From joints to vessels: How rheumatoid arthritis therapy alters the fate of the heart

Table 6 Comparative safety of disease-modifying antirheumatic drugs: Cardiovascular risks and patient considerations

Drug class	Drug	Prevention of adverse cardiovascular effects methods	Preferred patient category	Safety comparison
csDMARDs	Methotrexate	Homocysteine control (target level < 10 μmol/L); Folic acid supplementation (5-10 mg/day)-reduces the risk of hyperhomocysteinemia by 50%-70%. Regular monitoring: Blood pressure (BP), ECG, echocardiography (EchoCG) (with long-term use). Lipid profile, homocysteine levels (every 6-12 months)	Patients without severe cardiovascular disease	Safer than bDMARDs and tsDMARDs but requires monitoring
	Sulfasalazine	Caution in patients with conduction disorders; Use validated risk scores: SCORE2/SCORE2-OP for estimating 10-year CVD risk, QRISK3; Baseline & periodic evaluation: Lipid profile (LDL-C, HDL-C, triglycerides), hs-CRP, homocysteine (if high CVD risk). BP monitoring; ECG/Echocardiography	Patients with mild RA	Safer than biologics but less effective
	Leflunomide	BP control, salt restriction	Patients without a history of HTN	Similar to MTX in safety but more likely to cause HTN
	Hydroxychloroquine	ECG monitoring (QT interval). Before starting therapy: Measure baseline QT (corrected using Fridericia’s formula- QTc). Assess risks if QTc > 450 ms in men or > 470 ms in women (consider alternative medications). Repeat ECG 3-5 days after initiation and after each dose increase. Correction of electrolyte imbalances: Hypokalemia (K+ < 3.5 mmol/L) and hypomagnesemia (Mg2+ < 0.7 mmol/L) increase arrhythmia risk	Patients with very mild RA or SLE	Safest in this group but requires QT interval monitoring
bDMARDs (TNF inhibitors)	Adalimumab	Avoid in patients with HF class III-IV	Patients without severe CVD	Higher infection risk but lower CV risk than JAK inhibitors
	Certolizumab	BP monitoring, cardiac function assessment	Pregnant women (low placental transfer)	Similar to other TNF inhibitors
	Etanercept	Caution in HF	Patients with moderate CV risk	Considered safer than infliximab
	Golimumab	Monitor BP and HF symptoms	Patients intolerant to other TNF inhibitors	Comparable to other TNF inhibitors
	Infliximab	Avoid in HF class II–IV	Patients with severe RA but no CVD	Highest HF risk among TNF inhibitors
Other bDMARDs	Abatacept	BP control, ECG if risk factors present	Patients at high infection risk	Safer than TNF inhibitors regarding HF
	Anakinra	Not required	Patients with concomitant atherosclerosis	One of the safest biologics
	Sarilumab/Tocilizumab	Lipid monitoring, statins if needed	Patients without severe dyslipidemia	Higher CV risk than TNF inhibitors but lower than JAK inhibitors
	Olokizumab	Lipid profile monitoring	Patients resistant to other IL-6 inhibitors	Presumed similar to tocilizumab
	Rituximab	Premedication, slow infusion	Patients with lymphoproliferative disorders	Neutral CV effects but risk of infusion-related hypotension
tsDMARDs (JAK inhibitors)	Baricitinib	Avoid in patients with thrombosis history, BP control, anticoagulants for AF	Younger patients without thrombosis risk factors	Least safe regarding CV risk (FDA, EMA warning-thrombosis, MI, stroke)
	Tofacitinib	Lipid monitoring, BP control, avoid in smokers/obese patients	Patients unresponsive to bDMARDs	High CV risk, especially in smokers
	Upadacitinib	Thrombosis risk assessment before prescribing	Patients intolerant to other JAK inhibitors	Similar to other JAK inhibitors
	Filgotinib	General precautions as for other JAK inhibitors	Limited use, caution required	Presumed similar to tofacitinib

DMARDs: Disease-modifying antirheumatic drugs; RA: Rheumatoid arthritis; SLE: Systemic lupus erythematosus; CVD: Cardiovascular disease; HTN: Hypertension; HF: Heart failure; MI: Myocardial infarction; AF: Atrial fibrillation; LDL-C: Low-density lipoprotein cholesterol; ECG: Electrocardiogram; tsDMARDs: Targeted synthetic DMARDs; bDMARDs: Biologic DMARD; TNF: Tumor necrosis factor; IL-6: Interleukin-6; HDL-C: High-density lipoprotein cholesterol; hs-CRP: High-sensitivity C-reactive protein.