Late-Breaking Science: COVID-19 and CVD – what can we learn?

In the first presentation, Doctor Orianne Weizman (Centre Hospitalier Régional Universitaire de Nancy, France) described an analysis that investigated the impact of CV comorbidities on the prognosis of women hospitalised for COVID-19 in France. Of 2,878 hospitalised patients, 42% were women and around one-fifth (22%) of women experienced the primary outcome of in-hospital death or transfer to intensive care unit (ICU). Women had a lower risk of the primary outcome than men (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.53–0.73; p<0.001), which was primarily driven by a lower risk of ICU transfer. In multivariate analysis, factors such as age, body mass index and heart failure (HF) increased the risk of the primary outcome in women. Of note, 38% of hospitalised women with prior HF experienced the primary outcome, while 26% of women with HF died in hospital. These findings emphasise the need to assess disease patterns separately by sex and highlight the impact of pre-existing CVD on prognosis following COVID-19 infection.

Associate Professor Yutao Guo (Chinese PLA General Hospital, Beijing, China) subsequently described a study that investigated risk of thromboembolism (TE), major bleeding and all-cause mortality in 1,125 patients hospitalised with COVID-19 in Wuhan, China. Overall, TE (deep vein TE, ischaemic stroke and pulmonary TE) occurred in 7.3% of the cohort, while 10.0% experienced major bleeding and 8.1% died. In the 18.6% of patients who received parenteral anticoagulants, the risk of venous TE was significantly lower vs. no anticoagulation (adjusted HR 0.32; 95% CI 0.14–0.75; p=0.01), but the risk of major bleeding was higher (adjusted HR 1.56; 95% CI 1.01–2.42; p=0.04). In addition, atrial fibrillation (AF) was found to increase the risk of systemic TE (adjusted HR 3.16; 95% CI 1.06–9.46; p=0.04). Randomised controlled trials (RCTs) could help to assess if the potential benefits of anticoagulants in treating patients with COVID-19 outweigh major bleeding risk.

Then followed a presentation by Professor Giulio Stefanini (Humanitas University, Milan, Italy) on the effects of the COVID-19 pandemic on the standard of scientific publications. The quality of original research published in the New England Journal of Medicine, Lancet and Journal of the American Medical Association in the first four months of 2020 (339 articles) was assessed using the first four months of 2019 (297 articles) as a control. In early 2020, more studies had an observational design and fewer were RCTs vs. early 2019. Moreover, a study hypothesis and primary endpoint were less frequently defined in early 2020. The proportion of articles based on high-quality evidence according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach in 2020 was half that in 2019 (13.7% vs. 27.6%, respectively). When COVID-19 research was excluded, the differences between 2020 and 2019 were largely attenuated. Of note, no differences were found for publications reporting on CV research. Prof. Stefanini concluded that the results “underscore the need for a rigorous peer-review process and a balanced interpretation of findings during public emergencies to avoid a potential detrimental effect on clinical management.”

Next, Doctor Manan Pareek (Yale New Haven Hospital, CT, USA) presented preliminary results from the first 485 patients hospitalised with COVID-19 in the prospective Yale COVID-19 Cardiovascular Registry. Hospitalised COVID-19 patients were found to have a high burden of CV risk factors, particularly hypertension and obesity, and almost half (46%) had a history of established CVD, most commonly coronary artery disease and HF. Overall, 18% of patients died in hospital and 39% had a major CV event during hospitalisation, most frequently AF (19%) and myocardial infarction (17%). Independent predictors of death were advanced age, a history of ventricular arrhythmias, use of a P2Y₁₂ inhibitor, low platelet count or albumin, and high aspartate aminotransferase or troponin T. For major CV events, independent predictors included male sex, a history of atrial arrhythmias, use of a diuretic, any oxygen therapy, low albumin and high troponin T. Consistent with Dr. Weizman’s presentation from France, the US registry findings highlight the high baseline CV risk of hospitalised COVID-19 patients and the substantial adverse impact of CV comorbidities.

Prof. Landray finished the session with an update of RCTs on new treatments for COVID-19. He explained that, based on past CVD trials, the ongoing RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial was designed with simplicity in mind. Repurposed antivirals, immunomodulatory agents and targeted anti-SARS-CoV-2 treatments are being tested in RECOVERY, which has simple eligibility criteria (hospitalised patients with COVID-19) and mortality as the key outcome. Within 100 days of trial commencement, the first results were reported – it was shown that hydroxychloroquine and lopinavir-ritonavir did not reduce mortality and these findings have subsequently been confirmed by the WHO’s ongoing SOLIDARITY trial. RECOVERY then demonstrated a clear benefit for dexamethasone, which was shown to reduce mortality in patients requiring oxygen or ventilation.

Positive results have been shown in the first stage of the Adaptive COVID-19 Treatment Trial (ACTT-1), where remdesivir reduced the time to recovery of hospitalised patients, but mortality benefits were not observed. Further study of the effects of remdesivir is also part of the SOLIDARITY trial.

In a small RCT, the immunomodulatory agent, tocilizumab, did not appear to have an impact on mortality, but additional studies are ongoing, including testing in more than 800 patients in RECOVERY. Convalescent plasma and azithromycin are also being tested in RECOVERY and results are eagerly awaited. Prof. Landray explained that additional new potential therapies (e.g. monoclonal antibodies) may be added to RECOVERY in time and the platform may also be adapted to test potential new treatments during future outbreaks.

Prof. Landray concluded that randomisation is critical for the discovery of effective treatments and lessons learned during the search for COVID-19 treatments may also be important for tackling the burden of CVD and other common non-communicable diseases.