Cardiology Xagena

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Patients with heart failure, low ejection fraction, and heart rate above 77 bpm: beneficial effects of Ivabradine

Ivabradine ( Corlanor ) has been approved in heart failure with reduced ejection fraction ( HFrEF ) and elevated heart rate despite guideline-directed medical therapy ( GDMT ) to reduce cardiovascular death and hospitalization for worsening heart failure.
The median value of 77 b.p.m. is the lower bound selected for the regulatory approval in Canada, South Africa, and Australia.

Patient-reported outcomes ( PROs ) including symptoms, quality of life, and global assessment are considered of major interest in the global plan of care of patients with heart failure.
However, the specific impact of guideline-directed medical therapy, and specifically Ivabradine, on patient-reported outcome remains poorly studied.

In the subgroup of patients from SHIFT ( Systolic Heart failure treatment with the If inhibitor ivabradine Trial ) who had heart rate above the median of 77 b.p.m. ( pre-specified analysis ) and for whom the potential for improvement was expected to be larger, the aim was: (i) to evaluate the effects of Ivabradine on PRO ( symptoms, quality of life, and global assessment ); (ii) to consolidate the effects of Ivabradine on the primary composite endpoint of cardiovascular death and hospitalization for heart failure; and (iii) to reassess the effects of Ivabradine on left ventricular remodelling.

Comparisons were made according to therapy, and proportional hazards models ( adjusted for baseline beta-blocker therapy ) were used to estimate the association between Ivabradine and various outcomes.

In SHIFT, n = 3357 ( 51.6% ) patients had a baseline heart rate more than 77 b.p.m.

After a median follow-up of 22.9 months ( inter-quartile range 18-28 months ), Ivabradine on top of GDMT improved symptoms ( 28% vs. 23% improvement in NYHA functional class, P = 0.0003 ), quality of life ( 5.3 vs. 2.2 improvement in KCCQ ( Kansas City Cardiomyopathy Questionnaire ) overall summary score, P = 0.005 ), and global assessment [ from both patient ( improved in 72.3% ) and physician ( improved in 61.0% ) perspectives ] significantly more than did placebo ( both P less than 0.0001 ).

Ivabradine induced a 25% reduction in the combined endpoint of cardiovascular death and hospitalization for heart failure ( hazard ratio, HR=0.75; P less than 0.0001 ), which translates into a number of patients needed to be treated for 1 year of 17.

Patients under Ivabradine treatment have shown a significant reduction in left ventricular dimensions when reassessed at 8 months ( P less than 0.05 ).

In conclusion, in patients with chronic HFrEF, sinus rhythm, and a heart rate more than 77 b.p.m. while on GDMT, the present analysis brings novel insights into the role of Ivabradine in improving the management of HFrEF, particularly with regard to PRO ( Xagena )

Bouabdallaoui N et al, ESC Heart Fail 2019; Epub ahead of print