CArdiac Resynchronization In combination with BEta blocker treatment in advanced chronic Heart Failure (CARIBE-HF): the results of the CARIBE-HF study

Abstract

Objective Cardiac resynchronization therapy (CRT), combined with optimal medical therapy (OMT), is an established treatment for patients with advanced chronic heart failure (ACHF). In ACHF, carvedilol at the dose used in clinical trials, reduces morbidity and mortality. However, patients often do not tolerate the drug at the targeted dosage. The aim of the CARIBE-HF prospective observational study was to investigate the role of CRT in the implementation of carvedilol therapy in patients with ACHF.

Methods One hundred and six patients (aged 65 ± 12 [mean ± SD] years) with ACHF were enrolled and treated with OMT, in which carvedilol was titrated up to the maximal dose (phase 1). Subsequently, patients with left ventricular (LV) ejection fraction ≤ 35%, NYHA class III-IV and QRS interval ≥ 120 msec were assigned to CRT. Both CRT and NO-CRT patients underwent a long-term follow-up of 7 years (1193.98 ± 924 days), while eff orts to uptitrate the carvedilol dose were continued during the second phase (471 ± 310 days). Phase 1 was completed by 84 patients (79%), and 15 (18%) underwent CRT. The mean carvedilol dose in the CRT group was 19.0 ± 17.8 mg, against 32.7 ± 19.1 mg in the remaining 69 patients (P= 0.018). At the end of phase 2, CRT patients presented a signifi cantly greater variation of increasing in the carvedilol dose than NO-CRT patients (+20.0 ± 19.8 mg vs –0.3 ± 20.5 mg; P= 0.015), a greater NYHA class reduction (-0.8 ± 0.6 vs -0.2 ± 0.7; P= 0.011), and a greater increase in LV ejection fraction (10.8 ± 9 vs 3.1± 6.1; P= 0.018).

Conclusions The data from the CARIBE study suggest that, in ACHF, CRT may be eff ective in enabling the target dose of carvedilol to be reached. The signifi cant improvement seen in LV function was probably due to a synergistic eff ect of CRT and carvedilol. During the extended follow-up (mean 1193.98 ± 924 days) the mean dosage of carvedilol in the CRT group was signifi cantly higher (P < 0.02).

Key Words:

• Heart failure
• beta blockers
• resynchronization therapy