Autori: Luminita Iliuta, Roxana Enache

Editorial: InTech Open Access publisher , Cardiac Surgery, Book I, 2011.

Rezumat:

Postoperative rhythm disorders are a serious complication of coronary surgery and they are associated with increased morbidity and mortality, with longer intensive coronary unit (ICU) and hospital stays and therefore with increased economic costs. Prophylactic β-blocker therapy is clearly effective in reducing the incidence and the number of episodes of postcoronary artery bypass grafting (CABG) rhythm disorders. In patients with conduction abnormalities or severe left ventricular dysfunction the use of β-blockers is difficult and controversial. Data regarding the benefits of ivabradine used postoperatively in patients with conduction abnormalities or left ventricular dysfunction undergoing coronary surgery are scarce.
Objective. The aim of our study was to compare the efficacy and safety of pure heart rate lowering agent ivabradine versus metoprolol used perioperatively in CABG patients with conduction abnormalities (first degree atrioventricular block or bundle branch block) or LV dysfunction and also to determine whether prophylactic therapy with ivabradine can reduce hospital stay and economic costs after cardiac surgery by reducing the risk induced by increased heart rate.
Methods. This was an open-label, randomized clinical trial which enrolled 315 patients (mean age 62 ± 8 years, 65,7% men) undergoing CABG, with conduction abnormalities (47%), LV systolic dysfunction (43%) or both (10%). Exclusion criteria were: second and third degree atrioventricular block, bradycardia or conditions associated with increased risk for bradycardia (vagal predominance, sick sinus syndrome), NYHA class IV heart failure, cardiogenic shock, severe chronic obstructive pulmonary disease or pulmonary impairment, known hypersensitivity to beta blockers or ivabradine, active participation in another clinical trial, failure to comply with the hospital protocol or absence to follow-up. Two days before surgery, eligible patients were randomized in three groups: group A – 104 patients to receive metoprolol 100 mg once daily, group B – 106 patients to receive metoprolol 50 mg once daily and ivabradine 5 mg twice daily, and group C – 105 patients to receive ivabradine 5 mg twice daily. The treatment phase comprised 2 days preoperatively and at least 10 days postoperatively and the patients were followed-up for 30 days after surgery. Patients were evaluated 2 days before surgery, daily from Day 1 until Day 10, on Day 15, and 30 after surgery and clinical (NHYA class, ventricular rhythm, patient compliance, and quality of life) and laboratory parameters (blood tests, electrocardiogram, 24 hours ECG Holter monitoring and echocardiographic measures) were assessed. The efficacy endpoints were 30-days mortality, in-hospital occurrence of atrial fibrillation/arrhythmias, of third degree atrioventricular block and need for pacing, in-hospital worsening heart failure and duration of hospitalization and immobilization. Safety endpoints were bradycardia, gastrointestinal complaints, sleep disturbances, and cold extremities.
Results. There was no difference across the three groups in age, gender, number of grafts/patient, grafts type, risk score for atrial arrhythmias, treatment duration, percent of patients with left ventricular dysfunction or with conduction abnormalities, heart rate or systolic blood pressure. Heart rate reduction and prevention of postoperative atrial fibrillation or tachyarrhythmias with combined therapy (metoprolol and ivabradine) was proven more effective than with metoprolol or ivabradine alone during the immediate postoperative management of coronary surgery patients (7.6% events in group B versus 11.5% events in group A and 17% events in group C). In group C the frequency of early postoperative third degree atrioventricular block or need for pacing was lower (2.9%) than in group A (13.5%) and in group B (9.4%) (p <0.0001). The frequency of heart failure worsening was lower in patients treated with ivabradine only (1.9%) or ivabradine combined with metoprolol (6.6%) than in patients receiving only metoprolol (11.5%) (p <0.001). Ivabradine-treated patients’ quality of life was improved due to shortened hospital stay (the mean duration of hospital stay in the group A was 10.2 ± 6.3 days, compared to 8.5 ± 6.8 days in group B and 8.2 ± 6.4 days in group C), shortened immobilization duration in the immediate postoperative period (2.02 ± 3 days in group A, 1.06 ± 3 days in group B and 1.07 ± 3 days in group C), less atrial or ventricular arrhythmias, less worsening heart failure. Kaplan Meier curves generated for primary endpoints showed a superior efficacy and safety in Ivabradine groups. For the composite endpoint of efficacy endpoints and safety endpoints, the rates were 25.7% for ivabradine group, 26.4% for ivabradine plus metoprolol group and 40.4% for metoprolol group respectively. (p = 0.002). Conclusion. In patients treated with ivabradine the quality of life was improved due to shorter hospital stay, less atrial or ventricular arrhythmias, less need for permanent pacing, less worsening heart failure, shortened immobilization during the immediate postoperative period with subsequent improvement in the psychological status, as well as due to lack of significant side effects. Taking into account and the ivabradine efficacy and safety profile, the heart rate reduction in the early postoperative period after coronary surgery in patients with conduction abnormalities or LV dysfunction with ivabradine therapy emerged as the best treatment in this trial. Ivabradine should be regarded as an attractive alternative pharmacological strategy for rhythm and heart rate control in the early postoperative period in coronary artery bypass grafting in patiens with relative or absolute contraindications to beta blockers.

Cuvinte cheie: coronary artery bypass grafting, ivabradine, betablockers

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