What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Low-renin hypertension (n=1043). Intervention: Mineralocorticoid receptor antagonists (MRA) vs. ACEi/ARB, diuretics, ENaCi, or placebo. Primary outcome: Change in systolic blood pressure (MRA vs ACEi/ARB) (Mean difference -6.8 mmHg, 95% CI -9.6 to -4.1).

What does this research mean for the field?

Mineralocorticoid receptor antagonists effectively lower systolic blood pressure in patients with low-renin hypertension, reducing it by 6.8 mmHg compared to ACEi/ARB and by 4.8 mmHg compared to diuretics. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 11, 2024Open Access

Efficacy and safety of mineralocorticoid receptor antagonists for the treatment of low-renin hypertension: a systematic review and meta-analysis

Key Result

Mineralocorticoid receptor antagonists reduced systolic blood pressure by 6.8 mmHg compared to ACEi/ARB and by 4.8 mmHg compared to diuretics in patients with low-renin hypertension.

Study Design

Type

Meta-Analysis (n=1,043)

Structured PICO

Does mineralocorticoid receptor antagonist therapy reduce blood pressure in adults with low-renin hypertension?

Population

17 RCTs pooling 1,043 adults with low-renin hypertension (LRH).

Intervention

Mineralocorticoid receptor antagonists (MRA) as a class (e.g., spironolactone 25-400 mg/day or eplerenone 50-200 mg/day) for a median of 8 weeks.

Comparator

Placebo or active antihypertensive comparators (diuretics, ACEi/ARB, ENaCi, beta-blockers, or alpha-2 agonists).

Outcome

Change in systolic and diastolic blood pressure from baseline to the last time point measured.surrogate

MRA therapy effectively lowers blood pressure in patients with low-renin hypertension and is significantly more effective than ACE inhibitors or ARBs.

Main Result

Effect estimate: Mean difference -6.8 mmHg (95% CI -9.6 to -4.1)

Limitations

Heterogeneous population due to different definitions of low-renin hypertension
Primary aldosteronism was not rigorously excluded
Multiple different antihypertensives and doses were compared
Short or absent washout period in some cross-over studies
Incomplete assessment of tolerability and impact on end-organ function

Abstract

Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by -6.8 mmHg (95% confidence interval -9.6 to -4.1) and -4.8 mmHg (95% confidence interval -11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.

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