Ticagrelor in Patients with Stable Coronary Disease and Diabetes

Abstract

BACKGROUNDPatients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. METHODSIn this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTSA total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). CONCLUSIONSIn patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.)A BS TR AC T

Prolonged dual antiplatelet therapy in patients with non‐ST‐segment elevation myocardial infarction: 2‐year findings from EPICOR Asia

“…In fact, the high-risk population should be given longer duration of DAPT than others, which was verified in THEMIS (The Effect of Ticagrelor on Health Outcomes in diabetes Mellitus patients Intervention Study). 22 The results showed that patients aged 50 years or older with stable CAD and diabetes, even without a history of MI or stroke, had a lower incidence of ischemic CV events with long-term DAPT (median duration 39.9 months) vs single aspirin therapy. The THEMIS-PCI substudy showed that in the prespecified subgroup of patients with diabetes, stable CAD, and previous PCI, long-term DAPT (median duration 3.3 years) provided a favorable net clinical benefit, more so than in patients without a history of PCI.…”

“…In fact, the high‐risk population should be given longer duration of DAPT than others, which was verified in THEMIS (The Effect of Ticagrelor on Health Outcomes in diabetes Mellitus patients Intervention Study) . The results showed that patients aged 50 years or older with stable CAD and diabetes, even without a history of MI or stroke, had a lower incidence of ischemic CV events with long‐term DAPT (median duration 39.9 months) vs single aspirin therapy.…”

Antiplatelet therapies in diabetes

“…THEMIS randomized 19 220 people with diabetes, stable coronary artery disease and no previous myocardial infarction into aspirin only or aspirin and ticagrelor, with participants followed up for a median of almost 40 months. Ischaemic cardiovascular outcome was reduced significantly in the combination therapy (HR 0.90, 95% CI 0.81–0.99) but at the expense of a significant increase in intracranial bleeding (HR 1.71, 95% CI 1.18–2.48), making the joint outcome of vascular benefit and irreversible harm neutral (HR 0.93, 95% CI 0.86–1.02) [49]. However, in a prespecified subgroup analysis of 11 154 individuals with previous percutaneous coronary intervention (58% of the study population), there was a favourable joint vascular/bleeding outcome (HR 0.85, 95% CI 0.75–0.95) as fatal and intracranial bleeding did not show an increase in the combination therapy over aspirin alone [50].…”

Riwaroksaban — następny krok w leczeniu choroby niedokrwiennej serca

“…Miażdżyca należy do chorób towarzyszących nam przez całe życie, zatem lek winien być stosowany tak długo, jak to możliwe. Sądzę również, że niebawem pojawi się wiele analiz służących porównaniu wyników badań COMPASS [1], PEGASSUS [58] i THEMIS [59]. Perspektywa łączenia riwaroksabanu z silnym lekiem przeciwpłytkowym (tikagrelor) staje się coraz bardziej interesująca.…”