The American College of Chest Physicians (CHEST) has issued recommendations regarding the prevention and management of arterial thrombosis and thromboembolism among patients with COVID-19, as published in Chest.

The CHEST expert panel report recommendations are intended for physicians in different specialties who manage patients with COVID-19 and a history of an acute arterial thrombosis or thromboembolism.

CHEST’s expert panel developed its recommendations based on 11 key clinical questions regarding the use of antithrombotic therapy in patients with COVID-19. The clinical questions were based on the Population, Intervention, Comparator, and Outcome format.

The panel reviewed the available evidence, obtained through a literature search of PubMed, for COVID-19 as well as non-COVID-19-related evidence-based international guidelines for a number of medical conditions, including recent coronary syndrome or acute coronary syndrome (ACS) or percutaneous coronary intervention, previously known or newly diagnosed atrial fibrillation (AF), peripheral artery disease (PAD) or acute limb ischemia, or history of acute stroke or transient ischemic attack (TIA). Consensus on recommendations was achieved using a modified Delphi survey.

The existing evidence and panel consensus do not suggest a major departure from the management of arterial thrombosis as per evidence-based recommendations from before the COVID-19 pandemic.

COVID-19 With ACS

The CHEST panel issued a conditional recommendation for continuing (ie, unchanged) antiplatelet therapy in hospitalized patients with COVID-19 who have a pre-existing indication for antiplatelet therapy owing to previous ACS. Switching from ticagrelor or clopidogrel to prasugrel is feasible on a case-by-case basis if there are concerns for drug interactions. Current guidance is that patients with ACS receive dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor for 12 months after the initial event. The panel noted that the inflammatory response and hemodynamic changes related to COVID-19 may increase the risk for a prothrombotic state and a coronary thrombosis and that patients with COVID-19 and ST-segment elevation myocardial infarction are more likely to have a high thrombus burden.

A strong recommendation was made for use of dual antiplatelet therapy to reduce the risk of recurrent acute coronary syndrome or death among hospitalized patients with COVID-19 and confirmed ACS. According to the panel, high-quality evidence is lacking regarding antithrombotic regimens in patients with ACS and COVID-19, because randomized controlled trials on anticoagulation for COVID-19 excluded patients using DAPT, and the evidence is limited to primarily case reports or observational studies. “Despite limited evidence, it is reasonable to extrapolate from pre-COVID-19 data and strongly recommend DAPT as the standard of care also in patients with COVID-19 and ACS, in line with the recommendation for patients without COVID-19,” stated the panel authors.

A conditional recommendation was made for continuing DAPT for hospitalized patients with COVID-19 on DAPT for recent ACS who are receiving prophylactic-dose anticoagulant therapy. In addition, for hospitalized patients with COVID-19 on DAPT for recent ACS who are on therapeutic-dose parenteral anticoagulant therapy, the panel issued a conditional recommendation for individualized decisions that consider the risk of bleeding for continuing DAPT with anticoagulation. Among patients with therapeutic anticoagulation, consistent with international non-COVID-19 ACS guidelines, the panel advises individualized treatment decision-making to minimize the risk of bleeding and ischemia.

Myocardial Injury Without ACS

For hospitalized patients with COVID-19 and myocardial injury without ACS, the panel issued a conditional recommendation against initiation of DAPT. The authors noted that to consider use of DAPT, the benefit of reducing the risk of cardiovascular death or myocardial infarction needs to outweigh the risk of bleeding. For cases of isolated cardiac troponins elevation, evidence does not support that DAPT would decrease the risk of cardiac events.

COVID-19 and AF

Among hospitalized non-ICU patients with COVID-19 receiving oral anticoagulation for AF for whom discontinuation of oral anticoagulation is needed during hospitalization, the panel issued a conditional recommendation for switching to therapeutic dose LMWH or unfractionated heparin (UFH). In addition, the panel gave a conditional recommendation for switching to therapeutic-dose or prophylactic-dose LMWH or UFH, based on individualized decision-making, for hospitalized ICU patients with COVID-19 receiving oral anticoagulation for AF.

Among outpatients with COVID-19 and new-onset AF, a conditional recommendation was given for initiating a direct oral anticoagulant (DOAC) if their CHA2DS2-VASc score (ie, score for AF-related stroke risk) was at least 1 in male patients and at least 2 in female patients. In cases in which DOACs cannot be used, a vitamin K antagonist with high time in therapeutic range (>70%) is recommended. Another conditional recommendation was issued for hospitalized patients with COVID-19 and new-onset AF to start therapeutic-dose parenteral anticoagulation regardless of CHA2DS2-VASc score, and long-term oral anticoagulation is advised if the score is at least 1 in male patients or at least 2 in female patients.

COVID-19 and PAD

A conditional recommendation was made for continuing antiplatelet therapy in hospitalized patients with COVID-19 and stable PAD (ie, no acute limb events or revascularization procedures within the past 30 days) if concurrent prophylactic-dose anticoagulation for COVID-19 is administered. In a related conditional recommendation, among hospitalized patients with COVID-19 and stable PAD who are receiving single antiplatelet therapy and therapeutic-dose anticoagulation for COVID-19, individualizing the decision whether to continue the antiplatelet agent is advised.

COVID-19 and Ischemia

In its final recommendation, the CHEST panel conditionally advises that hospitalized patients with COVID-19 and acute limb-threatening ischemia have early revascularization in consultation with a vascular specialist, when conforming with clinical presentation, patient values, anatomy, and resources. The panel noted that compared with patients without COVID-19 with PAD, the degree of limb ischemia, rate of perioperative complications with revascularization, and limb amputation occurred significantly more frequently in patients with COVID-19. “Considering the lack of high-quality data, it is reasonable to consider the treatment of patients with COVID-19-associated acute limb-threatening ischemia similar to that of patients with the disease before the pandemic,” the authors stated.

COVID-19 and Stroke

For those hospitalized with COVID-19 and an acute stroke or TIA of no established etiology, the panel made a conditional recommendation was made for treatment with antiplatelet therapy according to current recommendations for patients without COVID-19. “Current evidence does not support the hypothesis that compared with antiplatelet treatment, anticoagulation reduces the risk of recurrent stroke further, and on the contrary, indicates that the risk of intracranial bleeding may be higher,” stated the report authors. “In this context, patients with COVID-19 with stroke of undetermined cause should be treated as the patients without COVID-19, that is, with antiplatelet rather than anticoagulant therapy.”

For hospitalized patients with COVID-19 who have an acute ischemic stroke and an indication for recanalization therapy, the panel conditionally recommends treatment with the indicated recanalization therapy. The authors noted that the evidence was low-quality and contradictory among the different techniques and clinical outcomes. “The available evidence suggests that among patients with acute ischemic stroke treated with recanalization, those with COVID-19 show higher rates of intracranial hemorrhage and worse clinical outcomes compared with patients without COVID-19,” stated the authors. “Considering the relatively large beneficial effect of recanalization treatments, particularly of endovascular treatment, and the relatively low absolute risk of symptomatic intracranial hemorrhage in patients with acute ischemic stroke and COVID-19, recanalization treatments likely also remain beneficial in these patients.”

Other Conditional Recommendations

Conditional recommendations were made for the following:

  • For outpatients with COVID-19 on antiplatelet therapy for a previous stroke, the panel advises against the addition of or change to oral or subcutaneous anticoagulation.
  • Among hospitalized patients with COVID-19 who are not in the intensive care unit (ICU) receiving antiplatelet therapy for a prior stroke, continuation of the antiplatelet and addition of prophylactic-dose low molecular-weight heparin (LMWH) is advised.
  • For carefully selected patients with an indication for therapeutic-dose anticoagulation with LMWH for COVID-19 and who have a favorable thrombotic or bleeding risk profile, continuing use of the antiplatelet and adding therapeutic-dose anticoagulation with LMWH can be considered.
  • For hospitalized patients with COVID-19 in the ICU who are receiving antiplatelet therapy for a previous stroke, the panel recommends continuation of the antiplatelet and addition of prophylactic-dose LMWH.

Additional Safety Considerations

With respect to safety considerations in patients with COVID-19 and arterial thrombosis and thromboembolism, the panel advised assessing for potential drug-to-drug interactions between P2Y12 inhibitors and protease inhibitors of hepatic CYP3A4. Protease inhibitors, including lopinavir plus ritonavir, atazanavir, and darunavir plus cobicistat, may inhibit the hepatic CYP3A4 and affect P2Y12 platelet receptor inhibitor activity, especially clopidogrel and ticagrelor. In addition, significant interactions can occur between DOACs and proposed antiviral therapies for COVID-19, particularly lopinavir plus ritonavir.

Applicability of Pre-Pandemic Guidelines

Overall, the available evidence from mostly observational studies suggests that patients with COVID-19 and arterial thrombosis and thromboembolism generally should be managed according to respective international guidelines for those without COVID-19, according to the panel.

“The existing evidence and panel consensus do not suggest a major departure from the management of arterial thrombosis as per evidence-based recommendations from before the COVID-19 pandemic,” stated the report authors. “More high-quality evidence is needed to inform management strategies in patients with COVID-19 and arterial thrombosis.”

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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