Diuretic therapy is the basis of drug therapy in symptomatic HF. It clearly improves symptoms and quality of life [9]. Diuretics are used in an acute setting for patients with volume overload in usually higher doses for the amelioration of symptoms (e. g., dyspnea, edema) and in patients with compensated HF to maintain a stable state (i. e., “weight”). The dose of diuretics should be as low as necessary, at the minimum effective dose, to reach and keep euvolemia. In the course of the disease, the potential for dose reductions should be checked regularly [2]. Especially in the elderly, confusion is frequently a consequence of fluid depletion due to restriction and the additional use of diuretics. Furthermore, it may be caused by hyponatremia as a consequence of the diuretic therapy [4].

Two randomized trials have investigated the value of beta-blockers in elderly patients with HF. In the SENIORS trial, therapy with nebivolol was compared with placebo. Mean age in this study was 76 years. Therapy with nebivolol led to a significant reduction of the primary endpoint all-cause mortality and cardiovascular hospitalizations (31.1% vs. 35.3%; relative risk reduction 12% [10]). The CIBIS-ELD trial compared therapy with the beta-blockers bisoprolol and carvedilol in older patients (mean age 73 years). No differences were found regarding tolerance or achieved target dose, but patients with bisoprolol more often suffered from bradycardias whereas carvedilol led to a reduction in the forced expiratory volume (FEV₁) [11]. This should be taken into account when choosing the “individual” beta-blocker. Furthermore, a later analysis of the CIBIS-ELD trial revealed that heart rate after up-titration, but not the dose of the beta-blocker, predicted all-cause mortality risk [12]. Elderly patients with a heart rate in the range of 55–64 bpm had the lowest mortality [12]. In the MERIT-HF trial, therapy with metoprolol succinate was compared with placebo in patients with HF. The study enrolled patients up to an age of 80 years and included a considerable percentage of elderly patients. A retrospective subgroup analysis found a similar reduction regarding mortality and morbidity in patients 69 years or older compared with those younger than 69 years [3, 13].

Randomized controlled studies in elderly patients with ACEi or angiotensin receptor blocker (ARB) do not exist. In the CONSENSUS trial (enalapril vs. placebo), mortality was significantly reduced in the enalapril arm (26% vs. 44% after 6 months). The mean age in this trial was 71 years, which means that a considerable percentage of elderly patients were enrolled [14]. Thus, a benefit for older patients can be deduced from this trial. Observational studies and a meta-analysis of studies in patients after myocardial infarction with HF confirm these findings [3].

To avoid severe hypotension or renal insufficiency, ACEi should be started in low doses after correction of hyponatremia or volume depletion in the elderly [15]. The dose of the diuretics might have to be raised transiently after reaching the maintenance dose of the ACEi [15]. In the further course of treatment, diuretics might be reduced again.

Since the RALES trial [16], the EPHESUS trial [17], and the EMPHASIS-HF trial [18], therapy with mineralocorticoid receptor antagonists (MRA) for patients with symptomatic HFrEF despite therapy with an ACEi and a beta-blocker is established and implemented in the guidelines. Randomized controlled trials with MRA in the elderly with HF also have not been performed. However, prespecified subgroup analyses both in the RALES and in the EMPHASIS-HF trial have shown that older HF patients benefit from treatment with an MRA to a similar extent as younger patients [16, 18, 19].

The most important adverse effect of MRA treatment is hyperkalemia. Particularly in older patients, renal markers and electrolytes should be checked regularly—especially with concomitant medication with an ACEi or an ARB. Higher age is an independent risk factor for developing hyperkalemia [3].

In the near future potassium binders like patiromer might help in reaching adequate HF medication despite the tendency toward hyperkalemia. Patiromer is a polymer that acts as an ion exchanger in the colon. The PEARL-HF trial enrolled 105 HF patients with a history of hyperkalemia resulting in discontinuation of the HF medication. In the patiromer group, potassium was significantly lowered resulting in higher dosages of the HF medication (i. e., spironolactone dose) [20].

Through inhibition of the I_f channel of the sino-atrial node, ivabradine slows the heart rate in sinus rhythm. In the SHIFT trial, additional administration of ivabradine on top of optimized HF medication (incl. beta-blocker) led to a significant decrease in HF hospitalizations and cardiovascular mortality (primary endpoint, relative risk reduction: 18%) [21] resulting in a corresponding recommendation in the current guidelines [2]. Likewise, for ivabradine no randomized study exists concerning efficacy in the elderly. However, in a subgroup analysis the efficacy and safety of ivabradine were evaluated across the age spectrum: Patients were divided into four groups (<53, 53–60, 60–69, and >69 years), and ivabradine use was associated with a relative risk reduction of the primary endpoint with no statistical difference in the elderly [22]. The authors conclude that, “age does not limit the appropriate use of ivabradine in patients with chronic HF and systolic dysfunction” [22].

In the past few years, a new drug class of “angiotensin receptor-neprilysin inhibition (ARNI)” emerged in HF therapy. The first and to date only substance in this class is “LCZ696” and comprises an angiotensin receptor blocker (ARB, valsartan) and sacubitril, which is an inhibitor of the neutral endopeptidase (neprilysin) reducing degradation of natriuretic peptides. The PARADIGM-HF trial compared therapy with sacubitril/valsartan with therapy with the ACEi enalapril [23]. The primary endpoint consisted of cardiovascular mortality and HF hospitalizations and was highly significantly reduced in the sacubitril/valsartan group (−20%). Furthermore, a significant reduction was shown for cardiovascular mortality (−20%), all-cause mortality (−16%), and HF hospitalizations (−21%). The overwhelming effects have resulted in the recommendation for an ARNI in the current guidelines for all patients who remain symptomatic despite therapy with an ACEi (or ARB), a beta-blocker, and an MRA [2, 24]. Regarding the elderly, the authors of a recent subgroup analysis stated that LCZ696 was more beneficial than enalapril across the spectrum of age in the PARADIGM-HF trial, with a favorable benefit–risk profile in all age groups including the elderly [25]. Besides, typical side effects of the therapy (hypotension, renal impairment, hyperkalemia) were similar in the age categories analyzed [25]. It should be kept in mind, especially regarding older patients, that sacubitril/valsartan provokes a significantly higher incidence of symptomatic hypotension than does therapy with an ACEi. Thus, patients with very low blood pressure during ACEi treatment should not be switched to an ARNI [26].

Maison et al. reported that digitalis is prescribed more frequently in older HF patients (>75 years) than in younger patients (≤75 years) at hospital discharge [27]. Overall the role and significance of cardiac glycosides in the treatment of chronic HF is currently still unclear [28]. There is one prospective, randomized study with digoxin (DIG trial) in patients with HFrEF [29], which was conducted before the current HF medication was established (i. e., very low rate of concomitant therapy with beta-blocker and MRA). Hospitalizations for HF were significantly reduced in the digoxin group whereas total mortality was not influenced. A subgroup analysis of the DIG trial showed that in patients with lower serum levels of digoxin (0.5–0.9 ng/ml), total mortality was significantly reduced in contrast to patients with high levels (excess mortality) [30]. Especially patients with advanced HF (NYHA III–IV, LVEF <25%) and patients with atrial fibrillation and high ventricular rate seem to benefit from the therapeutic use of cardiac glycosides regarding mortality and hospitalization rates [31]. A subgroup analysis of the DIG trial showed that digoxin reduced the 30-day all-cause hospital admission in older patients with chronic HF and indicated a trend to a lower 30-day all-cause mortality in those patients [32]. Owing to the narrow therapeutic range of cardiac glycosides, they should be used with caution especially in women and older patients, and digitoxin should be preferred particularly in patients with impaired renal function [2].

There are no trials to date on digitoxin or the effect of digitalis in HF patients with atrial fibrillation. A large randomized study investigating the role of digitoxin in patients with HF on contemporary drug therapy is under progress: the DIGIT-HF trial (Digitalis to Improve Outcomes in Patients with Advanced Systolic Chronic Heart Failure, EudraCT-No.: 2013-005326-38).

Generally, international guidelines consistently recommend that the drug therapy for elderly HF patients should be based on beta-blockers and ACEi (or ARB) [2‐4]. Furthermore, addition of an MRA should be considered. Cardiac glycosides may improve symptoms in those patients but should be used with caution especially in patients with reduced renal function to prevent intoxications. Digitoxin should be used rather than digoxin in such patients [4]. Individual doses of diuretics, normally loop diuretics, should be used to keep volume homeostasis. Electrolytes and renal function should be controlled on a regular basis.

Data from the INH registry (interdisciplinary network for heart failure) showed clearly that older patients in particular benefit from a pharmacological therapy according to the guidelines ([33]; Fig. 2).