April 2, 2009 - New findings from a landmark investigational study demonstrated that, for patients with atrial fibrillation who were at increased risk for stroke and could not take an oral anticoagulant (OAC) medication, taking Plavix (clopidogrel bisulfate) in addition to aspirin significantly reduced major vascular events by 11 percent over aspirin alone, at a median of 3.6 years of follow-up (6.8 percent vs. 7.6 percent per year, p=0.01).
The study results from the ACTIVE A trial, sponsored by Sanofi-aventis and Bristol-Myers Squibb Company, were presented this week at a late-breaking session during the ACC in Orlando. FL.
The greatest benefit was seen in the reduction of stroke, by 28 percent (2.4 percent vs. 3.3 percent per year, p
“For patients with atrial fibrillation who are at increased risk for stroke but cannot take oral anticoagulants, these findings suggest a potential change in clinical practice,” said ACTIVE A principal investigator Stuart Connolly, M.D., department of medicine, McMaster University, Hamilton, Ontario, Canada. “Stroke is a major concern since it results in significant morbidity and mortality.”
In addition to therapies to normalize heart rhythm, treatment guidelines recommend AF patients at moderate-to-high risk for stroke also receive OAC therapy, which is effective in preventing vascular events in these patients. However, there are many patients who cannot take OACs or cannot maintain their blood coagulation inhibition within the narrow therapeutic range required to reduce the risk of vascular events without increasing the risk of life-threatening bleeding complications such as intracranial hemorrhage. Studies show that less than half of AF patients overall use OACs.
ACTIVE A was a Phase III, double-blind, placebo-controlled trial designed to compare the combination of Plavix 75mg once daily plus aspirin (75-100mg daily recommended dose) to aspirin alone (75-100mg daily recommended dose) for preventing the first occurrence of a major vascular event, the primary endpoint, during the trial, with a median of 3.6 years of follow-up. Major vascular events included stroke, non-central nervous system (non-CNS) systemic embolism, heart attack, or vascular death. The trial included 7,554 patients with atrial fibrillation who could not take OACs and had at least one major risk factor for stroke (risk factors included: 75 years of age or older; on treatment for systemic hypertension; prior stroke, transient ischemic attack, or non-CNS systemic embolus; left ventricular dysfunction; documented peripheral vascular disease; and age 55 to 74 years with either diabetes requiring drug therapy or with documented previous heart attack or coronary artery disease). Patients were determined unsuitable for OAC by the physician if: they had specific risk of bleeding, the physician judged that OACs were inappropriate for the patient, or the patient wished to avoid OAC therapy.
Plavix plus aspirin therapy compared to aspirin alone, respectively, also resulted in:
- A non-statistically significant reduction in heart attacks of 22 percent (0.7 percent vs. 0.9 percent per year, p=0.08)
- No statistically significant reductions in the other components of the primary endpoint, including non-CNS systemic embolism (0.4 percent vs. 0.4 percent per year, RR=0.96, p=0.84), vascular death (4.7 percent vs. 4.7 percent per year, RR=1.00, p=0.97), or total death (6.4 percent vs. 6.6 percent per year, RR=0.98, p=0.69)
- Statistically significant increases, as expected, in the rate of major bleeding (2.0 percent vs. 1.3 percnet per year, RR=1.57, p
For more information: www.sanofi-aventis.com., www.bms.com