Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus

Oxlund, Christina Stolzenburg; Henriksen, Jan Erik; Tarnow, Lise; Schousboe, Karoline; Gram, Jeppe; Jacobsen, I.A.

doi:10.1097/hjh.0b013e3283638b1a

Cited by 120 publications

(71 citation statements)

References 43 publications

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“…In line with the data published by Hanselin et al, 23 the association of 2 or even 3 renin-angiotensin system blockers, a less efficacious and potentially harmful drug combination, 24,25 was used in 22% of patients, whereas diuretics (82%) and, notably, calcium antagonists (73%) were still underused. In particular, low-dose spironolactone, a recommended drug in patients with resistant hypertension 26,27 was prescribed in only 26% of patients (Table 2), even in a subset with normal renal function, which is much higher than in the US database explored by Hanselin et al 23 (5.9%) and slightly better than in 2 other cohorts of patients referred in The Utrecht center did not have detailed information on file on the subclassification of renin system inhibitors or diuretics.…”

Section: Discussionmentioning

confidence: 99%

Eligibility for Renal Denervation

Persu

Jin²,

Baelen³

et al. 2014

Hypertension

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Depending on populations studied and applied methods and definitions, the prevalence of treatment-resistant hypertension varies from 3% to 30%. 1,2 The SYMPLICITY studies [3][4][5] demonstrated that in this indication catheter-based endovascular sympathetic renal denervation (RDN) by means of low-frequency energy is feasible. It entails a 25-to 30-mm Hg decrease in office systolic blood pressure, 84% of patients achieving a decrease in office systolic blood pressure of ≥10 mm Hg with a rate of procedural adverse events <5% assessed 6 months after RDN. 4 However, as reviewedAbstract-Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center's criteria was 42.5% (95% confidence interval, 38.0%-47.0%) and 39.7% (36.2%-43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Accordingly, several national and international consensus papers 16,17 have proposed guidelines for evaluation and management of patients with resistant hypertension before considering RDN. The proportion of patients with truly resistant hypertension eligible for RDN and the reasons of noneligibility after thorough screening and optimization of drug treatment in expert centers remain elusive. In this study, we reviewed the reasons for noneligibility at 11 hypertension expert centers performing RDN for treatment-resistant hypertension and collaborating within the European Network COordinating research on Renal Denervation (ENCOReD). 8 Methods PatientsWe performed systematic reviews of the literature published elsewhere 6,7 and identified ENCOReD centers engaging in RDN. At the fourth ENCOReD network meeting, held...

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Section: Discussionmentioning

confidence: 99%

Eligibility for Renal Denervation

Persu

Jin²,

Baelen³

et al. 2014

Hypertension

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“…Previous trials have shown that unlike office BP, the 24-hour ambulatory BP is less or no subject to the white-coat effect. [52][53][54][55][56] Therefore, the placebo or white-coat effect seem not to contribute to the wide scatter in Symplicity HTN-3, 51 which was not different to the previous uncontrolled trials. 26,[40][41][42] For patients in Symplicity HTN-3, changes in medication were permissible until 2 weeks before the procedure.…”

Section: Open Questions Lack Of Blinded Randomized Datamentioning

confidence: 99%

“…This is obviously not the case because it just represents energy delivery to the arterial wall, and endothelial edema, not nerve ablation. Noteworthy, in 68% of patients 0 or 1 notch was observed (54), suggesting that energy delivery was substandard. Finally, there are interesting findings in the subgroup composition.…”

Section: Open Questions Lack Of Blinded Randomized Datamentioning

confidence: 99%

Renal Denervation for the Treatment of Cardiovascular High Risk-Hypertension or Beyond?

Böhm

Linz

Ukena

et al. 2014

Circulation Research

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Hypertension imposes a major burden of morbidity and mortality and is associated with sympathetic nervous system overactivity. Renal sympathetic denervation has been shown to reduce office blood pressure, ambulatory blood pressure, and sympathetic activity in patients with resistant hypertension. Therefore, the procedure has attracted a lot of attention. Beyond blood pressure, renal denervation has been shown to improve glucose tolerance, microalbuminuria, and arrhythmias in several experimental models and, in admittedly, often uncontrolled clinical studies. It has been demonstrated to reduce myocardial hypertrophy in a blood pressure–independent and blood pressure–dependent way. The first studies on heart failure with preserved and reduced ejection fraction are ongoing. Renal sympathetic denervation holds promise for future indications in hypertension and related comorbidities and consequences, such as metabolic disease, renal failure, and heart failure. Published data in a placebo-control blinded study, however, are needed. The aim of this review is to provide a critical and comprehensive overview of heretofore generated data on renal denervation in experimental models, in human hypertension, and on early developments in new indications, which should indicate the way to powered and performed, controlled clinical studies appropriately.

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“…In another multicenter, double-blind, placebo-controlled study in patients with 24-hour BP >130/80 mm Hg, despite triple antihypertensive therapy and type 2 diabetes mellitus, the effect of adding 25 mg of spironolactone (n=57) or placebo (n=55) has been evaluated. 8 Placebo-corrected BP changes were −8.9 mm Hg and −3.7 mm Hg for 24-hour SBP and diastolic BP (P<0.001), respectively. The reductions of BP in the above-mentioned trials, including PRAGUE-15, were significantly lower compared with BP reductions documented in previous trials.…”

Section: Aldosterone Antagonists In Resistantmentioning

confidence: 99%

Aldosterone Antagonists and Renal Denervation

et al. 2015

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A ctivation of the sympathetic nervous system plays an important role in the development and disease progression of hypertension and its comorbidities.1 Antihypertensive treatment approaches have focused on abrogation of activated neurohormonal systems associated with these conditions, including the renin-angiotensin-aldosterone system and the sympathetic nervous system. Despite the availability of effective antihypertensive drugs, certain patients remain uncontrolled to target blood pressure (BP) values.2 For these patients with uncontrolled hypertension, new device-based treatments have been developed, such as surgically implanted baroreceptor stimulators and catheter-based renal denervation. 3 The available evidence suggests that renal denervation reduces renal sympathetic activity and office BP, as well as ambulatory BP in open-label registries and randomized, controlled trials in certain patients, but not in all patients. 4The BP-lowering effect of intensified drug treatment, with special focus on aldosterone antagonist treatment, compared with catheter-based renal denervation has not been investigated in detail.In this issue, the prospective, randomized, open-label multicenter PRAGUE-15 trial by Rosa et al 5 investigated the efficacy and safety of catheter-based renal denervation (using Medtronic's Symplicity device) versus intensified pharmacological treatment, including spironolactone in patients with mild to moderate resistant hypertension (office systolic BP [SBP] at the baseline, >140 mm Hg; 24-hour BP at the baseline, >130 mm Hg). The adherence of patients was confirmed by plasma toxicological analyses at the beginning (but unfortunately not after 6 months), and secondary causes of hypertension were excluded systematically. The study provides interesting insights about the efficacy and safety of intensified drug treatment and catheter-based renal denervation in patients with resistant hypertension. Aldosterone Antagonists in ResistantHypertension: Effective and Safe?The significant BP change (24-hour SBP, −8.1 mm Hg; P=0.001 and office SBP, −14.3 mm Hg; P<0.001) in the intensified drug treatment group of PRAGUE-15 was mostly driven by patients in whom spironolactone was added and continued. Spironolactone has been shown to lower BP and affects hypertensive organ damage positively, the latter, in part, occurring BP independently. 6 Despite spironolactone being available for ≥50 years, the evidence of its use in prospective, randomized, placebo-controlled trials in patients with resistant hypertension is still limited. The addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT) trial 7 demonstrated that the addition of 25 mg of spironolactone (n=59) compared with placebo (n=58) in patients with resistant hypertension (on average treated with 4.5 antihypertensive drugs) is able to reduce daytime SBP by 5.4 mm Hg (P=0.024) and nighttime SBP by 8.6 mm Hg (P=0.011), whereas the fall of the respective diastolic values was not significant. In another multicenter, double-blind,...

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Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus

Abstract: Low dose spironolactone exerts significant BP and urinary albumin creatinine ratio lowering effects in high-risk patients with resistant hypertension and type 2 diabetes mellitus.

Cited by 120 publications

References 43 publications

Eligibility for Renal Denervation

Eligibility for Renal Denervation

Renal Denervation for the Treatment of Cardiovascular High Risk-Hypertension or Beyond?

Aldosterone Antagonists and Renal Denervation

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