Adverse cardiovascular effects of antirheumatic drugs: implications for clinical practice and research

Clinical manifestations of most rheumatic diseases have changed over the past few decades, largely due to advances in therapies targeting autoimmune and (auto)inflammatory pathways. Improvements in the management of rheumatic diseases have also now brought to the fore the issue of comorbidities. It has become evident that the burden of cardiovascular morbidity and mortality is increased in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and the spondyloarthropathies, amongst other conditions. As a result, efforts have switched toward investigating the effects of conventional antirheumatic and new biologic agents on inflammationinduced atherothrombosis. Evidence is accumulating suggesting a beneficial cardiovascular profile of some antirheumatic drugs, such as methotrexate and hydroxychloroquine, but it also indicates the possibility of a variety of adverse events developing in the short- and long-term. The aim of this review is to highlight cardiovascular adverse effects of the drugs widely used in the treatment of rheumatic diseases. The literature search was performed through PubMed, the Cochrane Library, Scopus, and Web of Science databases using the following terms: "antirheumatic drugs", "inflammation", "rheumatic diseases", "cardiovascular diseases", "adverse events", "toxicity", "drug design", and "drug interactions". Adverse events ranging from infusion-related hypertension and myocardial ischemia, to restrictive cardiomyopathy and congestive heart failure have been reported in large trials and case series on most antirheumatic drugs. Clinicians should be alert of the wide variety of cardiovascular adverse effects of individual antirheumatic drugs, and should carefully monitor blood pressure and markers of inflammation, thrombosis, myocardial ischemia, electrolytes, and lipid disturbances while administering these drugs. Future prospective studies should specifically investigate the cardiovascular safety of most antirheumatic drugs as part of mono- or combination therapy in relation to different dosage regimens, duration of therapy, age, and gender.