Taking the RA Threat to Heart During Pregnancy

Originally published by our sister publication Pharmacy Practice News

Obesity, gestational diabetes mellitus and acute cardiovascular (CV) complications are more common among pregnant women with rheumatoid arthritis (RA) than those without the inflammatory disorder. The rate of these complications has risen over time, leading to longer and more expensive childbirths for women with RA, according to a new study (Eur Heart J 2024;45[17]:1524-1536).

“Having RA is considered a significant risk factor for developing heart complications around the time of delivery. As such, it is important that the healthcare team—including obstetricians, rheumatologists and cardiologists—all work together with the patient to improve the heart and overall health of women with RA before, during and after their pregnancy,” said study author Salman Zahid, MD, a second-year fellow at the Oregon Health & Science University Knight Cardiovascular Institute, in Portland. “This can help prevent both short-term and long-term complications.”

Researchers analyzed nearly 13 million delivery hospitalizations from the National Inpatient Sample (2004-2019), the largest publicly available all-payor inpatient healthcare database in the United States. Nearly 12,000 deliveries, representing 0.01% of the sample, were among women with RA. After adjusting for age, race/ethnicity, comorbidities, insurance status and income, RA remained an independent risk factor for many complications during the peripartum period. For example, women with RA were 37% more likely to experience preeclampsia (adjusted odds ratio [aOR], 1.37; 95% CI, 1.27-1.47) than those without RA.

The researchers noted that preeclampsia “plays a substantial role in driving the occurrence of acute CV complications among individuals with RA.”

Women with RA also were twice as likely to experience arrhythmias (aOR, 2.00; 95% CI, 1.68-2.38), and more than twice as likely to experience peripartum cardiomyopathy (aOR, 2.10; 95% CI, 1.11-3.99), compared with those who did not have RA.

Furthermore, the risk for acute kidney injury (AKI) was significantly higher among pregnant women with RA than those who did not have the disorder. Specifically, 117 of 11,979 women with RA developed AKI versus 52 women in the non-RA cohort (P=0.02). Venous thromboembolism outcomes told a similar story: 92 cases of VTE occurred in women with RA versus 37 in the non-RA cohort (P<0.01), the investigators reported.

Deliveries among women with RA were more likely to require three days of hospitalization at a cost of $4,377 compared with two days and $3,718 for women without RA.

The researchers found that Black women are at a notably higher risk of developing acute CV complications related to RA than other ethnic groups. Individuals from lower socioeconomic backgrounds, especially those with the lowest income levels, showed higher rates of CV complications.

Dr. Zahid explained that these disparities likely stem from underlying biases, structural racism and limited access to care for socially disadvantaged groups, who often face undertreatment and inadequate screening. “Therefore, there is an immediate necessity for comprehensive initiatives aimed at meeting the unmet needs of at-risk populations in the U.S. to help reverse the troubling trends in maternal mortality,” he said.

He advocated for several ways in which medications should be used to safely manage RA and CV risk in women. For example, when pregnancy is planned or confirmed, certain disease-modifying antirheumatic drugs such as leflunomide and methotrexate should be discontinued, he noted. However, other medications such as anti–tumor necrosis factor-alpha agents, azathioprine, hydroxychloroquine or sulfasalazine can be safely continued as needed.

Statins are another class of agents that need to be weighed carefully, Dr. Zahid stressed. He first acknowledged that statins are commonly—and justifiably—used in people with RA and other inflammatory conditions to reduce their long-term cardiac complications. And although most women with lower cardiac risk generally should stop statin use during pregnancy and breastfeeding, for women with RA, “cardiac risk does not end at delivery,” he said. “Bringing statins back into treatment after pregnancy and breastfeeding may be appropriate to manage this risk.”

Dr. Zahid said he plans to continue to work on this area of research, noting that future studies should evaluate whether managing the underlying inflammatory state in RA with disease-modifying pharmacologic therapies would result in improved CV outcomes both during pregnancy and long term.

A Pharmacist’s Perspective

C. Michael White, PharmD, FCP, FCCP, a distinguished professor and the chair of pharmacy practice at the University of Connecticut School of Pharmacy, in Storrs, agreed with Dr. Zahid’s take on statin use in women with RA. “It was thought that since people with rheumatoid arthritis had lower LDL [low-density lipoprotein] on average than those without the disease, that they didn’t need statins and that statins might increase the severity of rheumatoid arthritis,” Dr. White said. “Luckily, more recent data have suggested that statins can actually reduce inflammation in concert with the biologic anti-inflammatory drugs and lower the risk of heart disease as well” (Front Med [Lausanne] 2018;5:24). (See sidebar for more published data.)

Dr. White noted that the LDL level that should be aimed for in pregnant women depends on the patient’s American Heart Association or American College of Cardiologist risk category, “as specified in the lipid guidelines just like the general population, and that aspirin or P2Y12 inhibitors could be used among pregnant women when warranted.”

The sources reported no relevant financial disclosures.