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

Abstract

Abstract-There is currently limited data on which drug should be used to improve blood pressure (BP) control in patients with resistant hypertension. This study was designed to assess the effect of the addition of 25 mg of spironolactone on BP in patients with resistant arterial hypertension. Patients with office systolic BP Ͼ140 mm Hg or diastolic BP Ͼ90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicenter trial. One hundred seventeen patients were randomly assigned to receive spironolactone (nϭ59) or a placebo (nϭ58) as an add-on to their antihypertensive medication, by the method of simple randomization. Analyses were done with 111 patients (55 in the spironolactone and 56 in the placebo groups). At 8 weeks, the primary end points, a difference in mean fall of BP on daytime ambulatory BP monitoring (ABPM), between the groups was Ϫ5.4 mm Hg (95% CI Ϫ10.0; Ϫ0. R esistant hypertension is a common clinical problem faced by both primary care clinicians and specialists worldwide. It is defined as blood pressure (BP) that remains above goal despite the concurrent use of 3 antihypertensive agents of different classes prescribed at optimal dosages; one of the 3 agents used should be a diuretic. 1 The exact prevalence of resistant hypertension is not known, but it is estimated from large clinical trials to affect at least 10% to 15% of all hypertensive patients. 2,3 If no secondary cause of hypertension is found, the use of multidrug treatment regimens including 3, 4, or more antihypertensive drugs is usually necessary to lower BP and thus prevent future cardiovascular events. 4 Spironolactone is a mineralocorticoid receptor antagonist that was shown to lower BP effectively in both general hypertensive patients and patients with primary aldosteronism. 5-7 A number of small, uncontrolled trials showed the positive effect of small doses of spironolactone in lowering BP in patients with resistant arterial hypertension. 8 -11 In the nonrandomized post hoc analysis of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, the addition of spironolactone to a triple-drug treatment led, during an average of 1.3 years of follow-up, to a significant decrease of systolic BP of 21.9 mm Hg and diastolic BP of 9.5 mm Hg. 12 However, evidence from randomized trials was lacking, and it was necessary to provide definite proof for the efficacy of spironolactone as an add-on treatment in resistant hypertension. 12,13 Therefore, we designed a prospective randomized trial to evaluate the effect of adding spironolactone in patients with resistant arterial hypertension. We decided to administer a low dose of spironolactone (25 mg/day) in the trial, since the effect of this dose seemed to be substantial

Dynamic resistant hypertension patterns as predictors of cardiovascular morbidity

“…As documented in recent reports, use of aldosterone antagonists may be beneficial at least in obese, especially black female, patients with RHT [17,26]. The use of such agents in the present study is low but similar or even higher than that documented in recent reports [7].…”

“…The use of such agents in the present study is low but similar or even higher than that documented in recent reports [7]. Nevertheless, the BMI in our study was in the overweight range, thus below that demonstrated for spironolactone to be effective [26]. In addition, patients, especially those with renal insufficiency, may not tolerate aldosterone blockade due to hyperkalemia or independent of this.…”

RAS-Mediated Adaptive Mechanisms in Cardiovascular Tissues: Confounding Factors of RAS Blockade Therapy and Alternative Approaches

“…The recent Addition of Spironolactone in Patients With Resistant Arterial Hypertension (ASPIRANT) clinical trial administrated 25 mg spironolactone, an anti-mineralocorticoid agent that inhibits aldosterone, to patients whose blood pressure was not controlled by three antihypertensive drugs, including a diuretic. Analysis of 111 patients indicated that spironolactone significantly decreased systolic blood pressure, though its effect was not prominent on respective diastolic blood pressure [61]. These studies suggest that spironolactone may be an effective alternative to treat elevated systolic blood pressure in patients with resistant hypertension.…”

Successful Treatment with an Antihypertensive Drug Regimen Including Eplerenone in a Patient with Malignant Phase Hypertension with Renal Failure

“…Regarding non-selective MR antagonists, Oka et al reported the use of multiple antihypertensive drugs including spironolactone for a patient with malignant hypertension caused by primary aldosteronism (13). In patients with resistant arterial hypertension including chronic kidney disease (CKD), Vaclavik et al reported that the addition of spironolactone to their antihypertensive medications significantly lowered the systolic blood pressure (14). In the present patient, the independent efficacy of eplerenone could not be evaluated.…”