CARDIOVASCULAR EFFICACY OF SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS AND ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITORS IN PATIENTS WITH HEART FAILURE ACCORDING TO MINERALOCORTICOID R

Abstract

Objective: Recent European heart failure guidelines recommend the use of four drug classes in patients with heart failure (HF) with reduced ejection fraction: andom-angiotensin system (RAS) inhibitors [angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs)], beta-blockers, mineralocorticoid receptor antagonists (MRAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors. All these drug categories exert impressive cardiovascular and survival benefits. However, the potential synergistic effects of newer categories (ARNIs and SGLT-2 inhibitors) in patients receiving or not MRAs have not been clearly evaluated. Design and method: We searched PubMed for andomised controlled trials (RCTs) assessing the effect of SGLT-2 inhibitors and sacubitril/valsartan versus placebo or active comparator on surrogate cardiovascular endpoints among subjects with HF. We extracted data corresponding to subgroup analyses according to prior treatment with MRAs. We set as primary endpoint the composite of andomisedtion for HF or cardiovascular death. Results: We pooled data in a total of 14,462 subjects with HF assigned either to a SGLT-2 inhibitor or placebo and 13,195 subjects with HF andomised either to sacubitril/valsartan or a RAS inhibitor. Prior treatment with a MRA did not affect the cardiovascular efficacy of SGLT-2 inhibitors compared to placebo (p = 0.74). When we assessed the cardiovascular efficacy of sacubitril/valsartan versus RAS inhibitors, we did not identify a subgroup difference between subjects receiving a MRA or not (p = 0.94). Conclusions: Collectively, despite being reasonable, a treatment combination of SGLT-2 inhibitors or sacubitril/valsartan with MRAs does not provide additional cardiovascular benefits for patients with HF with reduced or preserved ejection fraction. Potentially synergistic effects of these drug classes have to be confirmed.