Optimizing individual heart failure treatment

A mineralocorticoid receptor antagonist (MRA) is recommended in patients with chronic heart failure.^1–5 However, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) is less documented. Kitakaze and co-workers from Japan have performed a multicentre, randomized, double-blind, placebo-controlled, parallel-group study in 300 patients with AHF. The patients were randomized to eplerenone or placebo. The primary outcome was a composite of cardiac death or first rehospitalization due to cardiovascular disease within 6 months. No significant difference in primary outcome was found. The authors concluded that early initiation of eplerenone in patients with AHF could safely be utilized.

The PARADIGM-HF study⁶ did not analyse the effect of ventricular remodelling on patients with different aetiologies, which may affect clinical treatment outcomes. In a paper from Taiwan, Chang and co-workers aimed to compare left ventricular ejection fraction (LVEF) following sacubitril/valsartan (SAC/VAL) treatment and its association with clinical outcomes in 1576 patients. The authors found that patients with non-ischaemic cardiomyopathy (NICM) had a higher degree of LVEF improvement than those with ischaemic cardiomyopathy (ICM) following SAC/VAL treatment, and significant improvement of LVEF in NICM patients.

Anticancer drugs may be associated with different kinds of heart problems.^7–9 The anti-HER2 agent trastuzumab reduces risk of disease progression or death in breast cancer patients.⁹ However, HER2 isoforms are also expressed in cardiomyocytes and may cause increased risk of left ventricular (LV) dysfunction and a five- to seven-fold increased risk of heart failure.⁹ Paterson and co-workers from Canada aimed to characterize the cardiac and cardiometabolic phenotype of trastuzumab-mediated toxicity and potential interactions with cardiac pharmacotherapy. The study was an analysis of serial magnetic resonance imaging (MRI) and circulating biomarker data acquired from patients with HER2-positive early stage breast cancer participating in a randomized controlled clinical trial for the pharmacoprevention of trastuzumab-associated cardiotoxicity. The authors report that trastuzumab results in impaired cardiac function and early myocardial inflammation. Trastuzumab was also associated with deleterious changes to the cardiometabolic phenotype, which may contribute to the increased cardiovascular risk in this population.

The beneficial effect of β-blocker on heart failure with reduced ejection fraction (HFrEF) is well established.^1,10 However, its effect on the short-term outcome of heart failure with midrange ejection fraction (HFmrEF) is less clear. Zheng et al. from China have analysed the data of 1036 patients with LVEF between 40% and 49% in China The Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure (China, PEACE 5p-HF) study. Two primary outcomes were all-cause death and all-cause hospitalization. The authors concluded that in patients with HFmrEF, β-blocker use was associated with lower risk of all-cause death, but not with lower risk of all-cause hospitalization.

Uncontrolled blood pressure (BP) increases the risk of developing HF.¹ The effect of spironolactone on the BP of patients at risk of developing HF is yet to be determined. Ferreira and co-workers aimed to evaluate the effect of spironolactone on the BP of patients at risk for HF and whether renin can predict spironolactone’s effect in a prospective multicentre randomized open-label blinded endpoint (PROBE) trial including 527 patients at risk for developing HF randomly assigned to either spironolactone (25–50 mg/day) or usual care alone for a maximum of 9 months. The authors report that a higher proportion of patients on spironolactone had controlled BP in the spironolactone group and lower baseline renin levels predicted a greater response to spironolactone. The conclusion of the study was that spironolactone should be considered for lowering blood pressure in patients who are at risk of developing HF.

The pandemic caused by the SARS-CoV-2 virus has spread worldwide and many questions about the pathophysiology of the SARS-CoV-2 infection are unanswered. In a study from Spain, Masana and co-workers aimed at assessing the effect of statin therapy at hospital admission for COVID-19 on inhospital mortality. In a retrospective observational study, they report a significantly lower mortality rate in patients on statin therapy than the matched non-statin group and the mortality rate was even lower in patients who maintained their statin treatments during hospitalization compared with the non-statin group. Also, the Cox model suggested that statins were associated with reduced COVID-19-related mortality. The authors concluded that a lower SARS-CoV-2 infection-related mortality was observed in patients treated with statin therapy prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19. Several other observational studies have shown potential beneficial effects of lipid-lowering treatment on the course of COVID-19 with significantly improved prognosis and reduced mortality.^11–13 Findings from ongoing rigorously conducted and adequately powered randomized clinical trials (RCTs) can assess the possible efficacy of lipid-modulating agents in the prevention or treatment of various stages of COVID-19 and may open new horizons for research and clinical practice.¹⁴

Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEis/ARBs) is thought to affect COVID-19 through modulating levels of angiotensin-converting enzyme 2, the cell entry receptor for SARS-CoV2.^15,16 There are many observational studies on this topic.^17,18 In a meta-analysis, McMurray and co-workers included non-randomized observational COViD-19 studies, comparing ACE inhibitor/ARB treatment. Eighty six studies, including 459 755 patients (103 317 with hypertension), were analysed. In patients with hypertension, ACE inhibitor or ARB treatment was not associated with a greater likelihood of SARS-CoV-2 infection in 60 141 patients, hospitalization or case fatality in 18 735 patients with 2893 deaths. In all patients (irrespective of hypertension), findings were consistent for likelihood of SARS-CoV-2 infection in 363 865 patients. The authors concluded that ACE inhibitors and ARBs appear safe in the context of SARS-CoV-2 infection and should not be discontinued.

The rising prevalence of obesity and its associated comorbidities represents a growing public health issue, as a risk factor for both cardiovascular disease^19,20 and COVID-19. Many randomized controlled trials have demonstrated the clinical utility of orlistat in achieving weight loss when compared with lifestyle measures alone.^21–23 Collins and co-workers aimed to explore long-term cardiovascular outcomes after orlistat therapy in a propensity score matched cohort study of healthcare records of the Clinical Practice Research Datalink. The 36 876 patients with obesity who had completed a course of orlistat were matched with controls who had not taken orlistat. The authors concluded that orlistat was associated with lower rates of overall major adverse cardiovascular events, new onset heart failure, renal failure, and mortality during the median study follow-up of 6 years.

Heart failure patients are usually at high risk of polypharmacy and, consequently, potentially inappropriate prescribing leading to poor clinical outcomes.^24–26 We are pleased to publish a position statement from Coats and co-workers entitled ‘Position statement on HFrEF specific inappropriate prescribing’.

References