The moderately ill hospitalized COVID-19 patients who received full-dose heparin did not require much of cardiovascular or respiratory support and were also more likely to be discharged from hospital, according to findings of a large clinical trial published in The New England Journal of Medicine.¹ But, similar outcomes were not seen in the critically ill patients in intensive care.

Last year in April, hospitalized COVID-19 patients were administered either a low or full dose of heparin for up to 14 days after enrolment. Interim results, by the year end, showed that therapeutic anticoagulation did not reduce the need for organ support in the critically ill COVID-19 patients who needed intensive care. But, a month later, in January 2021, it was found that full-dose blood thinners improved outcomes and reduced the need for ventilation or other organ supportive interventions in the moderately ill hospitalized COVID-19 patients.

Moderately ill patients hospitalized with COVID-19 were defined as those who did not receive “organ support,” including high-dose oxygen therapy, mechanical ventilation, life support, medicines that increase blood pressure or medicines that change the force of the heart’s contraction.

For quicker analysis of data, three trials collaborated and aligned their design into one integrated, multiplatform, randomized clinical trial to study the impact of initial strategy of full (therapeutic) dose of heparin vs low (prophylactic) dose of heparin on in-hospital survival in moderately and critically ill patients with confirmed Covid-19. The outcomes in terms of the duration of intensive care unit (ICU)–level cardiovascular or respiratory organ support in critically ill patients with Covid-19 were also evaluated. The trials are:

• Randomized, Embedded, Multifactorial Adaptive Platform Trial for CommunityAcquired Pneumonia (REMAP-CAP)²
• Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4a): ACTIV-4a Antithrombotics Inpatient A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19³
• Antithrombotic Therapy to Ameliorate Complications of Covid-19 (ATTACC) ⁴

The final analysis of trial data included 1098 critically ill and 2219 moderately ill patients. For both moderately and critically ill patients, researchers looked at how long they were free of organ support up to 21 days after enrolment.

Analysis of data showed that in moderately ill patients, there was 99% chance that the full-dose heparin reduced the need for organ support and also improved survival leading compared to those who received low-dose heparin.

While therapeutic anticoagulation reduced major thrombotic events in severely ill patients, it did not increase the probability of survival to hospital discharge or the number of days free of cardiovascular or respiratory organ support and had a 95% probability of being inferior to usual-care pharmacologic thromboprophylaxis. There was also an 89% probability that therapeutic-dose anticoagulation led to a lower probability of survival to hospital discharge than usual-care thromboprophylaxis. According to the authors, though the incidence of major bleeding was numerically higher with therapeutic-dose anticoagulation than with usual-care thromboprophylaxis, it was still low (3.8%). 

References

1. Goligher EC, et al. REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators. Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N Engl J Med. 2021 Aug 4. doi: 10.1056/NEJMoa2103417.
2. Angus DC, et al. The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) study: rationale and design. Ann Am Thorac Soc. 2020;17:879-891.
3. https://clinicaltrials.gov/ct2/show/NCT04505774.
4. Houston BL, et al. Anti-thrombotic therapy to ameliorate complications of COVID-19 (ATTACC): study design and methodology for an international, adaptive Bayesian randomized controlled trial. Clin Trials 2020;17:491-500.

(Source: NIH Press Release, August 4, 2021)