Pharmacotherapy in Polish patients with heart failure with reduced ejection fraction: is it optimal?

Despite multidirectional therapy, morbidity, mortality, and hospitalization rates remain high in patients with heart failure with reduced ejection fraction (HFrEF), with a 5-year survival rate of 25%, highlighting the need for treatment optimisation [1].

This analysis characterizes the Polish HFrEF population before dapagliflozin therapy (study protocol No.: D1699R00034). The study included patients with HFrEF [left ventricular ejection fraction (LVEF) ≤ 40%], persistent heart failure (HF) symptoms, and in New York Heart Association (NYHA) class II–IV despite the use of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II type 1 receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitors (AR-NIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs), if indicated.

The cross-sectional analysis on baseline values included 221 HFrEF patients with a mean age of 70.8 ± 9.66 years (men, 72.85%). The dominant etiology was ischemic (59.7%), and most patients were in NYHA class II (72.3%) or III (25.9%), with a mean LVEF of 34% ± 6.8%. Mean N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were 3774.1 ± 4282 pg/mL. Over 50% of patients had sinus rhythm (56.1%) and preserved renal function, with a mean estimated glomerular filtration rate (eGFR) of 62.1 ± 24.5 mL/min/1.73 m². The patients were enrolled consecutively in 16 centers (4 HF dedicated).

The study population represented Polish HFrEF patients considered to be optimally treated with the recommended drug classes before dapa-gliflozin initiation (Fig. 1). The optimal guideline-directed medical therapy (GDMT) was confirmed by the opinion of an attending cardiologist.

Figure 1.

Treatment of Polish heart failure with reduced ejection fraction (HFrEF) patients with the recommended drug classes before dapagliflozin initiation; *None — no drug within that class; Small dose — up to 49% of optimal dose; High dose — 50–99% of optimal dose; Optimal dose — 100 or > 100%; Other or missing — other drugs within that class not listed in ESC 2021 guidelines (27 patients received other ACEi, 8 patients received other ARB treatment, 6 patients received other BB) or missing response (1 patient for ARNI, 1 patient for MRA); ACEI — angiotensin-converting enzyme inhibitors; ARB — angiotensin II type 1 receptor blocker; ARNI — angiotensin receptor-neprilysin inhibitors; BB — beta-blocker; GDMT — guideline-directed medical therapy; MRA — mineralocorticoid receptor antagonist; SBP — systolic blood pressure

Heart rate (HR) was well controlled (mean: 73.3 ± 10.57 beats/min). Most patients (95.5%) received beta-blockers. The mean systolic blood pressure (SBP) was 126.6 ± 15.1 mmHg; however, 36.2% of patients had an SBP above 130 mmHg, and 17.6% had diastolic blood pressure (DBP) above the recommended 80 mmHg.

The evaluation GDMT revealed that more than 90% of patients received ACEIs/ARBs/ARNIs and beta-blockers, but only 64.25% received MRAs. Nearly 50% of individuals were treated with high-dose (target dose ESC guideline-recommended) ACEIs/ARBs/ARNIs or beta-blockers, while only 62% received high-dose MRAs. Among drugs targeting the renin-angiotensin-aldosterone system (RAAS), ARBs were the least common. Only 5.4% of patients were not taking ACEIs/ARBs/ARNIs, compared with 4.5% for beta-blockers and 35.8% for MRAs. The underuse of MRAs may result from concerns about hyperkalemia and deterioration of renal function [2]. Hyperkalemia is a known risk factor for underprescribing MRAs, but some physicians are also reluctant to prescribe them to patients with low blood pressure (BP) [3]. Globally, MRA underuse in HFrEF patients is often driven by concerns about potential adverse events [4].

An important finding is that 41.2% of patients were not receiving medication from any of the three cornerstone drug classes (ARNIs, beta-blockers, MRAs). Among patients with an SBP exceeding 130 mmHg, ARNIs were less frequently used in combination with beta-blockers and MRAs than ACEIs or ARBs. Only about 25% of patients with elevated BP received optimal doses of ACEIs, while optimal doses of ARBs were prescribed in 14% of patients; beta-blockers in 17%; and MRAs in 31.9%.

The Polish HFrEF population reflects the population from the DAPA-HF trial [5] but they were older, which may be partially associated with higher NT-proBNP levels (Polish cohort 3777.1 vs. DAPA-HF 1428 pg/mL) [6], higher incidence of AF, similar characteristics including male pre-dominance, ischemic etiology of HF, NYHA class II, and mean LVEF (30–35%), HR, and SBP.

The types and doses of drugs indicate suboptimal treatment in the Polish population. Also, in the Dutch TITRATE-HF trial, 44% of HFrEF patients received quadruple therapy, only 1% target dose for all drug classes. Moreover 13% were not treated with any RAAS inhibitors, 43% did not receive ARNIs, 13% were not on beta-blockers, and 24% did not receive MRAs, not related to contraindications [7]. GDMT remains a challenge because of therapeutic inertia of cardiologists, polypharmacy, comorbidities, and low adherence.

The Polish cohort could benefit from further treatment optimisation, such as increased MRA administration, especially in patients with elevated BP, who should tolerate higher target drug doses.

In GDMT, each drug class has a unique mechanism of action that complements the others. MRAs lower BP significantly and are crucial for comprehensive HF management. In addition to MRAs, diuretics were used by patients in the Polish study, although they were prescribed only to 64% of individuals with an SBP above 130 mmHg. On the other hand, SGLT2is reduce blood sugar by promoting glucose excretion and enhance urinary sodium excretion, leading to mild diuresis and slight BP reduction [8]. They can also be safely used in patients with impaired kidney function, offering cardiovascular and renal benefits when the use of other drug classes is limited or contraindicated. For maximum benefit, concurrent optimisation of other drug classes is necessary.

The underuse of ARNIs is also noteworthy, given that it was used at similar rates in both the DAPA-HF and EVOLUTION-HF trials. However, considering that the DAPA-HF data were collected in 2017–2018 and the EVOLUTION-HF data in 2022–2023, the use of ARNIs in the Polish population appears insufficient over time. As a real-world evidence study, EVOLUTION-HF demonstrates the real use of medications by HFrEF patients.

In Poland, access to optimal therapy for HFrEF is limited by the lack of reimbursement for ARNIs, which may contribute to differences in treatment regimens. While SGLT2is (flozins) and MRAs are reimbursed, not all patients have access to optimal therapy, which may affect treatment outcomes. Moreover, flozins can be used regardless of BP and in cases of impaired kidney function, which may limit the use of other drugs in HFrEF treatment. Additionally, patient compliance is critical, because poor adherence can reduce the effectiveness of HF treatment and worsen prognosis, highlighting the need for improved patient engagement.

The analysis of data from major trials (EMPHASIS-HF, PARADIGM-HF, and DAPA-HF) shows that the combination of ARNIs, beta-blockers, MRAs, and SGLT2is in patients with chronic HFrEF provides significant survival benefits by prolonging life expectancy and delaying first hospitalization for HF or cardiovascular death by 2.7 to 8.3 years, depending on patient age [9].

Initiatives by the Polish Cardiac Society such as developing a structured care program for HF patients and maintaining a HF registry could contribute to better care for HF patients.

Data availability statement

The source data supporting the findings of this study are available from the corresponding author upon reasonable request.