Vorapaxar in patients with coronary artery bypass grafting: Findings from the TRA 2°P-TIMI 50 trial

Kosova, Ethan; Bonaca, Marc P.; Dellborg, Mikael; He, Ping; Ophuis, Ton Oude; Scirica, Benjamin M.; Tendera, Michał; Théroux, Pierre; Braunwald, Eugene; Morrow, David A.

doi:10.1177/2048872616644910

Cited by 8 publications

(6 citation statements)

References 32 publications

(29 reference statements)

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“…Several datasets provide examples of the high risk of MACE in revascularized versus non-revascularized patients (e.g. the CAPRIE 61,62 and TRA 2°P-TIMI 50 63 trials). Furthermore, a large database analysis demonstrated that the risk of operative mortality was doubled in patients who required a second coronary artery bypass grafting (CABG) procedure compared with those who required a first-time CABG procedure.…”

Section: Revascularizationmentioning

confidence: 99%

The myth of ‘stable’ coronary artery disease

et al. 2019

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Patients with known cardiovascular (CV) disease who have not suffered a recent acute event are often referred to as having 'stable coronary artery disease (CAD)'. The concept of 'stable' CAD is misleading for two key reasons: the continuing risks of CV events over the longer term, and the diverse but powerful spectrum of risk characteristics. The risks of CV events are frequently underestimated and occur despite current standards of care for secondary prevention, including lifestyle changes, optimal medical therapy, myocardial revascularization, and use of antiplatelet agents to limit thrombosis. In dispelling the myth of 'stable' CAD, we explore the pathophysiology of the disease and the relative contribution of plaque and systemic factors to CV events. A broader concept of the vulnerable patient, not just the 'vulnerable' plaque, takes into account the diversity and future risks of atherothrombotic events. We also evaluate new and ongoing research into medical therapies aimed at further reducing the risks of CV events in patients with chronic but not 'stable' atherothrombotic disease.

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Section: Revascularizationmentioning

confidence: 99%

The myth of ‘stable’ coronary artery disease

et al. 2019

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“…Among patients qualified on the basis of MI or PAD without history of TIA/stroke, a total of 2942 patients had a history of CABG prior to randomization and 367 patients underwent CABG during the investigation. 73 In the group of patients with a prior CABG, vorapaxar significantly reduced the risk of cardiovascular death, MI, or stroke (11.9% vs 15.6%, HR: 0.71, 95% CI: 0.58-0.88, P = .001). Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate/severe bleeding was significantly increased with vorapaxar in patients with a prior CABG (HR: 1.87, 95% CI: 1.28-2.72, P = .001).…”

Section: Additional Cohort Analysismentioning

confidence: 88%

“…However, there was no increase in fatal bleeding, reoperations to control bleeding, or ICH in patients with CABG who received vorapaxar within the 7 days preceding operation. 73…”

Section: Additional Cohort Analysismentioning

confidence: 99%

Role for Thrombin Receptor Antagonism With Vorapaxar in Secondary Prevention of Atherothrombotic Events: From Bench to Bedside

Moon

Franchi

Rollini

et al. 2017

J Cardiovasc Pharmacol Ther

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In spite of treatment with the current standard of care antiplatelet regimens including dual antiplatelet therapy, recurrence rates of ischemic events remain elevated for high-risk patients with atherosclerotic disease. This may be in part attributed to the fact that other key platelet activation pathways remain uninhibited and can thus continue to trigger platelet activation and lead to thrombotic complications. Thrombin is a powerful inducer of platelet activation and mediates its effects directly on platelets through protease activator receptors (PARs), particularly the PAR-1 subtype, making PAR-1 inhibition an attractive approach for reducing atherothrombotic events. These observations have led to the development of several PAR-1 antagonists. Vorapaxar is a direct inhibitor of PAR-1 and the only agent of this class approved for the prevention of recurrent ischemic events in patients with prior myocardial infarction or peripheral artery disease. In the present manuscript, we present a review of the pathophysiologic role of thrombin on thrombotic complications, the impact of vorapaxar on outcomes, including the most recent updates deriving from clinical trials, as well as future perspectives in the field.

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“…Secondary analyses from TRA 2°P-TIMI 50 and the TRACER trials indicated that PAD and CABG patients are potential groups in which further investigation of vorapaxar is warranted. 22 It is likely that the benefit of using vorapaxar as an add-on to DAPT would be more pronounced among patients with coexistent thrombo-inflammatory comorbidities, for example, person with diabetes. In OPTIMUS-5 study, the use of add-on vorapaxar to aspirin and clopidogrel therapy reduced platelet-mediated thrombogenicity and aspirin withdrawal led to an increase in platelet-mediated thrombogenicity.…”

Section: Discussionmentioning

confidence: 99%

“…21 In another subanalysis, among patients with prior CABG vorapaxar significantly reduced the risk of recurrent major CV events and bleeding was found to be similar as the overall TRA 2°P-TIMI 50 trial population. 22 Xu et al 23 further subdivided the TRA 2°P-TIMI 50 trial population according to age and weight. Their subanalysis concluded that the younger patients had reduction in vascular events and improved net clinical outcomes irrespective of body weight.…”

Section: Clinical Efficacy and Fda Approvalmentioning

confidence: 99%

Improving Outcomes in Cardiovascular Diseases: A Review on Vorapaxar

Chaudhary

Mohananey

Sharma

et al. 2021

Cardiology in Review

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Antiplatelet agents are the standard of practice in the management of atherosclerosis and acute coronary syndrome. In contrast to the available antiplatelet agents, vorapaxar represents a novel mechanism of action. It is an antagonist of the platelet protease-activated receptor-1 and inhibits thrombin-induced and thrombin receptor agonist peptide-induced platelet aggregation. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) trial led to the approval of vorapaxar by the Food and Drug Administration and European Medicines Agency for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or peripheral arterial disease. TRA 2°P-TIMI 50 trial showed that the use of vorapaxar (2.5 mg once/daily) in addition to standard dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor was effective in the secondary prevention of recurrent thrombotic events among patients with previous atherothrombosis, particularly in patients with prior MI; at the expense of an increase in major bleeding. Another recently published Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y12 Receptor Inhibitors Prasugrel and Ticagrelor (VORA-PRATIC) study showed that among post-MI patients treated with potent P2Y12 inhibitors (prasugrel or ticagrelor), vorapaxar reduced platelet-driven global thrombogenicity, an effect that persisted, albeit attenuated, in the absence of aspirin. The current review summarizes an up-to-date literature on pharmacokinetics, pharmacodynamics, and clinical efficacy of vorapaxar and proposes future directions of research.

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Vorapaxar in patients with coronary artery bypass grafting: Findings from the TRA 2°P-TIMI 50 trial

Abstract: In patients with a prior CABG, vorapaxar significantly reduced the risk of recurrent major cardiovascular events. In patients undergoing CABG while receiving vorapaxar, bleeding risk appeared similar to that seen in the overall trial population.

Cited by 8 publications

References 32 publications

The myth of ‘stable’ coronary artery disease

The myth of ‘stable’ coronary artery disease

Role for Thrombin Receptor Antagonism With Vorapaxar in Secondary Prevention of Atherothrombotic Events: From Bench to Bedside

Improving Outcomes in Cardiovascular Diseases: A Review on Vorapaxar

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