Impact of Pharmacotherapy Adherence on the Reduction of Major Adverse Cardiovascular Events (MACE) Among Atherosclerotic Cardiovascular Disease (ASCVD) Patients
Author(s)
Abheet Sharma, MPH1, Gautam Partha, M.S.1, Clodagh Foley, MPH2, Matthias Bischof, PhD3.
1Novartis Healthcare Pvt. Ltd., Hyderabad, India, 2Novartis Ireland Ltd., Dublin, Ireland, 3Novartis Pharma AG, Basel, Switzerland.
1Novartis Healthcare Pvt. Ltd., Hyderabad, India, 2Novartis Ireland Ltd., Dublin, Ireland, 3Novartis Pharma AG, Basel, Switzerland.
OBJECTIVES: Pharmacotherapy adherence is a critical determinant of clinical outcomes. Real-world suboptimal adherence may reduce treatment effectiveness versus clinical trials. Inclisiran and PCSK9 inhibitors (PCSK9is) are recommended for ASCVD patients with poor lipid control on maximum tolerated statins. This study evaluates the impact of real-world adherence on the prevention of MACE events among ASCVD patients.
METHODS: Adherence was stratified into three categories based on proportion of days covered (PDC): high (≥80%), intermediate (50-79%), and low (≤50%). PDC category patient proportions for inclisiran and PCSK9is were estimated using 2022-2023 U.S. Komodo Health data. LDL-C reduction per adherence category was inferred from Vupputuri S. et al. (2016), which analyzed statin adherence. Adherence-adjusted LDL-C reductions were derived by applying the PDC-based adherence proportions to the LDL-C reduction estimates from Vupputuri et al. (2016), and by adjusting the effect sizes reported in the network meta-analysis (60.01% for inclisiran, 58.08% for alirocumab, and 62.01% for evolocumab) in proportion to adherence levels. A payer-perspective cost-effectiveness model was used to estimate lifetime MACE incidence in 100,000 patients on inclisiran or PCSK9is in England and Wales.
RESULTS: Inclisiran adherence was high in 79%, intermediate in 11.9%, and low in 9.1% of patients; for PCSK9is, proportions were 56.0%, 16.9%, and 27.1%, respectively. Adherence-adjusted LDL-C reductions were 54.9% (inclisiran), 45.9% (alirocumab), and 48.9% (evolocumab). Lifetime MACE events were estimated to be 112,892, 117,409, and 115,898, respectively. Inclisiran prevented 4,517 additional MACE events over alirocumab and 3,006 over evolocumab.
CONCLUSIONS: When adjusting clinical trial data to adherence levels, the LDL-C lowering potential of inclisiran and PCSK9is changes. As more patients are adherent to inclisiran compared to PCSK9is, inclisiran has a higher adherence-adjusted LDL-C lowering effect, resulting in fewer events in inclisiran treated patients. This analysis highlights the substantial impact of real-world adherence on clinical outcomes in ASCVD patients treated with lipid-lowering therapies.
METHODS: Adherence was stratified into three categories based on proportion of days covered (PDC): high (≥80%), intermediate (50-79%), and low (≤50%). PDC category patient proportions for inclisiran and PCSK9is were estimated using 2022-2023 U.S. Komodo Health data. LDL-C reduction per adherence category was inferred from Vupputuri S. et al. (2016), which analyzed statin adherence. Adherence-adjusted LDL-C reductions were derived by applying the PDC-based adherence proportions to the LDL-C reduction estimates from Vupputuri et al. (2016), and by adjusting the effect sizes reported in the network meta-analysis (60.01% for inclisiran, 58.08% for alirocumab, and 62.01% for evolocumab) in proportion to adherence levels. A payer-perspective cost-effectiveness model was used to estimate lifetime MACE incidence in 100,000 patients on inclisiran or PCSK9is in England and Wales.
RESULTS: Inclisiran adherence was high in 79%, intermediate in 11.9%, and low in 9.1% of patients; for PCSK9is, proportions were 56.0%, 16.9%, and 27.1%, respectively. Adherence-adjusted LDL-C reductions were 54.9% (inclisiran), 45.9% (alirocumab), and 48.9% (evolocumab). Lifetime MACE events were estimated to be 112,892, 117,409, and 115,898, respectively. Inclisiran prevented 4,517 additional MACE events over alirocumab and 3,006 over evolocumab.
CONCLUSIONS: When adjusting clinical trial data to adherence levels, the LDL-C lowering potential of inclisiran and PCSK9is changes. As more patients are adherent to inclisiran compared to PCSK9is, inclisiran has a higher adherence-adjusted LDL-C lowering effect, resulting in fewer events in inclisiran treated patients. This analysis highlights the substantial impact of real-world adherence on clinical outcomes in ASCVD patients treated with lipid-lowering therapies.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO140
Topic
Clinical Outcomes, Patient-Centered Research
Topic Subcategory
Clinical Outcomes Assessment
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory), No Additional Disease & Conditions/Specialized Treatment Areas