TY - JOUR
T1 - Time-dependent cardiovascular treatment benefit model for lipid-lowering therapies
AU - Khan, Irfan
AU - Peterson, Eric D.
AU - Cannon, Christopher P.
AU - Sedita, Lauren E.
AU - Edelberg, Jay M.
AU - Ray, Kausik K.
N1 - Funding Information:
This study was funded by Sanofi and Regeneron Pharmaceuticals Inc.
Funding Information:
Irfan Khan is an employee and stockholder of Sanofi. Eric D. Peterson reports grant support from the American College of Cardiology, the American Heart Association, and Janssen; and consulting with Bayer, Boehringer Ingelheim, Merck, Valeant, Sanofi, AstraZeneca, Janssen, Regeneron, and Genentech. Christopher P. Cannon has received research grants from Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Merck, and Pfizer; and consultant fees from Aegerion, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, Boehringer Ingelheim, Bristol-Myers Squibb, Corvidia, Eli Lilly, HLS Therapeutics, Innovent, Janssen, Kowa, Merck, Pfizer, Rhoshan, and Sanofi. Jay M. Edelberg was an employee of Sanofi during the initial creation of the manuscript and has stayed on as an author while an employee of MyoKardia. Kausik K. Ray has received personal fees (data safety monitoring board) from AbbVie, Inc.; consultant fees/honoraria from Aegerion, Algorithm, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Eli Lilly and Company, Ionis Pharmaceuticals, Kowa, Medicines Company, MSD, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Resverlogix, Sanofi, and Takeda; and research grants from Amgen, Daiichi Sankyo, Kowa, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi. Lauren E. Sedita has no disclosures to report.
Funding Information:
Prashant Sinha, BE, Axtria, supported the development of the model. Kausik K. Ray acknowledges support from the National Institute of Health Research Imperial Biomedical Research Centre.
Publisher Copyright:
© 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2020/8/4
Y1 - 2020/8/4
N2 - BACKGROUND: With the availability of new lipid-lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time-dependent model from published randomized controlled trials summarizing the relationship between low-density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios over time. METHODS AND RESULTS: A cardiovascular treatment benefit model was specified with parameters as time since treatment initiation, magnitude of low-density lipoprotein cholesterol reduction, and additional patient characteristics. The model was estimated from randomized controlled trial data from 22 trials for statins and nonstatins. In 15 trials, the new time-dependent model had better predictions than cholesterol treatment trialists’ estimations for a composite of coronary heart disease death, nonfatal myocardial infarction, and ischemic stroke. In explored scenarios, absolute risk reduction ≥2% with intensive treatment with high-intensity statin, ezetimibe, and high-dose proprotein convertase subtilisin/kexin type 9 inhibitor compared with high-or moderate-intensity statin alone were achieved in higher-risk populations with 2 to 5 years of treatment, and lower-risk populations with 9 to 11 years of treatment. CONCLUSIONS: The time-dependent model accurately predicted treatment benefit seen from randomized controlled trials with a given lipid-lowering therapy by incorporating patient profile, timing, duration, and treatment type. The model can facilitate decision making and scenario analyses with a given lipid-lowering therapy strategy in various patient populations and time frames by providing an improved assessment of treatment benefit over time.
AB - BACKGROUND: With the availability of new lipid-lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time-dependent model from published randomized controlled trials summarizing the relationship between low-density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios over time. METHODS AND RESULTS: A cardiovascular treatment benefit model was specified with parameters as time since treatment initiation, magnitude of low-density lipoprotein cholesterol reduction, and additional patient characteristics. The model was estimated from randomized controlled trial data from 22 trials for statins and nonstatins. In 15 trials, the new time-dependent model had better predictions than cholesterol treatment trialists’ estimations for a composite of coronary heart disease death, nonfatal myocardial infarction, and ischemic stroke. In explored scenarios, absolute risk reduction ≥2% with intensive treatment with high-intensity statin, ezetimibe, and high-dose proprotein convertase subtilisin/kexin type 9 inhibitor compared with high-or moderate-intensity statin alone were achieved in higher-risk populations with 2 to 5 years of treatment, and lower-risk populations with 9 to 11 years of treatment. CONCLUSIONS: The time-dependent model accurately predicted treatment benefit seen from randomized controlled trials with a given lipid-lowering therapy by incorporating patient profile, timing, duration, and treatment type. The model can facilitate decision making and scenario analyses with a given lipid-lowering therapy strategy in various patient populations and time frames by providing an improved assessment of treatment benefit over time.
KW - Atherosclerotic cardiovascular disease
KW - Ezetimibe
KW - Low-density lipoprotein cholesterol
KW - PCSK9 inhibitor
KW - Statin
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U2 - 10.1161/JAHA.120.016506
DO - 10.1161/JAHA.120.016506
M3 - Article
C2 - 32720582
AN - SCOPUS:85089162434
VL - 9
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 15
M1 - e016506
ER -