The Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes and CVD: An Analysis of the COMPASS Trial

In this video, Deepak Bhatt, MD, MPH, highlights the findings from an analysis of the COMPASS trial that included patients with diabetes. For this prespecified analysis, Dr Bhatt and colleagues compared the effects of rivaroxaban plus aspirin vs placebo plus aspirin on preventing major vascular events among patients with diabetes vs patients without diabetes. 

Deepak L. Bhatt, MD, MPH, is the executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School in Boston, Massachusetts. He specializes in cardiovascular medicine and interventional cardiology. 

Additional Resources:

1. Bhatt DL, Eikelboom JW, Connolly SJ, et al; COMPASS Steering Committee and investigators. The role of combination antiplatelet and anticoagulation therapy in diabetes and cardiovascular disease: insights from the COMPASS trial. Circulation. 2020;141(23):1841-1854. doi:10.1161/CIRCULATIONAHA.120.046448

2. Bosch J, Eikelboom JW, Connolly SJ, et al. Rationale, design and baseline characteristics of participants in the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial. Can J Cardiol. 2017;33(8):1027-1035. doi:10.1016/j.cjca.2017.06.001

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TRANSCRIPT:

Deepak Bhatt: This is Dr. Deepak Bhatt from Brigham and Women’s Hospital and Harvard Medical School. It's really a pleasure to be able to present to you the top-line results from COMPASS Diabetes, which I just presented as a late-breaking clinical trial at the American College of Cardiology annual sessions—the virtual sessions—which was a fun thing to do, I should say.

So just to refresh, the overall COMPASS trial randomized 27,000 high ischemic risk, low bleeding risk patients with either coronary artery disease or peripheral artery disease or both to rivaroxaban plus aspirin vs aspirin alone. And the dose of rivaroxaban used was 2.5 milligrams twice a day. There was a third arm of the trial that I won't speak of that examined just low-dose rivaroxaban that looked pretty good but didn’t actually beat aspirin and, therefore, I won't say anything more about it. But the aspirin plus master dose of rivaroxaban that I mentioned—which is different from the atrial fibrillation dose, I should add—is one that is approved for use in patients like the ones in COMPASS by the FDA.

What we examined in the analysis I just presented—which was published, by the way, simultaneously in Circulation–was that subgroup of patients with diabetes at baseline vs those without diabetes and baseline. And what we found was that the results in those with diabetes was consistent with the overall trial and with those without diabetes, in terms of relative risk reductions really rather similar; in a statistical sense the so-called interaction term was nonsignificant meaning, statistically speaking, very similar relative risk reduction. However, given the larger absolute risk that patients with diabetes face, we found larger numerical reductions in absolute risk for the endpoints that we examined, including the primary endpoint of cardiovascular death, MI, stroke, for the expanded MACE that includes major adverse limb events, including amputations, for example; these were significantly reduced in those with diabetes as well as those without diabetes. In each of these large subgroups a statistically significant reduction, but again, in relative terms similar, but in absolute terms numerically higher in those with vs those without diabetes.

And for the endpoint of all-cause mortality, the absolute risk reduction in those with diabetes was 3-fold higher than in those without diabetes. So again, illustrating a fact that diabetic patients in particular we're talking here both those with concomitant atherosclerosis in the coronary arteries or the peripheral arteries or both, those are high-risk patients and therefore, they do derive substantial benefit from this dual pathway inhibition with aspirin and a vascular dose of rivaroxaban.

As far as bleeding goes, major bleeding was significantly increased in the overall trial, as well as those with diabetes and without diabetes and to a similar degree, both in relative and absolute terms about a 70% relative risk increase. However, fortunately, no significant increase in fatal bleeding or intracranial bleeding in the overall trial or in those with or without diabetes. Thus, the net clinical benefit was significantly better for the vascular dose of rivaroxaban plus aspirin in those with diabetes; it is also better in those without diabetes. But again, in terms of this net clinical benefit of irreversible harms, it was numerically much higher in those with diabetes vs those without diabetes 2.7% vs 1.0%

So overall, a really good net clinical benefit looking at bad stuff—irreversible outcomes—in favor of vascular dose rivaroxaban plus aspirin. True for the overall trial, true for those without diabetes and, in particular, truth for those with diabetes. So I believe with COMPASS diabetes, we've identified another large subgroup out of the COMPASS trial that derives substantial benefit of this pathway of dual inhibition—that is a vascular dose of rivaroxaban, 2.5 milligrams, twice a day, plus low-dose aspirin. And it's not to say that it's only patients with diabetes that benefit. We previously have shown other subgroups such as those with so-called polyvascular disease—that is plaque in multiple arterial beds—such as a patient with concomitant CAD or PAD benefit quite a bit. Those that were enrolled in the trial with a history of previous heart failure, not decompensated bad heart failure, but stable heart failure, they seem to benefit quite a bit. Indeed, patients who are higher baseline absolute risk seem to benefit more than just in the overall population.

But still, I would say, in particular, we should focus attention now on those with diabetes because those patients are easy to identify, and we know both from COMPASS, but also other trials and registries that those patients with diabetes and atherosclerosis, assuming that they're at low bleeding risk really can benefit from this dual pathway inhibition. Thank you very much for your attention.