McAllister, David

Background: Effective lipid lowering therapy reduces deaths due to atherosclerotic vascular disease (ASCVD). Proprotein convertase subtilsin/kexin type 9 inhibitor (PCSK9i) drugs have emerged as effective add-on therapy to lower low-density lipoprotein (LDL) levels. Although the use of PCSK9i is limited by cost, PCSK9i use in a low-cost healthcare system [Veteran Health Affairs (VHA)] is unknown. Methods: We queried a cohort of US Veterans with coronary artery disease (CAD), PAD or CeVD receiving outpatient care (January 2016 – December 2019) at 124 VHA medical centers to evaluate the initiation of PCSK9i. We fit a mixed effects logistic regression model [with results presented as odds ratio (OR)] to evaluate the association of social deprivation (assessed by median household income and community deprivation index), the patient’s primary diagnosis and VHA medical center enrollment with PCSK9i initiation. Findings: From 519,566 patients (median age 74 years), 337,766 (65%), 79,926 (15%) and 101,874 (20%) had CAD, PAD and CeVD. Among 2,115/519,566 (0.4%) initiated with PCSK9i therapy, 84.3% had CAD, while only 7.2% and 8.5% had PAD and CeVD respectively. PCSK9i initiation was lower in those earning $40,000 - $80,000 [OR 1.13 (1.01 – 1.27)] or > $80,000 [OR 1.41 (1.14 – 1.75)]. Even moderate community deprivation [OR 0.87 (0.77 – 0.97)] was associated with lower PCSK9i therapy. Compared to CAD patients, PAD [OR 0.50 (0.35 – 0.70)] and CeVD [OR 0.23 (0.15 – 0.37)] were less likely to receive PCSK9i. Interpretation: Despite low co-pay, PCSK9i initiation rates among US veterans, nationwide, is very low. PAD and CeVD patients are much less likely to receive PCSK9i therapy. Household income and community deprivation influence PCSK9i use.

Abstract Rationale Cardiovascular disease is a common comorbidity in patients with chronic obstructive pulmonary disease. Although β-blockers can be used safely in patients with chronic obstructive pulmonary disease, concerns remain regarding safety and efficacy interactions in patients using concomitant inhaled long-acting β-agonists. Objectives To compare the differential effects of long-acting β-agonist or inhaled corticosteroid use on clinical outcomes in patients with heightened cardiovascular risk treated and not treated with β-blockers. Methods We examined data from 16,485 participants in the SUMMIT study (Study to Understand Mortality and Morbidity in COPD) who were randomized to once-daily inhaled fluticasone furoate, vilanterol, fluticasone furoate/vilanterol combination, or placebo and examined the associations between treatment allocation and lung function, chronic obstructive pulmonary disease exacerbations, cardiovascular events, and all-cause mortality, stratified by baseline β-blocker therapy. Results Baseline β-blocker therapy was used by 31% (n = 5,159) of SUMMIT participants. There was no evidence of an interaction between baseline β-blocker therapy and the association between inhaled treatments and forced expiratory volume in 1 second at 3 months (P = 0.27), 6 months (P = 0.14), or 12 months (P = 0.33). The placebo-adjusted mean differences in post-bronchodilator forced expiratory volume in 1 second at 3 months in the vilanterol-alone group were 58 ml (95% confidence interval, 38–78) in those receiving baseline β-blocker therapy and 51 ml (95% confidence interval, 38–65) in those not receiving baseline β-blocker therapy. The placebo-adjusted mean differences in post-bronchodilator forced expiratory volume in 1 second at 3 months in the combination fluticasone furoate/vilanterol group were 85 ml (95% confidence interval, 65–105) in those receiving baseline β-blocker therapy and 68 ml (95% confidence interval, 54–82) in those not receiving baseline β-blocker therapy. Overall, there was no evidence of interaction by randomized treatment, including vilanterol alone or in combination with fluticasone furoate, for chronic obstructive pulmonary disease exacerbations (P = 0.18), cardiovascular composite events (P = 0.33), and all-cause mortality (P = 0.41). Conclusions There is no evidence to suggest that baseline β-blocker therapy reduces the respiratory benefits or increases the cardiovascular risk of inhaled long-acting β-agonists in patients with chronic obstructive pulmonary disease and heightened cardiovascular risk. Clinical trial registered with www.clinicaltrials.gov (NCT01313676).