Predictors of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibitor Prescriptions for Secondary Prevention of Clinical Atherosclerotic Cardiovascular Disease

Abstract

Background: Little is known about patterns of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitor) use among patients with established clinical atherosclerotic cardiovascular disease. This study’s objective was to describe PCSK9i prescribing patterns among patients with atherosclerotic cardiovascular disease. Methods: We used a national outpatient clinic registry linked to zip-code level on household income from the US Census to assess characteristics of patients with atherosclerotic cardiovascular disease and LDL-C (low-density lipoprotein cholesterol) <190 mg/dL between September 1, 2015, and September 30, 2019, who did and did not receive PCSK9i prescriptions and practice-level and temporal variation in PCSK9i prescriptions. We assessed predictors of PCSK9i prescription with a multivariable mixed effects regression model which included patient covariates as fixed effects and the cardiology practice as a random effect. Adjusted practice-level variation in PCSK9i prescribing was evaluated with median odds ratio (OR). Results: Of 2 148 100 patients meeting study inclusion criteria, 27 249 (1.3%) received PCSK9i prescriptions. Receiving a PCSK9i prescription was associated with White race (versus non-White: OR, 1.78 [95% CI, 1.55–1.83]); high estimated household income (versus low income: OR, 1.18 [95% CI, 1.08–1.29]), and urban or suburban (versus rural) practice location (urban: OR, 1.47 [95% CI, 1.32–1.64]; suburban: OR, 1.25 [95% CI, 1.13–1.39]). Hispanics had lower odds of receiving PCSK9i prescriptions (OR, 0.66 [95% CI, 0.57–0.76]). The adjusted median odds ratio was 2.68 (95% CI, 2.46–2.94), consistent with clinically significant practice-level variation in PCSK9i prescriptions. No differences in quarterly PCSK9i prescription rates were observed before and after price reductions for evolocumab and alirocumab initiated during the fourth quarter of 2018 and first quarter of 2019, respectively. Conclusions: This study highlights racial, socioeconomic, geographic, and practice-level variations in early PCSK9i prescriptions which persist despite adjustment for clinical and demographic factors. After adjustment, 2 randomly selected practices would differ in likelihood of PCSK9i prescription by a factor of >2.

PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021

“…50%), TG (15–20%), and Lp(a) (ca. 25%), as well as increasing HDL-C (5–10%) and apoA1 (3–5%) [ 173 , 175 ]. Available studies indicate that PCSK9 inhibitors used in monotherapy may reduce LDL-C by 60% an average and used in combination with statins and ezetimibe by up to 85% [ 8 , 9 ].…”

“…These agents (alirocumab and evolocumab) have been approved by both the US FDA and the European Medicine Agency (EMA) in the following indications: for use in adults with primary hypercholesterolaemia (familial heterozygous and non-familial) or mixed dyslipidaemia in addition to diet: (1) in combination with a statin or a statin and other lipid-lowering agents in patients, in whom the target LDL-C concentration cannot be achieved with the highest tolerated dose of a statin, or (2) alone or in combination with other lipid-lowering agents in statin-intolerant patients or those in whom statins are contraindicated. As evolocumab has been studied in patients with homozygous familial hypercholesterolaemia (the TAUSSIG and TESLA studies), it should also be considered in combination with other lipid-lowering agents in adults and adolescents aged at least 12 years with homozygous FH [ 175 ].…”

wind of change – PCSK9 inhibitors in hypolipidemic treatment. The Polish perspective

“…25%) levels, as well as, increasing the HDL-C (5-10%) and apoA1 (3-5%) levels. 9,13,14 The available research shows that PCSK9 inhibitors used in monotherapy can lower the LDL-C levels by 60% on average, and by up to 85% in polytherapy with statins and ezetimibe. 9 Evolocumab and alirocumab were approved for use by the FDA and European Medicine Agency (EMA) in the following cases: 1) in adults with primary hypercholesterolaemia (heterozygous familial and non-familial);…”

“…143 Evolocumab -according to the TAUSSIG and TESLA studies, it should be considered in combintion with other hypolipemising drugs in patients of more than 12 years of age with the homozygous FH. 9,14 The FOURIER 15 (evolocumab) and ODYSSEY OUTCOMES 16 (alirocumab) studies proved the great effectiveness of both PCSK9 inhibitors in the context of reducing the main endpoint (cardiovascular events) by 15%, and showed that alirocumab can additionally significantly reduce the number of deaths regardless of the cause (also by 15%). 9 Sub-analyses in subgroups of patients who suffered a myocardial infarction with stroke; several cardiovascular events; an epidemiologically recent myocardial infarction; a myocardial infarction with concomitant peripheral vascular disease or multifocal atherosclerosis; a myocardial infarction with other risk factors, namely diabetes, elevated hsCRP, Lp(a ), or with different baseline LDL-C levels, or finally in patients with a long follow-up period (> 3 years), not only showed significant effectiveness of PCSK9 inhibitors 16 , but also were a starting point for identifying patients at extreme cardiovascular risk and creating a reimbursement program that has been available in Poland for the patients with FH since the 1st of November 2018, and, subsequently, since the 1st of November 2020 for those who suffered a myocardial infarction.…”

Management of Dyslipidemia in Secondary Prevention of Cardiovascular Disease: The Gap between Theory and Practice

“…Thus, the effects of statin combined with PCSK9i might be attributed to the stabilization and regression of residual vulnerable coronary plaques in patients with CAD [ 17 ]. Based on the current recommended guidelines, PCSK9i administration is likely to be considered for patients with a very high CAD risk, so its administration may contribute to secondary prevention in patients with non-culprit segment plaques regardless of plaque vulnerability [ 18 , 19 ]. Even after combining statins, ezetimibe and PCSK9i, some patient subgroups fail to achieve LDL-C targets requiring alternative treatments.…”