Background: The 2019 ESC dyslipidaemia guidelines recommend a more intense LDL-cholesterol (LDL-C) reduction for patients with coronary artery disease (CAD). This results in a significant increase in the projected need for PCSK9 inhibitors (PCSK9i) with a substantial impact on treatment cost. Adding the novel lipid lowering agent bempedoic acid (BA) to established oral lipid lowering therapy could provide an affordable alternative to PCSK9i to attain the LDL-C treatment target, particularly in patients with statin intolerance.

Aims: To quantify the target populations for BA and PCSK9i as well as the related treatment costs to achieve the LDL-C target of the 2019 ESC dyslipidaemia guidelines assuming addition of BA to lipid lowering medication.

Methods: We included patients with angiographically documented CAD from the INTERCATH study, an observational cohort study ongoing since 2015. A Monte Carlo simulation incorporating an algorithm for intensification of lipid lowering medication was applied in order to achieve the LDL-C treatment goal of <55 mg/dL and a ≥50% reduction from baseline LDL-C. The algorithm added sequentially a statin, ezetimibe, optionally BA, and a PCSK9i, and considered both partial and total statin intolerance. Two scenarios of treatment intensification were simulated for both a moderate (2% full and 10% partial) and a high rate of statin intolerance (12% full): 1. without BA and 2. with BA. Treatment costs and preventable events were calculated for each scenario and the following annual medication cost in Germany: 6049€ evolocumab, 1551€ bempedoic acid.

Results: We included 1922 patients (mean age 69.3 years, median baseline LDL-C 86.0 mg/dL). The need for PCSK9i in scenario 1 would be 41.4% for a moderate and 46.1% for a high rate of statin intolerance. Addition of BA in scenario 2 would reduce the need for PCSK9i to 25.3% and 29.4% (Figure 1). Use of BA would lower the annual overall treatment cost incurred through use of PCSK9i ± BA per 1,000,000 CAD patients by 13.3% and 10.5%. The cost per prevented event in the entire cohort would be lower (-5.0 and -6.3%), however at the price of less prevented cardiovascular events (-8.7% and -4.5%). Amongst patients with full statin intolerance, the cost per prevented event would be reduced (-6.8% for both rates of statin intolerance) whilst more cardiovascular events would be prevented (+7.5% and +6.9%).

Conclusion: Use of BA in patients with CAD is projected to reduce the need for PCSK9i as well as the overall treatment cost for add-on lipid lowering therapy. The subpopulation of patients with full statin intolerance is set to profit particularly.

Figure 1: LDL-C distributions and lipid lowering medications

Upper: at baseline, Middle: after uptitration of LLM without BA (scenario 1), Lower: after uptitration of LLM with BA (scenario 2). Results for a moderate rate of statin intolerance (2% full, 10% partial) shown. For the baseline medication, difference to 100% is due to patients not taking LLM. LLM = lipid lowering medication, MIS/HIS = moderate/high-intensity statin, EZE = ezetimibe, BA = bempedoic acid, PCSK9i = PCSK9 inhibitor