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SAN DIEGO– A fuller picture of the benefits of vorapaxar for secondary cardiovascular prevention emerged from three separate secondary analyses of the pivotal Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P TIMI-50) trial presented at the annual meeting of the American College of Cardiology.
These new reports provided evidence that vorapaxar (Zontivity), a first-in-class, once-daily thrombin inhibitor with rapid onset and a half-life in excess of 7 days, reduces acute limb ischemia and the need for peripheral revascularization in patients with peripheral arterial disease (PAD), and also that the antiplatelet agent is particularly beneficial in patients with a history of coronary artery bypass graft surgery.
That being said, the three secondary analyses were post hoc and as such are inherently exploratory and hypothesis-generating rather than definitive, the investigators noted.
The Food and Drug Administration approved vorapaxar in May 2014 for the reduction of thrombotic cardiovascular events in patients with a history of MI or in patients with PAD in the absence of a previous stroke or TIA. Marketing approval was based chiefly on the results of the landmark 26,449-patient, double-blind, prospective, multinational TIMI 50 trial. In an analysis of the 20,170 randomized patients without a prior stroke or TIA, vorapaxar at 2.5 mg once daily, when added to standard therapy with aspirin and/or clopidogrel, reduced the 3-year rate of a composite outcome – comprised of cardiovascular death, MI, or stroke – by 20% compared with placebo, with a number-needed-to-treat of 63 (J. Am. Heart Assoc. 2015 [doi: 10.1161/JAHA.114.001505]).
At ACC 15, Dr. Ethan C. Kosova presented a subanalysis involving the 2,942 TIMI 50 participants who had undergone CABG surgery prior to the study. The rationale for taking a closer look at this group is that rates of venous graft occlusion and recurrent ischemic events remain high after CABG surgery, so the efficacy and safety of vorapaxar in this population are of particular interest.
Underscoring the high-risk nature of this population, at baseline the patients with a history of CABG were significantly older and had higher rates of hypertension, dyslipidemia, diabetes, PAD, heart failure, and chronic kidney disease than participants without prior CABG who had no history of stroke or TIA, observed Dr. Kosova of Brigham and Women’s Hospital, Boston.
The 3-year composite event rate of cardiovascular death, MI, or stroke occurred in 11.9% of the 1,471 patients with prior CABG who were randomized to vorapaxar compared with 15.6% of those on placebo. That translates into a 29% relative risk reduction and a number-needed-to-treat of 27, an even stronger result than in the general study population.
Moreover, the clinically relevant composite outcome consisting of cardiovascular death or MI occurred in 10.9% of those on vorapaxar compared with 14.3% of controls, for a 29% relative risk reduction and a number-needed-to-treat of 29, he continued.
The 3-year all-cause mortality was 5.8% in patients with prior CABG who received vorapaxar compared to 8% in those on placebo.
Vorapaxar, which inhibits protease-activated receptor-1 on platelets and vascular endothelium, increased the rate of GUSTO moderate-to-severe bleeding: 6.8% compared with 3.7% in controls.
“Putting together the efficacy and safety data to derive the net clinical outcome – the combined endpoint of all-cause mortality, MI, cerebrovascular accident, and GUSTO severe bleeding – the result was a 28% improvement with vorapaxar compared with placebo,” Dr. Kosova said.
In a separate presentation focused on the 3,787 patients who gained entry into the TIMI 50 trial on the basis of symptomatic PAD, Dr. Antonio Gutierrez reported that acute limb ischemia occurred in 109 of them during the trial. Fifty-four percent of these events were due to acute surgical graft thrombosis, 27% to in situ thrombosis of a native vessel, and lesser numbers were due to thromboembolissm or stent thrombosis.
The 3-year acute limb ischemia rate in patients with baseline PAD was 3.9% with placebo compared to 2.3% with vorapaxar, for a 42% relative risk reduction, according to Dr. Gutierrez of Brigham and Women’s Hospital.
Dr. Ian Gilchrist, also from Brigham and Women’s Hospital, reported that in TIMI 50 participants with a history of PAD, vorapaxar resulted in a 16% reduction in the need for peripheral revascularization procedures for claudication, with rates of 9.4% for vorapaxar and 11.6% for placebo. There was also a statistically significant 41% reduction in the rate of surgical peripheral revascularization procedures, with rates of 4.5% for vorapaxar and 7.7% for placebo.
The TIMI 50 trial was funded by Merck. Drs. Kosova, Gutierrez, and Gilchrist reported having no financial conflicts of interest.
SAN DIEGO– A fuller picture of the benefits of vorapaxar for secondary cardiovascular prevention emerged from three separate secondary analyses of the pivotal Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P TIMI-50) trial presented at the annual meeting of the American College of Cardiology.
These new reports provided evidence that vorapaxar (Zontivity), a first-in-class, once-daily thrombin inhibitor with rapid onset and a half-life in excess of 7 days, reduces acute limb ischemia and the need for peripheral revascularization in patients with peripheral arterial disease (PAD), and also that the antiplatelet agent is particularly beneficial in patients with a history of coronary artery bypass graft surgery.
That being said, the three secondary analyses were post hoc and as such are inherently exploratory and hypothesis-generating rather than definitive, the investigators noted.
The Food and Drug Administration approved vorapaxar in May 2014 for the reduction of thrombotic cardiovascular events in patients with a history of MI or in patients with PAD in the absence of a previous stroke or TIA. Marketing approval was based chiefly on the results of the landmark 26,449-patient, double-blind, prospective, multinational TIMI 50 trial. In an analysis of the 20,170 randomized patients without a prior stroke or TIA, vorapaxar at 2.5 mg once daily, when added to standard therapy with aspirin and/or clopidogrel, reduced the 3-year rate of a composite outcome – comprised of cardiovascular death, MI, or stroke – by 20% compared with placebo, with a number-needed-to-treat of 63 (J. Am. Heart Assoc. 2015 [doi: 10.1161/JAHA.114.001505]).
At ACC 15, Dr. Ethan C. Kosova presented a subanalysis involving the 2,942 TIMI 50 participants who had undergone CABG surgery prior to the study. The rationale for taking a closer look at this group is that rates of venous graft occlusion and recurrent ischemic events remain high after CABG surgery, so the efficacy and safety of vorapaxar in this population are of particular interest.
Underscoring the high-risk nature of this population, at baseline the patients with a history of CABG were significantly older and had higher rates of hypertension, dyslipidemia, diabetes, PAD, heart failure, and chronic kidney disease than participants without prior CABG who had no history of stroke or TIA, observed Dr. Kosova of Brigham and Women’s Hospital, Boston.
The 3-year composite event rate of cardiovascular death, MI, or stroke occurred in 11.9% of the 1,471 patients with prior CABG who were randomized to vorapaxar compared with 15.6% of those on placebo. That translates into a 29% relative risk reduction and a number-needed-to-treat of 27, an even stronger result than in the general study population.
Moreover, the clinically relevant composite outcome consisting of cardiovascular death or MI occurred in 10.9% of those on vorapaxar compared with 14.3% of controls, for a 29% relative risk reduction and a number-needed-to-treat of 29, he continued.
The 3-year all-cause mortality was 5.8% in patients with prior CABG who received vorapaxar compared to 8% in those on placebo.
Vorapaxar, which inhibits protease-activated receptor-1 on platelets and vascular endothelium, increased the rate of GUSTO moderate-to-severe bleeding: 6.8% compared with 3.7% in controls.
“Putting together the efficacy and safety data to derive the net clinical outcome – the combined endpoint of all-cause mortality, MI, cerebrovascular accident, and GUSTO severe bleeding – the result was a 28% improvement with vorapaxar compared with placebo,” Dr. Kosova said.
In a separate presentation focused on the 3,787 patients who gained entry into the TIMI 50 trial on the basis of symptomatic PAD, Dr. Antonio Gutierrez reported that acute limb ischemia occurred in 109 of them during the trial. Fifty-four percent of these events were due to acute surgical graft thrombosis, 27% to in situ thrombosis of a native vessel, and lesser numbers were due to thromboembolissm or stent thrombosis.
The 3-year acute limb ischemia rate in patients with baseline PAD was 3.9% with placebo compared to 2.3% with vorapaxar, for a 42% relative risk reduction, according to Dr. Gutierrez of Brigham and Women’s Hospital.
Dr. Ian Gilchrist, also from Brigham and Women’s Hospital, reported that in TIMI 50 participants with a history of PAD, vorapaxar resulted in a 16% reduction in the need for peripheral revascularization procedures for claudication, with rates of 9.4% for vorapaxar and 11.6% for placebo. There was also a statistically significant 41% reduction in the rate of surgical peripheral revascularization procedures, with rates of 4.5% for vorapaxar and 7.7% for placebo.
The TIMI 50 trial was funded by Merck. Drs. Kosova, Gutierrez, and Gilchrist reported having no financial conflicts of interest.
SAN DIEGO– A fuller picture of the benefits of vorapaxar for secondary cardiovascular prevention emerged from three separate secondary analyses of the pivotal Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P TIMI-50) trial presented at the annual meeting of the American College of Cardiology.
These new reports provided evidence that vorapaxar (Zontivity), a first-in-class, once-daily thrombin inhibitor with rapid onset and a half-life in excess of 7 days, reduces acute limb ischemia and the need for peripheral revascularization in patients with peripheral arterial disease (PAD), and also that the antiplatelet agent is particularly beneficial in patients with a history of coronary artery bypass graft surgery.
That being said, the three secondary analyses were post hoc and as such are inherently exploratory and hypothesis-generating rather than definitive, the investigators noted.
The Food and Drug Administration approved vorapaxar in May 2014 for the reduction of thrombotic cardiovascular events in patients with a history of MI or in patients with PAD in the absence of a previous stroke or TIA. Marketing approval was based chiefly on the results of the landmark 26,449-patient, double-blind, prospective, multinational TIMI 50 trial. In an analysis of the 20,170 randomized patients without a prior stroke or TIA, vorapaxar at 2.5 mg once daily, when added to standard therapy with aspirin and/or clopidogrel, reduced the 3-year rate of a composite outcome – comprised of cardiovascular death, MI, or stroke – by 20% compared with placebo, with a number-needed-to-treat of 63 (J. Am. Heart Assoc. 2015 [doi: 10.1161/JAHA.114.001505]).
At ACC 15, Dr. Ethan C. Kosova presented a subanalysis involving the 2,942 TIMI 50 participants who had undergone CABG surgery prior to the study. The rationale for taking a closer look at this group is that rates of venous graft occlusion and recurrent ischemic events remain high after CABG surgery, so the efficacy and safety of vorapaxar in this population are of particular interest.
Underscoring the high-risk nature of this population, at baseline the patients with a history of CABG were significantly older and had higher rates of hypertension, dyslipidemia, diabetes, PAD, heart failure, and chronic kidney disease than participants without prior CABG who had no history of stroke or TIA, observed Dr. Kosova of Brigham and Women’s Hospital, Boston.
The 3-year composite event rate of cardiovascular death, MI, or stroke occurred in 11.9% of the 1,471 patients with prior CABG who were randomized to vorapaxar compared with 15.6% of those on placebo. That translates into a 29% relative risk reduction and a number-needed-to-treat of 27, an even stronger result than in the general study population.
Moreover, the clinically relevant composite outcome consisting of cardiovascular death or MI occurred in 10.9% of those on vorapaxar compared with 14.3% of controls, for a 29% relative risk reduction and a number-needed-to-treat of 29, he continued.
The 3-year all-cause mortality was 5.8% in patients with prior CABG who received vorapaxar compared to 8% in those on placebo.
Vorapaxar, which inhibits protease-activated receptor-1 on platelets and vascular endothelium, increased the rate of GUSTO moderate-to-severe bleeding: 6.8% compared with 3.7% in controls.
“Putting together the efficacy and safety data to derive the net clinical outcome – the combined endpoint of all-cause mortality, MI, cerebrovascular accident, and GUSTO severe bleeding – the result was a 28% improvement with vorapaxar compared with placebo,” Dr. Kosova said.
In a separate presentation focused on the 3,787 patients who gained entry into the TIMI 50 trial on the basis of symptomatic PAD, Dr. Antonio Gutierrez reported that acute limb ischemia occurred in 109 of them during the trial. Fifty-four percent of these events were due to acute surgical graft thrombosis, 27% to in situ thrombosis of a native vessel, and lesser numbers were due to thromboembolissm or stent thrombosis.
The 3-year acute limb ischemia rate in patients with baseline PAD was 3.9% with placebo compared to 2.3% with vorapaxar, for a 42% relative risk reduction, according to Dr. Gutierrez of Brigham and Women’s Hospital.
Dr. Ian Gilchrist, also from Brigham and Women’s Hospital, reported that in TIMI 50 participants with a history of PAD, vorapaxar resulted in a 16% reduction in the need for peripheral revascularization procedures for claudication, with rates of 9.4% for vorapaxar and 11.6% for placebo. There was also a statistically significant 41% reduction in the rate of surgical peripheral revascularization procedures, with rates of 4.5% for vorapaxar and 7.7% for placebo.
The TIMI 50 trial was funded by Merck. Drs. Kosova, Gutierrez, and Gilchrist reported having no financial conflicts of interest.
AT ACC 15
Key clinical point: Vorapaxar reduced the composite outcome of cardiovascular death, MI, or stroke by 29% compared with placebo in patients with a history of MI and/or peripheral arterial disease and prior coronary artery bypass surgery.
Major finding: The novel antiplatelet agent also reduced acute limb ischemia events by 42% in patients with symptomatic peripheral arterial disease.
Data source: These were findings from post hoc, exploratory analyses of a 26,449-patient, randomized, double-blind pivotal trial of vorapaxar for secondary cardiovascular prevention.
Disclosures: The TRA 2°P TIMI-50 trial was sponsored by Merck. The presenters reported having no financial conflicts.