Journal Article

Short-term dose and duration-dependent glucocorticoid risk for cardiovascular events in glucocorticoid-naive patients with rheumatoid arthritis

Kremer, Joel M, Ocon, Anthony James, Reed, George, Curtis, Jeffrey R, Pappas, Dimitrios A

2021

Overview

ObjectivesRheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals.MethodsPatients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year.Results19 902 patients met criteria. 1106 CVE occurred (1.66/100 person-years). Increased aHR occurred at current doses of ≥5–9 mg 1.56 (1.18–2.06) and ≥10 mg 1.91 (1.31–2.79), without increased risk at 0–4 mg 1.04 (0.55–1.59). Cumulative dose over preceding 6 months showed increased aHR at 751–1100 mg 1.43 (1.04–1.98) and >1100 mg 2.05 (1.42–2.94), without increased risk at lower doses; duration of use over preceding 6 months exhibited increased aHR for >81 days of use 1.54 (1.08–2.32), without increased risk at shorter durations. One-year analyses were consistent.ConclusionsOver preceding 6-month and 1-year intervals, initiating glucocorticoids in steroid-naïve RA patients is associated with increased risk of CVE at daily doses ≥5 mg and increased cumulative dose and duration of use. No association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited
• Subject: Acute Coronary Syndrome - epidemiology / Adult / Aged / Angina, Unstable - epidemiology / Antirheumatic Agents - therapeutic use / Arrhythmias, Cardiac - epidemiology / Arthritis / Arthritis, Rheumatoid - drug therapy / Arthritis, Rheumatoid - physiopathology / Cardiovascular disease / Cardiovascular Diseases / Cardiovascular Diseases - epidemiology / Cardiovascular Diseases - mortality / Clinical medicine / Comorbidity / Diabetes / Dose-Response Relationship, Drug / Drug dosages / Duration of Therapy / Female / Glucocorticoids / Glucocorticoids - therapeutic use / Heart Disease Risk Factors / Heart failure / Heart Failure - epidemiology / Hospitalization - statistics & numerical data / Humans / Hypertension / Hypertension - epidemiology / Male / Middle Aged / Myocardial Infarction - epidemiology / Myocardial Revascularization - statistics & numerical data / Patients / Peripheral Arterial Disease - epidemiology / Prednisone / Prednisone - therapeutic use / Proportional Hazards Models / Pulmonary Embolism - epidemiology / Rheumatoid / Rheumatoid arthritis / Rheumatology / Risk factors / Sensitivity analysis / Stroke - epidemiology / Thromboembolism - epidemiology / Venous Thrombosis - epidemiology