MiscellaneousEffectiveness of Spironolactone Plus Ambrisentan for Treatment of Pulmonary Arterial Hypertension (from the [ARIES] Study 1 and 2 Trials)
Section snippets
Methods
Patients with World Health Organization (WHO) group I PAH who had received treatment in the randomized, placebo-controlled phase III trials ARIES-1 (n = 201) and ARIES-2 (n = 192) were eligible for analysis. The full methods and results for both studies have been reported previously.7, 8 Patients received for 12 weeks either placebo or the selective endothelin type-A receptor antagonist ambrisentan at 5 or 10 mg/day orally in ARIES-1 or 2.5 or 5 mg/day orally in ARIES-2. The primary end point
Results
Of patients randomized to placebo (n = 132) or ambrisentan 10 mg/day (n = 67), concurrent spironolactone use was identified for 21 (15.9%) and 10 (14.9%) patients, respectively. Compared with ambrisentan alone (n = 57), patients in the ambrisentan + spironolactone group (n = 10) were more likely to have WHO functional class III/IV and tended to have worse baseline 6-MWD, pulmonary vascular resistance, and plasma BNP concentration, although no clinically meaningful differences between treatment
Discussion
Despite increasing evidence implicating the involvement of vasoactive hormones such as aldosterone in the pathophysiology of PAH,2, 6, 10, 11, 12 reports on the clinical application of aldosterone antagonists in this disease are limited to only individual patients.3, 13 This study represents the first report describing data collected systematically in patients with PAH for whom spironolactone was identified as part of the therapeutic profile.
Akin to ARIES-1 and ARIES-2, we observed that
Acknowledgment
The authors wish to graciously acknowledge the efforts of the ARIES trial investigators.
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2021, ChestCitation Excerpt :Two previous studies suggest that AA therapy indeed is prescribed preferentially in patients with greater pulmonary vascular disease burden. First, in the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study (ARIES) trial of ambrisentan for PAH, enrolled patients were treated with spironolactone based on the discretion of their personal physician.19 Analysis of these patients demonstrated that 61% of patients were prescribed spironolactone to treat “RV failure,” “refractory edema,” or “electrolyte imbalances.”
This work was supported by grants HL105301 to Dr. Leopold; HL61795, HL48743, HL107192, HL070819, and HL108630 to Dr. Loscalzo; 1K08HL111207-01A1 to Dr. Maron from the US National Institutes of Health (Bethesda, Maryland) and the Lerner Foundation (Boston, Massachusetts) at Brigham and Women's Hospital (Dr. Maron) and grant 11POST6720000 to Dr. Maron from the American Heart Association (Dallas, Texas).
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