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APhA Staff

Can acetazolamide improve decongestion in acute decompensated heart failure?

Current guidelines recommend intravenous loop diuretics to improve symptoms of fluid overload in patients with acute decompensated heart failure. However, patients may be discharged from the hospital with residual clinical signs of volume overload, which can contribute to further heart failure. A group of European researchers (the ADVOR Study Group) recently investigated whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload.

The study, published on August 22, 2022, in the New England Journal of Medicine, involved 519 patients in a multicenter, parallel-group, double-blind, randomized, placebo-controlled trial. Patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro–B-type natriuretic peptide level of more than 1,000 pg/mL or a B-type natriuretic peptide level of more than 250 pg/mL were randomized to receive either I.V. acetazolamide (500 mg once daily) or placebo added to standardized I.V. loop diuretics (at a dose equivalent to twice the oral maintenance dose).

The primary endpoint was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Safety was also assessed.

The results of the trial indicated that successful decongestion occurred in 42.2% of patients in the acetazolamide group and in 30.5% of patients in the placebo group. Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, indicating improved diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.

The authors note that while the addition of acetazolamide to loop-diuretic therapy was associated with an improved diuretic efficiency and a shorter hospital stay, the risk of death from any cause or rehospitalization for heart failure did not differ significantly between the two trial groups.  ■

Baricitinib reduces mortality for hospitalized patients with COVID-19

Patients with severe COVID-19 often experience inflammatory-related hypoxic respiratory failure that can require mechanical ventilator support or lead to death. A recent study, published in the July 30, 2022, issue of The Lancet, evaluated the use of baricitinib, a Janus kinase (JAK) 1−2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.

The RECOVERY trial involved over 8,000 hospitalized patients in the U.K who were randomized to receive usual care plus 4 mg/day oral baricitinib for 10 days or until discharge if sooner, or usual care alone. At randomization, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab. The study results indicated that baricitinib reduced 28-day mortality by 13%, increased the probability of discharge within 28 days, and reduced the probability of invasive mechanical ventilation or death.  The researchers also performed a meta-analysis of results from the RECOVERY trial and all previous randomized controlled trials of baricitinib or other JAK inhibitor in patients hospitalized with COVID-19.

The analysis indicated that treatment with baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality. These benefits appear to be consistent regardless of treatment with remdesivir, systemic corticosteroids, or an IL-6 receptor blocker such as tocilizumab, supporting the use of baricitinib in addition to other immunosuppressive therapies in treating patients hospitalized with COVID-19.  ■

Doxycycline is effective for treating mild-to-moderate CAP

Successful treatment of community-acquired pneumonia (CAP) is complicated by growing concerns about the resistance and safety of the commonly used antimicrobial agents. A recent study published on July 29, 2022, in Clinical Infectious Diseases reviewed the evidence for use of doxycycline in treatment of adult patients with mild-to-moderate CAP and concluded that doxycycline is a viable treatment option, comparable to macrolides or fluoroquinolones, for adult patients with mild-to-moderate CAP.

Sang Ho Choi and colleagues at the University College London performed a systematic review and meta-analysis of 6 randomized controlled trials of doxycycline versus comparators (3 macrolides [roxithromycin, spiramycin, and erythromycin] and 3 fluoroquinolones [ofloxacin, fleroxacin, and levofloxacin]) to assess clinical efficacy. The primary outcome was the clinical cure rate.

Results of the analysis indicated that the clinical cure rate was similar between the doxycycline and comparator groups (87.2% vs. 82.6%), while subgroup analysis of two studies with a low risk of bias showed significantly higher clinical cure rates in the doxycycline group (87.1% vs. 77.8%).

Adverse event rates were comparable between the doxycycline and comparator groups. The authors concluded that monitoring of local susceptibility patterns and larger randomized clinical trials are required. ■

Aspirin or enoxaparin for preventing VTE

A recent study in JAMA showed that aspirin is inferior to enoxaparin for preventing symptomatic venous thromboembolism (VTE) in patients who undergo hip and knee arthroplasty procedures. While aspirin is less expensive and easier to administer than low-molecular-weight heparin (enoxaparin), evidence on the safety and efficacy of aspirin as a sole prophylactic agent is limited. Researchers at 31 hospitals in Australia (the CRISTAL Study Group) conducted a cluster-randomized, crossover, noninferiority design to assess the effects of aspirin compared with enoxaparin to prevent symptomatic VTE, including pulmonary embolism and deep venous thrombosis (DVT), within 90 days in patients undergoing hip or knee arthroplasty.

Over 9,000 eligible patients (5,675 in the aspirin group and 4,036 in the enoxaparin group) were enrolled in the study. Patients received either 100 mg/day aspirin or 40 mg/day enoxaparin group for 35 days after total hip arthroplasty or 14 days after total knee arthroplasty.

Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate was 3.45% in the aspirin group and 1.82% in the enoxaparin group.

The authors concluded that while the findings of superiority for enoxaparin met statistical significance, a cost-effectiveness analysis is needed to better understand the clinical relevance of the trial results.  ■