Primary Prevention of Subclinical Atherosclerosis in Young Adults: JACC Review Topic of the Week.

There is growing evidence that the atherosclerotic process that leads to symptomatic cardiovascular disease (CVD) starts at an early age. In young adults, exposure to low-density lipoprotein-cholesterol and other cardiovascular risk factor (CVRF) mediators, even at levels considered within normal limits, increases the prevalence of subclinical atherosclerosis and is associated with greater risk of cardiovascular events later in life. The optimal CVRF targets to prevent CVD in asymptomatic young individuals (<40 years) are unknown. The randomized controlled PRECAD (Prevent Coronary Artery Disease) trial has been developed to assess the potential benefit of an aggressive control of CVRF in otherwise healthy young adults. The hypothesis of PRECAD is that in subjects aged 20 to 39 years without known CVD, maintaining low-density lipoprotein-cholesterol <70 mg/dL and strict control of blood pressure and glucose will prevent the onset of atherosclerosis and/or its progression. The primary endpoint will be the change in total atherosclerosis burden, a surrogate for CVD.

Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.

BACKGROUND: Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. OBJECTIVES: We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. METHODS: Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. RESULTS: Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. CONCLUSIONS: Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).

Anticoagulation in Patients With COVID-19: JACC Review Topic of the Week.

Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).