One-Year Mortality After Intensification of Outpatient Diuretic Therapy

Abstract

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.

Figure 1. Diagram showing selection of study population.

*Patients who were readmitted within the initial 120 days, followed up for an additional 120 days, and had a second (or third, if diagnosed as inpatient) hospitalization. ACEI indicates angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; and BB, β blocker.

Figure 2. Incidence of worsening, patient status during follow‐up, and associated death rates.

A, Incidences of intensification events and heart failure (HF) hospitalizations according to years since HF diagnosis. B, Multistate model showing how many patients are in the 5 possible states at any time during 5 years of follow‐up. Arrows indicate how many patients die from each state and death rates per 100 person‐years (P.Y.).

Figure 3. Hazard ratios of 1‐year mortality after first intensification event, heart failure (HF) hospitalization, or both, according to time since HF diagnosis.

Patients with a worsening event 1 year are not included in the analyses for subsequent years. The multivariable Cox models are conducted at the end of each year, which is why patients have to survive until then to be included in the analyses. N_deaths indicates how many patients die within 1 year and the corresponding percentage of N_patients; and N_patients, number of patients in each group.

Figure 4. Absolute risk of 1‐year mortality and hazard ratios after first intensification event or heart failure (HF) hospitalization compared with age‐ and sex‐matched controls from the risk set in important subgroups.

The multivariable Cox models are conducted immediately after the worsening events, and all patients with a worsening event are included.