Renin-Angiotensin System-Modifying Antihypertensive Drugs Can Reduce the Risk of Cardiovascular Complications in Lupus: A Retrospective Cohort Study

Am J Med. 2023 Mar;136(3):284-293.e4. doi: 10.1016/j.amjmed.2022.11.016. Epub 2022 Dec 8.

Abstract

Background: Patients with systemic lupus erythematosus have a higher incidence of cardiovascular disease than the general population. Antihypertensive drugs that modify the renin-angiotensin system (RAS) are used to protect renal function in lupus nephritis and may also have extrarenal effects that lower cardiovascular disease risk due to their anti-inflammatory properties. In this study, we compared the effects of RAS vs non-RAS antihypertensive drugs on cardiovascular disease incidence in patients with lupus.

Methods: Using a medical insurance claims dataset, 220,168 patients with lupus were identified, of which 31,647 patients (4018 patients prescribed RAS drugs, 27,629 patients prescribed non-RAS drugs) were eligible for the study. Patients had a mean age of 46.1 years, were 93.0% female, and healthy (96.9% Charlson Comorbidity Index score 0-4). Patients in the 2 drug groups were propensity score matched using demographic data, risk factors, and comorbidities.

Results: Use of RAS vs non-RAS drugs lowered the relative risk (RR) of diagnosis of cardiovascular disease (RR 0.80; 95% confidence interval [CI], 0.74-0.87), which was more pronounced after propensity score matching (RR 0.62; 95% CI, 0.57-0.68). The decreased risk in cardiovascular disease occurred regardless of lupus nephritis status (with lupus nephritis: RR 0.51; 95% CI, 0.39-0.65; without lupus nephritis: RR 0.65; 95% CI, 0.59-0.72). RAS-modifying therapies significantly increased cardiovascular disease-free survival probability over a 5-year period (86.0% vs 78.3% probability).

Conclusions: RAS-modifying drugs reduced the risk of cardiovascular disease in patients with systemic lupus erythematosus in this dataset. These findings have the potential to impact clinical decision-making with regards to hypertension management in patients with lupus.

Keywords: ACE inhibitors (ACE-I); Angiotensin receptor blockers (ARB); Cardiovascular disease; Insurance claims database; Renin-angiotensin system (RAS); Retrospective cohort study; Systemic lupus erythematosus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / adverse effects
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / prevention & control
  • Female
  • Humans
  • Hypertension* / complications
  • Hypertension* / drug therapy
  • Lupus Nephritis* / complications
  • Lupus Nephritis* / drug therapy
  • Male
  • Middle Aged
  • Renin-Angiotensin System
  • Retrospective Studies
  • Risk Factors

Substances

  • Antihypertensive Agents
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists