Diuretic Dosage May Predict Heart Failure Risk
Abdel-Qadir HM, Tu JV, Yun L, Austin PC, Newton GE, Lee DS
Am Heart J. 2010;160:264-271.e1
Investigators from the University of Toronto, Toronto, Ontario, Canada, studied the effect of diuretic doses in patients aged 65 and older who were newly discharged from the hospital with heart failure.
The study authors hypothesized that increased dynamic furosemide doses would be independently associated with a higher risk for death and morbid adverse outcomes. They searched all ambulatory prescription claim records in the Ontario Drug Benefit pharmacare database, and divided their study participants into categories of "furosemide exposure" on the basis of changes in doses from the time of discharge through 5 years of follow-up, or until death: The categories were low dose (LD; 1-59 mg/day), medium dose (MD; 60-119 mg/day), or high dose (HD; ≥ 120 mg/day). Forty-six percent of patients changed furosemide dose categories within 1 year, and 63% of patients changed over the follow-up 5-year period.
Compared with the LD furosemide patients, the HD furosemide patients were younger, mostly men, and had more ischemic or valvular disease, diabetes, atrial fibrillation, hypotension, hyponatremia, and higher baseline creatinine.
In multiple Cox regression analyses, the study authors investigated the independent relationship between furosemide dose and outcomes of morbidity and mortality. After adjusting for multiple covariates, they found that the risk for hospitalization for heart failure, worsening renal dysfunction, and arrhythmias was higher with increased furosemide exposure (MD, HD) compared with LD exposure. Fracture risk was not increased with high furosemide doses. There was also a dose-dependent increase in deaths in the MD and HD groups relative to LD exposure.
Of patients discharged on HD furosemide, 79% died compared with 69% and 62% of patients discharged on MD and LD furosemide, respectively.
The study showed that dynamic changes from exposure to higher furosemide doses were associated with worsened clinical outcomes of morbidity and mortality in elderly patients with heart failure over 5 years after discharge from the hospital.
Heart failure is a leading cause of hospitalization and mortality. More than 80% of patients with heart failure receive loop diuretics, such as furosemide, for acute decomposition. The use of diuretic drugs has been associated with morbidity, including renal compromise and fractures, as well as sudden death and increased mortality risk. However, the degree and effect of changes in diuretic doses following discharge from the hospital and the long-term outcomes from increasing furosemide doses have not been estimated in ambulatory populations of elderly patients with heart failure beyond 1 year. To that end, the study authors evaluated elderly patients with heart failure, and after adjusting for multiple covariates, found that high furosemide doses were associated with a greater risk for death, recurrent hospitalization for heart failure, renal dysfunction, and arrhythmias -- but not with fracture. The study authors suggested that furosemide dose could be a significant, dynamic, and easy-to-use marker for prognosis in heart failure.
The authors acknowledged the limitations of their study. First, the study did not find how much of the increased risk for adverse outcomes was from confounding by indication for treatment because increasing furosemide dose often happens with worsening clinical status. Second, the authors did not study fine changes (eg, halving or doubling) of current furosemide doses that may have greater related effects than those that they had identified. Third, the authors did not study changes in laboratory markers or clinical measurements (eg, blood pressure) over time. Fourth, the authors did not include morbidity from less severe conditions that did not require hospitalizations or continued creatinine measurements. Lastly, limited sensitivity of renal dysfunction and arrhythmia codes in the administrative database may have affected risk estimates from the study.
A majority of patients with heart failure are elderly Medicare beneficiaries in whom heart failure is a leading cause of hospitalization that has significant impact on quality of life and increased costs of care. Therefore, the study's important implication for providers and payers is to watch patients with heart failure who are dependent on high furosemide doses. Further, the notable increase in morbidity and mortality risk from high furosemide doses warrants further testing of different drug-dosing strategies. In summary, there is urgency for promoting cost-effective disease management and quality of care in elderly heart failure populations following hospitalization, when they are continued on routine furosemide prescriptions with recurrent dose changes.
Abstract
Diuretic Dose and Long-term Outcomes in Elderly Patients With Heart Failure After Hospitalization
Abdel-Qadir HM, Tu JV, Yun L, Austin PC, Newton GE, Lee DS
Am Heart J. 2010;160:264-271.e1
Study Summary
Investigators from the University of Toronto, Toronto, Ontario, Canada, studied the effect of diuretic doses in patients aged 65 and older who were newly discharged from the hospital with heart failure.
The study authors hypothesized that increased dynamic furosemide doses would be independently associated with a higher risk for death and morbid adverse outcomes. They searched all ambulatory prescription claim records in the Ontario Drug Benefit pharmacare database, and divided their study participants into categories of "furosemide exposure" on the basis of changes in doses from the time of discharge through 5 years of follow-up, or until death: The categories were low dose (LD; 1-59 mg/day), medium dose (MD; 60-119 mg/day), or high dose (HD; ≥ 120 mg/day). Forty-six percent of patients changed furosemide dose categories within 1 year, and 63% of patients changed over the follow-up 5-year period.
Compared with the LD furosemide patients, the HD furosemide patients were younger, mostly men, and had more ischemic or valvular disease, diabetes, atrial fibrillation, hypotension, hyponatremia, and higher baseline creatinine.
In multiple Cox regression analyses, the study authors investigated the independent relationship between furosemide dose and outcomes of morbidity and mortality. After adjusting for multiple covariates, they found that the risk for hospitalization for heart failure, worsening renal dysfunction, and arrhythmias was higher with increased furosemide exposure (MD, HD) compared with LD exposure. Fracture risk was not increased with high furosemide doses. There was also a dose-dependent increase in deaths in the MD and HD groups relative to LD exposure.
Of patients discharged on HD furosemide, 79% died compared with 69% and 62% of patients discharged on MD and LD furosemide, respectively.
The study showed that dynamic changes from exposure to higher furosemide doses were associated with worsened clinical outcomes of morbidity and mortality in elderly patients with heart failure over 5 years after discharge from the hospital.
Viewpoint
Heart failure is a leading cause of hospitalization and mortality. More than 80% of patients with heart failure receive loop diuretics, such as furosemide, for acute decomposition. The use of diuretic drugs has been associated with morbidity, including renal compromise and fractures, as well as sudden death and increased mortality risk. However, the degree and effect of changes in diuretic doses following discharge from the hospital and the long-term outcomes from increasing furosemide doses have not been estimated in ambulatory populations of elderly patients with heart failure beyond 1 year. To that end, the study authors evaluated elderly patients with heart failure, and after adjusting for multiple covariates, found that high furosemide doses were associated with a greater risk for death, recurrent hospitalization for heart failure, renal dysfunction, and arrhythmias -- but not with fracture. The study authors suggested that furosemide dose could be a significant, dynamic, and easy-to-use marker for prognosis in heart failure.
The authors acknowledged the limitations of their study. First, the study did not find how much of the increased risk for adverse outcomes was from confounding by indication for treatment because increasing furosemide dose often happens with worsening clinical status. Second, the authors did not study fine changes (eg, halving or doubling) of current furosemide doses that may have greater related effects than those that they had identified. Third, the authors did not study changes in laboratory markers or clinical measurements (eg, blood pressure) over time. Fourth, the authors did not include morbidity from less severe conditions that did not require hospitalizations or continued creatinine measurements. Lastly, limited sensitivity of renal dysfunction and arrhythmia codes in the administrative database may have affected risk estimates from the study.
A majority of patients with heart failure are elderly Medicare beneficiaries in whom heart failure is a leading cause of hospitalization that has significant impact on quality of life and increased costs of care. Therefore, the study's important implication for providers and payers is to watch patients with heart failure who are dependent on high furosemide doses. Further, the notable increase in morbidity and mortality risk from high furosemide doses warrants further testing of different drug-dosing strategies. In summary, there is urgency for promoting cost-effective disease management and quality of care in elderly heart failure populations following hospitalization, when they are continued on routine furosemide prescriptions with recurrent dose changes.
Abstract