Efficacy of Spironolactone Therapy in Patients With True Resistant Hypertension

Abstract

Abstract-The role of spironolactone in resistant hypertension management is unclear. The aim of this prospective trial was to evaluate the antihypertensive effect of spironolactone in patients with true resistant hypertension diagnosed by ambulatory blood pressure monitoring. A total of 175 patients had clinical and complementary exams obtained at baseline and received spironolactone in doses of 25 to 100 mg/d. A second ambulatory blood pressure monitoring was performed after a median interval of 7 months. Paired Student t test was used to assess differences in blood pressure before and during spironolactone administration, and multivariate analysis adjusted for age, sex, and number of antihypertensive drugs to assess the predictors of blood pressure fall. There were mean reductions of 16 and 9 mm Hg, respectively, in 24-hour systolic and diastolic blood pressures (95% CIs: 13 to 18 and 7 to 10 mm Hg; PϽ0.001). Office systolic blood pressure and diastolic blood pressure also decreased (14 and 7 mm Hg). Controlled ambulatory blood pressure was reached in 48% of patients. Factors associated with better response were higher waist circumference, lower aortic pulse wave velocity, and lower serum potassium. No association with plasma aldosterone or aldosterone:renin ratio was found. Adverse effects were observed in 13 patients (7.4%). A third ambulatory blood pressure monitoring performed in 78 patients after a median of 15 months confirmed the persistence of the spironolactone effect. In conclusion, spironolactone administration to true resistant hypertensive patients is safe and effective in decreasing blood pressure, especially in those with abdominal obesity and lower arterial stiffness. Its addition to an antihypertensive regimen as the fourth or fifth drug is recommended. (Hypertension. 2010;55:147-152.)Key Words: ambulatory blood pressure monitoring Ⅲ resistant hypertension Ⅲ spironolactone R esistant hypertension (RH) is a common clinical condition defined as the failure to control office blood pressure (BP) despite a treatment with Ն3 different classes of antihypertensive drugs in optimal dosages, ideally including a diuretic. 1 Previous surveys have shown prevalence ranges from 10% to Ϸ30%. 1 Although there is no consensus about the better therapeutic scheme for resistant hypertensive patients, in general, diuretics, angiotensin-blocking agents, calciumchannel blockers, and ␤-blockers are used as the first-line choices. However, there is a lack of evidence about the optimal choice of a fourth-or fifth-line antihypertensive drug, and in this context there has been increasing interest in the role of aldosterone antagonists, particularly spironolactone.The efficacy and safety of spironolactone in reducing BP were demonstrated Ͼ2 decades ago. 2 Over the past 15 years, after many reports had suggested that primary hyperaldosteronism is probably more common than it was regarded previously, 3,4 several studies have been dedicated to evaluate the spironolactone effect in patients with refractoriness to treatment, mo...

Addition of Spironolactone in Patients With Resistant Arterial Hypertension (ASPIRANT)

“…29 Previous trials reported conflicting data about whether the BP response to spironolactone can be predicted by baseline aldosterone, ARR, or baseline potassium. 10,21,23,30,31 In our trial, the BP response to spironolactone treatment in patients with baseline ARR Յ7 and PRA Ͼ1.34 ng/mL per hour was significantly worse than the BP response of patients with ARR Ͼ7 and PRA Յ1.34 ng/mL per hour. This could possibly help to identify the patients for which treatment with spironolactone is most effective.…”

Resistant Hypertension, Elevated Aldosterone/Renin Ratio and Reduced RGS2: A Pathogenetic Link Deserving Further Investigations?

“…This underscores the contributory role of relative aldosterone excess to treatment resistance, such that even those with presumably low levels of aldosterone benefit from mineralcorticoid receptor antagonists use. (Nishizaka et al, 2003;Sartori et al, 2006;De Souza et al, 2010) This is in contrast with other studies that showed that high ARR predicted the antihypertensive efficacy of spironolactone (Eide et al, 2004); these contrasting results may be explained by the considerably higher spironolactone dose administered in patients with demonstrated PA, generating a strong difference in the two populations.…”

Aldosterone and Blood Pressure Regulation

“…24 However, the long-term use of this treatment strategy has only been established during the last several years. In their open label study population of 175 patients with resistant hypertension additionally treated with spironolactone for >1 year, de Souza et al 25 reported further impressive BP reductions, averaging 16/9 mm Hg.…”