ATLAS ACS-2 TIMI 51 was sponsored by Johnson & Johnson and Bayer. Dr. Gibson said that he has been a consultant to those companies and to numerous other pharmaceutical companies; has served on the speakers bureaus for Daiichi Sankyo, Eli Lilly, and The Medicines Company; and has received fees for educational presentations on behalf of Daiichi Sankyo and Eli Lilly. He has received research grants from Johnson & Johnson and Bayer. Dr. Armstrong has been a consultant to Eli Lilly, Sanofi-Aventis, Bristol-Myers Squibb, Merck, Regado, Hoffmann-LaRoche, GlaxoSmithKline, Pfizer, and Takeda, and he has received grant support from Boehringer Ingelheim, Hoffman LaRoche, Sanofi-Aventis, Schering Plough, and Merck. Dr. Bhatt said that he has received grant support from AstraZeneca, Regado, Portola, and GlaxoSmithKline.
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The ATLAS results were very dramatic. The 2.5 mg b.i.d. dose, on top of standard acute coronary syndrome therapy with aspirin and clopidogrel, not only reduced the primary end point, but also significantly reduced cardiovascular mortality and total mortality. That is an effect that we really look for but rarely see in phase III trials. It’s an important finding that will catch the attention of many clinicians. This is the first trial to show a benefit of adding oral anticoagulation, at a very low dose, on top of the background regimen we give today.
The dose that appeared optimal was 2.5 mg b.i.d., which produced the efficacy benefit with a modest increase in major bleeds and no significant increase in fatal bleeding events. The results showed an overall number needed to treat to prevent one all-cause death was 63, which is pretty good, with a substantially lower number needed to harm. The balance definitely favored a net benefit from adding rivaroxaban. The researchers found rivaroxaban’s "sweet spot" for this indication at the lower dosage.
These results are relevant to the vast majority of ACS patients, who still receive aspirin and clopidogrel for antiplatelet therapy. But physicians should not extrapolate these findings to the growing number of ACS patients treated with the alternative, more powerful antiplatelet drugs prasugrel and ticagrelor. The risk for bleeding might be much greater if treatment combined rivaroxaban with one of these drugs. The safety and efficacy of rivaroxaban when added to treatment with prasugrel or ticagrelor will need testing in future studies.
Elliott M. Antman, M.D., is professor of medicine at Harvard University in Boston. He is a senior investigator for the TIMI study group, which ran the ATLAS trial, but he did not directly participate in running the trial. He also served as principal investigator for the pivotal trial of prasugrel. He said that he had no other relevant disclosures. Dr. Antman made these comments in an interview.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION