WHAT’S NEW
Evidence of superiority
This is the first RCT to compare spironolactone with two other commonly used fourth-line antihypertensives—bisoprolol and doxazosin—in patients with resistant hypertension. The study demonstrated clear superiority of spironolactone in achieving carefully measured ambulatory and clinic-recorded BP targets versus a ß-blocker or an α-blocker.
CAVEATS
Findings not universal
Spironolactone is contraindicated in patients with severe renal impairment. Although multiple drug trials have demonstrated the medication’s safety and effectiveness, especially in patients with resistant hypertension, we should factor in the need for monitoring electrolytes and renal function within weeks of treatment initiation and periodically thereafter.7,8 In this study, spironolactone increased potassium levels, on average, by 0.45 mmol/L. No gynecomastia (typically seen in about 6% of men) was found in those taking spironolactone for a 12-week cycle.1
This single trial enrolled mostly Caucasian men with a mean age of 61. Although smaller observational studies that included African-American patients have shown promising results for spironolactone, the question of external validity or applicability to a diverse population has yet to be decisively answered.9
CHALLENGES TO IMPLEMENTATION
Potential for adverse reactions
The evidence supporting this change in practice has been accumulating for the past few years. However, clinicians who treat patients with resistant hypertension may have concerns about hyperkalemia, gynecomastia, and effects on renal function. More patient-oriented evidence is likewise needed to assist with the revision of guidelines and wider adoption of AAs by primary care providers.
References
1. 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;386:2059-2068.
2. Rosa J, Widimsky P, Tousek P, et al. Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 Study. Hypertension. 2015;65:407-413.
3. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA. 2014;311:507-520.
4. National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management (Clinical Guideline CG127). August 2011. https://www.nice.org.uk/guidance/cg127. Accessed March 4, 2016.
5. Dahal K, Kunwar S, Rijal J, et al. The effects of aldosterone antagonists in patients with resistant hypertension: a meta-analysis of randomized and nonrandomized studies. Am J Hypertens. 2015;28:1376-1385.
6. Václavík J, Sedlák R, Jarkovský J, et al. Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT). Medicine (Baltimore). 2014;93:e162.
7. Wei L, Struthers AD, Fahey T, et al. Spironolactone use and renal toxicity: population based longitudinal analysis. BMJ. 2010;340:c1768.
8. Oxlund CS, Henriksen JE, Tarnow L, et al. Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus. J Hypertens. 2013;31:2094-2102.
9. Nishizaka M, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003;16:925-930.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(4):266-268.