Background Factors related to systemic inflammation and disease severity have been associated with the increased risk of ischemic heart disease in rheumatoid arthritis (RA) patients. Disease activity in RA can often be effectively reduced with treatment with tumour necrosis factor inhibitors (TNFi), which also have been observed to modify cardiovascular risk factors, such as endothelial dysfunction.
Objectives To analyze the risk of acute coronary syndromes (ACS) in patients with RA treated with TNFi in comparison with biologics-naïve RA patients and the risk in the general population.
Methods A cohort comprising patients with RA and no previous ischemic heart disease, who started their first biologic (a TNFi) 2001-2010 (n=7,704, mean age 57 years, 76% women), and a cohort of biologics-naïve RA referents (3:1, n=23,112), matched by age, sex and county were identified by linkage of the National Patient Register and the Swedish Biologics Register. A second, similarily matched comparator cohort comprising population referents (5:1, n=38,520) was randomly selected from the Population Register. The outcome, incident ACS, was defined as a primary discharge diagnosis of myocardial infarction or unstable angina, or myocardial infarction as the underlying cause of death. The incidence rates of a first ACS were calculated and the risk of ACS compared between cohorts using Cox proportional hazards regression in three different risk windows. The models were adjusted for disease duration, joint surgery, comorbidity and socioeconomic factors, and in an analysis of a subpopulation included 2006 or later, dispensed prescribed drugs (for cardiovascular comorbidity and RA treatment).
Results Among the TNFi exposed RA patients, contributing 32,621 person-years ever after exposure to TNFi, 221 ACS were identified, resulting in a crude incidence rate (95% CI) of 6.8 (5.9-7.7) ACS per 1,000 person-years. The corresponding rate among biologics-naïve RA patients was 9.0 (8.4-9.7), and among the general population referents 3.6 (3.4-3.9) per 1,000 person-years. The fully adjusted hazard ratio, HR (95%CI), for TNFi exposed compared with biologics-naïve RA patients was 0.8 (0.7-0.95). A corresponding analysis in the subpopulation included 2006 or later, using a model adjusted also for prescribed drugs, resulted in the HR 0.7 (0.5-1.0). In comparison with the risk in the general population the risk of ACS among biologics-naïve RA patients was HR 2.0 (1.8-2.3), and among TNFi-exposed HR 1.6 (1.4-1.9). Similar risk estimates were observed using the other risk windows.
Conclusions A lower risk of ACS was observed in a cohort of TNFi exposed compared with biologics-naïve RA patients. Compared with the general population the risk among patients with RA was elevated, although less pronounced among the TNFi exposed. These results could be attributable to better inflammatory control in the TNFi exposed cohort or to other actions of the TNFi treatment.
Disclosure of Interest : L. Ljung Speakers bureau: fees for lectures from Bristol Myers Squibb and Abbvie, J. Askling: None declared, S. Rantapää-Dahlqvist: None declared, L. Jacobsson Speakers bureau: fees for lectures from Abbvie, Pfizer and UCB.
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