External applicability of the Effect of ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) trial: An analysis of patients with diabetes and coronary artery disease in the REduction of Atherothrombosis for Continued Health (REACH) registry

Aims: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry. Methods and results: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a ‘THEMIS-eligible population’ of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy. Conclusions: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be ‘THEMIS eligible.’ Clinical trial registration: http://www.clinicaltrials.gov identifier: NCT0199179

Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry

Background: Patients with symptomatic peripheral artery disease (PAD) are at high risk of ischemic events. However, data about predictors of this risk are limited. Hypothesis: We analyzed baseline characteristics and 4-year follow-up of patients enrolled in the international REduction of Atherothrombosis for Continued Health (REACH) Registry with symptomatic PAD and no history of stroke/transient ischemic attack to describe annual rates of recurrent ischemic events globally and geographically. Methods: The primary outcome was systemic ischemic events (composite of cardiovascular death, myocardial infarction, or stroke) at 4 years. The secondary outcome was limb ischemic events (composite of lower limb amputation, peripheral bypass graft, and percutaneous intervention for PAD) at 2 years. Multivariate analysis identified risk factors associated with recurrent ischemic events. Results: The primary endpoint rate reached 4.7% during the first year and increased continuously (by 4%-5% each year) to 17.6% by year 4, driven mainly by cardiovascular mortality (11.1% at year 4). Japan experienced lower adjusted ischemic rates (P < 0.01) vs North America. Renal impairment (P < 0.01), congestive heart failure (P < 0.01), history of diabetes (P < 0.01), history of myocardial infarction (P = 0.01), vascular disease (single or poly, P < 0.01), and older age (P < 0.01) were associated with increased risk of systemic ischemic events, whereas statin use was associated with lower risk (P = 0.03). The limb ischemic event rate was 5.7% at 2 years. Conclusions: Four-year systemic ischemic risk in patients with PAD and no history of stroke or transient ischemic attack remains high, and was mainly driven by cardiovascular mortality

Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention.

OBJECTIVE The effects of ticagrelor in the subpopulation of patients with ST-elevation myocardial infarction (STEMI) were consistent with those observed in the overall Platelet Inhibition and Patient Outcomes (PLATO) study. However, this subgroup included patients initially or ultimately treated conservatively. The aim of this study is to compare treatment using ticagrelor with treatment using clopidogrel in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS This post-hoc subgroup analysis compared ticagrelor with clopidogrel in 4949 PLATO patients with STEMI that were treated with primary PCI within 12 h of admission. The primary endpoint was cardiovascular death, myocardial infarction or stroke. The safety endpoint consisted of any major bleeding. Secondary endpoints included stent thrombosis. The analysis was not adequately powered to establish significance of any treatment effects. RESULTS During a median of 286 days, the primary endpoint occurred in 7.9% of ticagrelor-treated patients versus 8.6% of clopidogrel-treated patients (HR 0.91, 95% CI 0.75 to 1.12, p=0.38). Major bleeding occurred in 6.7% in ticagrelor-treated patients versus 6.8% of clopidogrel-treated patients (HR 0.97, 95% CI 0.77 to 1.22, p=0.79). No interactions were observed for the treatment effect of ticagrelor versus clopidogrel on the primary efficacy (p=0.40) and primary safety endpoints (p=0.15) as compared with the full PLATO population. Treatment with ticagrelor versus clopidogrel reduced the occurrence of definite stent thrombosis (HR 0.58, 95% CI 0.37 to 0.89, p=0.013). CONCLUSIONS In the subset of patients with STEMI treated with primary PCI, ticagrelor compared with clopidogrel was safe, and efficacy outcomes were consistent with the overall PLATO trial. TRIAL REGISTRATION NUMBER NCT00391872; Results

Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention

Objective The effects of ticagrelor in the subpopulation of patients with ST-elevation myocardial infarction (STEMI) were consistent with those observed in the overall Platelet Inhibition and Patient Outcomes (PLATO) study. However, this subgroup included patients initially or ultimately treated conservatively. The aim of this study is to compare treatment using ticagrelor with treatment using clopidogrel in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods This post-hoc subgroup analysis compared ticagrelor with clopidogrel in 4949 PLATO patients with STEMI that were treated with primary PCI within 12h of admission. The primary endpoint was cardiovascular death, myocardial infarction or stroke. The safety endpoint consisted of any major bleeding. Secondary endpoints included stent thrombosis. The analysis was not adequately powered to establish significance of any treatment effects. Results During a median of 286days, the primary endpoint occurred in 7.9% of ticagrelor-treated patients versus 8.6% of clopidogrel-treated patients (HR 0.91, 95% CI 0.75 to 1.12, p=0.38). Major bleeding occurred in 6.7% in ticagrelor-treated patients versus 6.8% of clopidogrel-treated patients (HR 0.97, 95% CI 0.77 to 1.22, p=0.79). No interactions were observed for the treatment effect of ticagrelor versus clopidogrel on the primary efficacy (p=0.40) and primary safety endpoints (p=0.15) as compared with the full PLATO population. Treatment with ticagrelor versus clopidogrel reduced the occurrence of definite stent thrombosis (HR 0.58, 95% CI 0.37 to 0.89, p=0.013). Conclusions In the subset of patients with STEMI treated with primary PCI, ticagrelor compared with clopidogrel was safe, and efficacy outcomes were consistent with the overall PLATO trial. Trial registration number NCT00391872; Results