The State of Current Management of the Heightened Risk for Atherosclerotic Cardiovascular Events in an Established Cohort of Patients With Lupus Erythematosus

Abstract

Aims: Patients with lupus erythematosus (LE) are at a heightened risk for clinical events, chiefly heart attacks and strokes, caused by atherosclerotic cardiovascular disease (ASCVD). To address this problem, we recently proposed new guidelines for categorization of levels of risk for future ASCVD events specifically in LE patients, with corresponding recommendations for management. Methods and Results: We included all participants in our established UPenn Longitudinal Lupus Cohort of patients with cutaneous LE, without or with concurrent systemic LE (n=370, LE-ASCVD Study Cohort, years 2007 to 2021). Of our LE-ASCVD Study Cohort, 336/370 (90.8%) had a designated primary care physician. By the new guidelines, the most recent plasma low-density lipoprotein cholesterol (LDLc) levels were above goal for 252/370 (68.1%) of the LE-ASCVD Study Cohort. Of the Study Cohort, 266 (71.9%) had hypertension, which was under- or un-treated in 198/266 (74.4%). Of current smokers, 51/63 (81.0%) have no chart documentation of smoking cessation counseling or clinic referral. Diabetes was generally well-managed, and hypertriglyceridemia was uncommon. Of the LE-ASCVD Study Cohort, 254 patients qualified for two widely used online calculators that estimate the risk of an ASCVD event in the next 10 years (10-year ASCVD event risk): the ACC-ASCVD Risk Estimator Plus and QRisk3. We also stratified these 254 patients into the categories of ASCVD event risk defined by Keyes et al. Surprisingly, these three methods for estimating ASCVD event risk showed clinically meaningful agreement for only 100/254 (39.4%), i.e., discordance for over 60% of LE patients that could affect their clinical management. The actual documented rate of ASCVD events for patients in the first 10 years after enrollment into the Cohort was 22.3% (95% CI 16.9%, 27.4%), indicating a high-risk population despite a preponderance of women and a median age of only 47 years at enrollment. Conclusion: We conclude that cutaneous LE patients are under-treated compared with the new guidelines and, accordingly, these patients experience a substantial burden of major adverse ASCVD events. Moreover, it is unclear how to accurately assess future ASCVD event risk in cutaneous LE patients - except that it is high - and this uncertainty may complicate clinical management. Efforts are underway to improve ASCVD event risk estimation and guideline implementation in lupus patients.

Eradicating Atherosclerotic Events by Targeting Early Subclinical Disease: It Is Time to Retire the Therapeutic Paradigm of Too Much, Too Late

“…The value of induction-phase therapy will also require evaluation in special at-risk populations, such as patients receiving thoracic radiation and other therapies for cancer, patients with specific autoimmune disorders known to worsen arterial disease and ASCVD event risk, 11,155 and patients with chronic kidney disease or HIV-AIDS. 156…”

“…Regarding currently approved therapies, nonadherence to clinical guidelines for lifestyle and medications has become a conspicuous, and unsolved, problem under the prevailing paradigm of too much, too late. 4–9,11 It arises from undermanagement by clinicians and noncompliance by patients, the latter in part from the burden of polypharmacy, particularly when administered daily or even more frequently. 4,6…”

“…2,3 Few do. 4–11 Based on the longstanding conviction expressed by many investigators that we can do a lot better for our patients with ASCVD, 12–16 I have called the current therapeutic paradigm too much, too late.…”