A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model.
adherence
adverse drug events
discontinuation
drug-drug interactions
multistate transition model
statins
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
revised:
26
03
2022
received:
03
11
2021
accepted:
09
04
2022
medline:
19
6
2023
pubmed:
4
5
2022
entrez:
3
5
2022
Statut:
ppublish
Résumé
The aim of this study was to describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. A retrospective new-user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012-2017). The statin DDI exposed and unexposed groups were matched (2:1) through propensity score matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs vs. those unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities. After concurrently starting stains and CYP3A, patients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4% [95% CI: 71.1, 71.6] vs. 73.3% [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4% [95% CI: 3.3, 3.5] vs. 3.2% [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0% [95% CI: 20.8, 21.3] vs. 19.5% [95% CI: 19.2, 19.8]). ADEs did not change these associations because those exposed to statin DDIs, vs. unexposed, were still less likely to discontinue statin therapy but more likely to discontinue CYP3A4-inhibitor therapy after experiencing an ADE. We did not observe any meaningful clinical differences in the probability of premature statin discontinuation between statin users exposed to statin DDIs and those unexposed.
Substances chimiques
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Cytochrome P-450 CYP3A Inhibitors
0
Cytochrome P-450 CYP3A
EC 1.14.14.1
CYP3A4 protein, human
EC 1.14.14.55
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2076-2087Informations de copyright
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
Kamal-Bahl SJ, Burke T, Watson D, Wentworth C. Discontinuation of lipid modifying drugs among commercially insured United States patients in recent clinical practice. Am J Cardiol. 2007;99(4):530-534. doi:10.1016/j.amjcard.2006.08.063
Vinogradova Y, Coupland C, Brindle P, Hippisley-Cox J. Discontinuation and restarting in patients on statin treatment: prospective open cohort study using a primary care database. BMJ. 2016;353:i3305. doi:10.1136/bmj.i3305
Lemstra M, Blackburn D, Crawley A, Fung R. Proportion and risk indicators of nonadherence to statin therapy: a meta-analysis. Can J Cardiol. 2012;28(5):574-580. doi:10.1016/j.cjca.2012.05.007
Geers HC, Bouvy ML, Heerdink ER. Estimates of statin discontinuation rates are influenced by exposure and outcome definitions. Ann Pharmacother. 2011;45(5):576-581. doi:10.1345/aph.1P607
Heeschen C, Hamm CW, Laufs U, Snapinn S, Böhm M, White HD. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation. 2002;105(12):1446-1452. doi:10.1161/01.CIR.0000012530.68333.C8
Wei L et al. Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart. 2002;88(3):229-233. doi:10.1136/heart.88.3.229
Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA. 2007;297(2):177-186. doi:10.1001/jama.297.2.177
Ho PM, Magid DJ, Shetterly SM, et al. Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease. Am Heart J. 2008;155(4):772-779. doi:10.1016/j.ahj.2007.12.011
Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med. 2013;158(7):526-534. doi:10.7326/0003-4819-158-7-201304020-00004
McGinnis B, Olson KL, Magid D, et al. Factors related to adherence to statin therapy. Ann Pharmacother. 2007;41(11):1805-1811. doi:10.1345/aph.1K209
Johnson ES, Bartman BA, Briesacher BA, et al. The incident user design in comparative effectiveness research. Pharmacoepidemiol Drug Saf. 2013;22(1):1-6. doi:10.1002/pds.3334
Csizmadi I, Collet J-P, Boivin J-F. Bias and confounding in pharmacoepidemiology. In: Strom BL, ed. Pharmacoepidemiology. New York: Wiley; 2006:791-809. doi:10.1002/9780470059876.ch47
Lund JL, Richardson DB, Sturmer T. The active comparator, new user study design in pharmacoepidemiology: historical foundations and contemporary application. Curr Epidemiol Rep. 2015;2(4):221-228. doi:10.1007/s40471-015-0053-5
Hachad H, Ragueneau-Majlessi I, Levy RH. A useful tool for drug interaction evaluation: the University of Washington Metabolism and Transport Drug Interaction Database. Hum Genomics. 2010;5(1):61-72. doi:10.1186/1479-7364-5-1-61
Daskalopoulou SS, Delaney JAC, Filion KB, Brophy JM, Mayo NE, Suissa S. Discontinuation of statin therapy following an acute myocardial infarction: a population-based study. Eur Heart J. 2008;29(17):2083-2091. doi:10.1093/eurheartj/ehn346
Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010;340(may19 4):c2197. doi:10.1136/bmj.c2197
Schulman KL, Lamerato LE, Dalal MR, et al. Development and validation of algorithms to identify statin intolerance in a US administrative database. Value Health. 2016;19(6):852-860. doi:10.1016/j.jval.2016.03.1858
Mann DM, Woodward M, Muntner P, Falzon L, Kronish I. Predictors of nonadherence to statins: a systematic review and meta-analysis. Ann Pharmacother. 2010;44(9):1410-1421. doi:10.1345/aph.1P150
Austin PC. Assessing balance in measured baseline covariates when using many-to-one matching on the propensity-score. Pharmacoepidemiol Drug Saf. 2008;17(12):1218-1225. doi:10.1002/pds.1674
de Wreede LC, Fiocco M, Putter H. An R package for the analysis of competing risks and multi-state models. J Stat Softw. 2011;38(7):1-30. doi:10.18637/jss.v038.i07
Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes. 2013;6(4):390-399. doi:10.1161/CIRCOUTCOMES.111.000071
Ofori-Asenso R, Ilomäki J, Tacey M, et al. Predictors of first-year nonadherence and discontinuation of statins among older adults: a retrospective cohort study. Br J Clin Pharmacol. 2019;85(1):227-235. doi:10.1111/bcp.13797
Bytyçi I, Penson PE, Mikhailidis DP, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022;ehac015. doi:10.1093/eurheartj/ehac015