Background/Purpose: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are currently used as an adjuvant treatment in lupus nephritis (LN) patients for the optimal control of proteinuria. However, it is not known if these agents have an atheroprotective effect, similar to that described in other at-risk populations. The aim of this study was to assess their atheroprotective role in LN.

Methods: Using the electronic database of the longitudinal observation cohort study of the University of Toronto Lupus Clinic, we identified 144 patients (123 females, mean age at disease onset 34±12.1 years, mean follow up time 14.9±8.6 years) with LN (diagnosis according to 1997 ACR criteria) who were treated with ACEIs/ARBs for, at least, 5 years for proteinuria. The control group comprised of 301 LN patients (262 females, mean age at disease onset 34.1±13.2, mean follow up time 13.4±7.9 years) who did not receive ACEIs/ARBs treatment. All patients were followed for the occurrence of atherosclerotic cardiovascular events (CVEs), consisting of transient ischemic attack and stroke, angina, myocardial infarction (MI), percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), congestive heart failure and pacemaker insertion as well as peripheral vascular disease. Patients with pre-existing CVEs were excluded. Statistical software SAS (version 9.3) was used for analysis; p<0.05 was considered significant.

Results: There were no significant differences in the cumulative occurrence of CVEs between the two groups [14/144, 9.7% for treated vs 26/301, 8.6% for untreated patients, p=0.708]; however, hard events (stroke, MI, CABG, PTCA) were less frequent in treated patients [6/144, 4.17% vs 16/301, 5.32%]. Details on the type of CVEs in the two groups are presented in the table.

TIA: transient ischemic attack, CHF: congestive heart failure, PVD: peripheral vascular disease

Patients treated with ACEIs/ARBs were more frequently hypertensive [100% vs 52.8%, p<0.001] and diabetic [10.4% vs 4.7%, p=0.021] whereas the controls had more frequently hypercholesterolemia [27.9% vs 18.1%, p=0.024] and elevated triglycerides [14% vs 4.9%, p=0.004]; other parameters did not differ significantly. Regression analysis (Weibull parametric model) failed to confirm ACEIs/ARBs non-use as an important predictor of future CVEs. The only significant predictors in both groups were age at LN diagnosis and cumulative corticosteroid dose.

Conclusion:    Our data do not support the hypothesis that ACEIs/ARBs may be protective against atherosclerotic CVEs in LN patients. In this cohort, only age at LN diagnosis and cumulative prednisone dose were important predictors for these outcomes.  

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/does-renin-angiotensin-system-blockade-protect-lupus-nephritis-patients-from-atherosclerotic-cardiovascular-events-a-case-control-study/