NEW YORK (Reuters Health) – Elderly patients with heart failure have an increasing mortality risk as their dose of furosemide increases, after taking into account multiple confounders, a Canadian team reports.
Dr. Douglas S. Lee of the Institute for Clinical Evaluative Sciences, Toronto, Ontario, along with colleagues there and elsewhere in Toronto, examined outcomes among 4270 heart failure patients (mean age 78.4 years) in relation to changes in furosemide dose over a 5-year follow-up period after they were discharged from the hospital.
“Dynamic furosemide exposures were classified as low dose (1-59 mg/d), medium dose (60-119 mg/d), or high dose (at least 120 mg/d),” the authors explain in their report in the August issue of the American Heart Journal.
They found that there were changes in drug dosages over time among patients initially discharged on any of the three dose categories, and that 63% of the subjects changed dose category during follow-up.
The statistical analysis of outcomes in relation to furosemide exposure was adjusted for “prior myocardial infarction, aortic/mitral valve disease, hypertension, diabetes, atrial fibrillation, cancer, cerebrovascular disease, chronic obstructive lung disease, dementia, smoking, New York Heart Association class, left ventricular ejection fraction, hypo/normo/hypernatremia, hypo/normo/hyperkalemia, creatinine, urea, cardiomegaly, heart rate, respiratory rate, preadmission use of furosemide, presenting and discharge systolic blood pressure, and discharge medications including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-adrenoreceptor antagonists, spironolactone, digoxin, potassium supplements, metolazone, and other diuretics.”
During follow-up, 79% of patients discharged on high-dose furosemide died compared with 69% in the medium dose group and 62% in the low-dose group. The adjusted mortality hazard ratios with dynamic time-varying furosemide dose were 1.96 with medium-dose furosemide and 3.00 with high-dose furosemide, using low-dose furosemide as the referent.
Similarly, “analysis of dynamic furosemide dose showed that higher furosemide dose exposure was independently associated with higher hospitalization risk in a dose-dependent fashion,” Dr. Lee and colleagues report.
They also observed a “prominent” increase in the risk of renal dysfunction and arrhythmias with furosemide exposure.
The team concludes, “Furosemide dose can serve as a powerful, dynamic, and easily used marker of prognosis in heart failure.” Hence, there is a need for vigilance in patients dependent on high-dose furosemide, they advise, and for “clinical trials testing different strategies of furosemide dosing.”
Diuretic dose and long-term outcomes in elderly patients with heart failure after hospitalization
Am Heart J 2010;160:264-271.