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Outpatient Management of Stable Heart Failure with Reduced Ejection Fraction
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Leah Reid, Jonathan Murrow, Kent Nilsson, Catherine Marti
Lowering myocardial oxygen demand (MVO2) in patients with HFrEF remains a therapeutic goal to mitigate the high-energy phosphate depletion associated with impaired contractility.30 Historically, pharmacologic means of reducing MVO2 have been limited to beta-adrenergic blockers. Though beta-blockers exert a pronounced salutary effect in HFrEF, optimal dosing to reduce heart rate is constrained by their concomitant impact on systemic arterial pressure. Ivabradine is a comparatively novel pharmacologic agent that reduces heart rate without affecting blood pressure, inotropy, and vascular resistance.31 Ivabradine works at the sinoatrial node where it inhibits the inward “funny” current (If ), which is critical in determining the automaticity (spontaneous pacemaker activity) rate of the pacemaker cells. Selective inhibition of If leads to an increase in diastole duration without alteration of other phases of the action potential, and thus lowers heart rate.31
Coronary Artery Disease
Published in Jahangir Moini, Matthew Adams, Anthony LoGalbo, Complications of Diabetes Mellitus, 2022
Jahangir Moini, Matthew Adams, Anthony LoGalbo
Sodium channel blockers and sinus node inhibitors can also be used for stable angina. Ranolazine is a sodium channel blocker that treats chronic angina. Common adverse effects include constipation, dizziness, headache, and nausea. Ivabradine, a sinus node inhibitor, inhibits the inward sodium/potassium current in the gated channel in sinus node cells. It slows down the heart rate without causing decreased contractility. Ivabradine is used for chronic stable angina pectoris when there is a normal sinus rhythm, and the patient cannot tolerate beta-blockers. It is also used in combination with beta-blockers when the patient’s symptoms are not adequately controlled only by a beta-blocker, and the heart rate is more than 60 beats per minute.
Angina pectoris in the elderly
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Wilbert S. Aronow, William H. Frishman
Ivabradine is a heart rate–lowering drug that acts specifically on the sinoatrial node (121). Ivabradine caused dose-dependent improvements in exercise tolerance and time to development of ischemia during exercise (122). In a subgroup of patients with heart rate of 70 beats/ min or higher, ivabradine did not affect the primary endpoint of cardiovascular death or hospital admission for fatal and nonfatal MI (123). However, ivabradine did reduce the secondary endpoint of hospital admission for fatal and nonfatal MI by 36% (p = 0.001) and coronary revascularization by 30% (p = 0.016) (123). In the Systolic Heart Failure Treatment with the IF inhibitor Ivabradine Trial (SHIFT), ivabradine showed reduction of cardiovascular outcomes in patients with heart failure and angina pectoris (124). A meta-analysis of three randomized controlled trials in 36, 577 patients with stable angina pectoris showed that ivabradine was not effective in reducing cardiovascular mortality, all-cause mortality, coronary revascularization, and hospital admission for worsening of heart failure but increased adverse events (125). In a study of 2403 patients with stable angina pectoris, 636 patients were treated with a combination of ivabradine plus metoprolol (126). This study showed that ivabradine combined with metoprolol reduced angina symptoms and use of nitroglycerin and improved quality of life with a 14.7-point increase in the EQ-5D questionnaire (126). Combining ivabradine with low-dose bisoprolol in patients with stable angina pectoris caused additional antianginal and anti-ischemic benefits and improved chronotropic reserve (127). Ivabradine should be considered for use in patients with stable angina pectoris and heart failure being treated with beta-blockers in whom coronary revascularization is incomplete or unsuitable (128).
Ivabradine, the hyperpolarization-activated cyclic nucleotide-gated channel blocker, elicits relaxation of the human corpus cavernosum: a potential option for erectile dysfunction treatment
Published in The Aging Male, 2020
Serap Gur, Laith Alzweri, Didem Yilmaz-Oral, Ecem Kaya-Sezginer, Asim B. Abdel-Mageed, Suresh C. Sikka, Wayne J. G. Hellstrom
A comprehensive approach to treat ED in elderly men can be provided by the management of ED determinants, including overall health status such as metabolic syndrome, functional and hormonal status, psychological factors, cardiovascular alterations, and other influences [14,65]. Thus, all aspects of ivabradine treatment and its side effects must be considered. For instance, ivabradine should be avoided in patients with bradycardia, cardiogenic shock, acute myocardial infarction, hypotension, sick sinus syndrome, unstable angina, and third-degree atrioventricular block [66]. Ivabradine provides additional benefits when used in combination with the other antianginal drugs such as β-blockers (except diltiazem and verapamil). HR reduction using ivabradine is similar to that of β-blockers. In symptomatic patients, combined treatment with beta-blockers and ivabradine provides a significant benefit [67,68]. Future studies with the novel indications can improve clinicians’ confidence in prescribing ivabradine [66]. Similarly, ivabradine may be safe and effective in several other clinical settings [8]. These findings need to be confirmed by further studies.
Outcome postponement as a potential patient centred measure of therapeutic benefit: examples in cardiovascular medicine
Published in Acta Cardiologica, 2020
Pierre Vladimir Ennezat, Thierry Le Jemtel, Shona Cosgrove, Jesper Hallas, Morten Rix Hansen
Ivabradine reduces heart rate by selective inhibition of the funny channel. The Systolic HF treatment with the If-channel inhibitor ivabradine Trial (SHIFT) trial led to the approval of ivabradine for the treatment of CHF [17]. The SHIFT trial randomised 6558 patients with symptomatic CHF, left ventricular ejection fraction ≤35% and heart rate ≥70 beats per minute (in sinus rhythm) to ivabradine up to 7.5 mg bid or placebo. During a median follow-up of 23 months, 793 patients (24%) receiving ivabradine and 937 patients (29%) receiving placebo died from a cardiovascular cause or were hospitalised for HF (HR 0·82, 95% CI 0.75–0.90; ARR 5%, NNT = 20). Ivabradine did not affect overall mortality: 503 patients (16%) receiving ivabradine and 552 patients (17%) receiving placebo experienced a fatal outcome (HR 0.9; 95% CI 0.80–1.02, p = .092). During the 2.5 years of trial running time, ivabradine postponed the overall primary endpoint (cardiovascular death and hospitalisation for HF) and HF hospitalisation by 30.8 and 34.9 days, respectively.
New drugs in preclinical and early stage clinical development in the treatment of heart failure
Published in Expert Opinion on Investigational Drugs, 2019
Juan Tamargo, Ricardo Caballero, Eva Delpón
The limited efficacy of many new drugs in recent RCTs has recently shifted new drug developmental efforts from classical drugs that unload the heart or inhibit neurohumoral activation to new therapeutic targets, including hemodynamically neutral drugs that does not change BP or HR and drugs that directly target the myocardium, including drugs that improve mitochondrial function, myocardial energy supply, systemic inflammation, endothelial and microvascular dysfunction and cardiovascular fibrosis, modulate abnormal cellular Ca2+ handling or modulate autophagy [113,149]. The aim of these new drugs directly improving cardiomyocyte and non-myocytic function is first slow and stop cardiac remodeling and then to reverse this process back toward normal (reverse remodeling). Another approach is to develop new drugs acting via signaling pathways different, but complementary, with those exhibited by evidence-based therapy. This strategy is supported by the improvement of clinical outcomes when ivabradine was added to standard background therapy. Nevertheless, there are some drugs, particularly mineralocorticoid receptor antagonism and ARNIs, that have not yet shown their full potential in patients with HFpEF.