Stroke Risk Increased in Rheumatoid Arthritis With Serious Infections, Cerebrovascular Disease

CT scan of stroke
CT scan of stroke
Stroke was more likely to occur in patients with RA who experienced another serious adverse event 30 days prior.

Factors such as serious infections and inadequate treatment of cardiovascular disease increase the risk of stroke in patients with rheumatoid arthritis (RA), according to research recently published in the Annals of the Rheumatic Diseases.

Yvette Meissner, MSc, from the epidemiology unit and German Rheumatism Research Centre in Berlin, Germany, and colleagues performed an analysis of 12,354 patients in the German biologics register RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) cohort with RA who were matched with 326 patients in a control group. Patients were included if they began a biologic disease-modifying antirheumatic drug (DMARD) or conventional synthetic DMARD (csDMARD) after a minimum of 1 csDMARD treatment failure. The researchers studied stroke incidence rates (IR) and risk factors in all patients, then analyzed the control group with 163 patients in a nested case-control group in a 1:2 ratio who had the same risk profile using a shared frailty model.

“The known risk factors age and smoking as well as hyperlipoproteinaemia and a poor physical function were associated with an increased risk,” Ms Meissner and colleagues wrote. “The IR for stroke was highest in patients who experienced another [serious adverse event] within 30 days prior to stroke.”

In an adjusted Cox model, risks per every 5 years of age carried a hazard ratio (HR) of 1.4 (95% CI, 1.3-1.5), while hyperlipoproteinaemia carried an HR of 1.6  (95% CI, 1.0-2.5), and smoking carried an HR of 1.9 (95% CI, 1.3-2.6). However, there was a decreased HR in patients who had better physical function (HR 0.9; 95% CI, 0.8-0.96).

There were 166 strokes across all patients with an IR of 3.2 per 1000 patient-years (95% CI, 2.7-3.7), an IR of 9.0 per 1000 patient-years (95% CI, 7.3-11.0) after a serious adverse event (SAE), and an IR of 94.9 30 days after the event (95% CI, 72.6-121.9).

The researchers noted patients in the nested case-control group with serious infections (HR 4.4; 95% CI, 1.6-12.5), untreated cardiovascular disease (HR 3.3; 95% CI, 1.5-7.2), and other serious adverse events (HR 2.6; 95% CI, 1.4-4.8) had major risk factors for stroke.

“In the nested case-control study, univariate analysis showed likewise that high levels of [C-reactive protein], [erythrocyte sedimentation rate] and [Disease Activity Score] 28 as well as a poor physical function were significantly associated with a higher risk for stroke,” the investigators wrote. “Significant but smaller effects were found for the comorbidities hyperlipoproteinaemia, chronic renal disease, and osteoporosis.”

Summary & Clinical Applicability

“Aside from traditional risk factors, we found that insufficient [cardiovascular] treatment and the occurrence of other SAEs [signigicant adverse events] increased the risk for stroke in patients with RA. These findings, on the one hand, underline the need for rigorous management of [cardiovascular] diseases, on the other hand support results found in the general population which suggest expanding the traditional risk model for stroke by incident other adverse events. This could help to identify patients and clinical situations at increased risk for stroke.”

Limitations & Disclosures

Limitations to the study included using patients with the same observation time when matching patients with stroke, which could have led to selecting patients with better disease control and fewer severe adverse events, and limitations in shared frailty models to evaluate model assumptions.

Dr Richter received honoraria from Pfizer; Dr Manger received speaking fees and was a consultant for Abbvie, BMS, MSD, Pfizer, Roche and UCB; Dr Tony received fees from Abbvie, Astra-Zeneca, BMS, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and Sanofi; Dr Wilden received personal fees from Pfizer; Dr Listing received personal fees from Sandoz and Pfizer; Dr Zink received grants and personal fees from AbbVie, BMS, MSD, Pfizer, Roche and UCB; and Dr Strangfeld received personal fees from BMS, MSD, Pfizer, Roche and Sanofi-Aventis.

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Meissner Y, Richter A, Manger B, et al. Serious adverse events and the risk of stroke in patients with rheumatoid arthritis: results from the German RABBIT cohort [published online May 8, 2017]. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-211209