Effect of If-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial.

Aims
This randomized, double-blind, placebo-controlled trial assessed whether heart rate (HR) reduction with ivabradine improves cardiac function in heart failure with preserved ejection fraction (HFpEF).

Methods and results
The prEserveD left ventricular ejectIon fraction chronic heart Failure with ivabradine studY (EDIFY) included 179 patients in New York Heart Association (NYHA) classes II and III, in sinus rhythm, with HR of ≥70 b.p.m., NT-proBNP of ≥220 pg/mL (BNP ≥80 pg/mL) and left ventricular ejection fraction of ≥45%. Ivabradine (or placebo) was titrated to 7.5 mg b.i.d. Patients were followed for 8 months on the change and assessed for three co-primary endpoints: echo-Doppler E/e′ ratio, distance on the 6-min walking test (6MWT), and plasma NT-proBNP concentration. At baseline, median E/e′ was 12.8 [interquartile range (IQR): 9.9–16.3], median distance on the 6MWT was 320 m (IQR: 247–375 m), and median NT-proBNP was 375 pg/mL (IQR: 253–701 pg/mL). Baseline median HR was 75 b.p.m. (IQR: 70–107 b.p.m.). A total of 171 patients (87 in the ivabradine group, 84 in the placebo group) were evaluated for treatment efficacy. After 8 months of treatment, findings showed a median change in HR of −13.0 b.p.m. (IQR: −18.0 to −6.0 b.p.m.) in the ivabradine group and −3.5 b.p.m. (IQR: −11.5 to 3.0 b.p.m.) in the placebo group [estimated between-group difference: 7.7 b.p.m.; 90% confidence interval (CI) −10 to −5.4; P < 0.0001]. No evidence of improvement was found in any of the three co-primary endpoints. There was almost no change in median E/e′ in either of the two groups [median change: +1.0 (IQR: −0.8 to 2.9) in the ivabradine group; −0.6 (IQR: −2.2 to 1.4) in the placebo group; estimated between-group difference: 1.4, 90% CI 0.3–2.5; P = 0.135]. There were no meaningful changes in the other co-primary endpoints and no apparent trends. There was no significant safety concern.

Conclusions
In patients with HFpEF, HR reduction with ivabradine did not improve outcomes. These findings do not support the use of ivabradine in HFpEF.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejhf.876

Effect of ivabradine in patients with heart failure with preserved ejection fraction: the EDIFY randomized placebo-controlled trial.

The Clinical Use of Ivabradine.

Cardiac fibrosis are central to various cardiovascular diseases. Research on the mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in recent years. However, while many anti-fibrotic treatments have been studied in animal models and seem promising, translation of experimental findings into human patients has been rather limited. Thus, several potential new treatments which have shown to reduce cardiac fibrosis in animal models have either not been tested in humans or proved to be disappointing in clinical trials. A majority of clinical studies are of small size or have not been maintained for long enough periods. In addition, although some conventional therapies, such as renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to reduce cardiac fibrosis in humans, cardiac fibrosis persists in patients with heart failure even when treated with these conventional therapies, indicating a need to develop novel and effective anti-fibrotic therapies in cardiovascular disease. In this review article, we summarize anti-fibrotic therapies for cardiovascular disease in humans, discuss the limitations of currently used therapies, along with possible reasons for the failure of so many anti-fibrotic drugs at the clinical level. We will then explore the future directions of anti-fibrotic therapies on cardiovascular disease, and this will include emerging anti-fibrotics that show promise, such as relaxin. A better understanding of the differences between animal models and human pathology, and improved insight into carefully designed trials on appropriate end-points and appropriate dosing need to be considered to identify more effective anti-fibrotics for treating cardiovascular fibrosis in human patients.

/pdf/a-clinical-perspective-of-anti-fibrotic-therapies-for-vmps5pl89a.pdf

A Clinical Perspective of Anti-Fibrotic Therapies for Cardiovascular Disease.

Effect of very high intensity statin therapy on regression of coronary atherosclerosis.

Objectives: To determine if heart rate (HR) reduction with ivabradine (IVA), a selective inhibitor of the pacemaker I f current, prevents cardiac dysfun

/pdf/heart-rate-reduction-by-ivabradine-reduces-diastolic-azz181ykrn.pdf

Heart rate reduction by ivabradine reduces diastolic dysfunction and cardiac fibrosis.

Aortic valve stenosis (AVS) is the most common valvular heart disease, and standard curative therapy remains open heart surgical valve replacement. The aim of our experimental study was to determine if apolipoprotein A‐I (ApoA‐I) mimetic peptide infusions could induce regression of AVS.

Jean-Gilles Latour

Papers

Heart rate reduction by ivabradine reduces diastolic dysfunction and cardiac fibrosis.

Abstract 6143: Regression of Aortic Valve Stenosis by ApoA-I Mimetic Peptide Infusions in Rabbits