- The combined use of antiretroviral medications lopinavir and ritonavir, previously used to treat SARS-Cov-1 and MERS-Cov patients, appeared to cause bradycardia in 22% of elderly, critically ill COVID-19 patients, in a small study in France.
- Bradycardia was resolved in all patients after discontinuation or dose reduction of both medications.
Embargoed until 4 a.m. CT/5 a.m. ET Thursday, July 9, 2020
DALLAS, July 9, 2020 — Older, critically ill patients with COVID-19 who received a combination of the antiretroviral medications lopinavir and ritonavir experienced bradycardia, a slow heart rate, more often, according to new research published today in Circulation: Arrhythmia and Electrophysiology, an American Heart Association journal.
The combination of antiretroviral medications lopinavir (LPV) and ritonavir (RTV) have been previously used to treat patients with SARS-Cov-1 and MERS-Cov, as well for HIV-1 patients. Among HIV-1 patients, a risk of bradycardia was also reported.
In this small, preliminary, prospective study, researchers recorded the risk of bradycardia in critically ill COVID-19 patients treated with this combination of medications. Bradycardia is classified as a heart rate below 60 beats per minute for a period of more than 24 hours. Bradycardia can cause problems if the slow heart rate leads to a decrease in blood flow to the body. This can lead to heart failure, fainting, chest pain and low blood pressure. In some people, bradycardia does not cause any symptoms.
The study included 41 patients with COVID-19 admitted to the intensive care unit at Amiens University Hospital, in Amiens, France, who were treated with 200 mg LPV and 50 mg RTV twice daily for 10 days. All patients received continuous electrocardiogram (ECG) monitoring.
Among the patients who received the LPV/RTV treatment:
- 22% experienced bradycardia for more than 24 hours;
- bradycardia occurred at least 48 hours after initiation of treatment, indicating that the medications may have caused bradycardia;
- a blood test measuring the concentration of ritonavir (RTV plasma concentration) at 72 hours after receiving the treatment showed higher concentrations of RTV in the patients who had bradycardia;
- no correlation was found between RTV plasma concentration, LPV plasma concentration and mean heart rate at 3-days after LPV/RTV treatment began;
- patients experiencing bradycardia were on average older than patients receiving the treatment who did not experience bradycardia (ages 62-80 vs. 54-68, respectively); and,
- bradycardia resolved after LPV/RTV were discontinued or doses were reduced.
Researchers noted, “[LPV and RTV] have complex pharmacokinetic characteristics [how the body processes a medication] … Bradycardia could be a sign of severe cardiological or neurological impairment since it is associated with lymphopenia [lower than normal number of white blood cells] that seems to reflect the severity of COVID-19 infection. Intensivists should be aware of this potential side effect in order to closely monitor LPV/RTV plasma levels, notably in elderly patients.”
Co-authors are Christophe Beyls, M.D.; Nicolas Martin, M.D.; Alexis Hermida, M.D.; Osama Abou-Arab, M.D., Ph.D.; and Yazine Mahjoub, M.D., Ph.D. Author disclosures are in the manuscript.
No funding sources were reported for this study.
- Available multimedia is on right column of release link - https://newsroom.heart.org/news/older-critically-ill-patients-with-covid-19-may-have-increased-risk-of-bradycardia-with-lopinavir-and-ritonavir?preview=14af2d14a0e4280a886a2e715e003926
- View the manuscript online.
- 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay: Executive Summary: A Report from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society
- 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay: A Report from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society
- About Arrhythmia
- Understanding Your Risk for Arrhythmia
- Follow AHA/ASA news on Twitter @HeartNews
- Follow news from the AHA’s Circulation: Arrythmia and Electrophysiology journal @CirculationEP
Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations and health insurance providers are available at https://www.heart.org/en/about-us/aha-financial-information.
About the American Heart Association
The American Heart Association is a relentless force for a world of longer, healthier lives. We are dedicated to ensuring equitable health in all communities. Through collaboration with numerous organizations, and powered by millions of volunteers, we fund innovative research, advocate for the public’s health and share lifesaving resources. The Dallas-based organization has been a leading source of health information for nearly a century. Connect with us on heart.org, Facebook, Twitter or by calling 1-800-AHA-USA1.
For Media Inquiries and AHA/ASA Expert Perspective: 214-706-1173
Michelle Kirkwood: 703-457-7838, firstname.lastname@example.org
For Public Inquiries: 1-800-AHA-USA1 (242-8721)