A major mechanism by which these agents are thought to provide benefit is by reducing myocardial oxygen demand by lowering heart rate through antagonism of sympathetic receptors in myocardial pacemaking tissue. This mechanism is supported by studies demonstrating strong associations between increasing resting heart rate HR and cardiovascular outcomes in patients with ischemic cardiomyopathy. Despite their beneficial effects, beta blockers have some untoward effects which become more pronounced in patients with HFrEF, including hypotension and decreased inotropy. The novel sinus node modifying agent ivabradine lowers heart rate by inhibiting the "funny current" I f channel which is critical in determining the automaticity rate of pacemaking cells in the sinoatrial node.
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The goal of the trial was to evaluate the heart rate reducing agent ivabradine compared with placebo among patients with chronic heart failure. Ivabradine inhibits the I f current in the sinoatrial node. Ivabradine was titrated up or down according to tolerability and heart rate. Overall, 6, patients were randomized. Cardiovascular mortality or heart failure hospitalization was Cardiovascular mortality was 7.
Among patients with moderate to severe heart failure, the use of the heart rate reducing agent ivabradine was beneficial. This agent reduced the composite outcome of cardiovascular mortality or heart failure hospitalization compared with placebo. While well tolerated, ivabradine was associated with more symptomatic and asymptomatic bradycardia. This represents a new approach to heart failure management, especially in patients who are unable to tolerate high-dose beta-blockers.
Lancet ; Heart rate as a risk factor in chronic heart failure SHIFT : the association between heart rate and outcomes in a randomised placebo-controlled trial. Presented by Dr. Description: The goal of the trial was to evaluate the heart rate reducing agent ivabradine compared with placebo among patients with chronic heart failure. Hypothesis: Ivabradine will be more effective at improving cardiovascular outcomes.
Principal Findings: Overall, 6, patients were randomized. Interpretation: Among patients with moderate to severe heart failure, the use of the heart rate reducing agent ivabradine was beneficial.
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Systolic Heart failure treatment with the IF inhibitor ivabradine Trial - SHIFT
Ivabradine, a funny current If inhibitor, has been developed for symptomatic therapy of angina and in chronic heart failure CHF with low ejection fraction. Ivabradine improved health-related quality of life significantly and reduced the number of recurrent hospitalizations for HF. Sub-studies conducted in subgroups with important co-morbidities, i. The acute cardiac effect is characterized by a reversal of the abnormal force—frequency relationship, thus resulting in preserved contractile function and increased stroke volume despite heart rate reduction.
Ivabradine and Outcomes in Chronic Heart Failure (SHIFT): A Randomised Placebo-Controlled Study
Study record managers: refer to the Data Element Definitions if submitting registration or results information. Placebo Comparator: Placebo Drug: Placebo Matching placebo tablets to be taken orally twice daily, at hours intervals, in the morning and in the evening during meals up to 42 months. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.