Large Study Shows Mixed Results of Intensified PLAVIX Dose

September 3, 2009 – The OASIS study group presented initial results of the CURRENT-OASIS 7 clinical trial Sunday at the European Society of Cardiology Congress in Barcelona, which did not show a statistical difference between the high-dose and standard-dose PLAVIX regimens, but subgroups did show some improvement.

Sanofi-aventis and Bristol-Myers Squibb cocommercialization and codevelopment partners for PLAVIX (clopidogrel bisulfate), were sponsors of the study.

CURRENT-OASIS 7 is the largest clinical trial (25,087 patients) to evaluate different dosing regimens of PLAVIX plus aspirin in a broad range of acute coronary syndrome (ACS) patients (UA/NSTEMI/STEMI). The study was designed to assess the efficacy and safety of an intensified clopidogrel regimen (600 mg loading dose day one, 150 mg days two through seven, and 75 mg days eight through 30) versus the approved PLAVIX dosage (300 mg loading dose day one and 75 mg days two through 30) for patients managed with an early invasive strategy with an intent for percutaneous coronary intervention (PCI).

The primary end-point (cardiovascular death, heart attack, or stroke at 30 days) for the entire study population (including subpopulations of patients that underwent PCI (70 percent) or not (30 percent) examining the difference between the high-dose and standard-dose PLAVIX regimens did not reach statistical significance (4.2 vs. 4.4 percent).

For clinically relevant subgroups that were prespecified for preliminary analyses, such as the PCI subgroup (17,232 patients), potentially medically relevant differences in patient outcomes were observed. In this subgroup, analysis showed an improvement in outcome for patients taking the higher dose regimen (600 mg loading/150 mg for days two through seven and 75 mg for days eight through 30) over the standard dose regimen (300 mg loading/75 mg for days two through 30), as shown by the reduction of the same composite end-point of cardiovascular death, myocardial infarction and stroke by 15 percent (4.5 vs. 3.9 percent). In addition, analysis showed an important 42 percent relative risk reduction in definite stent thrombosis (1.2 vs. 0.7 percent) with the higher dose regimen of clopidogrel over the standard loading dose.

The primary safety end-point was assessed by the stringent bleeding definition of OASIS and while a significant increase in the primary safety end-point of major bleeding with the high-dose compared to the standard-dose PLAVIX regimen was observed in the overall trial population (2.5 vs. 2 percent) and the PCI population (1.6 vs. 1.1 percent), there was no statistically significant difference in intracranial bleeding or fatal hemorrhage in the overall population and the PCI population.

For more information: www.PLAVIX.com, www.sanofi-aventis.com