Key result
Current hydroxychloroquine and chloroquine use links to ~270% higher sudden cardiac death risk versus non-users.
Why the study?
Longitudinal studies assessing the electrocardiographic and cardiotoxic effects of hydroxychloroquine and chloroquine were limited, despite interest in their use for COVID-19.
Does hydroxychloroquine or chloroquine use increase QTc-interval duration and the risk of sudden cardiac death in a general population cohort?
Cohort (n=14,594)
No
Does hydroxychloroquine or chloroquine use increase QTc-interval duration and the risk of sudden cardiac death in a general population cohort?
Effect estimate: HR 3.7 (95% CI 1.1-12.6)
Hydroxychloroquine and chloroquine use is associated with dose-dependent QTc prolongation and a nearly 4-fold increased risk of sudden cardiac death, highlighting significant cardiotoxicity.
May warrant QTc monitoring in hydroxychloroquine or chloroquine users; leaves open causal SCD confirmation.
AIMS:: Hydroxychloroquine and chloroquine ([hydroxy]chloroquine) are drugs used to treat malaria and rheumatological disorders and were recently suggested as beneficial for prevention and treatment of patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. However, longitudinal studies to assess the electrocardiographic and cardiotoxic effects of these drugs are limited. In this study, we aimed to investigate the effect of these drugs on QTc-interval and incidence of sudden cardiac death (SCD). METHODS: We designed a longitudinal follow-up study of individuals within the prospective population-based Rotterdam Study. Eligible individuals had available data on medication and repeated ECG measurements. The study period was between 1 January 1991 and 1 January 2014. We studied on current and past use of [hydroxy]chloroquine as a time-varying exposure; high versus low daily dose of [hydroxy]chloroquine. QTc-interval duration, and the occurrence of SCD were the main outcomes. SCD was defined as an unexpected and sudden death due to cardiac arrhythmia within one hour of the onset of acute symptoms, and in patients without cardiac symptoms within 24 hours before death. RESULTS: Among the study population of 14 594 individuals (58.8% women) with an average age of 65 years, 346 patients used [hydroxy]chloroquine at any time during follow-up. The total number of SCD cases was 609. In a multiple linear mixed model analysis, the current use of [hydroxy]chloroquine was associated with a significantly increased duration of the QTc-interval of 8.1 ms (95% CI: 3.6; 12.6) compared with non-users. The association was stronger among current-high daily dosage [15.3 (95%CI: 7.0; 23.6)] compared with current-low daily dosage [5.5 (95%CI: 0.4; 10.7)] users. In a Cox proportional hazard regression analysis, the risk of SCD was significantly higher in participants who were current users of [hydroxy]chloroquine than in non-users [adjusted hazard ratio; 3.7 (95%CI: 1.1; 12.6)]. CONCLUSIONS: In this longitudinal study, persons who received [hydroxy]chloroquine had an increased QTc-interval duration and the association was dose-dependent. [Hydroxy]chloroquine was associated with a significantly increased risk of SCD. As long as their activity against COVID-19 is controversial, cardiotoxicity is a strong argument against using these drugs to treat COVID-19 infections.
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Ahmadizar et al. (2020) conducted a cohort in General population (n=14,594). Hydroxychloroquine and chloroquine vs. Non-users was evaluated on Sudden cardiac death (HR 3.7, 95% CI 1.1-12.6). Current use of hydroxychloroquine and chloroquine was associated with a significantly increased risk of sudden cardiac death (HR 3.7) compared to non-users.
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