Double-Dose Clopidogrel Reduces Risk Of Death, Heart Attack Or Stroke In Patients Undergoing Angioplasty

Main Category: Cardiovascular / Cardiology
Also Included In: Vascular;  Heart Disease;  Stroke
Article Date: 03 Sep 2010 - 3:00 PDT

email to a friend   printer friendly   opinions  

A double-dose of the anti-clotting treatment clopidogrel, also known as Plavix, significantly reduces complications in heart patients undergoing angioplasty to clear blocked arteries.

Shamir R. Mehta, an interventional cardiologist and associate professor of medicine of the Michael G. DeGroote School of Medicine, led a landmark international study that found patients undergoing angioplasty benefited from a more aggressive antiplatelet regimen in which they received a double dose of the blood thinner for about a week.

Findings from the CURRENT-OASIS 7 (Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS) trial are being published simultaneously today in the online editions of the medical journals The Lancet and the Journal of Medicine. The results were also previously presented to the European Society of Cardiology Congress.

Clopidogrel and aspirin are widely used for patients with acute coronary syndrome who are undergoing angioplasty. In the CURRENT-OASIS 7 study, the authors compared various doses of clopidogrel and aspirin in preventing major cardiovascular events and stent thrombosis (narrowing of the inserted stent) in more than 17,000 patients undergoing angioplasty.

Although there was no significant difference between the two doses of clopidogrel in the overall population of patients, the authors found using a double-dose of clopidogrel reduced the risk of cardiovascular death, heart attack, or stroke by 14 per cent in the target population of over 17,000 patients undergoing angioplasty compared to the conventional dose. The double dose of clopidogrel also reduced stent thrombosis by 46 per cent in the target population compared to the standard dose.

Although risk of major bleeding increased 40 per cent with double-dosing, the risk of bleeding that was intracranial, fatal, or related to coronary artery bypass graft surgery did not increase.

Mehta also led investigators in simultaneously evaluating the optimal dose of aspirin and found that a higher dose of aspirin (300 to 325 mg) resulted in similar outcomes to a lower dose of aspirin (75 to 100 mg) and was not associated with higher rates of bleeding.

"Our findings show that a seven-day, double-dose of clopidogrel is more effective than the standard dose regimen in reduction of heart attacks and stent thrombosis in patients undergoing angioplasty," Mehta said. "Daily high-dose aspirin did not significantly differ from low-dose aspirin."

The study authors concluded that a double-dose regimen of clopidogrel can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early angioplasty (also known as percutaneous coronary intervention, or PCI). In those patients who are unlikely to undergo angioplasty, the standard dose of clopidogrel should be used.

CURRENT-OASIS 7 is a phase three, multicentre, multinational, randomized, parallel-group trial which enrolled about 25,000 patients scheduled to undergo angiography within 72 hours of arriving in a hospital emergency department or coronary care unit with unstable angina or a heart attack. Of these, more than 17,000 were suitable for angioplasty and underwent the procedure.

As soon as possible after their arrival, patients were randomly assigned to the high dose or standard dose of clopidogrel for seven days, then both groups received the standard dose. High-dose patients received 600 mg of clopidogrel on the first day - as early as possible after arrival to hospital - then 150 mg once a day for seven days, followed 75 mg daily for the remainder of the month. Those patients on the standard regimen received 300 mg on day one, followed by 75 mg once a day until day 30. Patients in both groups were randomly assigned to aspirin, either high-dose (300-325 mg once daily) or low-dose regimen (75-100 mg once daily).

The CURRENT-OASIS 7 involved 597 hospitals in 39 countries and is largest such trial ever performed in a broad range of patients with acute coronary syndromes.

The study was sponsored by Sanofi-Aventis and Bristol-Myers Squibb but was independently conducted by the Population Health Research Institute along with an international steering committee.

Source:
McMaster University

• Additional
• References
• Citations