Both Effects and Side Effects Must Be Taken Into Account

The Treatment of Heart Failure With Reduced Ejection Fraction by Dr. med. Dominik Berliner, Dr. med. Anja Hänselmann, Prof. Dr. med. Johann Bauersachs in issue 21/2020

I would like to express my gratitude and respect to the authors for their brief, yet comprehensive review of this complex topic (1). The pharmacologist, however, cannot stay silent when it comes to some points. Stating that angiotensin-II receptor blockers (ARBs) are an alternative treatment option for patients who do not tolerate ACE inhibitors falls short, as unlike ACE inhibitors, ARBs have not been convincingly shown to improve prognosis.. Not mentioning this brings the risk that colleagues will directly prescribe the ARB in their daily practice to avoid the adverse effects of ACE inhibitors. Data of the QUALIFY registry suggest that this is already the case: One in four RAS blocker prescriptions is for an ARB (2). From a purely statistical point of view, however, 55 patients (with arterial hypertension) need to be treated with an ARB over a period of 4.1 years to prevent one withdrawal due to adverse effects compared to ACE inhibitors (3). The prognosis of heart failure is influenced by treatment adherence, which is higher with ARBs than with ACE inhibitors (yet also inadequate!). Nonetheless, it is important to take the proof of efficacy into account. Immediately following this, the formulation must also be commented on that with the ARNI “the established inhibition” of the renin-angiotensin-aldosterone system (RAAS) would be used. It is precisely the inhibition by ARBs that is not supported by strong evidence.

The rationale behind the angiotensin receptor-neprilysin inhibitor (ARNI) combination should also be mentioned (4):

• Neprilysin breaks down angiotensin II; thus, it would be counterproductive to only inhibit this endopeptidase.
• The combination with an ACE inhibitor is not an option since neprilysin inhibition alone is already associated with a relevant increase in the risk of angioedema. In the pivotal study, the incidence was, despite preselection, almost twice as high compared to enalapril treatment. Thus, the combination of neprilysin inhibitor and ARB rather represents a compromise.

DOI: 10.3238/arztebl.m2021.0044

PD Dr. med. Jan Matthes (MMEd)

Zentrum für Pharmakologie

Universität zu Köln

Köln, Germany

Conflict of interest

The author declares no conflict of interest.

References

1. Berliner D, Hänselmann A, Bauersachs J: The treatment of heart failure with reduced ejection fraction. Dtsch Arztebl Int 2020; 117: 376–86

2. Komajda M, Schöpe J, Wagenpfeil S, et al.: Physicians‘ guideline adherence is associated with long-term heart failure mortality in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry. Eur J Heart Fail 2019; 21: 921–9

3. Li EC, Heran BS, Wright JM: Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev 2014; 2014 (8): CD009096

4. Matthes J: Sacubitril und Valsartan – Entresto®. In: Beck T, Fricke U. Neue Arzneimittel. Fakten und Bewertungen. Band 23. Wissenschaftliche Verlagsgesellschaft Stuttgart (in press).