THEMIS-PAD: Ticagrelor Reduces Risk of Limb Events in Patients with CAD and T2D; Greater Benefit in PAD

In patients with coronary artery disease (CAD) and type 2 diabetes (T2D), the risk of limb ischemic events was about 10-times higher in patients with, vs. without, peripheral artery (PAD) enrolled in the THEMIS study – and they had a greater absolute benefit from the reduction in limb events gained with ticagrelor. The results of the THEMIS-PAD study were presented during ESC Congress 2020.

Researchers led by Marc P. Bonaca, MD, FACC, examined data from the 19,220 patients (50+ years of age) with stable CAD and T2D and without a previous myocardial infarction or stroke randomly assigned to ticagrelor plus aspirin or placebo plus aspirin, to characterize the limb events in the group overall and by the presence of PAD, including: acute limb ischemia (ALI); major amputation of vascular etiology; peripheral revascularization (urgent, elective); and overall limb ischemia outcomes defined as composite of the individual events. They also evaluated the efficacy of adding ticagrelor to aspirin to reduce limb ischemic events and whether this effect was similar in patients with and without PAD.

During the THEMIS trial, limb ischemic events were prospectively reported to an electronic data capture system.

The median age of the 1,687 patients with PAD at baseline was 68 years and 27% were women; their median duration of T2D was 12 years, 41% had complications from diabetes and 15% were current smokers.

Results showed in patients on placebo, at three years, those with PAD (n=860) had a higher risk of events than those without PAD (n=8,741): limb ischemic events, 9.5% vs. 0.80% (hazard ratio [HR], 10.67); peripheral revascularization, 8.90% vs. 0.80% (HR, 10.54); major amputation of vascular etiology, 0.70% vs. 0.10% (HR, 9.96); and ALI, 0.60% vs. 0.01% (HR, 5.61).

In the overall THEMIS population of 19,220 patients, there were 171 leg ischemic events in the placebo group (1.59%) and 131 limb ischemic events in the ticagrelor group (1.30%; HR, 0.77). Broken down by type of event, peripheral revascularization occurred in 1.51% vs. 1.23% (HR, 079); ALI in 0.16% vs. 0.04% (HR, 0.24); and major amputation in 0.12% vs. 0.10% (HR, 0.63). There were more elective than nonelective peripheral revascularizations.

In the patients who had PAD at baseline, there were more limb events in the placebo than the ticagrelor group (9.50% vs. 7.60%, respectively; HR, 0.80). In those who did not have PAD at baseline, the rate of events was 0.80% and 0.70%, respectively (HR, 0.76).

The very high risk of limb events in patients with PAD, on top of CAD and T2D, and reductions with ticagrelor of about 50% for major adverse limb events and 20% for peripheral revascularization suggests long-term benefit with the drug for preventing cardiovascular and limb events, researchers said. They added that these results, along with those from PEGASUS-TIMI 54, show benefit for preventing limb events with ticagrelor, but more studies are needed not only to establish this in patients selected for PAD, but also determine its safety after peripheral vascularization.

Keywords: ESC Congress, ESC20, Aneurysm, Peripheral Arterial Disease, Angiography, Percutaneous Coronary Intervention

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