The role of spironolactone in the treatment of patients with refractory hypertension

Ouzan, J; Pérault, C.; Lincoff, A. Michael; Carré, Evelyne; Mertes, M.

doi:10.1016/s0895-7061(01)02342-1

Cited by 179 publications

(69 citation statements)

References 19 publications

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“…The incidence of PA increases with the severity of hypertension, and among resistant hypertensives, mineralocorticoid receptor blockade is of broad benefit (8)(9)(10). Among the seven diagnosed subtypes of PA, aldosteroneproducing adenoma (APA) and bilateral idiopathic primary hyperaldosteronism (IHA) are of equivalent prevalence, together accounting for 95% of diagnosed cases (5).…”

mentioning

confidence: 99%

TASK channel deletion in mice causes primary hyperaldosteronism

Davies¹,

Hu²,

Guagliardo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

172

166

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When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels removes an important background K current that results in a marked depolarization of ZG cell membrane potential. Although TASK channel deletion mice (TASK −/− ) adjust urinary Na excretion and aldosterone production to match Na intake, they produce more aldosterone than control mice across the range of Na intake. Overproduction of aldosterone is not the result of enhanced activity of the renin–angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of Na intake. In addition, TASK −/− mice fail to suppress aldosterone production in response to dietary Na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in TASK −/− mice. Thus, TASK −/− channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify TASK channels as a possible therapeutic target for primary hyperaldosteronism.

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mentioning

confidence: 99%

TASK channel deletion in mice causes primary hyperaldosteronism

Davies¹,

Hu²,

Guagliardo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

172

166

View full text Add to dashboard Cite

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“…6,7,31,32 This considerable underutilization is not likely explained by patient factors or physician practice preferences because their use is too low to be subjected to significant variations. Low awareness of the efficacy of these medications is likely a contributory factor, but may also not fully explain the low utilization rate.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][9][10] The National Ambulatory Medical Care Survey (NAMCS), an annual nationally representative sample of office visits in the US, collects blood pressure measurements, diagnoses and medications. We sought to assess the prevalence of resistant hypertension among office visits to physicians who typically manage hypertension, describe trends in physicians' use of recommended medications 2 years after publication of the AHA guidelines, and determine whether use of recommended medications varied by regional-level, physician-level, or patient-level characteristics.…”

Section: Introductionmentioning

confidence: 99%

Physician Underutilization of Effective Medications for Resistant Hypertension at Office Visits in the United States: NAMCS 2006–2010

et al. 2013

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BACKGROUND:The American Heart Association (AHA) published guidelines for treatment of resistant hypertension in 2008 recommending use of thiazide diuretics (particularly chlorthalidone), aldosterone antagonists, and fixed-dose combination medications, but it is unclear the extent to which these guidelines are being followed. OBJECTIVE: To describe trends in physician use of recommended medications for resistant hypertension and assess variations in medication use based on geography, physician specialty and patient characteristics. DESIGN: Cross-sectional analysis using the National Ambulatory Medical Care Survey from 2006 to 2010. STUDY SAMPLE: We analyzed visits of hypertension patients to family physicians, general internists, and cardiologists. Resistant hypertension was defined as concurrent use of ≥ 4 classes of blood pressure (BP) medications or elevated BP despite the use of ≥ 3 medications. Pregnant patients and visits with diagnosed heart failure or end-stage renal disease were excluded. MAIN OUTC OME: U se of A HA-r ec ommen d ed medications for management of resistant hypertension. RESULTS: Of 19,500 patient visits with hypertension, 1,567 or 7.1 % CI (6.6-7.7 %) met criteria for resistant hypertension. Thiazide diuretic use was reported in 58.9 % of visits pre-guidelines vs. 54.8 % postguidelines (p=0.37). Use of aldosterone antagonists was low and also did not change significantly after guideline publication (3.1 % vs. 4.5 %, p=0.27). Fixeddose combinations use was 42.0 % before and 37 % after guideline publication (p = 0.29). Each 10-year increase in patient age was associated with lower thiazide use (OR 0.87,, as was presence of comorbid ischemic heart disease (OR 0.62, CI 0.41-0.94). Medication use did not vary by geography or physician specialty. CONCLUSION: Use of AHA-recommended medications for resistant hypertension remains low after publication of guidelines. Healthcare systems should encourage more frequent prescribing of these medications to improve care in this high-risk population.

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“…Thus aldosterone antagonists may be helpful in resistant hypertension, regardless of the initial cause of the hypertension. Spironolactone has been reported to improve blood pressure in resistant hypertension, [10,11] but is problematic for men because of gynecomastia and mastalgia.…”

Section: Introductionmentioning

confidence: 99%

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

Spence

Bogiatzi

Kuk

et al. 2017

Journal of Translational Internal Medicine

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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.

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The role of spironolactone in the treatment of patients with refractory hypertension

Abstract: Spironolactone is a safe, effective therapy for patients with refractory hypertension.

Cited by 179 publications

References 19 publications

TASK channel deletion in mice causes primary hyperaldosteronism

TASK channel deletion in mice causes primary hyperaldosteronism

Physician Underutilization of Effective Medications for Resistant Hypertension at Office Visits in the United States: NAMCS 2006–2010

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

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