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The Evidence Speaks

The Evidence Speaks (July 2019)

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The Evidence Speaks Series is a recurring feature highlighting the latest in CHÉOS research. This series features summaries of select publications as well as in-depth features on the latest work from our investigators. The Series is designed to keep media and the research community up-to-date with CHÉOS’ current research results in the health outcomes field.

Grunau B, Kawano T, Scheuermeyer FX, Drennan I, Fordyce CB, van Diepen S, Reynolds J, Lin S, Christenson J. The association of the average epinephrine dosing interval and survival with favorable neurologic status at hospital discharge in out-of-hospital cardiac arrest. Ann Emerg Med. 2019 Jun 24 epub ahead of print.

A new publication led by CHÉOS Scientists suggests that modification to the current standard of care for treatment of out-of-hospital cardiac arrest may improve patient outcomes. Epinephrine is core component of the treatment of cardiac arrest that happen outside of the hospital; it improves the effectiveness of CPR by increasing blood flow to the heart. Current recommendations state that epinephrine should be given every three to five minutes. However, this recommendation is based on opinion, not data. To shed some light on this dosing recommendation, Drs. Grunau, Scheuermeyer, Fordyce, and Christenson conducted a secondary analysis of a previous large trial. The analysis used data from over 15,000 patients who received out-of-hospital CPR and at least 3 doses of epinephrine. The primary outcome was survival with favourable neurological status at hospital discharge. The median epinephrine dosing interval was 4.3 minutes and approximately 335 patients overall (about 2 per cent) survived with favourable neurological status. Patients receiving epinephrine at increased frequency were more likely to survive to hospital discharge and were more likely to be discharged with favourable neurological status. The analysis showed that, in patients who received epinephrine at an interval of less than 3 minutes during CPR, about 5 per cent survived with favourable neurological status while for longer intervals, this outcome occurred less often (2.1 per cent or less). These findings suggest that current recommendations about epinephrine dosing for out-of-hospital cardiac arrest may be sub-optimal. Importantly, this study was a secondary analysis of a previous trial and a prospective study specifically designed to study this question is needed for a more definitive conclusion.

Fervenza FC, Appel GB, Barbour SJ, Rovin BH, Lafayette RA,…et al.; MENTOR Investigators. Rituximab or cyclosporine in the treatment of membranous nephropathy. N Engl J Med. 2019 Jul;381(1):36-46.

Results of a new multi-centered clinical trial show that an alternative treatment for membranous nephropathy, a form of kidney disease, may be more effective than current drugs. The results, published in the New England Journal of Medicine, are from Membranous Nephropathy Trial of Rituximab (MENTOR), for which CHÉOS Scientist Sean Barbour serves as a co-investigator. MENTOR compared treatment outcomes of patients who received either cyclosporine or rituximab. Cyclosporine is an effective medication for membrane nephropathy — it is currently the preferred treatment in Canada and the U.S. — however, it causes frequent side effects and has a high incidence of relapse after treatment is finished. Rituximab is an alternative treatment for this disease and previous research suggests that it may be an effective alternative to cyclosporine. In this open-label study, 130 patients from 22 sites across North America were randomized to receive either cyclosporine or rituximab. The aspect of treatment that the investigators focused on was proteinuria — protein in the urine — a symptom of kidney disease. The main outcome compared in the trial was complete or partial remission of proteinuria at 24 months after initiation of treatment. Other outcomes included earlier occurrence of remission, treatment failure, and adverse events. At the end of the trial, 23 patients (35 per cent) in the rituximab group had a complete remission while none of the patients taking cyclosporine achieved remission. Forty per cent of patients in the rituximab group, compared to 80 per cent of patients in the cyclosporine group, had treatment failure by the end of the study. Overall, the study investigators concluded that rituximab was as good as cyclosporine at inducing remission at 12 months and was better at maintaining long-term proteinuria remission up to 24 months, with no increase in side effects or adverse events.

Chua D, Shalansky S, Sinova A, Mackay M. Factors affecting delay in filling prescriptions for dual antiplatelet therapy after coronary stenting. Can J Cardiol. 2019 Jul;35(7):931-4.

Patients undergoing coronary stent procedures at St. Paul’s Hospital (SPH) who live further from the hospital take longer to fill their post-procedure prescriptions, a potentially life-threatening delay. Percutaneous coronary intervention (PCI) with a coronary artery stent is a common procedure in patients with stable angina and acute coronary syndromes. Stent thrombosis after PCI is rare (occurring in 1 per cent of patients) but can cause serious complications and myocardial infarction. Dual antiplatelet therapy (DAPT) is recommended for prevention of stent thrombosis and patients are encouraged to fill their prescription immediately after discharge. Delays in DAPT therapy, even as short as 1 day, can double the risk of heart attack and mortality — recent cases of stent thrombosis at SPH have been attributed to delayed filling of DAPT prescription. CHÉOS Scientist Dr. Martha Mackay led a group of researchers to describe the factors that influence the timely filling of DAPT prescription. The group analyzed data for 651 patients who underwent PCI in 2015 and 2016. Eighty-four per cent of patients filled their prescription with 24 hours of the procedure. Age, sex, and drug insurance coverage did not influence prescription timing. The one factor that affected timing was living at an increased distance from SPH, define as greater than two-hours’ travel time. The authors suggested that, because of the logistical challenges related to living far from SPH, the hospital discharge process could be modified to facilitate immediate access to DAPT therapy. Some suggested approaches are to provide an interim supply of the medication, telephone follow-up after discharge, and closer collaboration with community pharmacies. The researchers did not evaluation clinical outcomes related to DAPT filling.