Vorapaxar (Zontivity—Merck Sharp & Dohme), the first in a new class of drug called a protease-activated receptor-1 (PAR-1) antagonist, has received FDA approval. The drug reduces the risk of heart attack, stroke, cardiovascular death, and need for procedures to restore the blood flow to the heart in patients with a history of heart attack or peripheral arterial disease. Vorapaxar (Zontivity—Merck Sharp & Dohme), the first in a new class of drug called a protease-activated receptor-1 (PAR-1) antagonist, has received FDA approval. The drug reduces the risk of heart attack, stroke, cardiovascular death, and need for procedures to restore the blood flow to the heart in patients with a history of heart attack or peripheral arterial disease. Vorapaxar inhibits the PAR-1 pathway, the primary receptor for thrombin, considered the most potent activator of platelets. This additional pathway is not targeted by aspirin or other antiplatelet agents such as clopidogrel (Plavix—Bristol-Myers Squibb).EfficacyApproval was based on a pivotal clinical trial that included 26,449 participants and was one of the largest secondary prevention studies of an antiplatelet medication, according to the manufacturer’s news release. The trial demonstrated vorapaxar’s significant benefit when used with aspirin and/or clopidogrel versus use of aspirin and/ or clopidogrel alone.Participants were treated with either vorapaxar added to aspirin and clopidogrel or placebo. Compared with patients receiving placebo, the vorapaxar group showed a significant 17% relative risk reduction over the 3 years of the study for the combined events of heart attack, stroke, cardiovascular death, and urgent procedures to improve blood flow to the heart (10.1% for the vorapaxar group compared with 11.8% for the placebo group).The treatment benefit was persistent over the course of the study and was not dependent on the elapsed time from prior heart attack to randomization. Patients were followed for up to 4 years, with a median follow-up of 2.5 years.For the key secondary composite efficacy endpoint of cardiovascular death, heart attack, and stroke alone, vorapaxar produced a significant 20% relative risk reduction: 7.9% versus 9.5% for placebo. These results were driven by an 18% relative risk reduction in heart attack (5.4% vs. 6.4% for placebo) and a 33% relative risk reduction in first stroke (1.2% vs. 1.6% for placebo).Bleeding riskLike other drugs that inhibit blood clotting, vorapaxar increases the risk of bleeding, including life-threatening and fatal bleeding, the trials showed. Bleeding is the most commonly reported adverse reaction in people taking vorapaxar. Vorapaxar must not be used in patients who have had a stroke, transient ischemic attack, or bleeding in the head, because the risk of bleeding in the head is too great. The drug’s prescribing information includes a boxed warning to alert health professionals about this risk.Patient counselingAdvise patients to read the Medication Guide. Summarize the benefits and potential adverse effects, including that patients may bleed and bruise more easily when taking vorapaxar. Tell patients to take vorapaxar exactly as prescribed and not to discontinue the drug without a discussion with the prescribing physician. Advise patients to inform their physician of any unanticipated, prolonged, or excessive bleeding or blood in their stool or urine, and to provide a list of prescription and OTC medications and dietary supplements they are taking, as these may affect their bleeding risk. Patients should inform their physician or dentist that they are taking vorapraxar before any dental or medical procedure.Vorapaxar (Zontivity)Manufacturer: Merck Sharp & DohmeDrug class: Protease-activated receptor-1 antagonistIndication: Reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial diseaseDosage: One 2.08-mg tablet once daily, with or without food■Vorapaxar should be used with daily aspirin and/or clopidogrel according to their indications or standard of care.■Vorapaxar increases the risk of bleeding in proportion to the patient’s underlying bleeding risk. Health professionals should consider the underlying risk of bleeding before initiating vorapaxar. General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, and history of bleeding disorders. There is no known treatment to reverse the antiplatelet effect of the drug.Of note: Use of certain other medications while taking vorapaxar—for example, anticoagulants, fibrinolytic therapy, chronic NSAIDs, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors—increases the risk of bleeding. Concomitant use of warfarin or other anticoagulants also should be avoided.Vorapaxar will be available in the third quarter of 2014, according to Merck Sharp & Dohme. Vorapaxar inhibits the PAR-1 pathway, the primary receptor for thrombin, considered the most potent activator of platelets. This additional pathway is not targeted by aspirin or other antiplatelet agents such as clopidogrel (Plavix—Bristol-Myers Squibb). EfficacyApproval was based on a pivotal clinical trial that included 26,449 participants and was one of the largest secondary prevention studies of an antiplatelet medication, according to the manufacturer’s news release. The trial demonstrated vorapaxar’s significant benefit when used with aspirin and/or clopidogrel versus use of aspirin and/ or clopidogrel alone.Participants were treated with either vorapaxar added to aspirin and clopidogrel or placebo. Compared with patients receiving placebo, the vorapaxar group showed a significant 17% relative risk reduction over the 3 years of the study for the combined events of heart attack, stroke, cardiovascular death, and urgent procedures to improve blood flow to the heart (10.1% for the vorapaxar group compared with 11.8% for the placebo group).The treatment benefit was persistent over the course of the study and was not dependent on the elapsed time from prior heart attack to randomization. Patients were followed for up to 4 years, with a median follow-up of 2.5 years.For the key secondary composite efficacy endpoint of cardiovascular death, heart attack, and stroke alone, vorapaxar produced a significant 20% relative risk reduction: 7.9% versus 9.5% for placebo. These results were driven by an 18% relative risk reduction in heart attack (5.4% vs. 6.4% for placebo) and a 33% relative risk reduction in first stroke (1.2% vs. 1.6% for placebo). Approval was based on a pivotal clinical trial that included 26,449 participants and was one of the largest secondary prevention studies of an antiplatelet medication, according to the manufacturer’s news release. The trial demonstrated vorapaxar’s significant benefit when used with aspirin and/or clopidogrel versus use of aspirin and/ or clopidogrel alone. Participants were treated with either vorapaxar added to aspirin and clopidogrel or placebo. Compared with patients receiving placebo, the vorapaxar group showed a significant 17% relative risk reduction over the 3 years of the study for the combined events of heart attack, stroke, cardiovascular death, and urgent procedures to improve blood flow to the heart (10.1% for the vorapaxar group compared with 11.8% for the placebo group). The treatment benefit was persistent over the course of the study and was not dependent on the elapsed time from prior heart attack to randomization. Patients were followed for up to 4 years, with a median follow-up of 2.5 years. For the key secondary composite efficacy endpoint of cardiovascular death, heart attack, and stroke alone, vorapaxar produced a significant 20% relative risk reduction: 7.9% versus 9.5% for placebo. These results were driven by an 18% relative risk reduction in heart attack (5.4% vs. 6.4% for placebo) and a 33% relative risk reduction in first stroke (1.2% vs. 1.6% for placebo). Bleeding riskLike other drugs that inhibit blood clotting, vorapaxar increases the risk of bleeding, including life-threatening and fatal bleeding, the trials showed. Bleeding is the most commonly reported adverse reaction in people taking vorapaxar. Vorapaxar must not be used in patients who have had a stroke, transient ischemic attack, or bleeding in the head, because the risk of bleeding in the head is too great. The drug’s prescribing information includes a boxed warning to alert health professionals about this risk.Patient counselingAdvise patients to read the Medication Guide. Summarize the benefits and potential adverse effects, including that patients may bleed and bruise more easily when taking vorapaxar. Tell patients to take vorapaxar exactly as prescribed and not to discontinue the drug without a discussion with the prescribing physician. Advise patients to inform their physician of any unanticipated, prolonged, or excessive bleeding or blood in their stool or urine, and to provide a list of prescription and OTC medications and dietary supplements they are taking, as these may affect their bleeding risk. Patients should inform their physician or dentist that they are taking vorapraxar before any dental or medical procedure.Vorapaxar (Zontivity)Manufacturer: Merck Sharp & DohmeDrug class: Protease-activated receptor-1 antagonistIndication: Reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial diseaseDosage: One 2.08-mg tablet once daily, with or without food■Vorapaxar should be used with daily aspirin and/or clopidogrel according to their indications or standard of care.■Vorapaxar increases the risk of bleeding in proportion to the patient’s underlying bleeding risk. Health professionals should consider the underlying risk of bleeding before initiating vorapaxar. General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, and history of bleeding disorders. There is no known treatment to reverse the antiplatelet effect of the drug.Of note: Use of certain other medications while taking vorapaxar—for example, anticoagulants, fibrinolytic therapy, chronic NSAIDs, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors—increases the risk of bleeding. Concomitant use of warfarin or other anticoagulants also should be avoided.Vorapaxar will be available in the third quarter of 2014, according to Merck Sharp & Dohme. Like other drugs that inhibit blood clotting, vorapaxar increases the risk of bleeding, including life-threatening and fatal bleeding, the trials showed. Bleeding is the most commonly reported adverse reaction in people taking vorapaxar. Vorapaxar must not be used in patients who have had a stroke, transient ischemic attack, or bleeding in the head, because the risk of bleeding in the head is too great. The drug’s prescribing information includes a boxed warning to alert health professionals about this risk. Patient counselingAdvise patients to read the Medication Guide. Summarize the benefits and potential adverse effects, including that patients may bleed and bruise more easily when taking vorapaxar. Tell patients to take vorapaxar exactly as prescribed and not to discontinue the drug without a discussion with the prescribing physician. Advise patients to inform their physician of any unanticipated, prolonged, or excessive bleeding or blood in their stool or urine, and to provide a list of prescription and OTC medications and dietary supplements they are taking, as these may affect their bleeding risk. Patients should inform their physician or dentist that they are taking vorapraxar before any dental or medical procedure. Advise patients to read the Medication Guide. Summarize the benefits and potential adverse effects, including that patients may bleed and bruise more easily when taking vorapaxar. Tell patients to take vorapaxar exactly as prescribed and not to discontinue the drug without a discussion with the prescribing physician. Advise patients to inform their physician of any unanticipated, prolonged, or excessive bleeding or blood in their stool or urine, and to provide a list of prescription and OTC medications and dietary supplements they are taking, as these may affect their bleeding risk. Patients should inform their physician or dentist that they are taking vorapraxar before any dental or medical procedure. Advise patients to read the Medication Guide. Summarize the benefits and potential adverse effects, including that patients may bleed and bruise more easily when taking vorapaxar. Tell patients to take vorapaxar exactly as prescribed and not to discontinue the drug without a discussion with the prescribing physician. Advise patients to inform their physician of any unanticipated, prolonged, or excessive bleeding or blood in their stool or urine, and to provide a list of prescription and OTC medications and dietary supplements they are taking, as these may affect their bleeding risk. Patients should inform their physician or dentist that they are taking vorapraxar before any dental or medical procedure. Vorapaxar (Zontivity)Manufacturer: Merck Sharp & DohmeDrug class: Protease-activated receptor-1 antagonistIndication: Reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial diseaseDosage: One 2.08-mg tablet once daily, with or without food■Vorapaxar should be used with daily aspirin and/or clopidogrel according to their indications or standard of care.■Vorapaxar increases the risk of bleeding in proportion to the patient’s underlying bleeding risk. Health professionals should consider the underlying risk of bleeding before initiating vorapaxar. General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, and history of bleeding disorders. There is no known treatment to reverse the antiplatelet effect of the drug.Of note: Use of certain other medications while taking vorapaxar—for example, anticoagulants, fibrinolytic therapy, chronic NSAIDs, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors—increases the risk of bleeding. Concomitant use of warfarin or other anticoagulants also should be avoided. Manufacturer: Merck Sharp & DohmeDrug class: Protease-activated receptor-1 antagonistIndication: Reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial diseaseDosage: One 2.08-mg tablet once daily, with or without food■Vorapaxar should be used with daily aspirin and/or clopidogrel according to their indications or standard of care.■Vorapaxar increases the risk of bleeding in proportion to the patient’s underlying bleeding risk. Health professionals should consider the underlying risk of bleeding before initiating vorapaxar. General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, and history of bleeding disorders. There is no known treatment to reverse the antiplatelet effect of the drug.Of note: Use of certain other medications while taking vorapaxar—for example, anticoagulants, fibrinolytic therapy, chronic NSAIDs, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors—increases the risk of bleeding. Concomitant use of warfarin or other anticoagulants also should be avoided. Manufacturer: Merck Sharp & Dohme Drug class: Protease-activated receptor-1 antagonist Indication: Reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease Dosage: One 2.08-mg tablet once daily, with or without food■Vorapaxar should be used with daily aspirin and/or clopidogrel according to their indications or standard of care.■Vorapaxar increases the risk of bleeding in proportion to the patient’s underlying bleeding risk. Health professionals should consider the underlying risk of bleeding before initiating vorapaxar. General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, and history of bleeding disorders. There is no known treatment to reverse the antiplatelet effect of the drug. Of note: Use of certain other medications while taking vorapaxar—for example, anticoagulants, fibrinolytic therapy, chronic NSAIDs, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors—increases the risk of bleeding. Concomitant use of warfarin or other anticoagulants also should be avoided. Vorapaxar will be available in the third quarter of 2014, according to Merck Sharp & Dohme.