Vasodilators for acute heart failure. A systematic review of randomized clinical trials with meta-analysis and trial sequential analysis

Abstract

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Danish Cardiovascular Academy Novo Nordisk Foundation. Background Acute heart failure (AHF) is an increasing public health concern with limited evidence for current treatments, such as vasodilators. Recent studies have shown mixed results regarding the efficacy of vasodilation in AHF, leading to downgraded recommendations in European Society of Cardiology (ESC) 2021 guidelines. Method We conducted a systematic review of randomized clinical trials (RCTs) to assess vasodilator therapy's effectiveness in managing AHF. The search for relevant studies was conducted without restrictions across the major databases: Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), Web of Science, and the Cochrane Central Register of Controlled Trials. The study protocol was published and registered at PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. We included RCTs that compared vasodilators to standard care, placebo, no-intervention, or co-interventions. Our primary outcome was all-cause mortality, while secondary outcomes included serious adverse events (SAEs), tracheal intubation and length of hospital stay. Systolic blood pressure difference was an exploratory outcome. We assessed the risks of bias in individual trials using the Cochrane Collaboration risk of bias tool. Results We included 46 RCTs comprising 28,374 patients with AHF. Meta-analysis and Trial Sequential Analysis showed that vasodilators did not reduce the risk of all-cause mortality (risk ratio (RR) = 0.96, 95% CI: 0.90 to 1.03; I2 = 0%; P = 0.26). However, meta-analysis showed evidence of a beneficial effect of vasodilators in reducing the need for tracheal intubation (RR = 0.82, 95% CI: 0.68 to 0.99; I2 = 55.05%; P = 0.04). No evidence of a difference was seen in the risk of SAEs (RR = 1.01, 95% CI: 0.97 to 1.06; I2 = 0%; P = 0.50) or length of hospital stay (Mean difference (MD) = -0.28, 95% CI: -0.73 to 0.16; I2 = 69.84%; P = 0.28). Finally, a significant decrease in systolic blood pressure (MD = -6.26, 95% CI: -8.06 to -4.46; I2 = 90.51%; P < 0.01) was demonstrated. Conclusion In patients hospitalised with AHF, vasodilator therapy did not result in a reduction of all-cause mortality, SAEs or length of hospital stay. However, the need for tracheal intubations was significantly decreased.Forest plot of all-cause mortalityForest plot of Tracheal intubation