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  • br Introduction Heart failure HF is a chronically progressiv

    2024-05-15


    Introduction Heart failure (HF) is a chronically progressive disease and one of the most important causes of morbidity and mortality worldwide despite recent improvements in its treatment [1], [2], [3]. The mortality and morbidity benefits of angiotensin converting enzyme inhibitor (ACEI) are well established in HF with reduced ejection fraction (HFrEF) [4], [5], [6]. Previous studies have also shown beneficial effects of angiotensin bromfenac blocker (ARB) in HFrEF patients who cannot tolerate ACEI [7], [8]. In the OPTIMAAL study, a randomized controlled trial to compare the effects of losartan 50mg and captopril 150mg, the captopril group had more favorable outcomes compared with the losartan group [9]. However, since the introduction of accelerated up-titration of renin angiotensin system blocker (RASB) to maximum tolerated dosages there are limited data directly comparing the beneficial effects between ACEI and ARB in HFrEF patients. Although current guidelines recommend that ARB could be used as an alternative treatment in HFrEF patients who are intolerant to ACEI, in real clinical practice ARB is widely prescribed as first-line therapy for HF instead of ACEI because of the side effects of the latter, such as cough and angioedema [10], [11]. We performed the present study using multicenter prospective registry data in Korea to evaluate the beneficial effects of ARB compared with ACEI or no use of RASB.
    Methods
    Results
    Discussion Unlike ACEIs, ARBs do not inhibit kininase which leads to bradykinin degradation and have a lower incidence of cough or angioedema as side effects, although the bradykinin accumulation induced by ACEI may produce beneficial vasodilatory effects [16], [17], [18]. If the beneficial effects of ARBs on clinical outcomes are similar to those of ACEIs in patients with HFrEF, ARBs may be a better choice of first-line therapy for HFrEF because of their good tolerability and low incidence of adverse effects compared with ACEIs. The VALIANT trial, a previous randomized controlled trial of valsartan, captopril, or valsartan plus captopril in patients with myocardial infarction complicated by heart failure with LV systolic dysfunction, indicated that valsartan is as effective as captopril [19]. In addition, bromfenac CHARM-Alternative trial showed that candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with HFrEF and intolerance to ACEI [7]. However, both the OPTIMAAL and ELITE II trials comparing losartan and captopril in HFrEF patients showed neither superiority nor non-inferiority of losartan 50mg relative to captopril 150mg, although it should be noted that these studies used a low dose of losartan [9], [20]. Previous studies documented that a high dose of RASB was associated with lower rates of death or re-hospitalization due to HF compared to a low dose of RASB and that accelerated up-titration of RASB to the maximum tolerated dosage is an effective and safe intervention for HF management [21], [22], [23]. However, subsequent to the introduction of up-titration of RASB, no observational studies or randomized controlled trials have been performed in which high dose ARB was compared with high dose ACEI in a head-to-head fashion and current guidelines still recommend ARB as only an alternative to ACEI in HFrEF patients [11], [24]. The present study evaluated ARB versus ACEI or no use of RASB in patients with HFrEF after development of the up-titration strategy, although this study is an observational study rather than a randomized controlled trial. Consistent with numerous previous studies, our data show that use of ARB at discharge was associated with lower mortality rates compared with no use of RASB and discontinuation rates were significantly lower for ARB at discharge compared with ACEI at discharge. Recently, the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan proved superior to enalapril in reducing the risks of death and hospitalization for HF [25]. However, there are no head-to-head comparisons of ARB versus ARNI for HF. Therefore, to evaluate the pure effect of ARB and to confirm our data, further randomized controlled trials of both ARB versus ARNI and ARB versus ACEI using a maximal tolerated dosage in patients with HFrEF are needed.