How effective is spironolactone for treating resistant hypertension?
EVIDENCE-BASED ANSWER:
Very effective. Spironolactone reduces systolic blood pressure (SBP) by 11 to 17 mm Hg and diastolic blood pressure (DBP) by up to 6 mm Hg in patients with resistant hypertension taking 3 or more medications (strength of recommendation [SOR]: C, meta-analysis of randomized controlled trials [RCTs] of disease-oriented evidence).
Investigators found a statistically significant reduction in office SBP and DBP among patients taking spironolactone compared with control groups (SBP: WMD = −15.7 mm Hg; 95% CI, −20.5 to −11 mm Hg; DBP: WMD = −6.21 mm Hg; 95% CI, −8.33 to −4.1 mm Hg). A significant decrease also occurred in 24-hour ambulatory home SBP and DBP (SBP: MD = −8.7 mm Hg; 95% CI, −8.79 to −8.62 mm Hg; DBP: WMD = −4.12 mm Hg; 95% CI, −4.48 to −3.75 mm Hg).
Patients treated with spironolactone showed a marked decrease in home SBP compared with alternative drug groups (WMD = −4.5 mm Hg; 95% CI, −4.63 to −4.37 mm Hg), but alternative drugs reduced home DBP significantly more than spironolactone (WMD = 0.6 mm Hg; 95% CI, 0.55-0.65 mm Hg). Marked heterogeneity was found in these analyses, and the authors also noted that reductions in SBP are more clinically relevant than decreases in DBP.
RECOMMENDATIONS
The 2017 American Heart Association/American College of Cardiology evidence-based guideline recommends considering adding a mineralocorticoid receptor agonist to treatment regimens for resistant hypertension when: office BP remains ≥ 130/80 mm Hg; the patient is prescribed at least 3 antihypertensive agents at optimal doses including a diuretic; pseudoresistance (nonadherence, inaccurate measurements) is excluded; reversible lifestyle factors have been addressed; substances that interfere with BP treatment (such as nonsteroidal anti-inflammatory drugs and oral contraceptive pills) are excluded; and screening for secondary causes of hypertension is complete.4
The United Kingdom’s National Institute for Health and Care Excellence (NICE) evidence-based guideline recommends considering spironolactone 25 mg/d to treat resistant hypertension if the patient’s potassium level is 4.5 mmol/L or lower and BP is higher than 140/90 mm Hg despite treatment with an optimal or best-tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker plus a calcium-channel blocker and diuretic.5
Editor’s takeaway
The evidence from multiple RCTs convincingly shows the effectiveness of spironolactone. Despite the SOR of C because of a disease-oriented outcome, we do treat to blood pressure goals, and therefore, spironolactone is a good option.
