Inpatient Insights
Dual antiplatelet therapy shows effectiveness for mild ischemic stroke
Prior research has shown that dual antiplatelet therapy can reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. A group of researchers in China investigated whether dual antiplatelet therapy could have the same effect with a more delayed initiation time window by analyzing a subgroup of data from a randomized clinical trial including 6,100 patients with mild ischemic stroke or TIA.
Patients were categorized into three groups according to time from symptom onset to treatment initiation (group 1: ≤24 hours; group 2: >24 to ≤48 hours; and group 3: >48 to 72 hours). All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days.
Results of the study, published on September 6, 2024, in JAMA Network Open, showed that new stroke occurred within 90 days in 97 patients (12.4%) in the population with time to treatment of 24 hours or less, in 211 patients (8.3%) in the group of more than 24 hours to 48 hours to treatment, and in 193 patients (7.0%) in the group of more than 48 hours to 72 hours to treatment. They concluded that patients with mild ischemic stroke or TIA can benefit from dual antiplatelet therapy with clopidogrel and aspirin when initiated up to 72 hours after symptom onset, without risk of moderate-to-severe bleeding. ■
Is isavuconazole appropriate as a first-line treatment for cerebral aspergillosis?
Cerebral aspergillosis is associated with high mortality, and while voriconazole or isavuconazole are recommended as first-line treatment for all forms of aspergillosis, little is known about the efficacy and safety of isavuconazole in treating cerebral aspergillosis. Members of the European Society of Clinical Microbiology and Infectious Diseases Fungal Infection Study Group conducted a European multicenter retrospective study of patients treated with isavuconazole for proven or probable cerebral aspergillosis between 2014 and 2022 and compared the outcomes with those of weighted control groups from the previously published French national cohort of cerebral aspergillosis, the Cerebral Aspergillosis Lesional Study (CEREALS).
Forty patients from 10 countries were included in the study, published on July 30, 2024, in Clinical Infectious Diseases. Isavuconazole was administered as a first-line treatment to 10 patients, primarily in combination therapy, resulting in control of cerebral aspergillosis in 70% of these patients. Isavuconazole was administered as monotherapy to 30 patients after a median of 65 days on another therapy, mostly because of adverse effects or therapeutic failure of the previous treatment. It achieved control of cerebral aspergillosis in 73% of these patients. Of the 40 patients included in the study, 17 patients (43%) underwent neurosurgery, and isavuconazole toxicity led to treatment interruption in 7.5% of the patients. Twelve-week mortality was 18%.
The CEREALS cohort showed comparable survival in patients receiving isavuconazole or voriconazole as a first-line treatment, and mortality of patients with cerebral aspergillosis treated with isavuconazole was similar to that reported with voriconazole. ■
Adding GLP-1s to SGLT-2 could improve cardiovascular and kidney outcomes
SGLT-2 inhibitors and GLP-1 receptor agonists both improve cardiovascular and kidney outcomes in patients with T2D. But are the benefits of SGLT-2 inhibitors affected by whether the patient also receives GLP-1 receptor agonists? To answer this question, researchers conducted a collaborative meta-analysis of trials included in the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium, restricted to participants with diabetes, to assess the presence of major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), hospitalization for heart failure, cardiovascular death, and chronic kidney disease progression among patients in 12 randomized, double-blind, placebo-controlled trials.
Of the more than 73,000 participants in the trials, approximately 3,000 were using GLP-1 receptor agonists at baseline. Findings from the study, which were published in the August 2024 issue of The Lancet Diabetes & Endocrinology, showed that SGLT-2 inhibitors reduced the risk of major adverse cardiovascular events in participants both receiving and not receiving GLP-1 receptor agonists, and that effects on hospitalization for heart failure or cardiovascular death and chronic kidney disease progression were also consistent regardless of GLP-1 receptor agonist use. Fewer serious adverse events occurred in patients using SGLT-2 inhibitors compared with placebo, regardless of GLP-1 receptor agonist use.
The authors concluded that their results support clinical practice guidelines recommending the use of these agents in combination to improve cardiovascular and kidney metabolic outcomes. ■
Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared with placebo?
Asthma can be difficult to treat in some of the more than 300 million patients affected by the disease worldwide. Researchers from several institutions in Australia conducted a secondary analysis of data from the AMAZES clinical trial—a double-anonymized placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations—to determine remission rates compared with placebo. Clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months evaluated at 12 months and a 5-item Asthma Control Questionnaire score of less than or equal to 1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (postbronchodilator FEV1 ≥80% or postbronchodilator FEV1 ≤5% decline from baseline) and complete remission (sputum eosinophil count <3% plus the other criteria).
The 335 patients in the study were given 500 mg azithromycin 3 times per week or placebo. Results of the analysis, published in the August 2024 issue of CHEST, showed that 12 months of treatment with azithromycin induced clinical remission in 50.6% of patients versus 38.9% with placebo. In addition, clinical remission plus lung function criteria was achieved by 50.8% of the patients who received azithromycin versus 37.1% for those receiving a placebo. Azithromycin induced remission in patients with both eosinophilic and noneosinophilic asthma.
The authors noted that a significant proportion of patients in the placebo arm achieved remission and postulated that the AMAZES study requirement of an initial intervention (optimization of asthma treatment and a ≥80% adherence during the 2-week run-in period to study initiation) may have led to a higher placebo effect. They concluded that the results of their analysis raise the hope of asthma remission as a realistic therapeutic goal. ■