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Moderate ischemic stroke patients may benefit from dual antiplatelet therapy
Does dual antiplatelet therapy with ticagrelor plus aspirin benefit patients with moderate acute ischemic stroke?
A worldwide group of researchers from Capital Medical University (China), National Clinical Research Center for Neurological Diseases (China), University of Paris, AstraZeneca (Sweden), George Washington University, Uppsala University (Sweden), Vall d’Hebron Hospital (Spain), and University of Texas at Austin conducted an exploratory post-hoc analysis of the THALES trial to compare results for patients with moderate stroke (baseline NIHSS score of 4–5) with patients with less severe stroke (NIHSS score of 0–3).
The study, published online in JAMA Neurology on July 9, 2021, included almost 10,000 patients with stroke from the THALES trial, which was conducted at 414 hospitals in 28 countries between January 2018 and December 2019.
Patients received either ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily on days 2–30) or placebo within 24 hours after symptom onset. All patients received 300 mg to 325 mg aspirin on day 1 followed by 75 mg to 100 mg aspirin daily on days 2 to 30. Patients were observed for 30 additional days.
The primary outcome was time to stroke or death within 30 days, and the primary safety outcome was time to severe bleeding.
The observed primary outcome event rate in patients with moderate stroke was 7.6% for those in the ticagrelor group and 9.1% for those in the placebo group, while the primary outcome event rate in patients with less severe stroke was 4.7% for those in the ticagrelor group and 5.7% for those in the placebo group. Severe bleeding was not observed in any of the groups.
The authors concluded that patients with moderate ischemic stroke may also benefit from dual antiplatelet therapy with ticagrelor and aspirin.
Do Z-drugs increase the risk of opioid overdose?
Zolpidem, zopiclone, and zaleplon (the Z-drugs) are often used to treat insomnia in patients taking prescription opioids. To determine whether rates of overdose among patients using both opioids and Z-drugs are higher than for patients using opioids alone, Szmulewicz and colleagues at Brigham and Women’s Hospital and Harvard Medical School performed a population-based cohort study. The results of the study were published in the July 2021 issue of the American Journal of Psychiatry.
All individuals 15 to 85 years of age receiving prescription opioids from 2004 to 2017, regardless of underlying indication and without evidence of cancer, were identified in the IBM MarketScan database. Patients with concomitant exposure to Z-drugs were matched 1:1 to patients with exposure to prescription opioids alone based on opioid prescribed, morphine equivalents, number of days’ supply, and hospitalization within the past 30 days. Records for over 500,000 exposed patients and an equal number of matched reference patients were analyzed.
Among the exposed patients, there were 52.5 overdose events per 10,000 person-years, compared with a 14.4 overdose events per 10,000 person-years among the reference patients. The authors conclude that the potential implications of these results are significant given the large number of patients receiving both opioids and Z-drugs.
Selecting the best inotropic agent for cardiogenic shock
Inotropic medications are a mainstay for treating cardiogenic shock, but how to select such medications is not clear. Researchers at University of Ottawa, collaborating with colleagues at University of Toronto, University of British Columbia, Tufts Medical Center, Mayo Clinic, and Hôpital Cardiologique du Haut Lévêque (France) conducted a double-blind randomized clinical trial to determine if milrinone or dobutamine was more effective at treating cardiogenic shock.
In the study, published in the August 5, 2021, issue of the New England Journal of Medicine, patients with cardiogenic shock were randomly assigned to receive either milrinone or dobutamine. The primary outcome was a composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke diagnosed by a neurologist, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite outcome.
A total of 192 participants (96 in each group) were enrolled. The results showed no significant difference between milrinone and dobutamine with respect to the primary composite outcome or important secondary outcomes. A primary outcome event occurred in 47 participants (49%) in the milrinone group and in 52 participants (54%) in the dobutamine group.
No significant between-group differences in safety outcomes or in surrogate markers of resuscitation, including heart rate, blood pressure, and serum lactate level, were observed. The incidence of adverse clinical outcomes, including in-hospital death, was high in both groups.
Researchers examine efficacy of tirzepatide for patients with type 2 diabetes
Because not all patients with type 2 diabetes are able to adequately control their disease using metformin, other treatments, including selective glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide, are needed. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, is under development as an additional tool for the treatment of type 2 diabetes.
Researchers at National Research Institute (Los Angeles), University of Leicester, Dallas Diabetes Research Center at Medical City, Centro de Investigaciones Metabólicas (Buenos Aires), and Eli Lilly investigated the efficacy and safety of once-weekly tirzepatide compared with semaglutide.
The open-label, 40-week, phase 3 trial, published in the August 5, 2021, issue of the New England Journal of Medicine, included almost 1,900 patients, in a 1:1:1:1 ratio, who received 5 mg, 10 mg, or 15 mg of tirzepatide or 1 mg of semaglutide. At baseline, the mean glycated hemoglobin level was 8.28%. The primary endpoint was the change in the glycated hemoglobin level from baseline to 40 weeks.
The estimated mean change from baseline in the glycated hemoglobin level was −2.01 percentage points, −2.24 percentage points, and −2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and −1.86 percentage points with semaglutide, indicating that tirzepatide at all doses was noninferior and superior to semaglutide. In addition, reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, −1.9 kg, −3.6 kg, and −5.5 kg, respectively). Serious adverse events were reported in 5% to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide.
Are polypills effective for CVD treatment?
Polypills, which combine lipid-lowering and blood-pressure–lowering medications, have been suggested as a means to address modifiable risk factors for cardiovascular disease (CVD), especially in low- and middle-income countries. Aspirin has been proven effective in patients with established CVD, but can it be effective in a polypill for the primary prevention of CVD?
Researchers in the Polypill Trialists’ Collaboration conducted an individual participant data meta-analysis of 3 large randomized controlled trials (TIPS-3, HOPE-3, and PolyIran, each with ≥1,000 participants and ≥2 years of follow-up) to further study this issue. Each trial evaluated a fixed-dose combination strategy of at least 2 blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularization. The study was published in The Lancet on August 29, 2021.
During a median follow-up of 5 years, the primary outcome occurred in 3.0% of the participants in the fixed-dose combination strategy group compared with 4.9% in the control group.
Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. The results also showed that treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity.
Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularization, and cardiovascular death in primary cardiovascular disease prevention irrespective of cardiometabolic risk factors.