Some Data May Be Worse Than No Data in the COVID Era

What your doctor is reading on Medscape.com:

MAY 14, 2020 — I will critique a research letter on anticoagulation in patients with COVID-19 recently published in the Journal of the American College of Cardiology (JACC). Do not mistake this critique for statistical minutia. There are larger implications.

Researchers from Mount Sinai Hospital in New York City reported a retrospective observational study of nearly 2800 patients with COVID-19 hospitalized in March and April. They studied the association between use of anticoagulation (AC) and in-hospital mortality.

This has become an important question because numerous studies have suggested a high rate of thrombotic complications in patients with COVID-19.

Key Findings

• In-hospital mortality for patients treated with AC was 22.5%, with a median survival of 21 days, compared with 22.8% and median survival of 14 days in patients who did not receive AC.   

• In patients who required mechanical ventilation (n = 395), in-hospital mortality was 29%, with a median survival of 21 days for those treated with AC vs 63% with a median survival of 9 days in patients who did not receive AC.

• Bleeding events occurred in 3% of patients who received AC vs 2% in those who did not receive AC.

Comments to the Media

The second author of the paper, Valentin Fuster, MD, who is also the editor-in-chief of JACC, spoke to the media.

To theheart.org | Medscape Cardiology , Fuster said, “I can tell you any family of mine who will have this disease absolutely will be on antithrombotic therapy and, actually, so are all of the patients at Mount Sinai now.”

To the Washington Post , Fuster said, “My opinion is cautious, but I must tell you I think this is going to help.” He also said the Mount Sinai hospital system changed its treatment protocols several days ago to begin giving patients with COVID-19 higher doses of blood thinners.

Critique

Let’s start with the (slightly) positive: Academic intensivist Josh Farkas, MD, from the University of Vermont, tweeted that he found the low rate of serious bleeding compelling. I find that overly optimistic. This paper provides little details of the drugs used other than noting that oral, subcutaneous, and intravenous formulations were included. Comparing only AC vs no AC belies the complexity of the differing drug classes, routes of administration, and dosing.

The most important and likely fatal flaw in this study is immortal time bias, which the authors do not acknowledge. Immortal time bias occurs in observational studies when the groups are defined by exposure (AC) or lack of exposure (no AC) after follow-up has begun.