Join us for an extra-hot summer episode featuring our critical appraisal expert, Rahul Ganatra MD, MPH @rbganatra. Prepare to marvel as he breaks down his recent tweetorial on the RECOVERY trial of dexamethasone for COVID-19; to gasp as Paul Williams updates us on statins and ASCVD prevention and to be enthralled by the dulcet tones of Matt Watto explaining the latest research on DAPT vs. monotherapy with ticagrelor. Bonus: a new hotcakes rating scale has arrived!
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RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report [published online ahead of print, 2020 Jul 17]. N Engl J Med. 2020;10.1056/NEJMoa2021436. doi:10.1056/NEJMoa2021436
Question: Does treatment with glucocorticoids reduce 28-day all-cause mortality among hospitalized COVID-19 patients?
Primary outcome: All-cause mortality; secondary: progression of respiratory distress, proportion of people discharged alive at 28 days
Duration of follow-up: 28 days
Comparison: Patients were randomized to receive 6 mg daily of either oral or IV dexamethasone for 10 days, or usual care. No placebo control arm.
Study population: 6,425 NHS patients in the United Kingdom hospitalized with COVID-19; 2,104 patients received dexamethasone and 4,321 received usual care
Results: Very positive. Authors reported a large absolute risk reduction in 28-day all-cause mortality among patients receiving dexamethasone. Notably, patients who received dexamethasone who were intubated or required oxygen (i.e. the sickest patients) appeared to benefit the most from receiving dexamethasone, with an absolute risk reduction of ~12% for all-cause mortality at 28 days. Conversely, patients who were not on supplemental oxygen did not experience a reduction in mortality; in fact, there was a trend towards harm in this subgroup.
Bottom line: Dexamethasone was associated with an absolute decrease in 28-day all-cause mortality among patients hospitalized with COVID19 requiring any level of respiratory support, but not those on room air. Benefit was greatest in patients who were intubated or had symptoms >7 days.
Orkaby AR, Driver JA, Ho Y, et al. Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older. JAMA. 2020;324(1):68–78. doi:10.1001/jama.2020.7848
Question: Among adults over 75 years of age without known ASCVD, is statin use associated with lower mortality?
Primary outcome All cause and CV mortality
Duration of follow-up Mean f/u 6.8 years
Comparison: 326,981 non-statin users
Study population VHA system users (mean age 81, 91% white, 97.3% men) identified by corporate data warehouse
Inclusion/exclusion criteria Patients without known ASCVD and statin use at time of inclusion
Results: Positive trial in that new statin use significantly associated with lower all cause and cardiovascular mortality. Secondary outcome also showed significantly lower ASCVD events (MI, TIA, CVA, revascularization)
Bottom line: New statin use in patients over the age of 75 without known ASCVD appears to decrease mortality and ASCVD risk. The benefit appears to be seen as early as 2 years. This is a predominantly white and male population, and the study was retrospective and relied on claims data, which may not have captured all relevant data. Also, simvastatin was the statin du jour at the time of the study, which does not reflect current practice.
Kim BK, Hong SJ, Cho YH, et al. Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial. JAMA. 2020;323(23):2407-2416. doi:10.1001/jama.2020.7580
Question: Is monotherapy with a P2Y12 safer than DAPT after DES placement for acute coronary syndrome (ACS)?
Primary outcome: Major bleeding and adverse cardiac and cerebrovascular events at 1-year
Study population and Comparison: This was a randomized controlled trial from Korea with over 3000 patients who completed 3 months of DAPT and then either continued DAPT (control group) or switched to ticagrelor monotherapy (intervention group) for the remainder of the year.
Results: This was a positive trial in that ticagrelor monotherapy had a lower rate of the primary outcome, which was mainly driven by a decrease in major bleeding. The secondary analysis did not find an increase in MACE (Cardiac death, MI, stent thrombosis or need for revascularization, stroke), but we cannot fully trust this finding since the study was underpowered to detect a difference in MACE.
Bottom line: Shortened duration dual antiplatelet therapy (DAPT) followed by ticagrelor monotherapy beyond 3 months is associated with less major bleeding compared to 12 months of DAPT. It should be noted that this study was conducted in Korea with ultra thin drug eluting stents and therefore, we must be careful before generalizing to other populations.
Further reading: The following meta-analysis of shortened duration DAPT followed by P2Y12 monotherapy (which included the TICO trial above) found less major bleeding without an increase in MACE (O’Donoghue, Circulation 2020).
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Listeners will hone their skills in critical appraisal as they appraise the design, methodology and primary findings of breaking research.
After listening to this episode listeners will…
Dr. Rahul Ganatra would like to acknowledge that he works with many of the authors on the statins paper. He, and the rest of The Curbsiders, report no relevant financial disclosures.
Ganatra RB, Roberts SP, Williams PN, Watto MF. “#229 Hotcakes: COVID on steroids, statins over 75, and shortened duration DAPT”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list August 10, 2020.
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