What accounts for the increased risk of death from coronavirus disease (COVID-19) seen among patients with cardiovascular disease? Does the disease itself put patients at risk or could certain treatments for cardiovascular conditions make patients more vulnerable to COVID-19?
A new study led by Brigham Health investigators and published in the New England Journal of Medicine provides new insights into the intersection of cardiovascular disease, cardiac medications and the COVID-19 pandemic. Using data for nearly 9,000 patients from across Asia, Europe and North America, the research team examined outcomes for patients with and without cardiovascular disease hospitalized with COVID-19.
The team found that underlying forms of cardiovascular disease, including coronary artery disease, cardiac arrhythmia and heart failure, were independently associated with increased risk of death for hospitalized patients. Importantly, the team found that common cardiac drugs, including antiplatelet therapy, beta blockers, angiotensin receptor blockers and antidiabetic drug therapy, were not associated with increased risk of death. And two drugs — statins and ACE inhibitors — were associated with decreased risk of death.
“Our goal was to definitively answer some of the most critical questions around COVID-19 for the field of cardiovascular medicine by looking at the data,” said lead author Mandeep Mehra, MD, The William Harvey Distinguished Chair in Advanced Cardiovascular Medicine and executive director of the Brigham’s Center for Advanced Heart Disease/Cardiomyopathy. “By leveraging this unique set of data from a global population of patients across three continents, we find evidence that these cardiac drugs do not appear to increase risk from COVID-19 and, in the case of two of the drugs analyzed, may be lifesaving for cardiovascular disease patients.”
COVID-19 Patient Registry Data Analysis
To conduct their analysis, Mehra and colleagues used de-identified data from a registry that included 169 hospitals located throughout the world. They included data from patients with cases of COVID-19 confirmed through laboratory testing who were hospitalized between January 1, 2020 and March 28, 2020.
The team looked at patients that either recovered and were discharged or died during hospitalization. Of the 8,910 hospitalized patients, 515 died. Several factors independently contributed to risk of death, including older age, coronary artery disease, heart failure and cardiac arrhythmias, smoking and chronic obstructive pulmonary disease. Men were more at risk of death than women. Among people who survived and recovered, significantly more patients took ACE inhibitors and statins compared to those who died.
The Next Wave of COVID-19 Cardiovascular Research
The authors’ analysis includes only hospitalized patients with COVID-19 so cannot answer questions about whether cardiac medications influenced outcomes for patients who did not seek hospital care. Another important question that remains unanswered is whether those not on a statin or ACE inhibitor due to a cardiovascular indication could be protected from death by being prescribed one of these medications. Clinical research studies would need to be conducted to answer these important questions.
Mehra and colleagues are beginning to answer questions about why medications such as statins and ACE inhibitors may be tied to reduced risk of death from COVID-19. In a separate paper published in The Lancet, Mehra and co-authors showed that the virus that causes COVID-19, SARS CoV-2, infects endothelial cells directly. They also present evidence of a diffuse endothelial cell inflammation across different organ systems. They hypothesize that medications that stabilize the endothelium, such as ACE inhibitors and statins, could play a beneficial role, especially in vulnerable populations.
For now, the NEJM study provides important data to inform the discussion about the connection between cardiovascular disease and risk of death from COVID-19. Already, the next wave of COVID-19 cardiovascular-related research is underway at the Brigham, with new information, analysis and data expected soon.
“We were well positioned to do this analysis because we were already conducting broad work on the database, and the Brigham has the capacity and the infrastructure to interpret and rapidly analyze large volumes of data,” said Mehra. “Our findings indicate that patients with cardiovascular disease should do everything they can to avoid acquiring COVID-19, but if they do become infected, they must not stop their medications. Based on our study, any concern about their medications interacting negatively with survival is a myth.”