Evidence shows that lowering blood pressure decreases the risk of adverse cardiovascular outcomes such as heart disease, stroke, and death.1,2 Meta-analyses suggest that lowering blood pressure decreases risk of these outcomes regardless of which agent is used.1,3
A 2010 Cochrane Review meta-analysis looked at randomized, controlled trials of patients with primary hypertension receiving spironolactone as monotherapy.4 In five trials (n=137), blood pressure results of patients receiving spironolactone were compared with those of patients taking placebo. Patients taking spironolactone had a statistically significant drop in systolic blood pressure of 20.09 mm Hg (95% confidence interval [CI] [16.58 – 23.06], p<0.00001) and a drop in diastolic pressure of 6.75 mm Hg (95% CI [4.8 – 8.69], p<0.00001) compared to those taking placebo. The authors found no statistically significant increase in efficacy with an increase in spironolactone dosage >50 mg/day. One additional study of 22 patients taking 25 mg/day of spironolactone found a drop in blood pressure (9.9/2.3 mm Hg) that was not statistically significant compared to 20 patients taking placebo.
Spironolactone is more commonly prescribed as add-on therapy for patients with resistant hypertension. Chapman et al evaluated 1,411 patients from the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm randomized trial who received spironolactone for uncontrolled hypertension in addition to their pre-existing regimen of antihypertensive drugs.5 The median dose of spironolactone was 25 mg during the period of observation. Blood pressure fell by an average of 21.9/9.5 mm Hg (p<0.001) among patients taking spironolactone for an average of 1.3 years.
Nishizaka et al enrolled 76 patients with resistant hypertension and a pre-existing antihypertensive drug regimen of a diuretic in addition to either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.6 Study participants received low-dose spironolactone (12.5 – 25 mg/day). Blood pressure was checked six weeks, three months, and six months following initiation of the study. If blood pressure remained uncontrolled at one of these checkpoints, the dose was titrated up to 50 mg/day. The mean decrease in blood pressure at the six-week mark was 21 ± 21 mm Hg for systolic pressure and 10 ± 14 mm Hg for diastolic pressure. At the six-month mark, the blood pressure of the 76 patients was evaluated again, and the mean decrease in blood pressure was 25 ± 20 mm Hg for systolic pressure and 12 ± 12 mm Hg for diastolic pressure.
Vaclavik et al conducted a randomized, double-blind, placebo-controlled study of 111 patients with resistant hypertension.7 Resistant hypertension was defined as office systolic blood pressure above 140 or diastolic blood pressure above 90 mm Hg. 58 patients received a placebo while 59 patients received 25 mg of spironolactone in addition to their pre-existing daily antihypertensive drug regimen. At eight weeks, there was a significant difference in ambulatory daytime blood pressure between participants receiving spironolactone and those receiving placebo of 5.4 mm Hg (95% CI [10.0 – 0.8], p=0.024) for systolic pressure. However, the difference for diastolic pressure, 1.0 mm Hg (95% CI [.0 – 2.0], p=0.358), was not significant. Similarly, systolic blood pressures dropped significantly in patients taking spironolactone versus placebo when measured with ambulatory monitoring at night (8.6 mm Hg), over 24 hours (6.6 mm Hg), and in the office (6.5 mm Hg), while diastolic pressures did not.
In another study of 161 patients with resistant hypertension, Vaclavik et al assessed the effect of adding low-dose spironolactone to antihypertensive regimens of three or more drugs, including at least one diuretic.8 Resistant hypertension was defined as office systolic blood pressure above 140 or diastolic blood pressure above 90 mm Hg. Of those who completed the study, 74 participants received 25 mg of spironolactone and 76 participants received a placebo. Blood pressure was measured at eight weeks in the office and with 24-hour ambulatory monitoring. The difference in the mean drop in blood pressure for those who received spironolactone compared to those who received the placebo was statistically significant for all measurements. The greatest drop was seen in the nighttime measurement with 13.0/6.4 mm Hg (p<0.001).
Williams et al conducted a double-blind, placebo-controlled, crossover study of patients with resistant hypertension.13 Of the 314 patients selected, 285 patients received spironolactone (25 – 50 mg), 282 doxazosin (4 – 8 mg), 285 bisoprolol (5 – 10 mg) and 274 placebos in addition to their baseline blood pressure medications. Treatment cycles for each drug were 12 weeks. Dosages for each drug were doubled after six weeks of the low dose. Patients receiving spironolactone had an average reduction in systolic blood pressure of 8.70 mm Hg (95% CI [9.72 – 7.69], p<0.0001) compared to placebo. The results suggest a dose-response effect as spironolactone had a 3.86 mm Hg drop (p<0.0001) in mean systolic blood pressure between the high dose (50 mg) and the low dose (25 mg).
- Turnbull F, Neal B, Ninomiya T, et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 2008; 336 (7653): 1121-1123.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 2014; 311 (5): 507-520.
- Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338 : b1665.
- Batterink J, Sn S, Am T, et al. Spironolactone for hypertension ( Review ) Spironolactone for hypertension. Cochrane Database Syst Rev 2010;(8): 8-10.
- Chapman N, Dobson J, Wilson S, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 2007; 49 (4): 839-845.
- Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens 2003; 16 (11 I): 925-930.
- Vaclavik J, Sedlak R, Plachy M, et al. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension 2011; 57 (6): 1069-1075.
- Václavík J, Sedlák R, JarkovskÝ J, Kociánová E, TáborskÝ M. Effect of spironolactone in resistant arterial hypertension. Med (United States) 2014; 93 (27): 1-9.
- Wolf R, Mendlowitz M, Roboz J, Styan G, Kornfeld P, Weigl A. Treatment of hypertension with spironolactone. JAMA 1966; 198 (11): 1143-1149.
- Jeunemaitre X, Chatellier G, Kreft-Jais C, et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987; 60 (10): 820-825.
- CRANSTON WI, JUEL-JENSEN BE. The effects of spironolactone and chlorthalidone on arterial pressure. Lancet 1962; 1 (7240): 1161-1164.
- Clement DL. Effect of spironolactone on systemic blood pressure, limb blood flow and response to sympathetic stimulation in hypertensive patients. Eur J Clin Pharmacol 1982; 21 (4): 263-267.
- Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015; 386 (10008): 2059-2068.
- Schohn DC, Jahn HA, Pelletier BC. Dose-related cardiovascular effects of spironolactone. Am J Cardiol 1993; 71 (3).