Patients with RA in the Setting of Cardiovascular Disease

WASHINGTON, D.C.—At ACR Convergence 2024, Christina Charles-Schoeman, MD, MS, professor of medicine and chief, Division of Rheumatology, University of California Los Angeles Medical Center, Santa Monica, Calif., gave a practical talk on the management of rheumatoid arthritis (RA) in the setting of cardiovascular disease (CVD).

Background

CVD is the leading cause of death in people with RA. Patients with RA have twice the risk of myocardial infarction, a 50% increased risk of stroke and double the risk of developing congestive heart failure.^1-3

These stats are bleak, but there’s a lot that we as rheumatologists can do to protect our patients. Multiple factors propagate atherosclerosis, and these can be separated into three main buckets: 1) RA and inflammation; 2) traditional CV risk factors; and 3) RA medications.

RA & Inflammation

Dr. Charles-Schoeman

When it comes to decreasing CV risks in patients with RA, getting the RA under control is an obvious place to start. “If you control the RA, you can reduce the risk of CVD,” noted Dr. Charles-Schoeman.

She pointed to prospective observational data that showed the incidence rate of first verified myocardial infarction was significantly lower in patients who responded to tumor necrosis factor (TNF) inhibitors than those who were non-responders.⁴

Traditional CV Risk Factors

Controlling traditional CV risk factors, such as hypertension, diabetes and smoking, also plays a crucial role in decreasing CV risks in our patients with RA. Up to 70% of CVD events in patients with RA can be attributed to CVD risk factors and RA characteristics combined.⁵

Dr. Charles-Schoeman first spoke to the benefits of controlling blood pressure. In the NHANES III Linked Mortality study, uncontrolled hypertension increased the risk of all-cause and CV disease mortality in U.S. adults. And interestingly, treatment for hypertension did not save lives—treatment with control of blood pressure did.⁶ “What matters is if the blood pressure is controlled,” she emphasized, “not if they’re taking meds or not. Patients taking pills without blood pressure at goal actually did the worst.”

So the next time your patient has high blood pressure at their clinic visit, don’t be reassured by seeing anti-hypertensives on the medication list. Adjustment of those medications to get blood pressure to goal is really where the money is.

Next, she turned toward smoking cessation, citing a “two-for-one” stat that could be the final push needed to inspire some patients to quit smoking. “This is one of my favorite studies to talk about smoking cessation with my patients,” she said. “Smoking cessation not only decreased CV events, but also reduced RA disease activity.”⁷

Then, Dr. Charles-Schoeman spoke to blood sugar. “We know that glucose control is important. Attaining a hemoglobin A1c of less than 7% can reduce CVD risk by 37% over 11 years.⁸ These are numbers that you can discuss with your patients,” she said.

RA Medications

RA medications have a spectrum of effects on CV risks, some positive and some negative. All RA medications decrease inflammation, which has anti-atherogenic effects. However, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, Janus kinase (JAK) inhibitors and other drugs have possible pro-atherogenic effects, too.

After data from the ORAL Surveillance study were published in 2022, the FDA issued a black box warning for all JAK inhibitors, noting an increased risk of serious heart-related events, cancer, blood clots and death.⁹ However, Dr. Charles-Schoeman and her colleagues recently published a post hoc analysis of the ORAL Surveillance study that provides data useful in the clinic.¹⁰ Data show that there’s a differential risk between tofacitinib and TNF inhibitors, primarily observed for those with a prior history of atherosclerotic CVD (ASCVD).

“In ORAL, 80% of the patients didn’t have a history of ASCVD,” she said, “and there was absolutely no difference in major adverse cardiac events (MACE) between tofacitinib and TNF inhibitors in these patients.”

What’s more, there was an inadequate use of statins in the ORAL trial, with only 23.4% of the total high-risk population using statins, and only 53% with a history of ASCVD treated with statins at baseline. This begs us to ask the question, “Does statin use make a difference on the occurrence of MACE in patients using tofacitinib?”

An abstract presented at ACR Convergence 2024 showed that it does. There was no difference in MACE between the tofacitinib and TNFi groups in patients treated with statins at baseline, regardless of whether they had ASCVD at baseline or not.¹¹

Conclusion

So how can we best care for our patients from a joint and CV perspective? “At the end of the day, it’s a balance of factors driving adverse CV outcomes,” concluded Dr. Charles-Schoeman. “We need to look at RA disease control and CV risk factors, and treat both. The good news is that atherosclerosis takes time to develop. You have time to intervene. So that blood pressure of 150/90? You [may] not have time to mention it at this visit, but at the next, mention it. It can make a difference.”

Samantha C. Shapiro, MD, is a clinician educator who is passionate about the care and education of rheumatology patients. She writes for both medical and lay audiences and practices telerheumatology.

References

1. van den Hoek J, Boshuizen HC, Roorda LD, et al. Mortality in patients with rheumatoid arthritis: a 15-year prospective cohort study. Rheumatol Int. 2017 Apr;37(4):487–493. doi:10.1007/s00296-016-3638-5
2. Solomon DH, Karlson EW, Rimm EB, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003 Mar 11;107(9):1303–1307. doi:10.1161/01.CIR.0000054612.26458.B2
3. Nicola PJ, Maradit-Kremers H, Roger VL, et al. The risk of congestive heart failure in rheumatoid arthritis: A population-based study over 46 years. Arthritis Rheum. 2005 Feb;52(2):412–420. doi:10.1002/art.20855
4. Dixon WG, Watson KD, Lunt M, et al. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor α therapy: Results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 2007 Sep;56(9):2905–2912. doi:10.1002/art.22809
5. Crowson CS, Rollefstad S, Ikdahl E, et al. Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2018 Jan;77(1): 48–54. doi:10.1136/annrheumdis-2017-211735
6. Zhou D, Xi B, Zhao M, et al. Uncontrolled hypertension increases risk of all-cause and cardiovascular disease mortality in US adults: The NHANES III linked mortality study. Sci Rep. 2018 Jun 20;8(1):9418. doi:10.1038/s41598-018-27377-2
7. Roelsgaard IK, Ikdahl E, Rollefstad S, et al. Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients. Rheumatology (United Kingdom). 2020 Aug 1;59(8):1997–2004. doi:10.1093/rheumatology/kez557
8. Joseph JJ, Deedwania P, Acharya T, et al. Comprehensive management of cardiovascular risk factors for adults with type 2 diabetes: A scientific statement from the American Heart Association. Circulation. 2022 Mar;145(9):e722–e759. doi:10.1161/CIR.0000000000001040
9. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022 Jan 27;386(4):316–326. doi:10.1056/nejmoa2109927
10. Charles-Schoeman C, Buch MH, et al. Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: A post hoc analysis from ORAL Surveillance. Ann Rheum Dis. 2023 Jan;82(1):119–129. doi:10.1136/ard-2022-222259
11. Giles J, Charles-Schoeman C, Buch M, et al. Use of statins and its association with major adverse cardiovascular outcomes with tofacitinib versus TNF inhibitors in a risk-enriched population of patients with rheumatoid arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9).