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POS0090 (2021)
RISK OF QT INTERVAL PROLONGATION ASSOCIATED WITH CHRONIC USE OF HYDROXYCHLOROQUINE IN RHEUMATIC PATIENTS AND THE EFFECT OF COTREATMENTS
M. Antivalle1, G. La Paglia1, M. C. Ditto2, S. Parisi2, E. Fusaro2, M. Agosti3, P. Sarzi Puttini1
1L. Sacco Universty Hospital, Rheumatology, Milano, Italy
2AOU Città della Salute e della Scienza di Torino; Rheumatology Unit;, Department of Medical Science, Torino, Italy
3Azienda Socio-Sanitaria Territoriale (ASST) di Vimercate, Department of Medical Science, Vimercate, Italy

Background: Hydroxychloroquine (HCQ) has been used safely for over 60 years in rheumatic patients. However, following its recent use in covid-19 disease, its safety has been questioned, following controversial reports of cardiac toxicity 1 , possibly related to a prolongation of the QT interval 2 .


Objectives: To explore the influence of chronic treatment with hydroxychloroquine on QT interval in rheumatic patients, and the possible effects of drug-to-drug interference 3 .


Methods: 12-lead electrocardiogram tracings were recorded with standard equipment in 229 ambulatory patients (SLE = 53, RA = 52, SSc = 56, UCTD = 38, Others = 30). The present analysis was performed on corrected QT intervals (QTc) calculated according to Framingham formula (QTc = QT+0.154 (1−RR)), with ULN = 449 ms in males, and 467 ms in females. Estimated glomerular filtrate rate (eGFR) was calculated from serum creatinine with the CKD-EPI equation. The influence on QTc values of demographic variables, chronic (≥3 months) HCQ treatment, and of the use of selected comedications -Statins, Angiotensin Converting Enzyme inhibitors (ACEi), Angiotensin Receptor Blockers (ARBs), Selective Serotonin Reuptake Inhibitors (SSRIs), Proton-Pump Inhibitors (PPI), Calcium Channel Blockers (CCBs) – were evaluated by parametric or non parametric statistical methods, as appropriate. All statistic al analyses were performed with the IBM SPSS statistical package version 25.


Results:

Demographic and clinical variables in patients treated with HCQ (HCQ+) and in controls (HCQ-).

N Age Yrs ±SD Female N % eGFR mL/min/1.73m 2 Statins N % ACEi N % ARB N % SSRI N % PPI N % CCB N %
All 229 58.02 ±14.36 206 90.0 87.14 18.96 29 12.7 48 21.8 19 8.3 14 6.1 138 60.3 30 13.1
HCQ+ 132 58.71 ±14.49 122 92.4 87.00 20.04 18 13.6 32 24.2 11 8.3 9 6.8 80 60.6 17 12.9
HCQ- 97 57.51 ±14.30 84 86.6 87.32 17.47 11 11.3 16 16.5 8 8.2 5 5.2 58 59.8 13 13.4
p 0.532 0.183 0.897 0.690 0.189 1.000 0.782 1.000 1.000

Demographic variables, and the use of evaluated comedications were not different in HCQ+ and HCQ- patients ( Table 1 ). In the whole population, the QTc mean duration was 416.72 ± 20.70 ms, and was correlated with age (r = 0.215, p= 0.001), but not with gender (p = 0.548), eGFR (r = -0.93, p = 0.163), or disease (p = 0.092). In only 4 patients (HCQ+: 3 (2.3%) – HCQ-: 1 (1%), p = 0.639) QTc duration was above ULN.

QTc duration was not associated with the use of Statins, ACEi, ARBs, or SSRIs (p = 0.454, 0.276, 0.475, and 0.131 respectively), but was significantly prolonged in patients treated with HCQ (421.26 ± 19.19 vs 410.55 ± 21.18 msec, p < 0.001), PPIs (420.57 ± 21.45 vs 410.89 ± 18.12 ms, p < 0.001), and CCBs (424.22 ± 25.97 vs 415.59 ± 19.62 ms, p < 0.033). Furthermore, as reported in Fig. 1 , our data show a trend - albeit not statistically significant - towards an additive effect on QT prolongation of the association of PPIs and CCBs with HCQ, even more evident in the case of association of the 3 drug classes.


Conclusion: In this study, the QTc interval was significantly prolonged in patients treated with hydroxychloroquine as compared to controls, although significant prolongation was extremely infrequent. Furthermore, our data revealed signs of drug-drug interference, suggesting that regular monitoring of the electrocardiogram is advisable in these patients, often undergoing cotreatment with multiple drugs.


REFERENCES:

[1]Imad M. Tleyjeh, et al. The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis. Mayo Clin Proc Innov Qual Outcomes. 2020 Nov 2 doi: 10.1016/j.mayocpiqo.2020.10.005 [Epub ahead of print].

[2]Teodoro J. Oscanoa, et al. Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: A Meta-analysis. Int J Antimicrob Agents.

[3]Byung Jin Choi, et al. Risk of QT prolongation through Drug-drug Interactions between Hydroxychloroquine and Concomitant Drugs Prescribed in Real-world Practice. Preprint from Research Square, 22 Sep 2020 DOI: 10.21203/rs.3.rs-79572/v1 PPR: PPR217328.


Disclosure of Interests: None declared

Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 254
Session: Rheumatoid arthritis - non biologic treatment and small molecules - PART 1 (Poster Tours)