Kent, Shia T.

Abstract Objective To estimate the real‐world risk of cardiovascular events among patients with migraine treated with erenumab and other migraine preventive medications. Background Migraine preventive treatment with calcitonin gene‐related peptide (CGRP) pathway inhibitors, such as erenumab and others, may theoretically result in cardiovascular effects due to a lack of compensatory vasodilation with CGRP pathway inhibition. Methods In this retrospective observational cohort study, we estimated the unadjusted cumulative risk (CR) of new‐onset hypertension, acute myocardial infarction (MI), or stroke among patients with migraine newly treated with erenumab, other anti‐CGRP pathway monoclonal antibodies (mAbs), standard oral preventive medications, and onabotulinumtoxinA using data from the MarketScan® Commercial and Medicare Supplemental medical claims database. Comparative analyses to assess the relative risk (RR) of vascular events were gated on the comparability of treatment groups with respect to baseline demographics and clinical characteristics. Potential bias due to unmeasured confounding was evaluated via negative control outcome (NCO) analyses. Confounding based on measured covariates and differential informative censoring were addressed with inverse probability weights. Results A total of 108,019 new users of migraine preventive medications were included. Unadjusted CR (95% confidence interval [CI]) of hypertension at 12 months of treatment was: erenumab, 9.34% (8.79–9.89%); other anti‐CGRP pathway mAbs, 9.42% (8.92–9.92%); standard oral preventive medications, 9.09% (8.77–9.41%); and onabotulinumtoxinA, 9.10% (8.39–9.81%). NCO analyses identified minimal concerns related to unmeasured confounding in erenumab versus other mAbs and erenumab versus onabotulinumtoxinA comparisons. Adjusted RRs (95% CIs) of acute MI and stroke, respectively, at 36 months of treatment were 1.02 (0.45–1.59) and 0.90 (0.56–1.25) for erenumab versus other mAbs and 0.87 (0.19–1.55) and 0.97 (0.42–1.52) for erenumab versus onabotulinumtoxinA. Conclusions In this analysis of the MarketScan medical claims database, we found no difference in the risk of vascular events in patients treated with erenumab versus other anti‐CGRP pathway mAbs or onabotulinumtoxinA.

Introduction: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease (ASCVD), yet little is known about Lp(a) testing patterns in real-world practice. We hypothesized that Lp(a) testing occurs in a different population than calculated low density lipoprotein (LDL-C) testing alone, and that elevated Lp(a) is associated with greater lipid-lowering therapy (LLT) initiation and cardiovascular (CV) events. Methods: We used data from 11 health systems participating in the National Patient-Centered Clinical Research Network. We created two cohorts based on lab tests from Jan 1, 2015 to Dec 31, 2019: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. We used logistic regression to assess the relationship between Lp(a) levels (< 50, 50-100, and > 100mg/dL) and initiation of LLT within 3 months; and cox proportional hazards to evaluate Lp(a) levels and time to all-cause hospitalization and the composite of MI, revascularization and ischemic stroke hospitalization. Results: Overall, 20,551 patients (0.06% per year) had Lp(a) tests, with median Lp(a) value 17.5mg/dL (Q1, Q3: 7.0, 56.0). Compared with the LDL-C cohort (N=82,204), the Lp(a) cohort more frequently had ASCVD (24.3% vs. 8.5%) or multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of LLT initiation (Figure 1). Elevated Lp(a) was not significantly associated with all-cause hospitalization; however, Lp(a) > 100mg/dL was correlated with composite CV hospitalization compared with Lp(a) < 50mg/dL [adj HR (95% CI): 1.24 (1.06-1.44), p=0.006]. Conclusions: Lp(a) testing occurs more often in adults with ASCVD and multiple CV events, but testing is infrequent. Elevated Lp(a) was associated with LLT initiation, including niacin, despite lack of evidence of CV benefit. There was an association between elevated Lp(a) and CV hospitalization outcomes.