Hydroxychloroquine and the cardiovascular system: lights and shadows

To review the dual impact of hydroxychloroquine (HCQ) on the cardiovascular system, focusing on both its cardioprotective effects and potential cardiotoxicity in patients with autoimmune diseases.

A structured narrative review of the literature was conducted using PubMed/MEDLINE up to March 2025. Relevant studies including clinical trials, observational studies, mechanistic research, and reviews were selected to summarise the molecular mechanisms and cardiovascular effects of HCQ.

HCQ exerts multiple beneficial cardiovascular effects through anti-inflammatory, antithrombotic, metabolic, and endothelial-protective mechanisms. It reduces cytokine production, oxidative stress, platelet activation, and improves lipid and glucose profiles, contributing to decreased cardiovascular risk in patients with systemic autoimmune diseases. However, HCQ may also induce cardiotoxic effects, particularly with long-term use or high cumulative doses. These include QT interval prolongation, conduction abnormalities, and a rare but severe form of cardiomyopathy related to lysosomal dysfunction and impaired autophagy. The risk is higher in patients with advanced age, renal dysfunction, pre-existing heart disease, or concomitant use of QT-prolonging drugs.

HCQ has a complex and context-dependent cardiovascular profile. While generally cardioprotective at standard doses, it may lead to rare but serious cardiac adverse effects in highrisk patients. A risk-adapted monitoring strategy is essential to optimise its benefit-risk balance in clinical practice.