Congestive heart failure is a major clinical problem facing most physicians, and diuretics are crucial in the management of these patients. A better strategy of using these important drugs was recently presented at the late-breaking trials conference at the American College of Cardiology (ACC) 2010 Scientific Sessions.
Dr. G. Michael Felker (from Duke Clinical Research Institute, Durham, NC) led a multi-centre randomized controlled trial that compared loop diuretics in continuous and intermittent infusion at conventional and high doses. There were 308 mostly male subjects with a diagnosis of chronic heart failure. The mean age of all subjects was 66. This was a double blind study where the subjects were randomly assigned to either continuous infusion or bolus dosing at conventional or high doses. The conventional dose was the subjects’ normal oral dose, while the high dose was 2.5 times greater. Patients with serum creatinine of over 3 mg/dL and those in whom coronary angiography was anticipated were excluded. The patients were reassessed after 48 hours and were either maintained on their assigned regimen, switched to oral diuretics, or had their dose increased by 50%.
The data on infusion don’t really apply to the vast majority of patients that we see in clinical practice. I normally consider IV infusion of furosemide in patients who are failing intermittent bolus of diuretics, but this trial doesn’t address this population well. In any event, infusion showed no advantages over intermittent dosing.
The results in the intermittent IV dosing group are more relevant. There was no difference in the primary outcome measurements between intermittent bolus at low or high doses of diuretics. In fact none of these therapies, including infusion, brought any significant difference in long-term outcomes. But after 72 hours, among patients on intermittent bolus, there was a trend that favoured high doses because of quicker symptom relief. The apparent benefits included weight loss averaging 3.9 kilos, decrease in the levels of congestion marker NT-proBNP and a significant reduction of dyspnea. One caveat with the high dose was that it increased creatinine levels more than the lower dose did. The main short-term risk of high-dose infusion was temporary impairment of renal function.
Kidney concerns countered
The trial compared IV low dose vs a dose 2.5 times greater. While the primary endpoint wasn’t achieved, important secondary endpoints were demonstrated, including more rapid diuresis and reduced shortness of breath. And the study appears to allay concerns that higher doses led to kidney failure or increased risk of death within 60 days. It wasn’t powered to answer that question definitively, though.
Another caveat is that diabetic patients (51% of subjects) weren’t analyzed separately. Loop diuretics can increase risk of diabetes complications. But the overall study results suggest that any problem of this sort is minor.
These findings will change my clinical practice. I’ll now give the initial dose intravenously instead of orally. If there’s no response in 1-4 hours, I’ll double up the standard ER dose.
For less ill patients who are volume overloaded, we should consider titrating their oral furosemide more aggressively based on change in weight, ankle swelling, and shortness of breath. Many patients tend to titrate diuretics downwards or omit their dose due to concerns of excessive urination. We should encourage patients to weigh themselves on a regular basis and adjust their dose upwards based on shortness of breath or a weight gain of 1 kg or greater.
Adjustments to the rescue
Physicians need to bear in mind that patients’ requirements for diuretics can vary tremendously and constant adjustment may be needed. This trial taught us that in unwell patients complaining of shortness of breath — provided one monitors renal function and electrolytes — increasing diuretics more rapidly can lead to a happier patient.
Gregory P. Curnew, MD, FRCPC is Associate Professor at McMaster University in Hamilton, ON, and Director of the Coronary Care Unit at Hamilton General Hospital.
Arjun Sharma is currently studying at Western University, Department of Psychology, London, ON, class of 2013.