Recent data raised question regarding the safety of everolimus (EVR) in the early post-operative period in de novo heart transplant (HT) recipients. Thus, we have decided to perform an interim analysis of the first 100 patients (out of 194 planned) from the multicenter randomized study EVERHEART (NCT01017029).

The study was designed to assess the incidence of a safety composite endpoint (pleural/pericardial effusions, wound healing delay, and acute renal failure) over a 6-month period in HT recipients randomized to receive early EVR 1-5 days (EE) vs. delayed EVR (DE) 4-6 weeks after HT. EVR was started at 0.5-1.5 mg daily dose, targeting 3-8 ng/ml through levels. DE received mycophenolate mofetil (MMF) as a bridge to EVR. Study was powered hypothesizing a 60% rate of the endpoint in the EE vs. 40% in the DE.

49 patients were randomized to EE and 51 to DE strategy. 36% received thymoglobuline induction. Primary endpoint occurred in 30 (61.2%) patients in the EE and in 29 (56.9%) in DE, with pericardial effusion as the most common contributing event. One patient died in each arm, and serious adverse event rate was similar in the two study groups (36.7 vs. 43.1%). Of note, only 3% of patients had a mechanical assist device before HT. Rejection rate was numerically lower in the EE group (30.6 vs. 33.3%), as well as creatinine clearance at month 1 (71.9±25.5 vs. 82.4±30.4ml/min/1.73m²) and at month 6 (64.6±18.2 vs. 67.5±24.3 ml/min/1.73m²).

Despite the limited sizing, this interim analysis of the EVERHEART study is reassuring regarding the safety of EVR in the early post HT phase: we did not note excess of EVR-related early adverse events and the two arms similarly influenced the combined endpoint. Smooth introduction of early EVR and a limited number of patients with mechanical assist devices may explain the improved safety profile, as compared with previous studies.

Potena, L.: Speaker’s Bureau, Novartis. Guarisco, R.: Employee, Novartis.

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