The Experts below are selected from a list of 6174 Experts worldwide ranked by ideXlab platform
Kenneth W Mahaffey - One of the best experts on this subject based on the ideXlab platform.
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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, 2017Co-Authors: Ralf E Harskamp, Harvey D White, Philip E Aylward, Giuseppe Ambrosio, Robert Clare, Claes Held, Yuliya Lokhnygina, David J Moliterno, Paul W Armstrong, Kenneth W MahaffeyAbstract: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...
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abstract 16787 use of Thienopyridine prior to presentation for acute coronary syndromes and association with safety and efficacy of vorapaxar insights from the tracer study
Circulation, 2014Co-Authors: Ralf E Harskamp, Harvey D White, Philip E Aylward, Giuseppe Ambrosio, Robert Clare, Claes Held, Yuliya Lokhnygina, David J Moliterno, Paul W Armstrong, Kenneth W MahaffeyAbstract:Background: In TRACER, vorapaxar, a novel PAR-1 antagonist, was compared with placebo in pts with NSTE ACS treated with standard of care, including >90% use of Thienopyridine at baseline. In this context, vorapaxar was associated with a modest efficacy signal and increased bleeding. We assessed use of Thienopyridine prior to hospitalization for the index ACS event and its association with efficacy and safety of vorapaxar. Methods: The TRACER trial included 12,944 pts randomized to vorapaxar or placebo and followed for a median of 502 days. Prior use of Thienopyridine was defined as being on treatment during the 7 days prior to the index ACS presentation. The main outcomes were a composite of cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization; a composite of cardiovascular death, myocardial infarction, and stroke; and bleeding complications. Safety outcomes were non-CABG-related GUSTO and TIMI bleeding. Results: The vast maj...
Harvey D White - One of the best experts on this subject based on the ideXlab platform.
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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, 2017Co-Authors: Ralf E Harskamp, Harvey D White, Philip E Aylward, Giuseppe Ambrosio, Robert Clare, Claes Held, Yuliya Lokhnygina, David J Moliterno, Paul W Armstrong, Kenneth W MahaffeyAbstract: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...
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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, 2015Co-Authors: Erin A Bohula, Sabina A Murphy, Marc P Bonaca, Benjamin M Scirica, Eugene Braunwald, Harvey D White, Philip E Aylward, Ramon Corbalan, Robert Gabor Kiss, David A MorrowAbstract: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...
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the efficacy and safety of vorapaxar with and without a Thienopyridine for secondary prevention in patients with prior myocardial infarction and no history of stroke or tia results from tra 2 p timi 50
Circulation, 2015Co-Authors: Erin A Bohula, Sabina A Murphy, Marc P Bonaca, Benjamin M Scirica, Eugene Braunwald, Harvey D White, Philip E Aylward, Ramon Corbalan, Robert Gabor Kiss, David A MorrowAbstract:Background —Vorapaxar antagonizes protease-activated receptor (PAR)-1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a prior 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 —TRA 2°P-TIMI 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26,449 patients with prior atherothrombosis. This pre-specified 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 TIA given its contraindication in that population. Randomization was stratified on the basis of planned Thienopyridine use. Thienopyridine was planned at randomization in 12,410 (73%). Vorapaxar significantly reduced the composite of cardiovascular death, MI and stroke when compared to placebo regardless of planned Thienopyridine therapy (planned Thienopyridine HR 0.80, 0.70-0.91, p<0.001; no planned Thienopyridine HR 0.75, 0.60-0.94, p=0.011; p-interaction=0.67). Findings were similar when patients were stratified by actual Thienopyridine use at baseline (p-interaction=0.82) and through 18 months (p-interaction=0.44). GUSTO moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned Thienopyridine (planned HR 1.50, 1.18-1.89, p<0.001; no planned HR 1.90, 1.17-3.07, p=0.009; p-interaction=0.37) or actual Thienopyridine use (p-interaction=0.24). Conclusions —Vorapaxar reduced cardiovascular death, MI, or stroke in stable patients with a history of prior MI, whether treated concomitantly with a Thienopyridine or not. The relative risk of moderate or severe bleeding was similarly increased irrespective of Thienopyridine use. Clinical Trial Registration Information —http://www.clinicaltrials.gov. Identifier: [NCT00526474][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00526474&atom=%2Fcirculationaha%2Fearly%2F2015%2F09%2F03%2FCIRCULATIONAHA.114.015042.atom
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abstract 16787 use of Thienopyridine prior to presentation for acute coronary syndromes and association with safety and efficacy of vorapaxar insights from the tracer study
Circulation, 2014Co-Authors: Ralf E Harskamp, Harvey D White, Philip E Aylward, Giuseppe Ambrosio, Robert Clare, Claes Held, Yuliya Lokhnygina, David J Moliterno, Paul W Armstrong, Kenneth W MahaffeyAbstract:Background: In TRACER, vorapaxar, a novel PAR-1 antagonist, was compared with placebo in pts with NSTE ACS treated with standard of care, including >90% use of Thienopyridine at baseline. In this context, vorapaxar was associated with a modest efficacy signal and increased bleeding. We assessed use of Thienopyridine prior to hospitalization for the index ACS event and its association with efficacy and safety of vorapaxar. Methods: The TRACER trial included 12,944 pts randomized to vorapaxar or placebo and followed for a median of 502 days. Prior use of Thienopyridine was defined as being on treatment during the 7 days prior to the index ACS presentation. The main outcomes were a composite of cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization; a composite of cardiovascular death, myocardial infarction, and stroke; and bleeding complications. Safety outcomes were non-CABG-related GUSTO and TIMI bleeding. Results: The vast maj...
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abstract 18595 efficacy of vorapaxar is not modified by Thienopyridine therapy results from tra 2 p timi 50 trial
Circulation, 2012Co-Authors: Marc P Bonaca, Sabina A Murphy, Benjamin M Scirica, Eugene Braunwald, Harvey D White, Philip E Aylward, Peer Grande, David A MorrowAbstract:Vorapaxar antagonizes the platelet protease-activated receptor (PAR)-1,the primary receptor for thrombin on human platelets. The addition of vorapaxar to standard therapy has been shown to reduce thrombotic events in patients with stable atherosclerosis. We investigated whether the efficacy and safety of vorapaxar in stable atherosclerosis were modified by Thienopyridine therapy. METHODS: The TRA2P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar 2.5 mg daily in 26,449 patients with established atherosclerotic vascular disease. Patients were stratified at randomization based on planned use of Thienopyridine therapy. The first efficacy endpoint was a composite of cardiovascular death (CVD), MI, or stroke and the primary safety endpoint was GUSTO moderate or severe bleeding. Analyses were adjusted for qualifying disease state (MI, stroke, PAD). Treatment with ASA ≤ 162 mg was recommended. RESULTS: Thienopyridine was planned in 15,356 (58%) and ASA was used in 24,734 (94%) overall. Patients randomized to vorapaxar had similar significant reductions in the primary endpoint regardless of planned Thienopyridine therapy (Figure, p-interaction 0.64) and after adjustment for qualifying disease state (MI, stroke, PAD). Findings were similar when patients were stratified by actual Thienopyridine use at baseline (Figure, p-interaction 0.76) and at 18 months (p-interaction 0.99). GUSTO moderate or severe bleeding was increased with vorapaxar with no significant interaction in those planned for Thienopyridine therapy (p-interaction 0.29) or those receiving Thienopyridines through 18 months (p-interaction 0.71). CONCLUSIONS: Vorapaxar reduced CVD, MI, or stroke in stable patients with a history of atherothrombotic events and this effect was present whether or not vorapaxar was used with a Thienopyridine. The increased risk of bleeding with vorapaxar was also similar regardless of Thienopyridine therapy.
Philip E Aylward - One of the best experts on this subject based on the ideXlab platform.
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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, 2017Co-Authors: Ralf E Harskamp, Harvey D White, Philip E Aylward, Giuseppe Ambrosio, Robert Clare, Claes Held, Yuliya Lokhnygina, David J Moliterno, Paul W Armstrong, Kenneth W MahaffeyAbstract: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...
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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, 2015Co-Authors: Erin A Bohula, Sabina A Murphy, Marc P Bonaca, Benjamin M Scirica, Eugene Braunwald, Harvey D White, Philip E Aylward, Ramon Corbalan, Robert Gabor Kiss, David A MorrowAbstract: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...
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the efficacy and safety of vorapaxar with and without a Thienopyridine for secondary prevention in patients with prior myocardial infarction and no history of stroke or tia results from tra 2 p timi 50
Circulation, 2015Co-Authors: Erin A Bohula, Sabina A Murphy, Marc P Bonaca, Benjamin M Scirica, Eugene Braunwald, Harvey D White, Philip E Aylward, Ramon Corbalan, Robert Gabor Kiss, David A MorrowAbstract:Background —Vorapaxar antagonizes protease-activated receptor (PAR)-1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a prior 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 —TRA 2°P-TIMI 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26,449 patients with prior atherothrombosis. This pre-specified 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 TIA given its contraindication in that population. Randomization was stratified on the basis of planned Thienopyridine use. Thienopyridine was planned at randomization in 12,410 (73%). Vorapaxar significantly reduced the composite of cardiovascular death, MI and stroke when compared to placebo regardless of planned Thienopyridine therapy (planned Thienopyridine HR 0.80, 0.70-0.91, p<0.001; no planned Thienopyridine HR 0.75, 0.60-0.94, p=0.011; p-interaction=0.67). Findings were similar when patients were stratified by actual Thienopyridine use at baseline (p-interaction=0.82) and through 18 months (p-interaction=0.44). GUSTO moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned Thienopyridine (planned HR 1.50, 1.18-1.89, p<0.001; no planned HR 1.90, 1.17-3.07, p=0.009; p-interaction=0.37) or actual Thienopyridine use (p-interaction=0.24). Conclusions —Vorapaxar reduced cardiovascular death, MI, or stroke in stable patients with a history of prior MI, whether treated concomitantly with a Thienopyridine or not. The relative risk of moderate or severe bleeding was similarly increased irrespective of Thienopyridine use. Clinical Trial Registration Information —http://www.clinicaltrials.gov. Identifier: [NCT00526474][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00526474&atom=%2Fcirculationaha%2Fearly%2F2015%2F09%2F03%2FCIRCULATIONAHA.114.015042.atom
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abstract 16787 use of Thienopyridine prior to presentation for acute coronary syndromes and association with safety and efficacy of vorapaxar insights from the tracer study
Circulation, 2014Co-Authors: Ralf E Harskamp, Harvey D White, Philip E Aylward, Giuseppe Ambrosio, Robert Clare, Claes Held, Yuliya Lokhnygina, David J Moliterno, Paul W Armstrong, Kenneth W MahaffeyAbstract:Background: In TRACER, vorapaxar, a novel PAR-1 antagonist, was compared with placebo in pts with NSTE ACS treated with standard of care, including >90% use of Thienopyridine at baseline. In this context, vorapaxar was associated with a modest efficacy signal and increased bleeding. We assessed use of Thienopyridine prior to hospitalization for the index ACS event and its association with efficacy and safety of vorapaxar. Methods: The TRACER trial included 12,944 pts randomized to vorapaxar or placebo and followed for a median of 502 days. Prior use of Thienopyridine was defined as being on treatment during the 7 days prior to the index ACS presentation. The main outcomes were a composite of cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization; a composite of cardiovascular death, myocardial infarction, and stroke; and bleeding complications. Safety outcomes were non-CABG-related GUSTO and TIMI bleeding. Results: The vast maj...
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abstract 18595 efficacy of vorapaxar is not modified by Thienopyridine therapy results from tra 2 p timi 50 trial
Circulation, 2012Co-Authors: Marc P Bonaca, Sabina A Murphy, Benjamin M Scirica, Eugene Braunwald, Harvey D White, Philip E Aylward, Peer Grande, David A MorrowAbstract:Vorapaxar antagonizes the platelet protease-activated receptor (PAR)-1,the primary receptor for thrombin on human platelets. The addition of vorapaxar to standard therapy has been shown to reduce thrombotic events in patients with stable atherosclerosis. We investigated whether the efficacy and safety of vorapaxar in stable atherosclerosis were modified by Thienopyridine therapy. METHODS: The TRA2P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar 2.5 mg daily in 26,449 patients with established atherosclerotic vascular disease. Patients were stratified at randomization based on planned use of Thienopyridine therapy. The first efficacy endpoint was a composite of cardiovascular death (CVD), MI, or stroke and the primary safety endpoint was GUSTO moderate or severe bleeding. Analyses were adjusted for qualifying disease state (MI, stroke, PAD). Treatment with ASA ≤ 162 mg was recommended. RESULTS: Thienopyridine was planned in 15,356 (58%) and ASA was used in 24,734 (94%) overall. Patients randomized to vorapaxar had similar significant reductions in the primary endpoint regardless of planned Thienopyridine therapy (Figure, p-interaction 0.64) and after adjustment for qualifying disease state (MI, stroke, PAD). Findings were similar when patients were stratified by actual Thienopyridine use at baseline (Figure, p-interaction 0.76) and at 18 months (p-interaction 0.99). GUSTO moderate or severe bleeding was increased with vorapaxar with no significant interaction in those planned for Thienopyridine therapy (p-interaction 0.29) or those receiving Thienopyridines through 18 months (p-interaction 0.71). CONCLUSIONS: Vorapaxar reduced CVD, MI, or stroke in stable patients with a history of atherothrombotic events and this effect was present whether or not vorapaxar was used with a Thienopyridine. The increased risk of bleeding with vorapaxar was also similar regardless of Thienopyridine therapy.
Wolfgang C Winkelmayer - One of the best experts on this subject based on the ideXlab platform.
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Thienopyridine use after coronary stenting in low income patients enrolled in medicare part d receiving maintenance dialysis
Journal of the American Heart Association, 2014Co-Authors: Tara I Chang, Maria E Montezrath, Matthew D Solomon, Jenny I Shen, Wolfgang C Winkelmayer, Glenn M ChertowAbstract:Background Coronary stenting in patients on dialysis has increased by nearly 50% over the past decade, despite heightened risks of associated stent thrombosis and bleeding relative to the general population. We examined clopidogrel, prasugrel or ticlopidine use after percutaneous coronary intervention (PCI) with stenting in patients on dialysis. We conducted 3-, 6-, and 12-month landmark analyses to test the hypothesis that Thienopyridine discontinuation prior to those time points would be associated with higher risks of death, myocardial infarction, or repeat revascularization, and a lower risk of major bleeding episodes compared with continued Thienopyridine use. Methods and Results Using the US Renal Data System, we identified 8458 patients on dialysis with Medicare Parts A+B+D undergoing PCI with stenting between July 2007 and December 2010. Ninety-nine percent of all Thienopyridine prescriptions were for clopidogrel. At 3 months, 82% of patients who received drug-eluting stents (DES) had evidence of Thienopyridine use. These proportions fell to 62% and 40% at 6 and 12 months, respectively. In patients who received a bare-metal stent (BMS), 70%, 34%, and 26% of patients had evidence of Thienopyridine use at 3, 6, and 12 months, respectively. In patients who received a DES, there was a suggestion of higher risks of death or myocardial infarction associated with Thienopyridine discontinuation in the 3-, 6-, and 12-months landmark analyses, but no higher risk of major bleeding episodes. In patients who received a BMS, there were no differences in death or cardiovascular events, and possibly lower risk of major bleeding with Thienopyridine discontinuation in the 3- and 6-month landmark analyses. Conclusions The majority of patients on dialysis who undergo PCI discontinue Thienopyridines before 1 year regardless of stent type. While not definitive, these data suggest that longer-term Thienopyridine use may be of benefit to patients on dialysis who undergo PCI with DES.
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abstract p382 continued Thienopyridine use at six months after pci is not associated with better outcomes in end stage renal disease requiring dialysis
Circulation, 2014Co-Authors: Tara I Chang, Maria E Montezrath, Matthew D Solomon, Jenny I Shen, Wolfgang C WinkelmayerAbstract:Introduction: While coronary disease is common in end-stage renal disease, there are few studies of Thienopyridine use after PCI in this population. Guidelines recommend 1 to 12 months of Thienopyridine use depending on stent type, but are based on patients without advanced kidney disease. However, patients on dialysis often have more severe coronary disease and higher risks of bleeding. We hypothesized that in patients on dialysis undergoing PCI with stenting: 1) most will discontinue Thienopyridines prior to 1 year; 2) discontinuation of Thienopyridines prior to 6 months post-PCI will associate with higher risks of death or MI, but a lower risk of bleeding. Methods: Using the US Renal Data System, we identified patients on dialysis with Medicare Parts A+B+D (with low-income subsidy) who had PCI with stenting between 7/07 and 12/09. Thienopyridine discontinuation was defined as >30-day gap in supply. We performed a landmark analysis, selecting patients who were event-free at 6 months after PCI, and categorized them as having discontinued Thienopyridines or not at that point. We propensity-matched patients for discontinued vs. continued use and fit Cox models to examine death, death or MI, and hospitalized bleeding. Results: We identified 4686 patients, 66% of whom received a drug-eluting stent [DES]. At 90-days, 78% of DES and 65% of bare metal stent (BMS) patients used a Thienopyridine; this proportion fell to 64% and 48% at 6 months, and 42% and 29% at 1 year. Overall rates of death and MI were high (Table). In the matched cohorts, patients who discontinued Thienopyridine use prior to 6 months (vs. continued use) had no significant differences in long-term outcomes (Table). Conclusions: In patients on dialysis who undergo PCI with stenting, most use Thienopyridines for
Laura Mauri - One of the best experts on this subject based on the ideXlab platform.
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myocardial infarction after late discontinuation of Thienopyridine therapy in the randomized dapt study
Journal of the American College of Cardiology, 2016Co-Authors: Laura Mauri, Ada Stefanescu, Dean Kereiakes, Donald E. Cutlip, Ralph B DagostinoAbstract:Background —Thienopyridine plus aspirin beyond one year after coronary stenting (PCI) reduces myocardial infarction (MI) risk and increases bleeding risk compared with aspirin alone. The hazard associated with late Thienopyridine discontinuation and risk factors for MI after discontinuation are poorly defined. Methods —In the Dual Antiplatelet Therapy (DAPT) Study, after PCI and 12 months of Thienopyridine (clopidogrel or prasugrel) plus aspirin, eligible patients remained on aspirin and were randomized to continued Thienopyridine vs. placebo for 18 months. At 30 months, patients stopped study drug and were observed for 3 months. Cumulative incidence of MI was assessed over 3 months after randomization (months 12-15) and 3 months after study drug discontinuation (months 30-33). The MI hazard for each of these periods was assessed across randomized treatment arms and by DAPT Score values < or ≥2. Results —Among the 11648 randomized patients, the monthly cumulative incidence of MI was lower with continued Thienopyridine vs. placebo at 12-15 months (0.12% vs. 0.37%, p<0.001 in all patients; 0.13% vs. 0.27%, p=0.02, in patients not treated with paclitaxel-eluting stents, PES), and higher at 30-33 months (0.30% vs. 0.15%, p=0.013, in all patients; in patients without PES, 0.18% vs. 0.17%, p=0.91). The majority of MIs in both time periods (74% and 76%) were not related to stent thrombosis (ST). After multivariable adjustment, treatment arm independently predicted MI at months 12-15 (p<0.001) and 30-33 (p=0.011). During months 12-15, patients with DAPT Scores < or ≥2 both had lower rates of MI with continued Thienopyridine (MI monthly incidence 0.16% vs. 0.51%, p<0.001, for scores ≥2; 0.08% vs. 0.24%, p=0.012, for scores<2, interaction p=0.064). Conclusions —Discontinuing Thienopyridine after either 12 or 30 months is associated with an early increase in MI risk, mainly unrelated to ST; the magnitude of risk is highest in the earlier time frame, and lower in patients not treated with PES. While higher DAPT Scores identify patients with greater absolute ischemic benefit (relative to bleeding harm) with continued Thienopyridine therapy, discontinuation at 12 months increases MI hazard regardless of DAPT score group. Clinical Trial Registration — https://clinicaltrials.gov Identifier: [NCT00977938][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00977938&atom=%2Fcirculationaha%2Fearly%2F2017%2F02%2F22%2FCIRCULATIONAHA.116.024835.atom
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MYOCARDIAL INFARCTION AFTER LATE DISCONTINUATION OF Thienopyridine THERAPY IN THE RANDOMIZED DAPT STUDY
Journal of the American College of Cardiology, 2016Co-Authors: Ada Stefanescu, Laura Mauri, Dean Kereiakes, Donald E. Cutlip, Ralph B. D'agostino, Joseph M. MassaroAbstract:Background —Thienopyridine plus aspirin beyond one year after coronary stenting (PCI) reduces myocardial infarction (MI) risk and increases bleeding risk compared with aspirin alone. The hazard associated with late Thienopyridine discontinuation and risk factors for MI after discontinuation are poorly defined. Methods —In the Dual Antiplatelet Therapy (DAPT) Study, after PCI and 12 months of Thienopyridine (clopidogrel or prasugrel) plus aspirin, eligible patients remained on aspirin and were randomized to continued Thienopyridine vs. placebo for 18 months. At 30 months, patients stopped study drug and were observed for 3 months. Cumulative incidence of MI was assessed over 3 months after randomization (months 12-15) and 3 months after study drug discontinuation (months 30-33). The MI hazard for each of these periods was assessed across randomized treatment arms and by DAPT Score values < or ≥2. Results —Among the 11648 randomized patients, the monthly cumulative incidence of MI was lower with continued Thienopyridine vs. placebo at 12-15 months (0.12% vs. 0.37%, p
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rationale and design of the dual antiplatelet therapy study a prospective multicenter randomized double blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronar
American Heart Journal, 2010Co-Authors: Stephen D. Wiviott, Laura Mauri, Dean J Kereiakes, Sharonlise T Normand, David J Cohen, David R Holmes, Sripal BangaloreAbstract:Background Dual antiplatelet therapy with aspirin and Thienopyridines (clopidogrel or prasugrel) is required after placement of coronary stents to prevent thrombotic complications. Although current clinical practice guidelines recommend 12-month treatment after drug-eluting stent placement, even longer durations may prevent thrombotic events. Study Design The Dual Antiplatelet Therapy (DAPT) Study is comparing the benefits and risks of 12 versus 30 months of dual antiplatelet therapy in preventing stent thrombosis or major adverse cardiovascular and cerebrovascular events in subjects undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery obstructive lesions. The DAPT Study is a multicenter, international, randomized, double-blind, placebo-controlled trial that will enroll 15,245 subjects treated with drug-eluting stent (DES) and 5,400 subjects treated with bare-metal stents (BMS). All subjects will receive 12 months of open-label Thienopyridine treatment in addition to aspirin. After 12 months, subjects who are free from death, myocardial infarction, or stroke (MACCE), repeat revascularization, and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events will be randomized to receive either 18 additional months of Thienopyridine (clopidogrel or prasugrel) (30 month DAPT arm) or placebo (12 month DAPT arm) plus aspirin. Coprimary end points are MACCE and stent thrombosis. The primary safety end point is GUSTO moderate or severe bleeding. Conclusions This randomized trial is designed to define the relative safety and effectiveness of 12 versus 30 months of dual antiplatelet therapy across the broad spectrum of patients receiving coronary stents.