Addressing an Unmet Need in Systolic HF With Ivabradine

Study Questions:

What is the role of ivabradine in patients with systolic heart failure (HF)?

Methods:

This article reviews several trials regarding the clinical benefits and the role of ivabradine in patients with systolic HF.

Results:

There are several studies that suggest that ivabradine improves symptoms and quality of life, prolongs survival, and prevents hospitalizations in patients with systolic HF. The first study added ivabradine to standard HF therapies that included diuretics, ACE inhibitor, and beta blockers in patients with Class II or III HF who were still symptomatic despite current treatment. Patients who received ivabradine on top of standard therapy showed significantly increased exercise endurance (p < 0.0001). VO2 max was also significantly increased (p < 0.0001). Additionally, there was improvement in functional class and quality of life (based on the Minnesota Living With Heart Failure Questionnaire) and a 16% improvement in ejection fraction. Another study randomized Class II or III HF patients to either ivabradine alone, ivabradine in combination with carvedilol, or carvedilol alone. These patients were already on optimal doses of ACE inhibitors but were beta-blocker naïve. The primary endpoint was to evaluate the effect on exercise duration, exercise capacity, quality of life, and reduction in heart rate with the different treatment strategies. Patients were initiated on lower doses of ivabradine twice daily (5 mg) and carvedilol twice daily (12.5 mg) with the goal of titrating after 2 weeks to 7.5 mg twice daily for ivabradine alone, 7.5 mg twice daily of ivabradine plus 12.5 mg twice daily of carvedilol, or 25 mg twice daily of carvedilol alone. More patients (88%) achieved maximal doses of ivabradine in the ivabradine-only group compared with the combination group (76%, p < 0.003) and when compared with carvedilol alone (18%, p < 0.001). The 6- minute walk test and peak VO2 improved in patients receiving either ivabradine alone or ivabradine in combination with carvedilol (p < 0.01 and p < 0.03, respectively) but was unchanged in patients treated with carvedilol alone. This benefit of ivabradine was also seen in quality of life, which was also significantly improved with the both ivabradine alone and the combination but not with carvedilol alone. Ivabradine has also been evaluated when added to standard HF therapy to determine if there is a reduction in cardiovascular death or hospital admissions from worsening HF. When added to standard therapy, patients treated with 7.5 mg twice daily of ivabradine demonstrated a significant reduction in the composite endpoint of cardiovascular death or hospital admission for worsening HF compared with placebo (p < 0.0001). Additionally, death secondary to pump failure was reduced by 26% in patients treated with ivabradine (p = 0.014). Not only has ivabradine demonstrated many clinical benefits in these trials, but it also has a favorable safety profile and was well tolerated.

Conclusions:

Several studies have shown a benefit to utilizing ivabradine in the management of Class II and III HF patients. Clinical evidence demonstrates that ivabradine provides improvement in symptoms and quality of life, prevents hospitalizations, and reduces death from pump failure, which makes it an attractive addition to our current armamentarium for managing this patient population. Ivabradine has also shown beneficial effects on symptoms and exercise tolerance with or without beta blocker therapy, making it an option especially in patients who may not tolerate beta blockers.

Perspective:

Ivabradine has been studied predominately in Class II and Class III HF patients who are generally stable. The optimal time for initiating therapy is still yet unknown, but it appears safe and well-tolerated when started at the same time as a beta blocker. However, the benefit of ivabradine in more advanced HF is unknown, and its use should be reserved specifically for Class II or Class III patients. Ivabradine certainly has a role in HF and should be considered as add-on therapy to a standard HF regimen. This may be accomplished in either the inpatient our outpatient setting.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Chronic Heart Failure

Keywords: Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, Benzazepines, Diuretics, Exercise Tolerance, Heart Failure, Systolic, Heart Rate, Quality of Life, Questionnaires


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