Abstract Body: Introduction: Mineralocorticoid receptor antagonists (MRAs) are established as first-line antihypertensive agents for patients with HF or secondary hypertension (HTN) caused by hyperaldosteronism. However, their role as first-line treatment for essential HTN in patients without HF remains underexplored.
Hypothesis: This study aims to compare MRA cardiovascular (CV) and renal outcomes in patients with essential HTN, without HF.
Methods: This retrospective study used TriNetX data on patients ≥40 yrs with essential HTN (2007–2025). Cohort 1 included patients on MRAs without HF, who were not using thiazide diuretics, while cohort 2 consisted of patients on thiazide diuretics without MRA treatment or HF. After matching, each group had 687,644 patients (mean age 67; 50% male, 47% female). Outcomes: all-cause mortality, HF, AMI, stroke, AKI/CKD, hypertensive urgency/emergency. Risk ratio (RR), hazard ratio (HR), 95% CI, and p-values were calculated to assess risk.
Results: The risk of all-cause mortality was significantly higher in cohort 1 (21.28%) compared to cohort 2 (15.50%), with a RR of 1.373, 95% CI: 1.363–1.383), p < 0.0001, and HR of 2.006 (95% CI: 1.99–2.022), p < 0.0001. Cohort 1 had higher incidence of HF (43.37%) vs cohort 2 (17.49%), with RR of 2.48, 95% CI: 2.465–2.494, p < 0.0001, and an HR of 3.856 (95% CI: 3.83–3.882), p < 0.0001. The risk of AMI was also higher in cohort 1 (9.92%) compared to cohort 2 (6.68%), with RR 1.486 (95% CI: 1.47–1.503), p < 0.0001, HR of 2.031 95% CI: 2.007–2.056, p < 0.0001. However, cohort 1 had a lower incidence of stroke (6.73%) vs cohort 2 (7.91%), with an RR of 0.851, 95% CI: 0.841–0.861, p < 0.0001, but lower survival with HR of 1.112, 95% CI: 1.098–1.126, p < 0.0001. Cohort 1 exhibited a higher risk of AKI/CKD (34.53%) vs cohort 2 (31.15%), with an RR of 1.109, 95% CI: 1.103–1.114, p < 0.0001, and an HR of 1.459, 95% CI: 1.451–1.468, p < 0.0001. Hypertensive urgency/emergency was less frequent in Cohort 1 1.94%vs 3.06%, RR of 0.633, 95% CI: 0.62–0.647, p < 0.0001, HR 0.888, 95% CI: 0.869–0.908, p < 0.0001.
Conclusion:
In patients with essential HTN without HF, MRAs were associated with higher rates of adverse CV outcomes and all-cause mortality compared to thiazide diuretics. However, MRAs showed a lower incidence of hypertensive crisis and CVA events. These findings suggest that while MRAs are suitable for HTN with HF, thiazide diuretics may offer better CV and mortality outcomes in essential HTN without HF.