Author + information
- Brent N. Reed, PharmD∗ ( and )
- Stephen S. Gottlieb, MD
- ↵∗Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, 20 North Pine Street, Office S428, Baltimore, Maryland 21201
In the ROPA-DOP (Randomized Evaluation of Heart Failure With Preserved Ejection Fraction Patients With Acute Heart Failure and Dopamine) study, Sharma et al. (1) compared intravenous (IV) bolus with continuous infusion furosemide in patients hospitalized with heart failure with preserved ejection fraction (HFpEF) (1). However, we noticed that the results did not include the actual doses of furosemide administered in the 2 groups at 24 and 72 h, nor how congestion was managed during the intervening 48 h.
Although clinicians were urged to double patients’ home doses, the extent to which this was done is unclear. Comparing the doses administered in the 2 arms is essential to interpreting ROPA-DOP, as diuretic dose has been previously associated with worsening renal function (WRF). In the DOSE (Diuretic Optimization Strategies Evaluation) trial, in which 27% of patients had HFpEF, more patients in the high-dose arm experienced increases in serum creatinine >0.3 mg/dl (23% vs. 14% in the low-dose arm; p = 0.04) (2). Similarly defined rates of WRF were also higher in the high-dose arm of the DAD-HF II (Dopamine in Acute Decompensated Heart Failure II) trial (24% vs. 7% in the low-dose arm; p = 0.044), in which 45% of subjects had HFpEF (3). Importantly, transient WRF may not confer long-term detriments in renal function (2,3), thus the findings in ROPA-DOP are of unclear importance.
It is also unclear how congestion was managed between 24 and 72 h in ROPA-DOP, as this was also left to clinician discretion. No information was provided regarding changes in diuretic dose or use of adjunct therapies (e.g., thiazide-type diuretics), which is also key to interpreting the trial. Adjustments between 48 and 72 h were also permitted in DOSE, and indeed management of patients differed between those in the bolus and the continuous infusion arms (2). Patients in the bolus arm were twice as likely to receive a dose increase (21% vs. 11%, respectively; p = 0.01) or thiazide-type diuretic (16% vs. 7%, respectively; p = 0.02), and the cumulative furosemide dose was 23% higher (592 mg vs. 480 mg, respectively), although this latter difference was just shy of statistical significance (p = 0.06). Nonetheless, the combination of factors favoring the bolus arm may explain the equivocal results in DOSE.
We agree that the preload-sensitive nature of HFpEF makes patients particularly susceptible to changes in intravascular volume and vascular tone. Previous studies have suggested that patients with HFpEF have greater interstitial congestion, relative to that of intravascular congestion (4) and experience greater reductions in stroke volume with vasodilation (5). However, based on this mechanism (and assuming doses were similar in the 2 groups), we would have expected higher rates of renal dysfunction with bolus administration due to more rapid shifts in intravascular volume.
In summary, we feel the omissions described here significantly limit interpretation of ROPA-DOP. Even if doses were similar but SDs were large, the small size of the study limits determination of whether renal dysfunction can be attributed to method of administration alone. These are important questions warranting further study, but we believe the data and methodology are currently insufficient for suggesting that continuous infusion diuretics worsen renal function in HFpEF.
Please note: Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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- Vaishnav J.,
- Kalathiya R.,
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