Table 2.

Main studies on JAK-inhibitors and cardiovascular safety in patients with rheumatoid arthritis

First author and reference	Objectives	Methods	Results
Charles-Schoeman et al.150	To evaluate the incidence of CV events, including major adverse CV events (including CV death, as coronary, cerebrovascular, cardiac, and non-cardiac vascular events, and non-fatal CV events, as MI and cerebrovascular events) and CHF	Data from six phase III studies and two LTE studies of tofacitinib (administered alone or with non-biological DMARDs) in patients with RA and inadequate response to DMARDs	Lower incidence of major adverse CV events and CHF; lipid levels increased in the first 3 months and stabilized thereafter; blood pressure remained stable
Charles-Schoeman et al.151	To evaluate the incidence of major adverse CV events (including MI, stroke, CV death)	Post hoc analysis of six phase III and two LTE studies over 7 years, in patients with RA and inadequate response to DMARDs, after a 24-week treatment with tofacitinib	Lower incidence of major adverse CV events; HDL-scholesterol increased, but not LDL-cholesterol or total cholesterol
Kume et al.152	To analyse the effects of tofacitinib on atherosclerosis, comparing the CIMT at the baseline and 54 weeks after	Open-label prospective study in which patients with RA received tofacitinib 10 mg/day for 54 weeks	The CIMT had a signifcant decrease after the observation period
Taylor et al.153	To evaluate the incidence of major adverse CV events (including MI, stroke, and CV death) and other CV events (hospitalization for unstable angina, hospitalization for heart failure, serious arrhythmia, resuscitated sudden death, cardiogenic shock, or coronary revascularizations); ATE (MI and ischaemic stroke); DVT/PE; CHF	Data from nine studies, placebo comparison up to 24 weeks included data from six studies. Randomized dose comparison between baricitinib doses of 2 and 4 mg used data from four studies and from the associated long‐term extension study	No association between baricitinib and the incidence of major adverse CV events, ATE or CHF. DVT/PE occurred in patients treated with 4 mg baricitinib, but there were no cases of DVT/PE in the placebo group
Xie et al.154	To evaluate the incidence of major adverse CV events (including MI, ischaemic, and haemorrhagic strokes) or cardiovascular death, and DVT/PE	Systematic review and meta-analysis of 26 randomised controlled trials comparing tofacitinib 5 mg against 10 mg, baricitinib 2 mg against 4 mg, upadacitinib 15 mg against 30 mg	No significant differences regarding the risk for major adverse CV events were found; baricitinib at the dose of 2 mg appeared to be safer than 4 mg

ATE, arterial thrombotic events; CHF, congestive heart failure; CIMT, carotid intima-media thickness; DVT/PE, deep vein thrombosis/pulmonary embolism; DMARDs, disease-modifying antirheumatic drugs; LTE studies, open-label long-term extension studies; MI, myocardial infarction.