Clinical outcomes associated with angiotensin receptor–neprilysin inhibitors versus mineralocorticoid receptor antagonist initiation in patients with hypertension without heart failure: a propensity score–matched study

Angiotensin receptor–neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs) lower blood pressure, but evidence directly comparing their clinical outcomes in patients with hypertension without heart failure is limited. We compared long-term outcomes associated with ARNI versus MRA initiation in this population. Adults with essential hypertension without heart failure were included if they had documented use of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker plus at least one additional antihypertensive drug class. Patients receiving sacubitril or spironolactone or eplerenone after a 1-year washout period were assigned to the ARNI and MRA cohorts, respectively. The primary outcome was all-cause mortality; secondary outcomes were a composite of acute myocardial infarction and stroke, acute kidney injury (AKI), acute myocardial infarction, and stroke. Outcomes were assessed for up to 1095 days. After 1:1 propensity score matching, 11,832 patients were included in each group. During follow-up, the rates of all-cause mortality in the ARNI and the MRA groups were 7.6% (894 patients) and 10.2% (1 201 patients), respectively. The ARNI group compared to MRA group was associated with a lower risk of all-cause mortality, stroke, and AKI, whereas no significant differences were observed in the composite cardiovascular outcome or acute myocardial infarction. Mean systolic blood pressure was modestly lower in the ARNI group, while diastolic blood pressure and the most recently recorded estimated glomerular filtration rate were similar between groups. These findings are hypothesis-generating and require confirmation in prospective studies.