#229 Hotcakes: COVID on steroids, statins over 75, and shortened duration DAPT

August 10, 2020 | By Sarah Phoebe Roberts

Updates on dexamethasone for COVID-19, statins and cardiovascular mortality, and ticagrelor monotherapy after acute coronary syndrome

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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Credits

• Producer: Sarah Phoebe Roberts
• Show Notes by: Sarah Phoebe Roberts
• Writer: Rahul Ganatra MD, Sarah Phoebe Roberts, Matthew Watto MD, Paul Williams MD
• Cover Art: Matthew Watto MD
• Hosts: Rahul Ganatra MD, Matthew Watto MD, Paul Williams MD
• Editor: Matthew Watto MD (written materials); Clair Morgan of nodderly.com

Sponsor

The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit. See info sheet for further directions. Note: A free VCU Health CloudCME account is required in order to seek credit.

How to Claim VCU CME Credit

Time Stamps

• 00:00 Intro, disclaimer
• 02:15 Picks of the Week
• 06:15 New Hotcakes rating scale
• 09:20 RECOVERY trial
• 17:30 Rapid home-testing for COVID
• 20:15 Statins and ASCVD prevention
• 32:30 Ticagrelor monotherapy after ACS
• 41:30 Outro

August 2020 Hotcakes: COVID on steroids, better living through statins, and (maybe) doing away with DAPT

RECOVERY trial of dexamethasone for COVID-19

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.

Statins, ASCVD and mortality in patients aged 75 and older

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.

DAPT and ticagrelor monotherapy among ACS patients 

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). 

Picks of the week 

1. Paul: U Talkin’ Talking Heads 2 My Talking Head podcast
2. Sarah: New hotcakes scale!
3. Rahul: Chromeo’s new Quarantine Casanova album 
4. Watto: 30 Rock season 1, episode 3 “Blind Date” 

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

Goal

Listeners will hone their skills in critical appraisal as they appraise the design, methodology and primary findings of breaking research. 

Learning objectives

After listening to this episode listeners will…  

1. Describe the results of a study comparing treatment with dexamethasone to usual care for COVID-19 
2. Recognize the utility of statins for adults aged 75+  
3. Compare dual antiplatelet therapy to monotherapy with ticagrelor for the prevention of major adverse cardiac events among patients with ACS 

Disclosures

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. 

Citation

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.