Acetazolamide improves congestion at 3 days in acute decompensated HF
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In the ADVOR trial, the addition of IV acetazolamide to standard IV loop diuretics improved acute congestion at 3 days in nearly 50% more patients vs. placebo in the setting of acute decompensated HF and volume overload.
“ADVOR is the first trial ever in acute heart failure to show a positive result with regards to very clinically important and relevant endpoints,” Wilfried Mullens, MD, PhD, professor at Ziekenhuis OostLimburg in Genk, Belgium, said during a press conference at the European Society of Cardiology Congress. “It was the largest diuretic trial that has ever been performed in acute heart failure with an endpoint of decongestion.
“In patients with acute heart failure, the addition of 500 mg of IV acetazolamide to standard intravenous loop diuretic therapy was associated with a 46% higher chance of successful decongestion after 3 days,” Mullens said.
The ADVOR trial was a prospective, multicenter, randomized, double-blind, controlled trial for which Mullens and colleagues enrolled 519 patients with acute decompensated HF plus volume overload. All patients had been taking loop diuretics for more than 1 month and had N-terminal pro-B natriuretic peptide of more than 1,000 pg/mL. Patients were assigned to either acetazolamide or placebo.
The primary endpoint was successful congestion within 3 days. Secondary endpoints included index hospital duration and a composite of all-cause death and HF hospitalization.
Mullens stated that, compared with prior diuretic trials in patients with acute decompensated HF, patients in the ADVOR trial were older and had higher baseline NT pro-BNP (mean age, 78 years; median NT pro-BNP, 6,173 pg/mL).
At 3 days, approximately 42.2% of patients in the acetazolamide arm had successful decongestion compared with 30.5% in the placebo arm, translating to a risk ratio of 1.46 (95% CI, 1.17-1.82; P = .0009) and a number needed to treat of 6.
Mullens highlighted an increasing treatment effect over consecutive days while patients were on acetazolamide compared with placebo (P = .015), and said the results show the benefits of treating decompensated HF early and aggressively.
Moreover, patients treated with acetazolamide had shorter hospital stays compared with those who received placebo (8.8 days vs. 9.9 days).
All-cause death or HF rehospitalization at 3 months was similar between the groups (acetazolamide, 29.7%; placebo, 27.8%; HR = 1.07; 95% CI, 0.78-1.48).
Results of the ADVOR trial were simultaneously published in The New England Journal of Medicine.
“The [ADVOR] trial supports the utilization of [acetazolamide], as it is a cheap drug, it’s off patent and it costs 8, not 8,000,” Mullens said during the press conference. “It’s easy to use; it’s safe; it’s been used for over 70 years; and is very effective to improve decongestion.”
Reference:
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Javed Butler, MD, MPH, MBA, FACC, FAHA, FESC
Most trials in patients with acute HF have not yielded positive results. The ADVOR trial was positive and reached its primary endpoint of better patient decongestion, and the combination of loop diuretics and acetazolamide led to better diuresis without any significant adverse events. These data are encouraging. However, we also need to know patient outcomes. Length of stay tended to be shorter in the active arm, which is an important health care resource utilization benefit. We do not have data on patient symptoms or quality of life scores. Importantly, postdischarge mortality and readmissions were not lowered, and while the trial was not powered for these outcomes, if anything, they tended to be in the opposite direction.
Thus, in summary, these are very encouraging results and should lead to a large study focused on patient-centric and clinical outcomes.
Clinicians may consider a combination of diuretics for patients with acute HF, irrespective of ejection fraction, based on these data; however, a follow up study with clinical outcomes will further add to the clinical interpretation of these data.
These studies are not easy to do, and the investigators should be congratulated on a difficult study very well done.
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Mullens W, et al. Hot Line 2. Presented at: European Society of Cardiology Congress; Aug. 26-29, 2022; Barcelona, Spain (hybrid meeting).
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