Caution Strongly Recommended When Using Chloroquine, Hydroxychloroquine in Patients With Cardiovascular Disease, COVID-19

Despite positive results seen from the use of chloroquine and hydroxychloroquine in some patients hospitalized with coronavirus disease 2019 (COVID-19), concerns have begun to mount worldwide about how these drugs affect patients’ cardiovascular health, specifically the heart. The drugs’ safety and efficacy in this area have come under fire due to the lack of actionable data from large-scale clinical trials.

The American Heart Association, the American College of Cardiology, and the Heart Rhythm Society issued joint guidance last week on their concerns with the use of hydroxychloroquine and azithromycin in patients with heart disease who contract the virus. “Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 19) Treatment” notes several severe complications from this combination’s use in patients with COVID-19:

• Irregular heartbeat
• Polymorphic ventricular tachycardia
• Long QT syndrome
• Increased risk of sudden death

The groups’ recommendations include withholding hydroxychloroquine and azithromycin in patients with baseline QT prolongation, monitoring cardiac rhythm, minimizing contact with caregivers, and correcting hypokalemia above 4 mEq/L and hypomagnesemia above 2mg/dL.

“The urgency of COVID-19 must not diminish the scientific rigor with which we approach COVID-19 treatment. While these medications may work against COVID-19 individually or in combination, we recommend caution with these medications for patients with existing cardiovascular disease,” stated Robert A. Harrington, MD, FAHA, president of the American Heart Association and chair of the department of medicine at Stanford University.

Cautionary tales also have emerged from Brazil and Sweden on the use of chloroquine and hydroxychloroquine in patients with cardiovascular disease (CVD). In Sweden, where social distancing is not mandatory, clinicians were instructed last week to not use chloroquine among patients with COVID-19 unless they are part of a clinical trial.

Magnus Gisslén, professor and senior doctor at the Sahlgrenska University Hospital in Gothenburg, Sweden, and colleagues noted “a serious effect on the heart” linked to using the medication, as well as that “the patients most at risk are those with pre-existing conditions in the heart. Those are often the older patients,” he said. “But if you get a too high dosage it can affect people who have no underlying conditions at all.”

In Brazil, a clinical trial on the use of chloroquine diphosophate to treat patients with COVID-19 was halted due to patient deaths. The trial randomized 81 patients to receive either 600 mg of chloroquine 2 times a day for 10 days (total dose, 12 g) or 450 mg of chloroquine for 5 days, with just a twice-daily dose on the first day (total dose, 2.7 g). Patients additionally were treated with ceftriaxone and azithromycin. Overall, 20 patients died: 16 in the high-dose group (n = 41) and 6 in the low-dose group (n = 40). The study authors concluded that the high dose led to severe arrhythmia; ventricular tachycardia, or sudden cardiac death, was blamed for 2 of the deaths in this group.

Meanwhile, preventing complications from comorbid CVD and COVID-19 is a prominent part of the DoD COVID-19 Practice Management Guide from the Pentagon—especially because almost 25% of patients with diagnosed COVID-19 also have suspected heart failure and “cardiogenic shock and cardiac arrest contributes to 7% to 33% of deaths.”

In a recent interview with CNN, Sanjay Gupta, MD, associate professor of neurosurgery at Emory University and associate chief of neurosurgery at Grady Memorial Hospital, both in Atlanta, Georgia, summed it up best: “We don’t know if this works. There is a potential for harm here. Maybe it’s a small potential, but there is a potential there. Wouldn’t that be a real tragedy for somebody who did not get any benefit from the medication and yet had some kind of harm happen to them? That’s why you do the studies.”