The THEMIS study published this week in NEJM, tested chronic ticagrelor + aspirin in diabetic patients with stable coronary artery disease (CAD), but with no prior history of Myocardial infarction (MI) or stroke. The tempting hypothesis behind this study is that reducing ischemic events might increase bleeding events, and this calls for careful cost/benefit assessment.
The THEMIS double blind randomized 19220 diabetic patients over 50 with a history of CAD but no history of MI or stroke to ticagrelor + aspirin vs. placebo + aspirin. Mean follow up was 40 months.
Primary efficacy end point was a composite of cardiovascular death, MI or stroke, while safety end point were TIMI major bleeding.
Treatment was more often discontinued in the ticagrelor + placebo arm (34.5% vs 25.4%).
The incidence of cardiovascular ischemic events (primary end point), as expected, was lower in the ticagrelor arm (7.7% vs 8.5%; p=0.04) but this lower rate of ischemic events came at a high cost. The incidence of TIMI major bleeding was over twice as high than that of the ticagrelor arm (2.2% vs 1%; p<0.001). This included intracranial bleeding rate (0.7% vs 0.5%; p=0.005).
This higher rate of bleeding did not increase mortality rate, since fatal bleeding rate was similar (0.2% vs 0.1%; p=0.11).
Exploratory incidence (not specified in the original protocol) of irreversible damage end point (death, MI, stroke, fatal bleeding and intracranial bleeding) resulted similar between the aspirin + ticagrelor group and the aspirin + placebo group (10.1% vs 10.8%).
In diabetic patients with stable CAD with no history of MI or stroke, the combination of aspirin + ticagrelor resulted in reduced ischemic events rate at the cost of increased major bleeding, when compared to aspirin + placebo.
Original Title: Ticagrelor in Patients with Stable Coronary Disease and Diabetes.
Reference: P.G. Steg et al. N Engl J Med. 2019 Oct 3;381(14):1309-1320.
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