Analysis of EUCLID Trial Reports on Outcomes of CLI Patients
January 9, 2018—In European Journal of Vascular and Endovascular Surgery (EJVES), Lars Norgren, MD, et al published findings from an evaluation of patients with critical limb ischemia (CLI) who were enrolled in the EUCLID trial (2018;55:109–117).
As explained in EJVES, the EUCLID trial investigated the effect of monotherapy with ticagrelor versus clopidogrel in 13,885 patients with peripheral artery disease (PAD). The trial's primary endpoint was cardiovascular death, myocardial infarction, or ischemic stroke. The trial excluded patients planned for revascularization or amputation within 3 months.
The current analysis focuses on the subgroup with CLI, defined by rest pain (58.8%), major tissue loss (9%), or minor tissue loss (32.2%). The background of the investigation is that CLI implies an increased risk of cardiovascular morbidity and mortality, and the optimal antithrombotic treatment is not established.
The investigators reported that 643 (4.6%) patients in EUCLID had CLI at baseline, dominated by milder forms of CLI because of the trial design. Diabetes mellitus was more common in the CLI group, although coronary disease, carotid disease, and hypertension were more common in the non-CLI group. A majority of CLI patients (62.1%) had only lower extremity PAD. In patients enrolled based on ankle-brachial index (ABI) criteria, mean ABI was 0.55 ± 0.21 for those with CLI versus 0.63 ± 0.15 for those without CLI.
The primary efficacy endpoint significantly increased among patients with CLI compared with those without CLI, with a rate of 8.85 versus 4.28 per 100 patient-years (adjusted for baseline characteristics, hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.16–1.76; P = .0009). When acute limb ischemia requiring hospitalization was added to the model, significant differences remained (adjusted HR, 1.38; 95% CI, 1.13–1.69; P = .0016). One-year mortality was 8.9%.
The investigators observed a trend toward increased lower limb revascularization among patients with CLI. Bleeding (thrombolysis in myocardial infarction major, fatal, intracranial) did not differ between those with and without CLI.
This analysis demonstrated that patients with CLI had a significantly higher rate of cardiovascular mortality and morbidity versus those without CLI. Further efforts are required to reduce the risk of cardiovascular events in PAD, especially in patients with CLI, advised the investigators in EJVES.