Background Mortality is increased following a hospitalization for decompensated heart failure (HF), during which diuretics are usually intensified. It is unclear how risk is affected after outpatient intensification of diuretic therapy for HF. Methods and Results From nationwide administrative registers, we identified all Danish patients who were diagnosed with HF from 2001 to 2016 and received angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and β blocker within 120 days. Subsequent follow-up tracked progressive events of diuretic intensification and HF hospitalization. Intensification events were defined as new addition or doubling of loop diuretic or addition of thiazide to loop diuretic. These events were included in multivariable Cox regression models, calculating 1-year mortality hazard after each year since inclusion. Patients with an intensification event or hospitalization were risk set matched to 2 nonworsened HF controls and absolute 1-year mortality risks were calculated using Kaplan-Meier estimates. We included 74 990 patients, their median age was 71 years, and 36% were women. Intensification events were associated with significantly increased mortality at all times during follow-up. One-year mortality was 18.0% after an intensification event, 22.6% after HF hospitalization, and 10.4% for matched controls with neither. In a multivariable Cox model adjusted for age, sex, ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease, and diabetes mellitus, the hazard ratio for 1-year death after an intensification event was 1.75 (95% CI, 1.66-1.85), and it was 2.28 (95% CI, 2.16-2.41) after HF hospitalization. Conclusions In a nationwide cohort of patients with HF, outpatient intensification events were associated with almost 2-fold risk of mortality during the next year. Although HF hospitalization was associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.
Keywords: diuretics; heart failure; hospitalization; mortality; outpatient.