxar insights from the tracer trial
    European heart journal. Acute cardiovascular care, 2017
    Co-Authors: Ralf E Harskamp, Philip E Aylward, Yuliya Lokhnygina, David J Moliterno, Claes Held, Robert Clare, Harvey D White, Paul W Armstrong, Giuseppe Ambrosio, Kenneth W Mahaffey
    Abstract:

    Background:Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We hypothesized that patients with NSTE ACS already receiving thienopyridine prior to the ACS event may show differential efficacy/safety effects with vorapaxar vs. placebo added to their standard care.Methods:We studied 12,944 patients from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial with respect to thienopyridine use before admission for the index NSTE ACS event. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, rehospitalization for ischemia, and urgent revascularization. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Safety endpoints were bleeding complications.Results:Only 1513 patients (11.7%) were re...

  • effect of age on efficacy and safety of vorapaxar in patients with non st segment elevation acute coronary syndrome insights from the Thrombin Receptor Antagonist for clinical event reduction in acute coronary syndrome tracer trial
    American Heart Journal, 2016
    Co-Authors: Luciana Armaganijan, Philip E Aylward, Claes Held, Harvey D White, Paul W Armstrong, Pierluigi Tricoci, Zhen Huang, Frans Van De Werf, Karen P Alexander, David J Moliterno
    Abstract:

    Background Antithrombotic therapy plays an important role in the treatment of non–ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. Methods Efficacy and safety of vorapaxar (a protease-activated Receptor 1 Antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. Results The median age of the population was 64years (25th, 75th percentiles=58, 71). Also, 1,791 patients (13.8%) were ≤54years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively ( P value for interaction=.435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively ( P value for interaction=.574). Conclusion Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.

  • efficacy and safety of vorapaxar with and without a thienopyridine for secondary prevention in patients with previous myocardial infarction and no history of stroke or transient ischemic attack results from tra 2 p timi 50
    Circulation, 2015
    Co-Authors: Erin A. Bohula, Philip E Aylward, Benjamin M Scirica, Ramón Corbalán, Marc P. Bonaca, Sabina A Murphy, Harvey D White, Robert Gabor Kiss, Eugene Braunwald, David A Morrow
    Abstract:

    Background—Vorapaxar antagonizes protease-activated Receptor 1, the primary Receptor for Thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use. Methods and Results—The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26 449 patients with previous atherothrombosis. This prespecified analysis included 16 897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or transient ischemic attack given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization...

  • glycoprotein iib iiia Receptor inhibitors in combination with vorapaxar a platelet Thrombin Receptor Antagonist among patients with non st segment elevation acute coronary syndromes from the tracer trial
    American Journal of Cardiology, 2015
    Co-Authors: Jan H Cornel, Philip E Aylward, Yuliya Lokhnygina, David J Moliterno, Robert Clare, Paul W Armstrong, Lars Wallentin, Pierluigi Tricoci, Edmond Chen, Sergio Leonardi
    Abstract:

    We evaluated the interaction between protease-activated Receptor-1 Antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa Receptor inhibitors in patients with non–ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non–ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa Receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa Receptor inhibitors modified vorapaxar's effect on non–coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non–CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa Receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa Receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIb/IIIa group; adjusted HR 1.34, 95% CI 0.44 to 4.07 in the no–GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa Receptor inhibitor use plus dual antiplatelet therapy in a population with non–ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa Receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

Marc P. Bonaca - One of the best experts on this subject based on the ideXlab platform.

  • high sensitivity troponin i in stable patients with atherosclerotic disease in the tra 2 p timi 50 trial
    Clinical Chemistry, 2017
    Co-Authors: Alon Eisen, Benjamin M Scirica, Marc P. Bonaca, Harvey D White, Mikael Dellborg, João Morais, Michal Tendera, Jose C Nicolau, Petr Jarolim, Keith A A Fox
    Abstract:

    BACKGROUND: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined. METHODS: We measured hs-TnI (Abbott ARCHITECT) in 15833 patients with prior MI, ischemic stroke, or peripheral arterial disease from the placebo-controlled Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)–Thrombolysis in Myocardial Infarction (TIMI) 50 trial of the platelet inhibitor vorapaxar, excluding patients with recent MI (<30 days). hs-TnI was categorized into 5 groups based on the detection limit (1.9 ng/L), 99th percentile reference limit (26 ng/L), and tertiles in between (1.9–26 ng/L), as well as sex-specific reference limits. RESULTS: Higher hs-TnI concentration was associated with older age, male sex, and increased atherosclerosis burden. hs-TnI identified a graded 3-year risk of cardiovascular death, MI, or stroke from 5.0% to 18.6% ( P 26 ng/L vs 26 ng/L vs 0.3% with hs-TnI <1.9 ng/L; P interaction = 0.82). CONCLUSIONS: In stable patients with established atherosclerosis, hs-TnI concentrations effectively stratified the risk of new or recurrent cardiovascular (CV) events, in particular CV death and MI. High-risk patients with prior MI identified by increased hs-TnI had a substantial absolute improvement in net clinical outcome with vorapaxar.

  • universal classification system type of incident myocardial infarction in patients with stable atherosclerosis observations from Thrombin Receptor Antagonist in secondary prevention of atherothrombotic ischemic events tra 2 p timi 50
    Journal of the American Heart Association, 2016
    Co-Authors: Stephen Kidd, Benjamin M Scirica, Marc P. Bonaca, Sabina A Murphy, Harvey D White, Eugene Braunwald, Gaetano M De Ferrari, Basil S Lewis, Piera Angelica Merlini, David A Morrow
    Abstract:

    Background Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first‐in‐class platelet protease‐activated Receptor ‐1 Antagonist, on new or recurrent MI. Methods and Results We analyzed data from TRA 2°P‐TIMI 50, a multinational, randomized, double‐blind, placebo‐controlled trial of vorapaxar. This analysis included 20 770 patients with previous MI or peripheral arterial disease without a history of transient ischemic attack or stroke. Each new or recurrent MI after randomization that met the trial end point definition was further categorized according to the European Society of Cardiology, American College of Cardiology, American Heart Association, World Heart Federation Universal Definition classification of type and size. Of 1095 incident MIs, 77% were spontaneous (Type 1), with a smaller number (9.8%) of secondary MIs (Type 2). Vorapaxar reduced Type 1 MI (hazard ratio [HR] 0.84, CI 0.73–0.98, P =0.024), with a similar pattern for Type 2 MI (HR 0.74, CI 0.49–1.10, P =0.13). Notably, vorapaxar showed a consistent pattern of reduction across size of MIs, including MIs in the highest Universal MI size class (≥10× upper reference limit, HR 0.83, CI 0.70–0.98, P =0.025). As such, there was a significant reduction in larger, spontaneous MIs (Type 1, ≥10× upper reference limit, HR 0.81, CI 0.67–0.99, P =0.036), and a consistent pattern with respect to fatal MI (HR 0.66, CI 0.39–1.11, P =0.12). Conclusions Among stable patients with established atherosclerosis, the most common type of incident MI is spontaneous MI, and the reduction in MI with vorapaxar was consistent across MIs of varying type and size, including spontaneous infarctions ≥10× upper reference limit. Clinical Trial Registration URL: . Unique identifier: NCT00526474.

  • universal classification system type of incident myocardial infarction in patients with stable atherosclerosis observations from Thrombin Receptor Antagonist in secondary prevention of atherothrombotic ischemic events tra 2 p timi 50
    Journal of the American Heart Association, 2016
    Co-Authors: Stephen Kidd, Benjamin M Scirica, Marc P. Bonaca, Sabina A Murphy, Harvey D White, Eugene Braunwald, Gaetano M De Ferrari, Basil S Lewis, Piera Angelica Merlini, David A Morrow
    Abstract:

    Background Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first‐in‐class platelet protease‐activated Receptor ‐1 Antagonist, on new or recurrent MI. Methods and Results We analyzed data from TRA 2°P‐TIMI 50, a multinational, randomized, double‐blind, placebo‐controlled trial of vorapaxar. This analysis included 20 770 patients with previous MI or peripheral arterial disease without a history of transient ischemic attack or stroke. Each new or recurrent MI after randomization that met the trial end point definition was further categorized according to the European Society of Cardiology, American College of Cardiology, American Heart Association, World Heart Federation Universal Definition classification of type and size. Of 1095 incident MIs, 77% were spontaneous (Type 1), with a smaller number (9.8%) of secondary MIs (Type 2). Vorapaxar reduced Type 1 MI (hazard ratio [HR] 0.84, CI 0.73–0.98, P =0.024), with a similar pattern for Type 2 MI (HR 0.74, CI 0.49–1.10, P =0.13). Notably, vorapaxar showed a consistent pattern of reduction across size of MIs, including MIs in the highest Universal MI size class (≥10× upper reference limit, HR 0.83, CI 0.70–0.98, P =0.025). As such, there was a significant reduction in larger, spontaneous MIs (Type 1, ≥10× upper reference limit, HR 0.81, CI 0.67–0.99, P =0.036), and a consistent pattern with respect to fatal MI (HR 0.66, CI 0.39–1.11, P =0.12). Conclusions Among stable patients with established atherosclerosis, the most common type of incident MI is spontaneous MI, and the reduction in MI with vorapaxar was consistent across MIs of varying type and size, including spontaneous infarctions ≥10× upper reference limit. Clinical Trial Registration URL: . Unique identifier: NCT00526474.

  • efficacy and safety of vorapaxar with and without a thienopyridine for secondary prevention in patients with previous myocardial infarction and no history of stroke or transient ischemic attack results from tra 2 p timi 50
    Circulation, 2015
    Co-Authors: Erin A. Bohula, Philip E Aylward, Benjamin M Scirica, Ramón Corbalán, Marc P. Bonaca, Sabina A Murphy, Harvey D White, Robert Gabor Kiss, Eugene Braunwald, David A Morrow
    Abstract:

    Background—Vorapaxar antagonizes protease-activated Receptor 1, the primary Receptor for Thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use. Methods and Results—The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26 449 patients with previous atherothrombosis. This prespecified analysis included 16 897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or transient ischemic attack given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization...

  • vorapaxar in patients with diabetes mellitus and previous myocardial infarction findings from the Thrombin Receptor Antagonist in secondary prevention of atherothrombotic ischemic events timi 50 trial
    Circulation, 2015
    Co-Authors: Matthew A. Cavender, Benjamin M Scirica, Marc P. Bonaca, Sabina A Murphy, Dominick J. Angiolillo, Anthony J. Dalby, Mikael Dellborg, João Morais, Ton Oude Ophuis, Michal Tendera
    Abstract:

    Background— Vorapaxar reduces cardiovascular death, myocardial infarction (MI), or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis. Methods and Results— We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16 896) excluded such patients. The primary end point of cardiovascular death, MI, or stroke occurred more frequently in patients with DM than in patients without DM (rates in placebo group: 14.3% versus 7.6%; adjusted hazard ratio, 1.47; P <0.001). In patients with DM (n=3623), vorapaxar significantly reduced the primary end point (11.4% versus 14.3%; hazard ratio, 0.73 [95% confidence interval, 0.60–0.89]; P =0.002) with a number needed to treat to avoid 1 major cardiovascular event of 29. The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% versus 2.6%; hazard ratio, 1.60 [95% confidence interval, 1.07–2.40]). However, net clinical outcome integrating these 2 end points (efficacy and safety) was improved with vorapaxar (hazard ratio, 0.79 [95% confidence interval, 0.67–0.93]). Conclusions— In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events. Clinical Trial Registration— URL: . Unique identifier: [NCT00526474][1]. # CLINICAL PERSPECTIVE {#article-title-22} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00526474&atom=%2Fcirculationaha%2F131%2F12%2F1047.atom