Limb Outcomes With Ticagrelor Plus Aspirin in Patients With Diabetes Mellitus and Atherosclerosis
Marc P Bonaca1, Deepak L Bhatt2, Tabassome Simon3
1University of Colorado, CPC Clinical Research, Aurora, Colorado, USA.
Insights
Ticagrelor significantly reduced limb events like revascularization and acute limb ischemia in patients with type 2 diabetes mellitus and atherosclerosis. However, this benefit came with an increased risk of bleeding.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Diabetes Research
Background:
- Ticagrelor use in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) is known to reduce major adverse cardiovascular events (MACE) but increase bleeding.
- Limb events, including revascularization, acute limb ischemia (ALI), and amputation, represent significant morbidities in patients with T2DM and atherosclerosis.
Purpose of the Study:
- To investigate the specific impact of ticagrelor on the incidence of limb events in patients with T2DM and atherosclerosis.
- To evaluate whether peripheral artery disease (PAD) modifies the effect of ticagrelor on limb events, MACE, and bleeding.
Main Methods:
- The study randomized 19,220 patients with T2DM and CAD to receive either ticagrelor or a placebo, in addition to aspirin.
- Patients were followed for a median of 3 years, with limb events (ALI, amputation, revascularization), MACE, and bleeding events independently adjudicated.
- Peripheral artery disease (PAD) status at baseline was recorded and analyzed for its influence on treatment outcomes.
Main Results:
- Peripheral artery disease (PAD) was present in 8.8% of patients and was associated with significantly higher risks of MACE and limb events in the placebo group.
- Ticagrelor demonstrated a significant reduction in overall limb events (HR: 0.77; P=0.022), specifically for revascularization and ALI.
- The beneficial effect of ticagrelor on limb events was consistent regardless of PAD status, with no significant interaction found for MACE or major bleeding.
Conclusions:
- Patients with T2DM and atherosclerosis face a high risk of limb-related complications.
- Ticagrelor effectively decreases the risk of limb events in this population, though it is associated with an increased risk of bleeding.
- Further research is warranted to fully elucidate the benefit-risk profile of ticagrelor, particularly in combination with aspirin, for patients with PAD, including those without CAD.
Background:
Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis.
Objectives:
This study sought to determine the effect of ticagrelor on limb events.
Methods:
Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline.
Results:
Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; Pinteraction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (Pinteraction = 0.40) or TIMI major bleeding (Pinteraction = 0.3239).
Conclusions:
Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795).
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