TY - JOUR
T1 - Estimating potential cardiovascular health benefits of improved population level control of LDL cholesterol through a twice-yearly siRNA-based approach
T2 - A simulation study of a health-system level intervention
AU - the ORION investigators
AU - Ray, Kausik K.
AU - Gunn, Laura H.
AU - Conde, Lorena Garcia
AU - Raal, Frederick J.
AU - Wright, R. Scott
AU - Gosselin, Nathalie H.
AU - Leiter, Lawrence A.
AU - Koenig, Wolfgang
AU - Schwartz, Gregory G.
AU - Landmesser, Ulf
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/4
Y1 - 2024/4
N2 - Background and aims: Inclisiran, an siRNA therapy, consistently reduces low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing. Potential cardiovascular benefits of implementing inclisiran at a population level, added to statins, were evaluated through simulation. Methods: For each participant in the ORION-10 and ORION-11 trials comparing inclisiran with placebo, baseline 10-year cardiovascular risk was estimated using the SMART equation. The time-adjusted LDL-C difference from baseline observed 90–540 days after baseline was assumed to persist and used to estimate potential reduction in 10-year cardiovascular risk. Impact on 500,000 ORION-like individuals was simulated with Monte-Carlo. Results: Mean baseline LDL-C and predicted 10-year major vascular risk among patients randomized to inclisiran (n = 1288) versus placebo (n = 1264) were 2.66 mmol/L versus 2.60 mmol/L and 24.9% versus 24.6%, respectively. Placebo-corrected time-adjusted absolute reduction in LDL-C with inclisiran was −1.32 mmol/L (95% CI −1.37 to −1.26; p < 0.001), which predicted a 10-year cardiovascular risk of 18.1% with inclisiran versus 24.7% with placebo (absolute difference [95% CI], −6.99% [−7.33 to −6.66]; p < 0.001) NNT 15. Extrapolating to 500,000 inclisiran-treated individuals, the model predicted large population shifts towards lower quintiles of risk with fewer remaining in high-risk categories; 3350 to 471 (≥80% risk), 11,793 to 3332 (60–<80% risk), 52,142 to 22,665 (40–<60% risk), 197,752 to 141,014 (20–<40% risk), and more moving into the lowest risk category (<20%) from 234,963 to 332,518. Conclusions: Meaningful gains in population health might be achieved over 10 years by implementing at-scale approaches capable of providing substantial and sustained reductions in LDL-C beyond those achievable with statins.
AB - Background and aims: Inclisiran, an siRNA therapy, consistently reduces low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing. Potential cardiovascular benefits of implementing inclisiran at a population level, added to statins, were evaluated through simulation. Methods: For each participant in the ORION-10 and ORION-11 trials comparing inclisiran with placebo, baseline 10-year cardiovascular risk was estimated using the SMART equation. The time-adjusted LDL-C difference from baseline observed 90–540 days after baseline was assumed to persist and used to estimate potential reduction in 10-year cardiovascular risk. Impact on 500,000 ORION-like individuals was simulated with Monte-Carlo. Results: Mean baseline LDL-C and predicted 10-year major vascular risk among patients randomized to inclisiran (n = 1288) versus placebo (n = 1264) were 2.66 mmol/L versus 2.60 mmol/L and 24.9% versus 24.6%, respectively. Placebo-corrected time-adjusted absolute reduction in LDL-C with inclisiran was −1.32 mmol/L (95% CI −1.37 to −1.26; p < 0.001), which predicted a 10-year cardiovascular risk of 18.1% with inclisiran versus 24.7% with placebo (absolute difference [95% CI], −6.99% [−7.33 to −6.66]; p < 0.001) NNT 15. Extrapolating to 500,000 inclisiran-treated individuals, the model predicted large population shifts towards lower quintiles of risk with fewer remaining in high-risk categories; 3350 to 471 (≥80% risk), 11,793 to 3332 (60–<80% risk), 52,142 to 22,665 (40–<60% risk), 197,752 to 141,014 (20–<40% risk), and more moving into the lowest risk category (<20%) from 234,963 to 332,518. Conclusions: Meaningful gains in population health might be achieved over 10 years by implementing at-scale approaches capable of providing substantial and sustained reductions in LDL-C beyond those achievable with statins.
KW - 10-Year cardiovascular risk
KW - Atherosclerotic cardiovascular disease
KW - Inclisiran
KW - Low-density lipoprotein
KW - Population health
KW - SMART equation
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U2 - 10.1016/j.atherosclerosis.2024.117472
DO - 10.1016/j.atherosclerosis.2024.117472
M3 - Article
C2 - 38447434
AN - SCOPUS:85186663914
SN - 0021-9150
VL - 391
JO - Atherosclerosis
JF - Atherosclerosis
M1 - 117472
ER -