Adding ticagrelor to aspirin for patients with diabetes, coronary artery disease (CAD) and peripheral artery disease (PAD) without a history of myocardial infarction (MI) or stroke lowers the risk of adverse limb events, according to study results presented Tuesday at the European Society of Cardiology (ESC) 2020 virtual congress.
THEMIS was a large, multicenter, international trial that randomized patients with diabetes and coronary artery disease without a history of MI or stroke to ticagrelor plus aspirin. Patients at high risk for bleeding or who required anticoagulation were excluded.
The THEMIS trial showed that, compared with aspirin alone, ticagrelor plus aspirin significantly reduced the rate of the primary composite endpoint, major adverse cardiovascular events (MACE; cardiovascular death, MI or stroke). The study did show an increase in bleeding with the addition of ticagrelor. Both of these effects were consistent in patients with or without peripheral artery disease (PAD).
Diabetes has been recognized as a key risk factor for adverse limb events.
Marc P. Bonaca, MD, MPH, of CPC Clinical Research, Aurora, Colorado, presented an analysis of THEMIS focusing on the efficacy and safety of the addition of ticagrelor (AstraZeneca) to aspirin in patients with and without PAD. His presentation was among the late-breaking science sessions Tuesday at ESC.
At baseline, PAD patients tended to be at higher risk than patients without PAD. PAD patients were older (PAD mean age 68 years vs. no-PAD age 66) and had more comorbidities (hypertension, 95% vs. 92%; dyslipidemia, 92% vs. 87; current smoking, 15% vs. 11%; diabetes complications, 41% vs. 24%; all p-values <0.001), renal dysfunction (median estimated glomerular filtration rate 71 mL/min/1.73m2 vs. 75 mL/min/1.73m2; p<0.001) and a higher rate of prior coronary revascularization (83% vs. 80%; p=0.005).
Patients in the ticagrelor arm of THEMIS had a significantly lower risk of limb ischemic outcomes (defined as a composite of acute limb ischemia, major amputation of vascular etiology and peripheral revascularization; ticagrelor plus aspirin 1.3% vs. aspirin-only 1.59%; hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.96; p=0.022).
This was true across the components of the composite outcome, the most frequent of which was peripheral limb revascularization (1.23% vs. 1.51%; HR, 0.79; 95% CI, 0.62-0.99). While the trend toward an advantage for ticagrelor continued when stratifying the revascularization by elective (i.e., claudication) and non-elective (i.e., critical limb ischemia) procedures, this advantage was not statistically significant in either arm (elective: 1.1% vs. 1.3%; HR, 0.80; 95% CI, 0.62-1.02; non-elective: 0.2% vs. 0.3%; HR, 0.57; 95% CI, 0.31-1.05).
Stratifying the results by the presence of PAD at baseline, again, the addition of ticagrelor continued to show a trend toward better outcomes, but this was not statistically significant (PAD: 7.6% vs. 9.5%; HR, 0.80; 95% CI, 0.58-1.11; no PAD: 0.7% vs. 0.8%; HR, 0.76; 95% CI, 0.55-1.05).
Bonaca concluded by saying that the findings suggest that patients with PAD may benefit from long-term ticagrelor with a lower risk of adverse cardiovascular and limb outcomes. However, he added that further studies dedicated to patients selected on the basis of PAD and to evaluate the safety and efficacy of ticagrelor after peripheral revascularization are needed.
The THEMIS trial was funded by AstraZeneca.