engleski

Risk of hyperkalemia with sacubitril/valsartan vs. RAAS inhibitor use in heart failure with reduced and preserved ejection fraction: a meta-analysis of 6 RCTs including 17.362 patients

Background: Hyperkalemia is a potential complication associated with the use of pharmacotherapies inhibiting the renin- angiotensin- aldosterone system (RAAS). Among patients with heart failure (HF) with reduced and preserved ejection fraction (HFrEF and HFpEF, respectively), dose up- titration of therapies inhibiting RAAS might be compromised due to fear of hyperkalemia. The use of RAAS inhibition is guideline-directed for reduction of mortality and morbidity in HFrEF, although no beneficial effects of these therapies on hard endpoints in HFpEF have been demonstrated. However, due to the high prevalence of hypertension in the HFpEF subgroup, the use of RAAS inhibitors in this population is common. Purpose: To determine whether the risk of hyperkalemia is reduced or enhanced by the use of sacubitril/valsartan (LCZ696), a drug that combines angiotensin receptor and neprilysin inhibitor in comparison with traditional RAAS inhibitors such as enalapril or valsartan among patients with HFrEF and HFpEF. Methods: MEDLINE and EMBASE databases were systematically searched to find randomized controlled clinical trials (RCTs) that examined the use of sacubitril/ valsartan vs. enalapril or valsartan or matching placebo in patients with HF. All included studies included data on hyperkalemia events during follow-up. Hyperkalemia was defined as serum potassium >5.5 mmol/L in a majority of studies. Random-effects meta- analysis with restricted maximum likelihood (REML) was performed with prespecified analysis according to HFrEF and HFpEF subgroups. Relative risk (RR) with 95% confidence intervals (95% CI) were reported as the main outcome measures. Heterogeneity across studies was inspected by I2 statistic. Results: A total of six RCTs encompassing 17.362 patients with pooled 2563 events of hyperkalemia (1250 in sacubitril/valsartan group and 1313 in RAAS inhibitor group). The crude average incidence of hyperkalemia was 16% in HFpEF and 14% in the HFpEF population. All included RCTs were multicentric and published in a period between 2012 and 2020 ; three trials included 9.744 patients with HFrEF while three trials enrolled 7.618 patients with HFpEF. Events of hyperkalemia were reported during the median follow-up period that ranged from 2 to 35 months.Low to moderate heterogeneity was detected across studies. The main finding (Figure 1) is that the use of sacubitril/valsartan was no different concerning the risk of hyperkalemia compared to RAAS inhibitors across the HF spectrum (RR 1.004, 95% CI 0.882-1.141), and for the main result, no significant heterogeneity was detected (p=0.120). This effect was consistent in both HFrEF (RR 1.048, 95% CI 0.838-1.310) and HFpEF subgroups (RR 1.015, 95% CI 0.799-1.289) with no significant heterogeneity detected across studies. Conclusion: In patients with HFrEF or HFpEF, treatment with sacubitril/valsartan is not associated with an increased risk of hyperkalemia compared to conventional RAAS inhibitor treatment.

heart failure ; HFrEF ; HFpEF ; HFmrEF ; sacubitril-valsartan ; ARNI ; Entresto ; hyperkalemia ; risk ; ACE-I ; ARB

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