The potential experimental therapies for Covid-19 have important cardiovascular side effects and toxicities. Data for these side effects are extrapolated from patients treated for autoimmune diseases (Chloroquine/Hydroxychloroquine, Rocilizumab), hepatitis (Ribavarin, Interferon alfa), or human immunodeficiency virus infection Lopinivir/Ritonivir) (17).
Azithromycin, Hydroxychloroquine and Lopinavir/Ritonavir can cause conduction disorders especially QT prolongation. The combination of Hydroxychloroquine and Azithromycin is not recommended due to a synergistic effect increasing the risk of severe arrhythmia and deleterious impact on the cardiovascular system (49). The QT interval should be monitored closely especially in the setting of Long QT Syndrome with Covid-19 (4, 53). Other adverse cardiac events related with these drugs are less common, but include the following: ventricular hypertrophy, hypokinesia, heart failure, pulmonary arterial hypertension, and valvular dysfunction. Irreversible myocardial damage is seen in 12.9%, death in 30.8%, however cardiac function normalizes in the majority of patients (44.9%) upon withdrawal of Chloroquine and Hydroxychloroquine (17, 54). On 17 June 2020, World Health Organization announcement to stop the use of hydroxychloroquine for Covid – 19 patients was based on data from Solidarity and the Recovery trials. Both showed that hydroxychloroquine does not result in the reduction of mortality of hospitalized COVID-19 patients, when compared with standard care. (55)
Lopinavir/Ritonavir may interact with antiplatelets, oral anticoagulants, digoxin, statins, and many others as it is a potent liver enzyme (CYP3A4) inhibitor (56).
Tocilizumab has been shown to influence lipid metabolism in rheumatoid arthritis patients. However recently, the ENTRACE clinical trial supported the cardiovascular safety of Tocilizumab in these patients (57). Interleukin 6 targeting has not been tested for secondary prevention in cardiovascular disease.
There is no evidence that Angiotensin-converting-enzyme inhibitors / Angiotensin II receptor blockers / Angiotensin receptor Neprilysin inhibitors or low-dose Acetylsalicylic acid worsen outcomes in patients with confirmed or suspected Covid-19 or increase susceptibility to Covid-19. Covid-19 is not an indication to stop Angiotensin-converting-enzyme inhibitors / Angiotensin II receptor blockers / Angiotensin receptor Neprilysin inhibitors or low-dose Acetylsalicylic acid as stopping these medications may cause worsening of patient’s heart condition, unless symptomatic hypotension or shock, acute kidney injury, or hyperkalemia appears (11, 49). This applies to children, adolescents and adults.
According to British Congenital Cardiac Association, The Canadian Cardiovascular Society and other organizations, patients with heart failure and hypertension should preferentially choose acetaminophen over non-steroidal anti-inflammatory drugs for fever or pain to avoid decompensation of these cardiovascular conditions, however there is yet no firm evidence (11, 53). Fever-triggered malignant ventricular arrhythmia is the major concern in Brugada syndrome with Covid-19 infection, therefore, fever should be aggressively treated with paracetamol (30).
In patients with catecholaminergic polymorphic ventricular tachycardia and Covid-19, beta-blockers and flecainide should be continued with monitoring of drug interactions with antiviral drugs (4).