2 A hierarchal analysis of eligibility for PCSK9 inhibition in Ireland: bridging the divide between the NCPE managed access protocol and ESC/EAS guidelines

Introduction In 2019, the national center for pharmacoeconomics (NCPE) released a managed access protocol (MAP) for the prescribing of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in Ireland. To be eligible for a PCSK9i, patients must have had a myocardial infarction or coronary artery bypass grafting, LDL of >4.0 mmol/L, treated with high dose statin and ezetimibe. In contrast, the 2019 ESC/EAS guidelines on the management of dyslipidemias recommend that patients at ‘very high risk’ with an LDL-C of >1.4 mmol/L on a maximally tolerated dose of a statin and ezetimibe, be considered for PCSK9i. We aimed to define the proportion of patients who are suitable for a PCSK9i following completion of cardiac rehabilitation based on these criteria. Method We retrospectively analysed data on patients undergoing cardiac rehabilitation in our center from January 2018 to December 2019. We then applied the NCPE MAP and the ESC/EAS criteria to assess eligibility for a PCSK9i in the cohort. ‘Very high risk’ was defined as documented atherosclerotic coronary artery disease as per ESC dyslipidaemias guidelines. Results The analysis includes 299 patients, who had complete lipid profiles at baseline and 6 months of follow-up, and who have a history of coronary artery disease. Baseline characteristics, mean age 62.5 years, 76% male. 202 (67.6%) patients had a history of MI or CABG making them eligible for a PCSK9i based on NCPE clinical criteria. Only 1 patient (0.5%) in this group was on a high dose statin, ezetimibe and had a 6 month LDL-C of >4.0 mmol/L making them eligible for a PCSK9i as per NCPE MAP criteria. In contrast to the NCPE MAP criteria all 299 patients were deemed eligible for a PCSK9i based on ESC/EAS clinical criteria of ‘very high risk’. 160 patients (53.5%) had an LDL-C level >1.4 mmol/L at 6 months despite maximally tolerated statin therapy, mean LDL-C 2.29 mmol/L. Only a minority of patients in this cohort were on ezetimibe, 30/160 (18.7%), however previous studies have shown that on average ezetimibe reduces LDL-C by 25% in combination with statins. Based on this, we sought to define the cohort who would potentially be eligible if they had been on ezetimbe and experienced a 25% reduction in LDL-C. 81/160 patients had a 6-monthly LDL-C >1.8 mmol/L and were on high dose statin therapy, we included these patients in our final analysis, resulting in 37.1% (111/299) patients in our cohort being eligible for a PCSK9i based on current ESC guidelines, results are summarized in figure 1. Discussion Our results highlight the discrepancy between current ESC/EAS guidelines and the reimbursement criteria for PCSK9i in Ireland. This discrepancy results in minimal patients with coronary artery disease being eligible for a PCSK9i in Ireland. The results also highlight that a significant proportion of patients in clinical practice do not meet LDL-C goals post cardiac rehabilitation, these targets should be met in order to reduce future cardiovascular risk and improve outcomes for patients.