Effects of eplerenone on resistance to antihypertensive medication in patients with primary or secondary hyperaldosteronism

Abstract

Background and Objectives: Resistant hypertension is an important problem; nearly half of diagnosed hypertensives are not controlled to target blood pressure levels, and approximately 90% of strokes occur among patients with resistant hypertension. Primary aldosteronism accounts for approximately 20% of resistant hypertension, but the role of secondary hyperaldosteronism in resistant hypertension is seldom considered. We assessed the effects of eplerenone in patients with hypertension and either primary or secondary hyperaldosteronism. Methods: Patients with a history of resistant hypertension and a supine plasma aldosterone level ≥ 360 pmol/L were randomized to eplerenone versus placebo in a fully blinded study for one year. A medication intensity score was developed to assess the resistance of hypertension to medication (blood pressure × medication intensity). We assessed the effects of eplerenone on blood pressure and on resistance to concomitant medication. Results: Final results were available in 37 patients (19 on eplerenone and 18 on placebo). Resistance to medication, as assessed by the intensity of concomitant medication required to maintain blood pressure control, was markedly reduced by eplerenone: medication intensity scores declined by −0.50 ± 1.04 (SD) on placebo versus −2.11 ± 1.45 with eplerenone (P = 0.0001), the Systolic Resistance Score declined by −80.00 ± 122.93 on placebo versus −334.05 ± 21.73 on eplerenone (P = 0.0001), and the Diastolic Resistance Score increased by 1.28 ± 31.65 on placebo and declined by −40.74 ± 57.08 on eplerenone (P = 0.009). Conclusions: Eplerenone significantly reduced resistance to concomitant antihypertensive medication in both primary and secondary hyperaldosteronism.

Adverse Effects of Aldosterone: Beyond Blood Pressure

“…Concordantly, in resistant hypertension, treatment with MR antagonists has been demonstrated to reduce BP and mitigate treatment resistance, especially when aldosterone concentrations are elevated. 10 , 11 Thus, there is highly consistent evidence across community populations supporting the role of aldosterone and MR activation in the development and propagation of elevated pressure. Though actions of aldosterone as an agonist of MR in the renal collecting duct epithelium and the resulting sodium and volume retention are known to cause elevated BP, and hypertension is a well‐established risk factor for adverse cardiovascular, cerebrovascular, and renal outcomes, the widespread tissue distribution of the MR and evidence from preclinical models and human disease states have made it clear that aldosterone–MR activity has pathologic consequences over and above those caused by hypertension alone.…”