Remdesivir-Associated Significant Bradycardia: A Report of Three Cases
Abstract
Recently, remdesivir was approved by the United States Food and Drug Administration for patients with Coronavirus disease 2019 (COVID-19). We herein describe 3 patients with COVID-19 who showed significant bradycardia and QTc prolongation after remdesivir administration. Bradycardia did not respond to atropine treatment in 2 of the patients, one of whom received theophylline and the other required a temporary pacemaker. Fortunately, the patients’ heart rate and rhythm returned to normal after the discontinuation of remdesivir, albeit it lengthened their hospital stays. Careful monitoring during remdesivir infusion may decrease the risk of adverse cardiovascular side effects.
1. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW. Extrapulmonary manifestations of COVID-19. Nat Med 2020;26:1017-1032.
2. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for Coronavirus disease 2019 (COVID-19): a Review. JAMA 2020;323:1824-1836.
3. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, Hohmann E, Chu HY, Luetkemeyer A, Kline S, Lopez de Castilla D, Finberg RW, Dierberg K, Tapson V, Hsieh L, Patterson TF, Paredes R, Sweeney DA, Short WR, Touloumi G, Lye DC, Ohmagari N, Oh MD, Ruiz-Palacios GM, Benfield T, Fätkenheuer G, Kortepeter MG, Atmar RL, Creech CB, Lundgren J, Babiker AG, Pett S, Neaton JD, Burgess TH, Bonnett T, Green M, Makowski M, Osinusi A, Nayak S, Lane HC; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med 2020;383:1813-1826.
4. Dyer O. Covid-19: Remdesivir has little or no impact on survival, WHO trial shows. BMJ 2020;371:m4057.
5. WHO Solidarity Trial Consortium; Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernández García C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, García PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portolés A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Røttingen JA, Swaminathan S. Repurposed antiviral drugs for Covid-19 - interim WHO solidarity trial results. N Engl J Med 2021;384:497-511.
6. Bonow RO, Hernandez AF, Turakhia M. Hydroxychloroquine, Coronavirus disease 2019, and QT prolongation. JAMA Cardiol 2020;5:986-987.
7. Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. Clin Infect Dis 2020:ciaa478.
8. RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704.
9. Jorgensen SCJ, Kebriaei R, Dresser LD. Remdesivir: review of pharmacology, pre-clinical data, and emerging clinical experience for COVID-19. Pharmacotherapy 2020;40:659-671.
10. Aleissa MM, Silverman EA, Paredes Acosta LM, Nutt CT, Richterman A, Marty FM. New perspectives on antimicrobial agents: remdesivir treatment for COVID-19. Antimicrob Agents Chemother 2020;65:e01814-01820.
11. Gubitosa JC, Kakar P, Gerula C, Nossa H, Finkel D, Wong K, Khatri M, Ali H. Marked sinus bradycardia associated with remdesivir in COVID-19: a case and literature review. JACC Case Rep 2020;2:2260-2264.
12. Layland J, Carrick D, Lee M, Oldroyd K, Berry C. Adenosine: physiology, pharmacology, and clinical applications. JACC Cardiovasc Interv 2014;7:581-591.
13. Fan Q, Zhang B, Ma J, Zhang S. Safety profile of the antiviral drug remdesivir: An update. Biomed Pharmacother 2020;130:110532.
14. Gupta AK, Parker BM, Priyadarshi V, Parker J. Cardiac adverse events with remdesivir in COVID-19 infection. Cureus 2020;12:e11132.
15. Varga ZV, Ferdinandy P, Liaudet L, Pacher P. Drug-induced mitochondrial dysfunction and cardiotoxicity. Am J Physiol Heart Circ Physiol 2015;309:H1453-1467.
16. Michaud V, Dow P, Al Rihani SB, Deodhar M, Arwood M, Cicali B, Turgeon J. Risk assessment of drug-induced long QT syndrome for some COVID-19 repurposed drugs. Clin Transl Sci 2021;14:20-28.
17. Haghjoo M, Golipra R, Kheirkhah J, Golabchi A, Shahabi J, Oni-Heris S, Sami R, Tajmirriahi M, Saravi M, Khatami M, Varnasseri M, Kiarsi M, Hejazi SF, Yousefzadeh Rahaghi M, Taherkhani M, Ashraf H, Keshmiri MS, Akbarzadeh MA, Bozorgi A, Mottaghizadeh F, Hedayat B, Heidarali M, Hajhossein Talasaz A. Effect of COVID-19 medications on corrected QT interval and induction of torsade de pointes: results of a multicenter national survey. Int J Clin Pract 2021:e14182.
18. Sodero A, Squitieri M, Mazzeo S, Pasca M, Matà S, Pieri F, Bessi V, Sorbi S. Acute symptomatic sinus bradycardia in high-dose methylprednisolone therapy in a woman with inflammatory myelitis: a case report and review of the literature. Clin Med Insights Case Rep 2019;12:1179547619831026.
19. Stroeder J, Evans C, Mansell H. Corticosteroid-induced bradycardia: case report and review of the literature. Can Pharm J (Ott) 2015;148:235-240.
20. Amaratunga EA, Corwin DS, Moran L, Snyder R. Bradycardia in patients with COVID-19: a calm before the storm? Cureus 2020;12:e8599.
2. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for Coronavirus disease 2019 (COVID-19): a Review. JAMA 2020;323:1824-1836.
3. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, Hohmann E, Chu HY, Luetkemeyer A, Kline S, Lopez de Castilla D, Finberg RW, Dierberg K, Tapson V, Hsieh L, Patterson TF, Paredes R, Sweeney DA, Short WR, Touloumi G, Lye DC, Ohmagari N, Oh MD, Ruiz-Palacios GM, Benfield T, Fätkenheuer G, Kortepeter MG, Atmar RL, Creech CB, Lundgren J, Babiker AG, Pett S, Neaton JD, Burgess TH, Bonnett T, Green M, Makowski M, Osinusi A, Nayak S, Lane HC; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med 2020;383:1813-1826.
4. Dyer O. Covid-19: Remdesivir has little or no impact on survival, WHO trial shows. BMJ 2020;371:m4057.
5. WHO Solidarity Trial Consortium; Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernández García C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, García PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portolés A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Røttingen JA, Swaminathan S. Repurposed antiviral drugs for Covid-19 - interim WHO solidarity trial results. N Engl J Med 2021;384:497-511.
6. Bonow RO, Hernandez AF, Turakhia M. Hydroxychloroquine, Coronavirus disease 2019, and QT prolongation. JAMA Cardiol 2020;5:986-987.
7. Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. Clin Infect Dis 2020:ciaa478.
8. RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704.
9. Jorgensen SCJ, Kebriaei R, Dresser LD. Remdesivir: review of pharmacology, pre-clinical data, and emerging clinical experience for COVID-19. Pharmacotherapy 2020;40:659-671.
10. Aleissa MM, Silverman EA, Paredes Acosta LM, Nutt CT, Richterman A, Marty FM. New perspectives on antimicrobial agents: remdesivir treatment for COVID-19. Antimicrob Agents Chemother 2020;65:e01814-01820.
11. Gubitosa JC, Kakar P, Gerula C, Nossa H, Finkel D, Wong K, Khatri M, Ali H. Marked sinus bradycardia associated with remdesivir in COVID-19: a case and literature review. JACC Case Rep 2020;2:2260-2264.
12. Layland J, Carrick D, Lee M, Oldroyd K, Berry C. Adenosine: physiology, pharmacology, and clinical applications. JACC Cardiovasc Interv 2014;7:581-591.
13. Fan Q, Zhang B, Ma J, Zhang S. Safety profile of the antiviral drug remdesivir: An update. Biomed Pharmacother 2020;130:110532.
14. Gupta AK, Parker BM, Priyadarshi V, Parker J. Cardiac adverse events with remdesivir in COVID-19 infection. Cureus 2020;12:e11132.
15. Varga ZV, Ferdinandy P, Liaudet L, Pacher P. Drug-induced mitochondrial dysfunction and cardiotoxicity. Am J Physiol Heart Circ Physiol 2015;309:H1453-1467.
16. Michaud V, Dow P, Al Rihani SB, Deodhar M, Arwood M, Cicali B, Turgeon J. Risk assessment of drug-induced long QT syndrome for some COVID-19 repurposed drugs. Clin Transl Sci 2021;14:20-28.
17. Haghjoo M, Golipra R, Kheirkhah J, Golabchi A, Shahabi J, Oni-Heris S, Sami R, Tajmirriahi M, Saravi M, Khatami M, Varnasseri M, Kiarsi M, Hejazi SF, Yousefzadeh Rahaghi M, Taherkhani M, Ashraf H, Keshmiri MS, Akbarzadeh MA, Bozorgi A, Mottaghizadeh F, Hedayat B, Heidarali M, Hajhossein Talasaz A. Effect of COVID-19 medications on corrected QT interval and induction of torsade de pointes: results of a multicenter national survey. Int J Clin Pract 2021:e14182.
18. Sodero A, Squitieri M, Mazzeo S, Pasca M, Matà S, Pieri F, Bessi V, Sorbi S. Acute symptomatic sinus bradycardia in high-dose methylprednisolone therapy in a woman with inflammatory myelitis: a case report and review of the literature. Clin Med Insights Case Rep 2019;12:1179547619831026.
19. Stroeder J, Evans C, Mansell H. Corticosteroid-induced bradycardia: case report and review of the literature. Can Pharm J (Ott) 2015;148:235-240.
20. Amaratunga EA, Corwin DS, Moran L, Snyder R. Bradycardia in patients with COVID-19: a calm before the storm? Cureus 2020;12:e8599.
| Files | ||
| Issue | Vol 16 No 2 (2021): J Teh Univ Heart Ctr | |
| Section | Case Report(s) | |
| DOI | https://doi.org/10.18502/jthc.v16i2.7390 | |
| Keywords | ||
| Arrhythmias; cardiac Bradycardia COVID-19 Remdesivir | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Shirvani M, Sayad B, Shojaei L, Amini A, Shahbazi F. Remdesivir-Associated Significant Bradycardia: A Report of Three Cases. J Tehran Heart Cent. 2021;16(2):79-83.
