Causes of ineligibility in randomized controlled trials and long-term mortality in patients with non-ST-segment elevation acute coronary syndromes

Purpose To determine the long-term mortality of patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) that are eligible versus those not eligible in randomized controlled trials (RCT), and how each exclusion criteria is associated with outcome. Methods Common causes of exclusion in six published RCT on intravenous antithrombotic therapy were prospectively assessed in a cohort of 452 consecutive patients with NSTEACS that were followed for up to 3 years. Results Forty-one percent of patients had one or more exclusion criteria establishing the ineligible group. These patients were older, more likely to have coronary risk factors, ischemic ECG changes, heart failure at admission, higher creatinine levels and a lower ejection fraction than eligible patients. There were no differences between both groups in the antithrombotic treatment received or in the performance of revascularization procedures during hospitalization or in the prescription of antiplatelet treatment and beta-blockers at discharge. Cumulative 3-year mortality rate was 25% in ineligible patients compared to 9% in eligible patients (p < 0.001). The hazard ratio (HR) of mortality was of 9.1 (95% CI: 4.5–18.7) for severe renal dysfunction; 6.0 (3.3–11.4) for concomitant non-vascular diseases; 3.0 (1.6–5.5) for contraindications to anticoagulation; 2.5 (1.1–5.7) for heart failure; and 2.3 (1.1–4.6) for prior cerebrovascular disease. After adjusting for baseline differences, ineligible patients had a HR of total mortality of 1.88 (1.04–3.38), and of cardiac mortality of 2 (1.01–3.98). Conclusion Patients with NSTEACS who are ineligible in RCT have a higher risk profile and a two-fold adjusted long-term mortality than eligible patients, especially those with comorbid conditions and those with contraindications to anticoagulation.