FDA Approves Prasugrel as Antiplatelet Agent

Last month, the Food and Drug Administration approved the antiplatelet agent prasugrel to reduce the risk of clotting during percutaneous coronary intervention, with labeling that includes a boxed warning about the potential for significant and sometimes fatal bleeding associated with the drug.

Specifically, prasugrel, a thienopyridine, was approved for reducing thrombotic cardiovascular events, including stent thrombosis, in the following patients with acute coronary syndrome who will be managed with percutaneous coronary intervention (PCI): those with unstable angina or non-ST elevation myocardial infarction (NSTEMI) and those with ST-elevation MI (STEMI), when managed with either primary or delayed PCI.

In the pivotal phase III TRITON-TIMI 38 trial of 13,608 patients with a threatened or actual myocardial infarction who were about to undergo angioplasty, prasugrel (Effient) was more effective than clopidogrel (Plavix) at reducing subsequent nonfatal myocardial infarction (9.1% vs. 7%). Patients with a history of stroke were more likely to have a repeat stroke on prasugrel, however. There was also a greater risk of significant bleeding events with prasugrel.

Because of that higher risk, prasugrel's labeling includes a boxed warning about the bleeding, which advises against using the drug in patients with active pathological bleeding, a history of transient ischemic attacks or stroke, or urgent need for surgery, including coronary artery bypass graft surgery.

“Effient offers physicians an alternative treatment for preventing dangerous blood clots from forming and causing a heart attack or stroke during or after an angioplasty procedure,” Dr. John Jenkins, director of the Office of New Drugs at the FDA's Center for Drug Evaluation and Research, said in a statement. “Physicians must carefully weigh the potential benefits and risks of Effient as they decide which patients should receive the drug.”

In February 2009, the FDA's Cardiovascular and Renal Drugs Advisory Committee voted unanimously that the drug's benefits outweighed its risk and backed prasugrel's approval. The drug was developed by Eli Lilly & Co. and Daiichi Sankyo Inc., and is available in 5-mg and 10-mg tablets. Treatment is started with a 60-mg single oral loading dose, followed by 10 mg once daily. The label says that 5 mg per day should be considered for patients who weigh less than 60 kg and advises that patients should also take 75–325 mg of aspirin a day.

Because of the large number of patients now receiving stents, “achieving a consistent and effective level of platelet inhibition is paramount to preventing stent thrombosis and myocardial ischemic events,” Dr. Curtiss Stinis, an interventional cardiologist at Scripps Clinic and Research Foundation, La Jolla, Calif., said in an interview. Noting that the effectiveness of clopidogrel can vary widely across individual patients, and that some patients do not have an adequate response to clopidogrel, despite increasing the dose, he said that for such patients, “prasugrel offers an alternative.” Dr. Stinis is director of peripheral interventions in the division of cardiovascular diseases at the Scripps Foundation.

In his own practice, Dr. Stinis said he expects that prasugrel will “definitely be useful” in patients who had had an inadequate response to clopidogrel by blood test assay, or who have already had an episode of stent thrombosis. He added, however, that it was likely that he would still routinely prescribe clopidogrel to patients who have an adequate response to that drug, and to elderly patients or patients with a previous stroke who are likely at a higher risk of bleeding with prasugrel.

Dr. Stinis said that he has been a speaker for Eli Lilly in the past.

Alicia Ault contributed to this report.

Last month, the Food and Drug Administration approved the antiplatelet agent prasugrel to reduce the risk of clotting during percutaneous coronary intervention, with labeling that includes a boxed warning about the potential for significant and sometimes fatal bleeding associated with the drug.

Specifically, prasugrel, a thienopyridine, was approved for reducing thrombotic cardiovascular events, including stent thrombosis, in the following patients with acute coronary syndrome who will be managed with percutaneous coronary intervention (PCI): those with unstable angina or non-ST elevation myocardial infarction (NSTEMI) and those with ST-elevation MI (STEMI), when managed with either primary or delayed PCI.

In the pivotal phase III TRITON-TIMI 38 trial of 13,608 patients with a threatened or actual myocardial infarction who were about to undergo angioplasty, prasugrel (Effient) was more effective than clopidogrel (Plavix) at reducing subsequent nonfatal myocardial infarction (9.1% vs. 7%). Patients with a history of stroke were more likely to have a repeat stroke on prasugrel, however. There was also a greater risk of significant bleeding events with prasugrel.

Because of that higher risk, prasugrel's labeling includes a boxed warning about the bleeding, which advises against using the drug in patients with active pathological bleeding, a history of transient ischemic attacks or stroke, or urgent need for surgery, including coronary artery bypass graft surgery.

“Effient offers physicians an alternative treatment for preventing dangerous blood clots from forming and causing a heart attack or stroke during or after an angioplasty procedure,” Dr. John Jenkins, director of the Office of New Drugs at the FDA's Center for Drug Evaluation and Research, said in a statement. “Physicians must carefully weigh the potential benefits and risks of Effient as they decide which patients should receive the drug.”

In February 2009, the FDA's Cardiovascular and Renal Drugs Advisory Committee voted unanimously that the drug's benefits outweighed its risk and backed prasugrel's approval. The drug was developed by Eli Lilly & Co. and Daiichi Sankyo Inc., and is available in 5-mg and 10-mg tablets. Treatment is started with a 60-mg single oral loading dose, followed by 10 mg once daily. The label says that 5 mg per day should be considered for patients who weigh less than 60 kg and advises that patients should also take 75–325 mg of aspirin a day.

Because of the large number of patients now receiving stents, “achieving a consistent and effective level of platelet inhibition is paramount to preventing stent thrombosis and myocardial ischemic events,” Dr. Curtiss Stinis, an interventional cardiologist at Scripps Clinic and Research Foundation, La Jolla, Calif., said in an interview. Noting that the effectiveness of clopidogrel can vary widely across individual patients, and that some patients do not have an adequate response to clopidogrel, despite increasing the dose, he said that for such patients, “prasugrel offers an alternative.” Dr. Stinis is director of peripheral interventions in the division of cardiovascular diseases at the Scripps Foundation.

In his own practice, Dr. Stinis said he expects that prasugrel will “definitely be useful” in patients who had had an inadequate response to clopidogrel by blood test assay, or who have already had an episode of stent thrombosis. He added, however, that it was likely that he would still routinely prescribe clopidogrel to patients who have an adequate response to that drug, and to elderly patients or patients with a previous stroke who are likely at a higher risk of bleeding with prasugrel.

Dr. Stinis said that he has been a speaker for Eli Lilly in the past.

Alicia Ault contributed to this report.

Last month, the Food and Drug Administration approved the antiplatelet agent prasugrel to reduce the risk of clotting during percutaneous coronary intervention, with labeling that includes a boxed warning about the potential for significant and sometimes fatal bleeding associated with the drug.

Specifically, prasugrel, a thienopyridine, was approved for reducing thrombotic cardiovascular events, including stent thrombosis, in the following patients with acute coronary syndrome who will be managed with percutaneous coronary intervention (PCI): those with unstable angina or non-ST elevation myocardial infarction (NSTEMI) and those with ST-elevation MI (STEMI), when managed with either primary or delayed PCI.

In the pivotal phase III TRITON-TIMI 38 trial of 13,608 patients with a threatened or actual myocardial infarction who were about to undergo angioplasty, prasugrel (Effient) was more effective than clopidogrel (Plavix) at reducing subsequent nonfatal myocardial infarction (9.1% vs. 7%). Patients with a history of stroke were more likely to have a repeat stroke on prasugrel, however. There was also a greater risk of significant bleeding events with prasugrel.

Because of that higher risk, prasugrel's labeling includes a boxed warning about the bleeding, which advises against using the drug in patients with active pathological bleeding, a history of transient ischemic attacks or stroke, or urgent need for surgery, including coronary artery bypass graft surgery.

“Effient offers physicians an alternative treatment for preventing dangerous blood clots from forming and causing a heart attack or stroke during or after an angioplasty procedure,” Dr. John Jenkins, director of the Office of New Drugs at the FDA's Center for Drug Evaluation and Research, said in a statement. “Physicians must carefully weigh the potential benefits and risks of Effient as they decide which patients should receive the drug.”

In February 2009, the FDA's Cardiovascular and Renal Drugs Advisory Committee voted unanimously that the drug's benefits outweighed its risk and backed prasugrel's approval. The drug was developed by Eli Lilly & Co. and Daiichi Sankyo Inc., and is available in 5-mg and 10-mg tablets. Treatment is started with a 60-mg single oral loading dose, followed by 10 mg once daily. The label says that 5 mg per day should be considered for patients who weigh less than 60 kg and advises that patients should also take 75–325 mg of aspirin a day.

Because of the large number of patients now receiving stents, “achieving a consistent and effective level of platelet inhibition is paramount to preventing stent thrombosis and myocardial ischemic events,” Dr. Curtiss Stinis, an interventional cardiologist at Scripps Clinic and Research Foundation, La Jolla, Calif., said in an interview. Noting that the effectiveness of clopidogrel can vary widely across individual patients, and that some patients do not have an adequate response to clopidogrel, despite increasing the dose, he said that for such patients, “prasugrel offers an alternative.” Dr. Stinis is director of peripheral interventions in the division of cardiovascular diseases at the Scripps Foundation.

In his own practice, Dr. Stinis said he expects that prasugrel will “definitely be useful” in patients who had had an inadequate response to clopidogrel by blood test assay, or who have already had an episode of stent thrombosis. He added, however, that it was likely that he would still routinely prescribe clopidogrel to patients who have an adequate response to that drug, and to elderly patients or patients with a previous stroke who are likely at a higher risk of bleeding with prasugrel.

Dr. Stinis said that he has been a speaker for Eli Lilly in the past.

Alicia Ault contributed to this report.