Antimalarials exert a cardioprotective effect in lupus patients: Insights from the Spanish Society of Rheumatology Lupus Register (RELESSER) analysis of factors associated with heart failure

Abstract

Background/objectives Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. Methods Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. Results The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p<0.0001), cardiac arrhythmia (7.38 [4.00-13.42], p<0.0001), pulmonary hypertension (3.71 [1.84-7.25], p<0.0002), valvulopathy (6.33 [3.41-11.62], p<0.0001), non-cardiovascular damage (1.29 [1.16-1.44], p<0.000) and calcium/vitamin D treatment (5.29 [2.07-16.86], p=0.0015). Female sex (0.46 [0.25-0.88], p=0.0147) and antimalarials (0.28 [0.17-0.45], p<0.000) proved to be protective factors. Conclusions Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect.

Association of Hydroxychloroquine Dose With Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus

“…In fact, we observed a 38% reduction in the risk of adverse cardiac events per each 1‐mg/kg increase in baseline HCQ weight‐based dose. This finding is contrary to our original hypothesis and in concordance with multiple previous studies that have shown an association of HCQ use with lower cardiovascular risk (4,5,7). This inverse association between HCQ weight‐based dose and adverse cardiac events was not observed among smokers, except for those who were taking HCQ for over 5 years.…”

“…Current knowledge of HCQ-related heart failure in SLE is mostly limited to case reports and case series (7,14,16,17). Similar to our results, a recent cross-sectional study that included 117 patients with SLE and heart failure and 3,506 SLE controls found a decreased odds of heart failure among HCQ users (OR 0.28 [95% CI 0.17-0.45], P < 0.001) (7). However, this study did not look at HCQ doses but rather compared HCQ users versus nonusers, who are inherently 2 very different populations of patients with SLE.…”

“…Current knowledge of HCQ‐related heart failure in SLE is mostly limited to case reports and case series (7,14,16,17). Similar to our results, a recent cross‐sectional study that included 117 patients with SLE and heart failure and 3,506 SLE controls found a decreased odds of heart failure among HCQ users (OR 0.28 [95% CI 0.17–0.45], P < 0.001) (7). However, this study did not look at HCQ doses but rather compared HCQ users versus nonusers, who are inherently 2 very different populations of patients with SLE.…”

“…Hydroxychloroquine (HCQ) is usually started soon after a diagnosis of systemic lupus erythematosus (SLE) is made and has shown to reduce the risk of end-organ damage and disease flares and to improve overall survival (1)(2)(3). Multiple retrospective studies have also demonstrated a cardioprotective effect of HCQ, with a lower risk for coronary artery disease (CAD) and cardiovascular events among HCQ users with SLE and other rheumatic diseases (4)(5)(6)(7). This risk reduction is thought to be related to the positive effect of HCQ on traditional cardiovascular risk factors such as hyperlipidemia, diabetes mellitus, and prothrombotic states (8)(9)(10).…”

Adverse events in rheumatoid arthritis patients under antimalarial treatment—Is there cardiovascular compromise?

“…Thus, a meta-analysis involving patients with RA and SLE showed that using CQ/HCQ reduced the risk of cardiovascular disease in patients with rheumatic diseases (RR 0.72, 95% CI: 0.56-0.94, p = 0.013) (Liu et al, 2018) (Souza Botelho et al, 2021. Furthermore, studies after this meta-analysis have corroborated the results in patients with SLE (Lo et al, 2021b;Rúa-Figueroa et al, 2022).…”