Eligible-and-enrolled vs. eligible-but-not-enrolled patients with chronic ischaemic heart failure in randomized clinical trials of myocardial regeneration

Abstract

Introduction: Clinical trial applicability to routine clinical practice is a fundamental consideration. Little is known about factors that determine enrolment (vs. non-enrolment) in chronic ischaemic heart failure (CIHF) interventional randomized controlled trials (iRCT).

Aim: To compare clinical characteristics and medical therapy in eligible-and-enrolled (E-E) vs. eligible-but-not-enrolled (E-NE) patients in CIHF myocardial regeneration iRCTs.

Material and methods: Clinical characteristics and medical treatment were compared for E-E and E-NE in 4 periods (32 months): P1 (iRCT#1 recruitment), P2 (between iRCT#1 and iRCT#2), P3 (iRCT#2 recruitment), P4 (post iRCT#2). iRCT#1 and iRCT#2 shared inclusion/exclusion criteria.

Results: Evaluation involved 5,436 hospitalized patients (P1-P4; CIHF-526). 283 were iRCT eligible (53.8%). The eligibility rate was similar throughout P1-P4 (43.1-58.5%, p = 0.08). Eligible patient characteristics and pharmacotherapy did not differ in recruitment vs. non-recruitment periods. Principal reasons for ineligibility were recent/planned cardiac intervention outside iRCT (22.8%), age above threshold (14.6%) and coexisting disease as the exclusion criterion (12.2%). Primary reasons for eligible patient non-enrolment (n = 89) were other trial participation (52.8%) and no consent (28.1%). E-E patients did not differ from E-NE in characteristics including CIHF medical management and clinical stage; the exception was more severe left ventricular impairment in E-E (LVEF 31.2 vs. 33.9%, p = 0.039; end-diastolic volume 197.8 vs. 160.4 ml, p < 0.0001).

Conclusions: CIHF medical management was similar in E-E and E-NE. Ineligibility resulted mainly from recent/planned intervention outside iRCT and age > 80 years. LV impairment was more severe in E-E patients, consistent with higher-risk patient enrolment in CIHF-iRCTs. This contrasts with typical lower-risk patient enrolment in other cardiovascular RCT types and populations.

Keywords: eligibility; enrolment; heart failure; myocardial regeneration; randomized clinical trials; selection bias.