Vorapaxar in patients with peripheral artery disease and acute coronary syndrome: Insights from Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER)

Jones, W. Schuyler; Tricoci, Pierluigi; Huang, Zhen; Moliterno, David J.; Harrington, Robert A.; Sinnaeve, Peter; Strony, John; Werf, Frans Van de; White, Harvey D.; Held, Claes; Armstrong, Paul W.; Aylward, Philip E.; Chen, Edmond; Patel, Manesh R.; Mahaffey, Kenneth W.

doi:10.1016/j.ahj.2014.06.017

Cited by 45 publications

(23 citation statements)

References 21 publications

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“…The agent is metabolised in the liver through CYP enzyme pathways and has an estimated half-life of 126-269 h. The compound was tested in combination with ASA and/or clopidogrel in RCTs. The TRACER trial was a phase III, prospective, randomised, double-blind, placebo controlled secondary prevention trial evaluating the early administration of a LD of vorapaxar 40 mg, followed by 2.5 mg/day compared with placebo for one year in approximately 13,000 patients with recent NSTEMI (169). The TRA2P-TIMI 50 trial was a phase III, randomised, double-blind, placebo-controlled study enrolling 26,447 patients with a previous stroke, MI, or PAD assessing vorapaxar 2.5 mg/day compared with placebo, in addition to ASA and/ or clopidogrel for one year for secondary prevention (170).…”

Section: Par-1 Antagonists Vorapaxar (Sch 530348)mentioning

confidence: 99%

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

Müller¹,

Chatterjee²,

Rath³

et al. 2015

Thromb Haemost

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SummaryPlatelets play a pivotal role in chronic inflammation leading to progression of atherosclerosis and acute coronary events. Recent discoveries on novel mechanisms and platelet-dependent inflammatory targets underpin the role of platelets to maintain a chronic inflammatory condition in cardiovascular disease. There is strong and clinically relevant crosslink between chronic inflammation and platelet activation. Antiplatelet therapy is a cornerstone in the prevention and treatment of acute cardiovascular events. The benefit of antiplatelet agents has mainly been attributed to their direct anti-aggregatory impact. Some anti-inflammatory off-target effects have also been described. However, it is unclear whether these effects are secondary due to inhibition of platelet activation or are caused by direct distinct mechanisms interfering with inflammatory pathways. This article will highlight novel platelet associated targets that contribute to inflammation in cardiovascular disease and elucidate mechanisms by which currently available antiplatelet agents evolve anti-inflammatory capacities, in particular by carving out the differential mechanisms directly or indirectly affecting platelet mediated inflammation. It will further illustrate the prognostic impact of antiplatelet therapies by reducing inflammatory marker release in recent cardiovascular trials.

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Section: Par-1 Antagonists Vorapaxar (Sch 530348)mentioning

confidence: 99%

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

Müller¹,

Chatterjee²,

Rath³

et al. 2015

Thromb Haemost

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“…Two recent secondary analyses of vorapaxar in patients with PAD have failed to demonstrate significant reductions in cardiovascular endpoints; however, vorapaxar has been associated with decreased incidence of acute limb ischemia and peripheral revascularization [38,39]. As a result, future investigations of vorapaxar may focus on acute limb ischemia and lower extremity revascularization.…”

Section: Novel Antiplatelet Agentsmentioning

confidence: 97%

Limb Ischemia: Cardiovascular Diagnosis and Management from Head to Toe

2015

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Peripheral arterial disease (PAD) affects an estimated 27 million people in Europe and North America. Limb ischemia, defined as ischemic rest pain, ischemic ulcerations, or ischemic gangrene, represents the most severe manifestation of PAD and is associated with significant cardiovascular and limb morbidity and mortality. Critical limb ischemia (CLI), defined as limb ischemia symptoms for greater than 2 weeks, is characterized by a cascade of hemodynamically significant macrovascular atherosclerotic obstruction and microvascular changes culminating in decreased muscle perfusion, disrupted muscle energy metabolism, and inflammation. In contrast, acute limb ischemia (ALI) is defined as limb ischemia symptoms characterized by sudden onset of less than 2 weeks duration resulting in hemodynamically compromised limb perfusion. Diagnosis of both ALI and CLI is dependent on history, physical examination, and a combination of anatomic and hemodynamic assessment of the limb. Given that the risk factors for ALI and CLI overlap with risk factors for atherosclerotic coronary and neurovascular disease, the management of limb ischemia is focused on both endovascular or surgical limb salvage and cardiovascular risk factor control. Despite advancements in endovascular and surgical revascularization techniques, limb morbidity remains high; clinical trials of angiogenic and cell-based therapies are ongoing. Cardiovascular risk reduction in patients with limb ischemia also remains suboptimal and future studies will focus on novel antiplatelet agents.

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“…In a subgroup analysis of PAD patients, no benefit was observed with dual antiplatelet therapy. 25 Vorapaxar, a novel protease-activated receptor 1 (PAR-1) inhibitor that targets thrombin-induced platelet activitaion, 26 28 There have been no trials comparing vorapaxar alone with any of the other antiplatelet medications available.…”

Section: Antiplatelet Therapymentioning

confidence: 99%