- Email: [email protected]
Spironolactone is the most effective “add-on” medication for resistant hypertension
Journal of the American Society of Hypertension
-(-)
(2015) 1
Hypertension Highlight SPIRONOLACTONE IS THE MOST EFFECTIVE ‘‘ADD-ON’’ MEDICATION FOR RESISTANT HYPERTENSION Conventional wisdom and consensus recommendations1 for the treatment of resistant hypertension suggest that mineralocorticoid receptor antagonists, primarily spironolactone, should be considered as ‘‘add-on’’ pharmacotherapy in patients with uncontrolled resistant hypertension. However, there is actually very limited available clinical trial data to support this recommendation. The recently published PATHWAY-2 study2 was a double-blind, placebo controlled, crossover trial, where patients with resistant hypertension, whose home blood pressure was not controlled on a combination of an angiotensinconverting enzyme inhibitor or an angiotensin receptor blocker þ calcium channel blocker þ diuretic (so-called A þ C þ D therapy), were each treated for 12 weeks with spironolactone 25–50 mg daily, doxazosin 4–8 mg daily, bisoprolol 5–10 mg daily, and placebo in random order. The primary finding of the study was that spironolactone was significantly more effective than the other study medications in lowering mean home systolic blood pressure. The risk of severe hypokalemia was only 2% in the spironolactone group. Strengths of this study include the crossover design, use of home blood pressures as the primary endpoint, use of reasonable doses of study medications, reasonable choice of background medication, and fairly strict assessment of patient adherence with study medications—all issues that have plagued previous studies of resistant hypertension. The superiority of spironolactone was most apparent in subjects with lower baseline plasma renin levels. However, even in the small number of patients with higher baseline renin levels, bisoprolol and doxazosin were not superior to spironolactone. As such, these data do not support routinely measuring plasma renin levels in this population.
1933-1711/$ - see front matter http://dx.doi.org/10.1016/j.jash.2015.10.005
The PATHWAY-2 study strengthens the evidence that spironolactone should be considered as ‘‘add-on’’ therapy for resistant hypertension. Of course, a couple of caveats do apply. First, patients with estimated glomerular filtration rate (eGFR) <45 mL/min were excluded, and the mean eGFR was 91 mL/min; as such, the relative efficacy and safety of spironolactone in the increasing number of patients with resistant hypertension and chronic kidney disease remains unclear. Finally, whether addition of spironolactone is superior to simply increasing the dose of thiazide-type diuretic or changing to a potentially more efficacious diuretic such as chlorthalidone remains untested. Michael J. Bloch, MD, FACP, FASH, FSVM, FNLA Department of Medicine University of Nevada School of Medicine Reno, NV, USA Vascular Care, Renown Institute for Heart and Vascular Health Reno, NV, USA [email protected]
References 1. Calhoun DA, Jones D, Textor S. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 2008;51:1403–19. 2. Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug resistant hypertension (PATHWAY-2): a randomized, double blind, crossover trial. Lancet 2015. http://dx.doi.org/10.1016/S0140-6736(15)00257-3.
-(-)
(2015) 1
Hypertension Highlight SPIRONOLACTONE IS THE MOST EFFECTIVE ‘‘ADD-ON’’ MEDICATION FOR RESISTANT HYPERTENSION Conventional wisdom and consensus recommendations1 for the treatment of resistant hypertension suggest that mineralocorticoid receptor antagonists, primarily spironolactone, should be considered as ‘‘add-on’’ pharmacotherapy in patients with uncontrolled resistant hypertension. However, there is actually very limited available clinical trial data to support this recommendation. The recently published PATHWAY-2 study2 was a double-blind, placebo controlled, crossover trial, where patients with resistant hypertension, whose home blood pressure was not controlled on a combination of an angiotensinconverting enzyme inhibitor or an angiotensin receptor blocker þ calcium channel blocker þ diuretic (so-called A þ C þ D therapy), were each treated for 12 weeks with spironolactone 25–50 mg daily, doxazosin 4–8 mg daily, bisoprolol 5–10 mg daily, and placebo in random order. The primary finding of the study was that spironolactone was significantly more effective than the other study medications in lowering mean home systolic blood pressure. The risk of severe hypokalemia was only 2% in the spironolactone group. Strengths of this study include the crossover design, use of home blood pressures as the primary endpoint, use of reasonable doses of study medications, reasonable choice of background medication, and fairly strict assessment of patient adherence with study medications—all issues that have plagued previous studies of resistant hypertension. The superiority of spironolactone was most apparent in subjects with lower baseline plasma renin levels. However, even in the small number of patients with higher baseline renin levels, bisoprolol and doxazosin were not superior to spironolactone. As such, these data do not support routinely measuring plasma renin levels in this population.
1933-1711/$ - see front matter http://dx.doi.org/10.1016/j.jash.2015.10.005
The PATHWAY-2 study strengthens the evidence that spironolactone should be considered as ‘‘add-on’’ therapy for resistant hypertension. Of course, a couple of caveats do apply. First, patients with estimated glomerular filtration rate (eGFR) <45 mL/min were excluded, and the mean eGFR was 91 mL/min; as such, the relative efficacy and safety of spironolactone in the increasing number of patients with resistant hypertension and chronic kidney disease remains unclear. Finally, whether addition of spironolactone is superior to simply increasing the dose of thiazide-type diuretic or changing to a potentially more efficacious diuretic such as chlorthalidone remains untested. Michael J. Bloch, MD, FACP, FASH, FSVM, FNLA Department of Medicine University of Nevada School of Medicine Reno, NV, USA Vascular Care, Renown Institute for Heart and Vascular Health Reno, NV, USA [email protected]
References 1. Calhoun DA, Jones D, Textor S. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 2008;51:1403–19. 2. Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug resistant hypertension (PATHWAY-2): a randomized, double blind, crossover trial. Lancet 2015. http://dx.doi.org/10.1016/S0140-6736(15)00257-3.