Link between hydroxychloroquine, CV events reinforced
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Treatment with hydroxychloroquine or chloroquine may increase the rates of several CV adverse events, including QT prolongation, cardiomyopathy, arrhythmias and HF, researchers found.
“These drugs are being promoted as a possible treatment for the SARS-CoV-2 infection,” Elad Maor, MD, PhD, associate professor of cardiology at Tel Aviv University Sackler School of Medicine and interventional cardiologist at Sheba Medical Center in Tel HaShomer in Israel, told Healio. “Our findings are very important in that context and suggest that clinicians around the world who are considering the off-label use of [hydroxychloroquine/chloroquine] should be careful, especially in the case of patients with cardiac comorbidities and/or potential drug interactions.”
Mixed messaging around the drugs
In April, the FDA issued a safety alert warning health care professionals and patients to avoid the use of hydroxychloroquine and chloroquine outside of hospital or clinical trial settings due to potential increased risk for serious heart-related adverse events and death.
Studies have been mixed regarding whether these drugs lead to adverse CV events. A study published in Europace in September found that hydroxychloroquine may be safe for the short-term treatment of patients with COVID-19 who were chosen for therapy after undergoing risk assessment.
In this observational pharmacovigilance analysis published in the British Journal of Clinical Pharmacology, Adam Goldman, of the department of epidemiology and preventive medicine at Tel Aviv University School of Public Health, and colleagues analyzed data from 6,677,225 reports (mean age, 53 years; 74% women) from the FDA’s Adverse Event Reporting System database on hydroxychloroquine or chloroquine from July 2014 to September 2019.
“Real-world data regarding cardiovascular safety of [hydroxychloroquine/chloroquine] (not as part of clinical trials) is very limited,” Maor said in an interview. “During the first wave of COVID-19, there was a worldwide interest in the off-label use of these drugs. That was the motivation for this project. The aim was to assess the cardiovascular safety of these drugs using FDA databases that are available to researchers from all around the world.”
After applying exclusion criteria, researchers identified 4,895 reports of adverse events related to hydroxychloroquine (n = 4,718) or chloroquine (n = 177). Of these reports, 14.2% were CV adverse events.
Hydroxychloroquine and chloroquine were linked to higher reporting rates of major CV adverse events compared with the full database. This included QT prolongation (0.9%; reported OR = 4.5; 95% CI, 3.3-6.1), cardiomyopathy (1.8%; reported OR = 29; 95% CI, 23.3-35.9), HF (2.8%; reported OR = 2.2; 95% CI, 1.9-2.7) and cardiac arrhythmias (2.4%; reported OR = 2.2; 95% CI, 1.8-2.7). This did not significantly differ between age and sex groups.
CV adverse events occurred more often in patients with Sjogren’s syndrome and systemic lupus erythematosus.
Adverse CV events associated with hydroxychloroquine and chloroquine led to subsequent hospitalization in 39% of patients and mortality in 8% of patients.
Overdose from hydroxychloroquine increased the frequency of ventricular arrhythmias (24.5%) and QT prolongation (34.5%).
Need for additional research
“Our analysis is based on pre-COVID-19 data,” Maor told Healio. “There is a critical need for real-world safety [data] from the current COVID-19 pandemic due to the different indication dosing and duration of the treatment. More real-world safety data [are] also warranted with respect to drug interaction (for example, azithromycin).”
For the latest news on COVID-19 including case counts, information about the global public health response and emerging research, please visit the COVID-19 Resource Center on Healio.
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