Lipid Lowering Treatment and Eligibility for PCSK9 Inhibition in Post-Myocardial Infarction Patients in Italy: Insights from Two Contemporary Nationwide Registries

Abstract

Introduction. The current use of lipid lowering therapies and the eligibility for proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors of patients surviving a myocardial infarction (MI) is poorly known. Methods. Using the data from two contemporary, nationwide, prospective, real-world registries of patients with stable coronary artery disease, we sought to describe the lipid lowering therapies prescribed by cardiologists in patients with a prior MI and the resulting eligibility for PCSK9 inhibitors according to the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) and the Italian regulatory agency (Agenzia Italiana del Farmaco; AIFA) criteria. The study cohort was stratified according to the following low-density lipoprotein cholesterol (LDL-C) levels at the time of enrolment: <70 mg/dl; 70–99 mg/dl and ≥100 mg/dl. Results. Among the 3074 post-MI patients with LDL-C levels available, a target level of LDL-C < 70 mg/dl was present in 1186 (38.6%), while 1150 (37.4%) had LDL-C levels ranging from 70 to 99 mg/dl and the remaining 738 (24.0%) an LDL-C ≥ 100 mg/dl. A statin was prescribed more frequently in post-MI patients with LDL-C levels <70 mg/dl (97.1%) compared to the other LDL-C groups (p<0.0001). A low dose of statin was prescribed in 9.3%, while a high dose in 61.4% of patients. Statin plus ezetimibe association therapy was used in less than 18% of cases. In the overall cohort, 293 (9.8%) and 450 (22.2%) resulted eligible for PCSK9 inhibitors, according to ESC/EAS and AIFA criteria, respectively. Conclusions. Post-MI patients are undertreated with conventional lipid lowering therapies. A minority of post-MI patients would be eligible to PCSK9 inhibitors according to ESC/EAS guidelines and Italian regulatory agency criteria.

KLRD1, FOSL2 and LILRB3 as potential biomarkers for plaques progression in acute myocardial infarction and stable coronary artery disease

“…PPI network construction unravelled 9 seed genes using NTA. On the other hand, by reanalyzing GSE59867, the results demonstrated that immune system responses, especially innate immune response, were activated in STEMI patients compared to stable CAD patients, which may be due to the lipid accumulation and further deterioration of coronary vessel status [21][22][23]. The status can be partly reversed by β-blockers not calcium antagonists [24].…”

PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD)

“…Researchers have documents that PCSK9 inhibitors could be used for treating hypercholesterolemia conditions. 13,[61][62][63] Besides, loss-of-function mutations in the PCSK9 gene reduce LDL levels and safety in cardiovascular disease cases. 26,46,64 In addition to its effect on lipoprotein synthetic procedure and its pro atherosclerotic property, PCSK9 acts as a mediator in glucose metabolism, weight complications and so on.…”

Statins plus ezetimibe in the era of proprotein convertase subtilisin/ kexin type 9 inhibitors

“…53 Another analysis considered PCSK-9 eligibility according to the ESC / EAS and Agenzia Italiana del Farmaco (AIFA) regulatory agency criteria using data from 2 Italian, nationwide, prospective, real -world registries of patients with stable coronary artery disease. 54 Similar to the ACC, the AIFA criteria consider post -MI patients eligible for PCSK-9 inhibitor use if they show LDL -C levels higher than 100 mg/dl despite treatment with high -potency statins + ezetimibe, or ezetimibe alone in the presence of well -documented statin intolerance. Despite the ESC / EAS guideline recommendations to lower LDL -C levels in post -MI patients to a target level below 70 mg/dl using high -intensity statin therapy in combination with ezetimibe, if needed, the analysis revealed that numerous patients were undertreated with conventional lipid -lowering therapies.…”

“…Despite the ESC / EAS guideline recommendations to lower LDL -C levels in post -MI patients to a target level below 70 mg/dl using high -intensity statin therapy in combination with ezetimibe, if needed, the analysis revealed that numerous patients were undertreated with conventional lipid -lowering therapies. 54 A low -dose statin was prescribed in 9.3% of patients, and a high dose, in 61.4%; statin + ezetimibe therapy was used in less than 18% of cases. In the 3074 post--MI patients with LDL -C data available, a target level below 70 mg/dl was achieved in only 1186 patients (38.6%), and around a quarter (24%) presented a LDL -C level higher than or equal to 100 mg/dl.…”

“…In the overall post -MI cohort treated with statins and / or ezetimibe (2977 patients), 293 (9.8%) and 450 (22.2%) would have been eligible for PCSK-9 inhibitor use according to the ESC / EAS and AIFA criteria, respectively. 54 While the ESC / EAS recommendations are more conservative than those of the ACC or AIFA, there must be a balance between setting levels too high, which excludes a significant proportion of patients at very high -risk who would gain clinical benefit from PCSK-9 inhibitor use, and lower levels, which are not the prescribed treatment regimen. In this light, the real -life effectiveness of statin use is significantly compromised by poor adherence and compliance.…”