lished HCQ as standard of care, low-level observational evidence
should not have been mistaken as a signal that the drugs caused
harm. The only way to sort out the value of HCQ would be to randomize
patients in a proper trial. Given the short disease course of
COVID-19, the answer could have been known by now.
The antiviral drug remdesivir is a good example of how to know
scientifically. Remdesivir has been studied in two double-blind
RCTs. One smaller and underpowered trial showed no benefit 11 ;
the other, a larger study 12 , found a reduction in the length of stay
in the hospital and trend toward lower death rates. Based on the
larger trial, it looks like remdesivir has a benefit.
GETTING TO THE HEART OF MEDICINE
trial. International Journal of Antimicrobial Agents. Published online March 20,
2020:105949. doi:10.1016/j.ijantimicag.2020.105949
10 Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine
with or without a macrolide for treatment of COVID-19: a multinational
registry analysis. The Lancet. 2020;0(0). doi:10.1016/S0140-6736(20)31180-6
11 Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19:
a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet.
2020;395(10236):1569-1578. doi:10.1016/S0140-6736(20)31022-9
12 Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of
Covid-19 — Preliminary Report. New England Journal of Medicine. 2020;0(0):null.
doi:10.1056/NEJMoa2007764
Dr. Mandrola practices electrophysiology for Baptist Health Louisville.
Another aspect of this novel disease that needs randomization
is the use of anti-thrombotic drugs. COVID-19 seems to induce
a thrombotic state. This has caused doctors to use anticoagulant
therapy both in the hospital and post-discharge. That makes sense;
it is plausible. But anticoagulants come with significant bleeding
risks. And, as we learned with PVCs after MI, the only way to know
is do an RCT.
Ventilator protocols, the use of corticosteroids and IL-6 blockade
are all plausible approaches to COVID-19 that would benefit
from proper study. Policymakers could even get in the knowledge
game with cluster randomized trials of different strategies of disease
mitigation in the coming months.
The message of cardiology is simple: when in doubt, randomize.
References:
1 Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson WS. Evidence
based medicine: what it is and what it isn’t. BMJ. 1996;312(7023):71-72.
doi:10.1136/bmj.312.7023.71
2 Echt DS, Liebson PR, Mitchell LB, et al. Mortality and Morbidity in Patients
Receiving Encainide, Flecainide, or Placebo. New England Journal of Medicine.
1991;324(12):781-788. doi:10.1056/nejm199103213241201
3 Cholesterol Treatment Trialists’ (CTT) Collaboration, Fulcher J, O’Connell
R, et al. Efficacy and safety of LDL-lowering therapy among men and women:
meta-analysis of individual data from 174,000 participants in 27 randomised
trials. Lancet. 2015;385(9976):1397-1405. doi:10.1016/S0140-6736(14)61368-4
4 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to
prevent stroke in patients who have nonvalvular atrial fibrillation. Annals of
internal medicine. 2007;146(12):857-867.
5 Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety
of new oral anticoagulants with warfarin in patients with atrial fibrillation: a
meta-analysis of randomised trials. The Lancet. 383(9921):955-962. doi:10.1016/
S0140-6736(13)62343-0
6 Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous
thrombolytic therapy for acute myocardial infarction: a quantitative review
of 23 randomised trials. Lancet. 2003;361(9351):13-20. doi:10.1016/S0140-
6736(03)12113-7
7 McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with
Heart Failure and Reduced Ejection Fraction. New England Journal of Medicine.
2019;0(0):null. doi:10.1056/NEJMoa1911303
8 Desai A, Gyawali B. Endpoints used in phase III randomized controlled trials
of treatment options for COVID-19. EClinicalMedicine. 2020;0(0). doi:10.1016/j.
eclinm.2020.100403
9 Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin
as a treatment of COVID-19: results of an open-label non-randomized clinical
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