RAS-modifying drugs reduce CVD risk in lupus patients

Use of antihypertensive agents that modify the renin-angiotensin system (RAS) helps lower the risk of cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE), suggests a study.

“These findings have the potential to impact clinical decision-making with regards to hypertension management in patients with lupus,” the researchers said.

A total of 220,168 patients with SLE had been identified from a medical insurance claims dataset, of whom 31,647 (mean age 46.1 years, 93.0 percent female, 96.9 percent had Charlson Comorbidity Index score 0‒4) met the eligibility criteria. Among those included in the study, 4,018 received RAS-modifying drugs and 27,629 non-RAS drugs.

Subsequently, the researchers propensity-score matched patients in the two cohorts using demographic data, risk factors, and comorbidities.

Compared with non-RAS drugs, treatment with RAS-modifying therapies resulted in a reduced risk of CVD diagnosis (relative risk [RR], 0.80, 95 percent confidence interval [CI], 0.74‒0.87). This finding was more pronounced following propensity score matching (RR, 0.62, 95 percent CI, 0.57‒0.68). [Am J Med 2023;136:284-293.E4]

Notably, the reduction in CVD risk transpired independent of lupus nephritis status (with lupus nephritis: RR, 0.51, 95 percent CI, 0.39‒0.65; without lupus nephritis: RR, 0.65, 95 percent CI, 0.59‒0.72). In addition, RAS-modifying therapies were associated with better CVD-free survival probability over 5 years (86.0 percent vs 78.3 percent).

“The data shown indicate that use of RAS-modifying drugs to treat hypertension in patients with systemic lupus erythematosus reduced the risk of CVD in this dataset,” the researchers said. “Understanding and quantifying these data can have an immediate impact by augmenting existing clinical decision-making and lead to lupus-specific hypertension management guidelines.”

CVD prevention and treatment

Several factors can help in the prevention and treatment of CVD among patients with SLE, which clinicians must be aware of. These include regular exercise, smoking cessation, consuming heart-healthy meals, and achieving an ideal body mass index. [Rheumatology (Oxford) 2004;43:7-12]

Use of statins, which hold anti-inflammatory and antithrombotic effects, can also help lower lipid levels in SLE patients, potentially leading to a reduced CVD risk. For instance, a 2015 study of SLE patients using high-dose statins reported a reduced risk of coronary artery disease and CVD. [Rheumatol Int 2007;27:1071-1077; Atherosclerosis 2015;243:11-18]

Treatment with hydroxychloroquine also contributes to longer survival in lupus, reduced thrombosis risk, and lipid-lowering effects and offers significant benefits on minimizing CVD risk. [Ann Rheum Dis 2007;66:1168-1172; Arthritis Rheum 2010;62:863-868; J Rheumatol 1999;26:325-330]

“In hypertensive patients without lupus, the American College of Cardiology/American Heart Association recommend angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, diuretics, and calcium channel blockers (used alone or in combination) for primary treatment,” the researchers said. [Hypertension 2018;71:1269-1324]

“When comparing these antihypertensive drugs with each other, several studies showed similar decreases in cardiovascular risk and cardiovascular mortality in patients of the general population regardless of drug class,” they added. [J Hypertens 2018;36:1637-1647; Lancet 2016;387:957-967; Cochrane Database Syst Rev 2018;11CD008170; BMJ 2008;336:1121-1123]

RAS drugs have been shown to influence blood pressure, sodium retention, and fluid balance, but these agents also possess other benefits such as reducing the actions of angiotensin II, which is inflammatory and fibrotic, according to the researchers. [Endocrinology 2003;144:2179-2183; Compr Physiol 2014;4:1201-1228; Int J Mol Sci 2018;19:876]