Background/Purpose Subjects with rheumatoid arthritis (RA) are at a higher risk of developing cardiovascular (CV) disease compared to the general population, with an increased incidence of congestive heart failure (CHF) possibly mediated by chronic inflammation. Anti-tumour necrosis factor (TNFi) drugs might reduce the incidence of new CHF by supressing inflammation. However, TNFi are associated with a worsening of existing CHF. The aim of this analysis was to compare the incidence of CHF in subjects with RA treated with TNFi to that in those receiving non-biologic drugs (nbDMARDs).

Methods Patients with a physician diagnosis of RA enrolled in the British Society for Rheumatology Biologics Register, a national prospective cohort study established in 2001 to monitor the long-term safety of TNFi. Potential CHF events were verified according to Framingham criteria by a cardiologist from death certificates and from clinical follow-up forms of consultants. New CHF which occurred within 6 months after another cardiac event (eg. myocardial infarction) was excluded. Risk of CHF was compared between the two cohorts using a Cox regression model, propensity scores adjusted. Subjects were censored at first episode of CHF, death, first missed dose of TNFi + 180 days, last returned clinician follow-up or 31/01/2014, whichever came first.

Results A total of 87 validated first CHFs were analysed: 48 in 3,662 nbDMARD subjects and 39 in 12,397 TNFi-exposed subjects. After adjustment for differences in baseline characteristics, the hazard ratio (95%-confidence interval) of CHF in patients on TNFi compared to nbDMARD was: 0.31 (0.18-0.52). Similar results were found for analysis limited to first TNFi only and in patients without prior history of ischaemic heart disease.

Conclusion No increased risk of CHF was observed in those patients selected for TNFi therapy compared to those receiving nbDMARD therapy. A reduced risk of CHF was noted in patients treated with TNFi.

Table. Association between exposure to TNFi and development of first CHF

	nbDMARD (n=3662)	TNFi (n=12397)
Years of follow-up per subject, median (IQR)	5.0 (2.5-7.7)	5.1 (1.9-8.0)
Person-years of exposure, pyrs	18 698	62 244
Number of verified CHFs, n (%)	48 (1.31)	39 (0.31)
Crude incidence rate of verified CHFs per 10 000 person-years (95%-confidence interval)	25.67 (19.53-34.40)	6.27 (4.58-8.58)
Risk of CHF between nbDMARD and TNFi
–          Unadjusted HR (95%-CI)	Referent	0.24 (0.16-0.37)
–          Age- and gender adjusted HR (95%-CI)	Referent	0.47 (0.30-0.72)
–          PD-adjusted HR (95%-CI)	Referent	0.25 (0.14-0.44)

Fully adjusted model by propensity score (PD) consisting of age, gender, DAS28, disease duration, HAQ, steroid use, NSAIDs, COXIBs, hypertension, diabetes mellitus, angina pectoris, myocardial infarction, smoking history and use of statins, antiplatelets, ACE-inhibitors, warfarin and digoxin.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incidence-of-congestive-heart-failure-in-subjects-with-rheumatoid-arthritis-receiving-anti-tumour-necrosis-factor-drugs-results-from-the-british-society-for-rheumatology-biologics-register-for-rheuma/