Key result
SGLT2 inhibitors cut AKI risk ~31% in HFrEF without increasing hypotension or volume depletion.
Why the study?
Physicians are sometimes reluctant to initiate guideline-directed therapy in HFrEF due to concerns of adverse events, prompting an evaluation of hypotension, volume depletion, and acute kidney injury risks with SGLT2 inhibitors.
Do SGLT2 inhibitors increase the risk of hypotension, volume depletion, and acute kidney injury in patients with HFrEF?
Meta-Analysis (n=10,050)
Do SGLT2 inhibitors increase the risk of hypotension, volume depletion, and acute kidney injury in patients with HFrEF?
SGLT2 inhibitors are safe to initiate in HFrEF patients without clinically relevant risks of hypotension or volume depletion, and they offer protection against acute kidney injury.
Supports safe SGLT2 inhibitor initiation in HFrEF without hypotension or volume depletion concerns; confirms AKI risk reduction across trials.
AIMS: Physicians are sometimes reluctant to initiate guideline-directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium-glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations. METHODS AND RESULTS: We determined summary risk ratios (RRs) by conducting a meta-analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta-analyses by computing fragility and/or reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10 050 patients with HFrEF entered the final meta-analysis. Hypotension was reported in 4.5% (219/4836) on SGLT2 inhibitors and in 4.1% (202/4846) on placebo (RR 1.09, 95% confidence interval [CI] 0.91-1.31, p = 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (473/5019) on SGLT2 inhibitors and in 8.7% (438/5031) on placebo (RR 1.07, 95% CI 0.95-1.21, p = 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% [95/4888]) on SGLT2 inhibitors than on placebo (2.8% [140/4899]) providing lower incidence of AKI (RR 0.69, 95% CI 0.51-0.93, p = 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI. CONCLUSION: Sodium-glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors.
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Vukadinović et al. (2022) conducted a meta-analysis in Heart failure and reduced ejection fraction (HFrEF) (n=10,050). Sodium-glucose cotransporter 2 (SGLT2) inhibitors vs. Placebo was evaluated on Hypotension (RR 1.09, 95% CI 0.91-1.31, p=0.36). SGLT2 inhibitors in HFrEF patients did not significantly increase the risk of hypotension (RR 1.09; 95% CI 0.91-1.31) or volume depletion, but significantly reduced the risk of AKI (RR 0.69; P=0.02).
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