Key messages

Antiplatelets are a group of different medicines that can prevent potentially fatal clot formation in the blood vessels ('thrombotic events'). For hospitalised patients with COVID-19, they probably slightly reduce thrombotic events but probably do not affect deaths, clinical worsening or improvement in COVID-19 compared with placebo or standard care.

However, antiplatelets may result in a slight increase in serious unwanted effects ('adverse events') and probably increase major bleeding.

Similarly, in non-hospitalised people, antiplatelets slightly decrease thrombotic events. They may result in little to no difference in deaths or serious unwanted effects, however the evidence on admission to hospital or death and major bleeding events is very uncertain.

There are 14 further studies that have not completed yet, and the results of three other completed studies are not yet available.

What are antiplatelets?

Antiplatelets are a group of drugs which, in different ways, stop blood from changing to a gel-like substance called a clot, which we mean by the term 'thrombotic events'. They are taken mainly by mouth, usually by people who are at high risk of developing a clot (people who have already experienced or who tend to build up a clot).

A clot could lead to a stroke, coronary heart disease, poor blood circulation in the legs, thromboses in the legs or clot obstruction ('embolism') in the lung circulation that could lead to shortness of breath, heart failure and death.

How might antiplatelets treat COVID-19?

People with COVID-19 might be at risk from blood clots. Antiplatelets prevent clots from forming in the body, and this could in turn prevent complications that lead to death and clinical deterioration.

What did we want to find out?

We wanted to know whether antiplatelets in addition to usual care are effective for adults with COVID-19, when compared to usual care with or without a placebo (a treatment that looks and tastes the same as the study drug but with no active ingredient), and whether they cause unwanted effects. We were particularly interested in:

– number of deaths from any cause up to 28 days after treatment, or longer if reported;
– whether people got better or worse after treatment (including unwanted effects of the disease itself, like thrombotic events);
– unwanted effects of the treatment (especially major bleeding).

What did we do?

We searched for studies that reported on people with COVID-19 who received antiplatelets together with usual care, or usual care alone (with/without placebo). We summarised the results of the studies and rated our confidence in the evidence, based on common criteria about the reliability of the evidence.

What did we find?

We identified four studies, including 17,541 people with moderate to severe COVID-19 (hospitalised). Of these, one compared acetylsalicylic acid (aspirin) with usual care, two studies compared 'P2Y12 inhibitors' (e.g. clopidogrel, prasugrel, ticagrelor) with usual care, and a fourth one compared either acetylsalicylic acid or P2Y12 inhibitors with usual care. The studies included people with a confirmed or suspected diagnosis of SARS-CoV-2 infection. Two studies compared acetylsalicylic acid to placebo in 4209 non-hospitalised people with confirmed mild COVID-19.

We also found 14 ongoing studies, two studies without published results and another that had been withdrawn after a preprint version. We found no studies that included people with COVID-19 infection but no symptoms.

Main results

Antiplatelets:

– probably make little or no difference to deaths by 28 or 180 days, worsening up to day 28 (new invasive mechanical ventilation or death) or improvement (discharged alive) up to day 28, and they probably slightly decrease thrombotic events;

– may result in a slight increase in serious unwanted effects and probably increase major bleeding events.

In people not in hospital, with mild disease, antiplatelets may result in little to no difference in death within 45 days, or in the incidence of serious adverse events, and they may slightly decrease the incidence of thrombotic events. The evidence for these participants is very uncertain about the effects on worsening (hospitalisation or death within 45 days) and on major bleeding events. Studies did not report on quality of life and general unwanted effects.

What are the limitations of the evidence?

The studies were conducted in populations from high- to middle-income countries, many of them prior to the roll-out of COVID-19 vaccination programmes and before Omicron became the most prevalent variant. We have moderate confidence in the evidence for mortality, worsening/improvement up to day 28, and major bleeding events or thrombotic events in hospitalised people. We have low confidence in the evidence for the effects on serious unwanted effects, because they occurred rarely. For non-hospitalised people, our confidence in the evidence is low for the effects on death, thrombotic events and serious adverse events, and very low for the effects on worsening and major bleeding events (those events were rare and the time period between symptom onset and treatment was long). Information about other unwanted effects and quality of life was not available.

How up-to-date is this evidence?

Our evidence is up-to-date to 22 December 2022.