The CURRENT-OASIS-7 trial missed its primary endpoint but found a benefit for high dose clopidogrel in the large subset of patients who underwent PCI. Results of the trial were presented at the ESC.
The trial randomized 25,087 unstable angina or acute MI patients who were scheduled to undergo angiography within 72 hours of hospital arrival to a high dose regimen (600 mg loading dose of clopidogrel, followed by 150 mg per day for seven days) or the standard regimen (300 mg on the first day followed by 75 mg/day).
At 30 days the primary endpoint, the combined rate of cardiovascular death, MI, and stroke occurred in 4.4% of patients on the standard-dose Plavix compared to 4.2% of patients on the high dose. The difference did not achieve statistical significance.
A little more than two-thirds of the study patients underwent PCI. Among the PCI patients, the risk of stent thrombosis was reduced by 30% and the risk of MI was reduced by 22% in the group that received the high dose group compared to the group that received the standard dose. The high dose group had more major bleeding, but there was no increase in intracerebral or fatal bleeds. No benefit of the higher dose was found in the group of patients who did not have PCI.
In a second randomization, patients received either high-dose (300-325 mg once daily) or low-dose (75-100 mg once daily) aspirin. There were no significant differences in outcome between these two groups.
“What this implies is that the combination of high-dose clopidogrel combined with usual doses of aspirin may be the optimal treatment strategy in PCI patients,” said study chair Salim Yusuf, in a press release from McMaster University issued by the ESC.
Click here to download the CURRENT-OASIS-7 slides.
Note to readers: The following press release was issued by the ESC, which states the following about its press releases:
“This press release accompanies both a presentation and an ESC press conference given at the ESC Congress 2009. Written by the investigator himself/herself, this press release does not necessarily reflect the opinion of the European Society of Cardiology.”
CardioBrief readers may be interested to know that the press release contains no statement that the trial missed its primary endpoint. By contrast, this information is prominently featured in a press release issued by Sanofi Aventis and Bristol-Myers Squibb (click here to download a PDF of the company press release).
Here is the press release from McMaster University issued by the ESC :
Double doses of clopidogrel better than standard doses for heart patients undergoing angioplasty, an international study finds
Barcelona, Spain, 30 August: A landmark international study led by McMaster University researchers found high doses of the blood thinner clopidogrel (Plavix) significantly reduce complications in heart patients undergoing angioplasty to clear blocked arteries.
Angioplasty, also known as percutaneous coronary intervention (PCI), carries with it the risk of a heart attack and stent thrombosis, the formation of life-threatening blood clots inside stents that prop open narrowed arteries.
An international group of researchers from 39 countries found patients undergoing angioplasty benefited from a more aggressive antiplatelet regimen in which they were given double the standard dose for about a week.
“The superiority of the high dose clopidogrel regimen in reducing stent thrombosis and related heart attacks in those undergoing PCI is clear in our study and will be of great relevance to interventional cardiologists,” said interventional cardiologist Dr. Shamir R. Mehta, an associate professor of medicine in the Michael G. DeGroote School of Medicine at McMaster University and the principal investigator of the trial.
The investigators simultaneously evaluated the optimal dose of aspirin and found that 300 mg of aspirin resulted in similar outcomes to 100 mg of aspirin and was not associated with higher rates of bleeding. There was also no benefit of the higher dose of clopidogrel in the 7,000 individuals not undergoing PCI.
Mehta presented results of the CURRENT-OASIS 7 (Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS) trial at the annual European Society of Cardiology Congress in Barcelona, Spain, where the prevention of heart disease is the focus of this year’s presentations by researchers from around the world.
CURRENT-OASIS 7 is a Phase III, multicentre, multinational, randomized, parallel-group trial which enrolled 25,087 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, about 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 a month. High-dose patients received 600 mg of clopidogrel on the first day – as early as possible before angioplasty – 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 more intensive high-dose 600 mg clopidogrel regimen reduced the risk of stent thrombosis by an incremental 30 per cent and the risk of heart attack by a further 22 per cent over and above the standard regimen in 68 per cent of patients (17,232 out of 25,087) undergoing angioplasty. There was an increase in major bleeding, but no increase in bleeds into the brain or those that were fatal.
“What this implies is that the combination of high-dose clopidogrel combined with usual doses of aspirin may be the optimal treatment strategy in PCI patients,” said Dr. Salim Yusuf, chair of the CURRENT-OASIS 7 steering committee, a professor of medicine in the Michael G. DeGroote School of Medicine and director of the Population Health Research Institute at McMaster University and Hamilton Health Sciences.
The CURRENT-OASIS 7 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.
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