Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes Mellitus and Cardiovascular Disease

Abstract

Background: Patients with established coronary artery disease or peripheral artery disease often have diabetes mellitus. These patients are at high risk of future vascular events. Methods: In a prespecified analysis of the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies), we compared the effects of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) versus placebo plus aspirin in patients with diabetes mellitus versus without diabetes mellitus in preventing major vascular events. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included all-cause mortality and all major vascular events (cardiovascular death, myocardial infarction, stroke, or major adverse limb events, including amputation). The primary safety end point was a modification of the International Society on Thrombosis and Haemostasis criteria for major bleeding. Results: There were 10 341 patients with diabetes mellitus and 17 054 without diabetes mellitus in the overall trial. A consistent and similar relative risk reduction was seen for benefit of rivaroxaban plus aspirin (n=9152) versus placebo plus aspirin (n=9126) in patients both with (n=6922) and without (n=11 356) diabetes mellitus for the primary efficacy end point (hazard ratio, 0.74, P =0.002; and hazard ratio, 0.77, P =0.005, respectively, P interaction =0.77) and all-cause mortality (hazard ratio, 0.81, P =0.05; and hazard ratio, 0.84, P =0.09, respectively; P interaction =0.82). However, although the absolute risk reductions appeared numerically larger in patients with versus without diabetes mellitus, both subgroups derived similar benefit (2.3% versus 1.4% for the primary efficacy end point at 3 years, Gail-Simon qualitative P interaction <0.0001; 1.9% versus 0.6% for all-cause mortality, P interaction =0.02; 2.7% versus 1.7% for major vascular events, P interaction <0.0001). Because the bleeding hazards were similar among patients with and without diabetes mellitus, the prespecified net benefit for rivaroxaban appeared particularly favorable in the patients with diabetes mellitus (2.7% versus 1.0%; Gail-Simon qualitative P interaction =0.001). Conclusions: In stable atherosclerosis, the combination of aspirin plus rivaroxaban 2.5 mg twice daily provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral end points in patients with and without diabetes mellitus. Given their higher baseline risk, the absolute benefits appeared larger in those with diabetes mellitus, including a 3-fold greater reduction in all-cause mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01776424.

10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2021

“…In the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial of 27,395 patients with established coronary artery disease and/or peripheral artery disease, aspirin plus rivaroxaban 2.5 mg twice daily was superior to aspirin plus placebo in the reduction of cardiovascular ischemic events including major adverse limb events. The absolute benefits of combination therapy appeared larger in patients with diabetes, who comprised 10,341 of the trial participants (152,153). A similar treatment strategy was evaluated in the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease (VOYAGER PAD) trial (154), in which 6,564 patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban 2.5 mg twice daily plus aspirin or placebo plus aspirin.…”

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines

“…Finally, a huge difference regarding the interval between MI and randomization in the PEGASUS-TIMI 54 (1.7 year) and COMPASS trial (7.1 years) should be highlighted. Several minor differences between the investigated populations should also be noted [17][18][19][20][21][22][34][35][36] (Tab. 7).…”

“…The combination of ASA plus rivaroxaban provided a similar relative degree of clinical benefit in patients with and without diabetes mellitus. However, due to a higher baseline risk, the absolute benefits appeared larger in patients with diabetes mellitus, including a three-fold greater reduction in all-cause mortality [36].…”

“…According to the citations in the ESC guidelines [10,11], the indications for use of rivaroxaban in combination with ASA in patients with CCS after ACS are based on the results of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial [22,[35][36][37].…”

Up-to-date potential of antithrombotic therapy in patients with coronary artery disease and diabetes

“…Потому следует представить данные субанализа [25] исследования COMPASS, опубликованного в 2020г, целью которого явилась оценка частоты описанных выше базовых конечных точек основного протокола среди 2 групп пациентов: принимавших АСК 100 мг в режиме монотерапии и получавших комбинированное лечение АСК 100 мг/сут. в сочетании с ривароксабаном 2,5 мг 2 раза/сут.…”