# Therapeutic-dose heparin combined with antiplatelets in noncritically ill patients with COVID-19: a secondary analysis of a multiplatform randomized controlled trial

## TL;DR

This study found that adding antiplatelets to heparin treatment in noncritically ill hospitalized COVID-19 patients did not improve survival without organ support.

## Contribution

The study provides new evidence that antiplatelet agents do not improve outcomes when combined with therapeutic-dose heparin in noncritically ill hospitalized COVID-19 patients.

## Key findings

- Exposure to antiplatelets with heparin did not improve survival without organ support compared to heparin alone.
- Bleeding events were rare despite potential increased bleeding risk from antiplatelet use.

## Abstract

Therapeutic-dose heparin improves outcomes in noncritically ill patients hospitalized for COVID-19. The effect of antiplatelet exposure in addition to therapeutic-dose heparin is unknown.

To evaluate the effect of antiplatelet exposure in addition to therapeutic-dose heparin on survival without organ support.

We conducted an observational secondary analysis of a multiplatform randomized controlled trial, analyzing noncritically ill patients hospitalized for COVID-19 who received an antiplatelet agent (acetylsalicylic acid or P2Y12 inhibitor) and therapeutic-dose heparin (combination) compared with therapeutic-dose heparin alone (control). We used a 3-level ordinal primary outcome: (1) survival without organ support, (2) survival with organ support, and (3) mortality by day 21. Propensity scores were estimated using logistic regression. Balanced analytic groups were established using stabilized inverse probability of treatment weighting. A proportional odds model was used to estimate the effect of antiplatelet exposure.

Among 1021 patients, 194 (19.0%) were exposed to an antiplatelet (95.4% acetylsalicylic acid) and therapeutic-dose heparin. All patients were used to calculate the propensity scores and stabilized weights. After applying inverse probability of treatment weighting, the effective sample size was 60 in the combination group and 652 in the control group. Means and prevalences of continuous and dichotomous variables were similar between groups, with no evidence of misclassification. Exposure to an antiplatelet was not associated with improved survival without organ support (76.3% vs 80.5%; odds ratio, 1.07; 95% CI, 0.71-1.64).

In noncritically ill patients hospitalized for COVID-19 receiving therapeutic-dose heparin, exposure to an antiplatelet agent was not associated with improved survival without organ support.

•Heparin is useful in noncritically ill COVID-19 patients, but the antiplatelet effect is unclear.•We analyzed COVID-19 patients who received heparin with or without exposure to antiplatelets.•Exposure to heparin and antiplatelets did not improve outcomes compared with heparin alone.•Exposure to heparin and antiplatelets may increase bleeding risk, but bleeding events were rare.

Heparin is useful in noncritically ill COVID-19 patients, but the antiplatelet effect is unclear.

We analyzed COVID-19 patients who received heparin with or without exposure to antiplatelets.

Exposure to heparin and antiplatelets did not improve outcomes compared with heparin alone.

Exposure to heparin and antiplatelets may increase bleeding risk, but bleeding events were rare.