Important therapeutic goals in chronic heart failure are to improve quality of life and to reduce the risk of hospitalization and mortality. According to current evidence, guideline-based therapy with the four drug groups ACE inhibitors/ARNIs, beta blockers, mineralocorticoid receptor antagonists and SGLT-2 inhibitors achieves the best effects. This has been proven in various studies.
The prevalence of heart failure in the general population varies with age group. While in <55-Jährigen bei etwa 1% liegt, sind bei>70-year-olds, they are more than 10% affected by heart failure. Women are affected slightly more often. If left untreated, heart failure patients have a significant mortality risk [1,2]. Maren Weferling, MD, Kerckhoff Klinik, Bad Nauheim, Germany, explained that heart failure is most frequently associated with coronary heart disease (CHD) and hypertension [1]. Other causes of heart failure range from cardiomyopathies to arrhythmias, storage diseases, and myocarditis to vitiation and thoracic radiation. But cardiotoxic drugs (e.g., chemotherapy, checkpoint inhibitors) and drug abuse (e.g., cocaine) also increase the risk for heart failure, the speaker explained.
NT-proBNP/BNP: high negative predictive value.
Heart failure is a clinical syndrome with symptoms and, when appropriate, signs of heart failure that may be due to structural or functional damage to the heart [1,2]. According to Dr. Weferling [1], if a patient’s history and/or physical examination and/or ECG substantiates a suspicion of heart failure, the recording of cardiac congestion parameters is indicated ( Fig. 1). NT-proBNP/BNP is a parameter with a very high negative predictive value. Subsequent echocardiography is required only if NT-proBNP/BNP values are elevated. The classification of heart failure is based on the ejection fraction (EF): if the EF is below 40%, it is considered reduced (HFrEF, Heart Failure with Reduced Ejection Fraction), If the EF is ≥50%, it is considered to be preserved (HFpEF, Heart Failure with preserved Ejection Fraction) and the area in between is assigned to the HFmrEF (Heart Failure with Mildly Reduced Ejection Fraction) attributed.
Therapy with the “Fantastic Four” is considered the gold standard nowadays
In HFrEF as well as in HFmrEF, the use of the “Fantastic Four” is propagated nowadays, i.e., one representative of each of the following groups of agents is applied simultaneously or in quick succession (Fig. 2) [2]:
- ACE inhibitor/ARNI
- Beta blocker
- Mineralocorticoid receptor antagonists (MRA).
- SGLT-2 inhibitors (dapagliflozin/empagliflozin)
It is recommended that all four medications be titrated up to the maximum tolerated dose. “Because the greatest prognostic benefit has been seen under the maximum dose,” the speaker explained. The same algorithm applies to drug therapy for HFmrEF as for HFrEF. Why HFmrEF, in contrast to HFrEF (class I), received “only” a class IIb recommendation had to do with the fact that the evidence base was based on results from subgroup analyses of studies with HFrEF and HFpEF patients, and not on stand-alone studies of HFmrEF patients, Dr. Weferling explained. Loop diuretics are used only for symptomatic therapy and are indicated primarily for congestive symptoms/edema.
ARNI or ACE inhibitor?
If patients receiving an ACE inhibitor remain symptomatic, it is recommended to switch to an ARNI (angiotensin receptor neprilysin inhibitor). In stable HFrEF patients, there is also the option of using ARNI instead of ACE inhibitors as first-line therapy [3]. “ARNIs inhibit the degradation of vasoactive peptides, have diuretic and natriuretic effects, and simultaneously have an antiproliferative effect,” the speaker explained. The latter refers to preventing negative cardiac remodeling. Moreover, ARNIs have a vasodilatory effect and inhibit sympathetic tone (CAVE: hypotension). In the PARADIGM-HF trial, a 20% risk reduction for cardiovascular death and hospitalization was achieved in the ARNI treatment arm (sacubitril/valsartan) compared with the ACE-i arm (enalapril) [3]. Only NT-proBNP may be used as a progression parameter in patients receiving ARNI treatment, as neprilysin affects BNP [4].
SGLT-2 inhibitors convince
The benefit of SGLT-2-i has been demonstrated in numerous studies. Among others, it has been shown that diabetic and non-diabetic patients with heart failure benefit from SGLT-2-i therapy. “In patients with impaired pump function, prognosis improves,” Dr. Weferling summarized [1]. SGLT-2-i is a substance that inhibits sodium-glucose cotransporter-2 in the proximal tubule of the kidney. This results in glucosuria, which has a diuretic effect and a concomitant reduction in blood pressure. At the same time, these substances also have a nephroprotective effect.
With regard to dapagliflozin, the DAPA-HF study demonstrated a reduction in cardiovascular mortality and a reduction in the rate of worsening heart failure [5]. The standard dose (starting and target dose) of dapagliflozin is 1×10 mg/d.
For empagliflozin, corresponding evidence of benefit was provided in the EMPEROR-REDUCED study. The SGLT-2-i was found to be significantly superior to placebo in the primary endpoint (cardiovascular-related death, hospitalization for heart failure symptoms) [6]. Also for empagliflozin, the standard dose (starting and target dose) is 1×10 mg/d.
Patients should be informed that genitourinary infections or vulvovaginitis are a possible side effect.
What to do in case of lack of response to therapy?
If the four-drug combination (ACE inhibitor/ARNI, beta blocker, MRA, SGLT-2-i) is not sufficient despite maximum tolerated dosing, ivabradine or vericiguat (both: class II-b recommendation) can be resorted to, Dr. Weferling said [1]. Ivabradine is an active ingredient from the group of “If” inhibitors, which lowers the heart rate at the sinus node and reduces the oxygen demand of the heart. Vericiguat is a vasodilating agent from the group of guanylate cyclase stimulators. If drug therapy has been fully established but the ejection fraction is ≤35 and the QRS complex is normal (<130), ist die Indikation für einen Defibrillator (Implantable cardioverter defibrillator, ICD) gegeben. Ist der QRS-Komplex breit (>130 ms), a resynchronization pacemaker should be added to improve cardiac pumping efficiency [1].
Congress: Freshup Hausarztmedizin
Literature:
- «Herzinsuffizienz, Cardiomyopathie, Vitien», Dr. med. Maren Weferling, Freshup Hausarztmedizin, 17./18.03.2023.
- McDonagh TA, et al.: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal 2021; Volume 42, Issue 36: 3599–3726,
- McMurray JJ, et al.: PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014; 371(11): 993–1004.
- Zile MR, et al.: Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. J Am Coll Cardiol 2016; 68(22): 2425–2436.
- McMurray JJV, et al.; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019; 381(21): 1995–2008.
- Packer M, et al.: EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med 2020 Oct 8; 383(15): 1413–1424.
- Ponikowski P, et al. : 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal 2016; 37 (27): 2129–2200.
HAUSARZT PRAXIS 2023; 18(5): 16–17
