Application of PCSK9 Inhibitors in Practice

Abstract

Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) are set to revolutionize the treatment of hypercholesterolemia in the management of atherosclerotic risk, but numerous reports have detailed unprecedented barriers to access for these drugs. To overcome these challenges, our group created a model to facilitate provision of this new therapy for patients who qualify according to FDA criteria. This report details the real-world follow-up experience of PCSK9i use in a large patient cohort structured to ensure rigor in data collection, analysis, and interpretation. The 271 patients approved and actively followed in our PCSK9i clinic between July 2015 and August 2018 represent a 97% approval rate from insurance, with 28% of prescriptions requiring at least one appeal. Over 50% of patients were statin intolerant. On average, there was a median lapse of 15 days between initial visit and insurance approval. PCSK9i therapy was affordable for most patients, with an average monthly out-of-pocket expense of $58.05 (median $0). Only 2.3% of patients were unable to initiate or continue therapy due to cost. Reductions from baseline in LDL cholesterol and Lp(a) were comparable to published reports with median reductions of 60% and 23% at one year, respectively. PCSK9i therapy was well tolerated overall, though 9% of patients reported adverse events, and 5% of patients discontinued due mostly to musculoskeletal and flu-like symptoms. Our practice model demonstrates that PCSK9i therapy can be accessed easily and affordably for the majority of eligible patients, resulting in dramatic improvement in lipid profile results. Moreover, our registry data suggest that results from the prospective clinical trials of PCSK9i on LDL and Lp(a) reduction and on tolerability are applicable to a real-world cohort.

Cardiovascular events, diabetes and guidelines: the virtue of simplicity

“…The most common adverse events include myalgia, myositis with increased creatine phosphokinase (CPK), and rhabdomyolysis in very few cases. Myalgias are not considered significant as long as they do not increase CPK or cause myositis or rabdomyolysis [44]. If the striated muscle hurts it is because it is affected, but how it is affected is still unknown.…”

Efficacy and safety of alirocumab in statin-intolerant patients over 3 years: open-label treatment period of the ODYSSEY ALTERNATIVE trial

“…[1][2][3][4] Recently published real-world studies indicate that 42.9-67.0% of patients are statin intolerant before receiving PCSK9 inhibitor monoclonal antibody therapy, thereby emphasizing statin intolerance as an important realworld therapeutic challenge. [5][6][7][8] In the 24-week, randomized, double-blind ODYSSEY ALTERNATIVE study (NCT01709513), the PCSK9 inhibitor alirocumab 75 mg administered every 2 weeks (Q2W; with possible dose adjustment to 150 mg Q2W) reduced low-density lipoprotein cholesterol (LDL-C) by 45.0% vs 14.6% with ezetimibe in patients with primary hypercholesterolemia who were intolerant to statins, defined as the inability to tolerate $2 statins, including 1 at the lowest-approved starting dose, due to muscle symptoms. 9 All patients who had successfully completed the double-blind treatment period (DBTP) were eligible to enter an optional open-label treatment period (OLTP).…”

Ineffective Subtilisin/Kexin Type 9 (PCSK9) Inhibitors Monotherapy in Dyslipidemia with Low-Density Lipoprotein Cholesterol (LDL-C) Receptor Abnormalities: A Report of 2 Cases

“…The ODYSSEY trial showed that PCSK9 inhibitors are effective either when used alone or in combination with other lipid-lowering agents, while the FOURIER trial showed that PCSK9 inhibitors were effective on a background of statin therapy [ 3 , 5 ]. A 30 mg/dL drop in LDL-C, or a 59% reduction from LDL-C baseline, was revealed by the FOURIER trial when PCSK9 inhibitors were added to statin therapy [ 6 ]. A common indication for monotherapy with PCSK9 inhibitors is statin intolerance.…”