Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High‐Risk Lesions

Abstract

Objective To evaluate whether biologic disease‐modifying antirheumatic drugs (DMARDs) decrease cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and whether biologic DMARDs might have a beneficial effect on coronary plaque formation or progression. Methods In this single‐center observational cohort study, 150 patients underwent computed tomographic angiography for evaluation of coronary atherosclerosis (total, noncalcified, mixed/calcified, and low‐attenuation plaque); 101 had repeat assessments within a mean ± SD of 6.9 ± 0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and hospitalization for heart failure. The Framingham‐D'Agostino score was used to assess cardiovascular risk. The segment stenosis score was used to measure plaque burden. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results After adjustment for the segment stenosis score, the Framingham‐D'Agostino score, and time‐varying Disease Activity Score in 28 joints using the C‐reactive protein level using marginal structural models, current biologic DMARD use was associated with lower long‐term CVD risk (OR 0.15 [95% CI 0.04–0.60]). Noncalcified and low‐attenuation plaque presence moderated the effect of biologic DMARDs on CVD risk; specifically, biologic DMARD use was associated with lower CVD risk in patients with noncalcified or low‐attenuation plaque at baseline (OR 0.21 [95% CI 0.04–0.99] and OR 0.08 [95% CI 0.01–0.70], respectively), but not in those without noncalcified or low‐attenuation plaque. Per‐segment plaque progression analyses showed that biologic DMARD exposure was associated with transition of noncalcified to mixed/calcified plaque (OR 4.00 [95% CI 1.05–15.32]). Biologic DMARD exposure predicted a lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments (OR 0.40 [95% CI 0.17–0.93]), but not among those with calcification. Biologic DMARD treatment also predicted low‐attenuation plaque loss (P = 0.042). Conclusion Our findings indicate that in RA, biologic DMARD use is associated with reduced CVD risk, protective calcification of noncalcified lesions, and lower likelihood of new plaque formation in patients with early atherosclerosis.

Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-naïve, early rheumatoid arthritis

“…Collectively, these data speak to several study findings 33 34 indicating benefits of RA therapies not only include effect on systemic inflammation, 35 but cardiometabolic profile 36 and a targeted effect on key immune mediators of CVD. Similarly, a prospective cohort study suggested that after accounting for other risk factors and treatment response, subjects actively receiving bDMARDs experienced lower CV event risk, which was not observed in those who discontinued.…”

<p>Rheumatoid Arthritis as a Risk Factor for Coronary Artery Calcification and Obstructive Coronary Artery Disease in Patients with Chest Pain: A Registry Based Cross-Sectional Study</p>

“…Another recent CTA study by Karpouzas et al, in the same population, proposes bDMARD use to slow the coronary atherosclerosis in RA patients. 37 In the present study, we found a tendency of increased odds for CACS ≥ 400 and obstructive CAD in RA patients on csDMARD treatment, which was not seen in patients on bDMARD treatment. However, due to few patients, the estimates for bDMARDs presented with 95% CIs ranging from a small negative to a strong positive association.…”

Derivation and internal validation of a multi-biomarker-based cardiovascular disease risk prediction score for rheumatoid arthritis patients

“…However, the risk score demonstrated good fit in subanalyses of patients who were and were not receiving statins. The MBDA-based CVD risk score accounts for the level of inflammation, the treatment of which has potential to reduce CVD risk in RA patients [21][22][23]. The score may have utility for RA patients who are receiving statins because the statin dose may not yet have been optimized and because the non-statin treatment options for elevated CVD risk in RA patients may include DMARDs.…”

“…Synovial and systemic inflammation in RA patients contribute to CVD risk independently of traditional risk factors [4]. In observational studies, the risk for CVD events was greatest in RA patients with high disease activity [16][17][18][19][20] and effective RA treatment appeared to reduce the risk for atherosclerosis [21] and CVD events [22,23]. Traditional CVD risk factors, such as diabetes, may be exacerbated by RA-related mechanisms [24,25].…”