A Cochrane review included 5 cross-over studies (137 patients, duration ranging from 4 to 6 weeks) and 1 parallel group study (25 patients received spironolactone and 25 patients received placebo for 8 weeks). None of the included studies reported results for all cause mortality, cardiovascular mortality, non-cardiovascular mortality, serious adverse events, fatal and non-fatal myocardial infarction, and fatal and non-fatal stroke. The cross-over studies found a reduction in systolic blood pressure (SBP) of 20.09 mmHg (95% CI 16.58 to 23.06) and a 6.75 mmHg (95% CI 4.8 to 8.69) reduction in diastolic blood pressure (DBP). There may be a dose response effect with spironolactone up to 50 mg/day, but the confidence intervals around the mean end-of-study blood pressure for doses ranging 25-500 mg/day all overlapped. It appears that doses >50mg/day do not produce further reductions in either SBP or DBP. One cross-over study found that spironolactone 25 mg/day did not statistically significantly change SBP or DBP compared to placebo, SBP -9.9 (95% CI -21.15 to 1.35); DBP -2.34 (95% CI -7.92 to 3.06). The risks of potential side effects, hyperkalemia, gynaecomastia, upper gastrointestinal bleeds, with the use of spironolactone must be weighed against the benefits of decreased blood pressure with no proven decrease in adverse cardiovascular outcomes.
Comment: The quality of evidence is downgraded by study quality (inadequate or unclear allocation concealment and blinding) and by indirectness (lack of long-term data and lack of data on adverse cardiovascular outcomes).