CHAPTER 2.2 62 Eligibility using multiple criteria in theoretical trial design For a theoretical design, the strongest determinants of eligibility were background therapy of ACEI/ARB and BB and history of MI or coronary revascularization by PCI or CABG in which half and a-third of patients remain eligible, respectively when these are considered in addition to liberal ranges for age, LVEF ≤ 40% and NYHA functional classes II to IV (Figure 4A). Factoring a further exclusion of patients with implanted devices, COPD, cancer, stroke, estimated GFR ≤ 30 ml/min/1.73m2, hemoglobin <10g/dL and potassium ≥5.5mmol/L, leaves about one-fifth (18%) eligible. Eliminating NYHA class IV led to only marginal decrease in total eligible participants (17%) (Figure 4B). Similarly, a stricter upper limit for LVEF at ≤ 35% resulted in eligibility that is not different to LVEF ≤40% (Figures 4C and D), indicating that eligibility was more strongly driven by background HF therapy than LVEF or NYHA functional class. In an alternative design with prior HF hospitalization as cardiovascular risk enrichment, overall eligibility became substantially restricted from 18% to 5% remaining eligible. (Supplementary figure 2). For a trial design which considers a triple HF background therapy (add-on MRA), overall eligibility was halved in comparison to a broader double therapy of ACEI/ARB+BB. (Supplementary figure 3).
RkJQdWJsaXNoZXIy MjY0ODMw