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BackgroundResistant hypertension is associated with a high risk of cardiovascular disease, chronic kidney disease and mortality. Yet, its management is challenging. This study aims to establish the comparative effectiveness of pharmacologic and interventional treatments by conducting a network meta-analysis.MethodsMEDLINE, Cochrane Register of Controlled Trials and Web of Science Core Collection were systematically searched in March 2022. Randomized controlled trials comparing treatment options for management of resistant hypertension were included. Outcomes were blood pressure changes, measured in the office and in 24h ambulatory blood pressure measurement. We applied a frequentist random effects model to perform a network meta-analysis combining placebo medication and sham procedure as the reference comparator.ResultsFrom 4771 records, 24 studies met the inclusion criteria with 3458 included patients in total. 12 active treatment alternatives were analyzed. Among all comparators, spironolactone had the highest-ranking probability and was considered the most effective treatment to reduce office systolic blood pressure (−13.30 mmHg [−17.89; −8.72];P< 0.0001) and 24h systolic blood pressure (−8.46 mmHg [−12.54; −4.38]; P < 0.0001) in patients with resistant hypertension.ConclusionAmong all pharmacologic and interventional treatments, spironolactone is the most effective in reducing office and 24h systolic blood pressure in patients with resistant hypertension. More comparative trials and especially trials with long-term follow up are needed.Graphical Abstract |