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Hypertension Global Newsletter #3 Hype
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Comparative safety and effectiveness of aldosterone antagonists versus beta-
blockers as fourth agents in patients with apparent resistant hypertension.

Desai R, et al. Hypertension. 2022 Oct;79(10):2305-2315.

While aldosterone antagonists (AAs) are effective
in reducing short-term BP in patients with resistant
hypertension (RH), there is limited evidence
regarding long-term effectiveness and safety
of AAs vs. beta blockers (BBs) as fourth-line
antihypertensive agents in patients with RH.

This real-world, retrospective, cohort study using
IBM MarketScan commercial claims and Medicare
supplemental claims (2007–2019), aimed to
compare the effectiveness of AAs vs. BBs on
major adverse cardiovascular events (MACE).
It also evaluated safety outcomes, including
hyperkalemia, gynecomastia, and kidney function
deterioration.

Current guidance for patients with RH
includes optimization of the background three
antihypertensive drug regimen, which commonly
includes an ACEi or ARB, a long-acting CCB, and
a thiazide-like diuretic. Following this background
regimen optimization, AA (e.g., spironolactone
or eplerenone) is recommended as the preferred
fourth agent, in part because aldosterone excess
is common in RH, which results in excess volume
retention and organ damage.

In 80,598 patients with RH (mean age 61 years, 51% male), 6626 initiated an AA and 73,972 initiated BB as the fourth
antihypertensive agent. The authors found that initiation of AA did not significantly reduce MACE risk relative to BB initiation
(adjusted HR, 0.77% [95% CI, 0.50–1.19]) but did substantially increase the risk of hyperkalemia (aHR, 3.86 [95% CI, 2.78–
5.34]), gynecomastia (aHR, 9.51 [95% CI, 5.69–15.89]), and kidney function deterioration (aHR, 1.63 [95% CI, 1.34–1.99]).
The authors suggest that a definitive long-term RCT to evaluate comparative effectiveness and safety of AAs and other fourth-
line antihypertensive agents is warranted to better understand whether more intensive BP lowering in patients with RH incurs a
net benefit.

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