Letter Regarding Article by Hood et al, “The Spironolactone, Amiloride, Losartan, and Thiazide (SALT) Double-Blind Crossover Trial in Patients With Low-Renin Hypertension and Elevated Aldosterone-Renin Ratio”
To the Editor:
We appreciated the article by Hood et al that was recently published in Circulation.1 This study is of particular interest because it demonstrates equal efficacy of therapy with bendroflumethiazide and spironolactone in patients with low-renin (LR) hypertension, thus potentially offering an alternative treatment for this form of hypertension.
We believe that these important results obtained in LR hypertensive patients with a high aldosterone/renin ratio should not be applied to patients with primary aldosteronism (PA). In fact, the authors selected a low percentage of patients with resistant hypertension, thus determining an underestimation of patients with PA.2 The inclusion of all patients with LR, regardless of aldosterone levels, results in the inclusion of a nonhomogeneous population of hypertensive patients with a low prevalence of PA3; in fact, patients with LR/low aldosterone do not constitute patients with PA and respond better to thiazides than to spironolactone. Aldosterone levels of the patients in the placebo group are relatively low, indicating that a low percentage of patients with LR/normal-high aldosterone were recruited, a requested prerequisite for suspecting that a patient has PA.4 We also think that the prerequisite of the response to spironolactone is not indicative of an increased prevalence of PA; in fact, LR essential hypertensives respond to spironolactone, and PA patients respond to thiazides.
The importance of the equal efficacy of spironolactone treatment is highlighted by the fact that thiazides can have detrimental effects on glucose and lipid metabolism but also an effect on potassium levels (−0.4 mEq/L in the short period of the trial), which could be even higher if the blood sampling was obtained with avoidance of the use of fist clenching, tourniquet, and Vacutainer for blood withdrawal; furthermore, a difference of 1.1 mm Hg, which is not significant in this trial for the relatively low number of patients recruited, could be significant in a larger population. Finally, the efficacy of spironolactone increases over time, and usually >2 months are required to obtain the full effect. The effect of thiazides, however, is faster; therefore, the 5 weeks of the trial could have underestimated the full effect of spironolactone.
Patients with LR hypertension constitute 30% of the essential hypertensive population,5 including a proportion of patients often resistant to conventional medications.2 This stimulating trial by Hood et al1 demonstrates that spironolactone is a valid option for the treatment of LR hypertensives, combining high efficacy with neutral metabolic effects.