Factors associated with clinically relevant drug-drug interactions with statins in outpatients with coronary artery disease
DOI: 10.15343/0104-7809.202044506514 Mundo
Keywords:
Drug Interactions. Use of Medicines. Statins. Coronary Artery Disease. Cardiovascular diseases.Abstract
The concomitant use of statins with other drugs is quite common and contributes to an increased risk of drug interactions
that may become manifested clinically as adverse drug reactions. The objective of the study was to determine the
factors associated with clinically relevant drug interactions with drug-drug statins in patients seen at the multiprofessional
cardiology outpatient clinic of a university hospital. This was a cross-sectional study conducted with 148 patients.
The dependent variable was whether or not there were clinically relevant drug interactions with statins according to
the Scientific Statement from the American Heart Association. A logistic regression was performed to analyze the
association of the occurrence of clinically relevant drug interactions with statins and independent variables. The median
number of drugs used was seven (IQR=3) and the number of cardiovascular drugs was five (IQR=2), where 91.2%
(n=135) had polypharmacy. The most prevalent diseases in the studied population were systemic arterial hypertension
and dyslipidemia. The median number of diseases was five. The prevalence of clinically relevant drug interactions with
statins was 43.2%. A positive association was identified between clinically relevant drug interactions with statins and the
number of diseases (OR=4.025; CI=1.895-8.553). All potential drug interactions with simvastatin found were of clinical
relevance. The most prevalent interactions were: amlodipine + simvastatin and warfarin + simvastatin. The identification
of factors associated with drug interactions allows directing measures to prevent adverse events in more exposed
populations, such as those with multiple comorbidities.
Downloads
References
Circulation. 2016. 133(4),422–33. doi: 10.1161/CIRCULATIONAHA.114.008727.
2. Celermajer DS, Chow CK, Marijon E, Anstey NM, Woo KS. Cardiovascular disease in the developing world. J Am Coll Cardiol. 2012.
60 (14), 1207e1216. doi: 10.1016/j.jacc.2012.03.074. Epub 2012 Aug 1.
3. Lu Y, Cheng Z, Zhao Y, Chang X, Chan C, Bai Y, et al. Efficacy and safety of long-term treatment with statins for coronary heart
disease: A Bayesian network meta-analysis. Atherosclerosis. 2016. 254, 215-227. doi: 10.1016/j.atherosclerosis.2016.10.025.
4. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL
cholesterol: A meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010. 376(9753), 1670–81. doi:10.1016/
S0140- 6736(10)61350-5
5. Malta DC, Szwarcwald CL. Population-based surveys and monitoring of noncommunicable diseases. Rev Saude Publ. 2017. 51,1S-
4S. doi: 10.1590/S1518-8787.201705100supl1ap 1
6. Wiggins BS, Saseen JJ, Page RL, Reed BN, Sneed K, Kostis JB, et al. Recommendations for Management of Clinically Significant
Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the
American Heart Association. Circulation. 2016.134(21), e468-e495. doi: 10.1161/CIR.0000000000000456
7. IBM Micromedex® Drug Interaction Checking (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. [acesso
em 10 mai 2019] Disponível em: https://www.micromedexsolutions.com/.
8. Nunes BP, Batista SRR, Andrade FB, Junior RBS, Lima-Costa MF, Facchini LA. Multimorbidade em indivíduos com 50 anos ou mais
de idade: ELSI-Brasil. Rev Saude Publ. 2018. 52 (2), 1-10s. doi: 10.11606/s1518-8787.2018052000637
9. Hoepers, ATC. Prevalência de multimorbidade na população de Florianópolis com idade igual ou superior a 40 anos: clusters e
networking das morbidades [tese]. Santa Catarina: Universidade Federal de Santa Catarina; 2015. 1-160.
10. Forman DE, Maurer MS, Boyd C, Brindis R, Salive ME, Horne FF, et al. Multimorbidity in older adults with cardiovascular disease. J
Am Coll Cardiol. 2018. 71, 2149–2161. doi: 10.1016/j.jacc.2018.03.022.
11. Schwartz J, Schmader K, Hanlon JT, Abernethy DR, Gray S, Dunbar-Jacob J, et al. Pharmacotherapy in Older Adults with
Cardiovascular Disease: Report from an American College of Cardiology, American Geriatrics Society, and National Institute on Aging
Workshop. J Am Geriatr Soc. 2019. 67(2), 371-380. doi: 10.1111/jgs.15634.
12. Cadogan CA, Ryan C, Hughes CM. Appropriate polypharmacy and medicine safety: when many is not too many. Drug safety. 2016.
39 (2), 109-116. doi: 10.1007/s40264-015-0378-5.
13. Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE, et al. Explaining the decrease in US deaths from coronary disease,
1980–2000. N Eng J of Med. 2007. 356(23), 2388-2398. doi: 10.1056/NEJMsa053935
14. Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug–drug interactions:population database analysis 1995–2010. BMC Med. 2015. 13 (1), 74. doi: 10.1186/s12916-015-0322-7
15. Thai M, Hilmer S, Pearson SA, Reeve E, Gnjidic D. Prevalence of potential and clinically relevant statin-drug interactions in frail and
robust older inpatients. 2015. 32(10), 849-856. doi: 10.1007/s40266-015-0302-9
16. Hanlon JT, Perera S, Newman AB, Thorpe JM, Donohue JM, Simonsick EM, et al. Potential Drug-Drug and Drug-Disease Interactions
in Well Functioning Community Dwelling Older Adults. J Clin Pharm Ther. 2017. 42(2), 228–233. doi: 10.1111/jcpt.12502.
17. Samardzic I, Benkovic I, Vrca VB. Incidence of statin-drug interactions in Croatian community pharmacy. Pharmazie. 2017.
72(3),187-191. doi: 10.1691/ph.2017.6855.
18. Nascimento RCRM, Junior AAG, Alvares J, Gomes IC, Godman B, Bennie M, et al. Statin use in Brazil: findings and implications.
Curr Med Res Opin. 2018. 34(10), 1809-1817. doi: 10.1080/03007995.2018.1451312
19. Brasil. Ministério da Saúde. Programa Aqui Tem Farmácia Popular. Disponível em: <http://www.saude.gov.br/acoes-e-programas/
farmacia popular/sobre-o-programa>. Acesso em: 07 nov. 2019.
20. Brasil. Ministério da Saúde. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Assistência Farmacêutica
e Insumos Estratégicos. Relação Nacional de Medicamentos Essenciais: RENAME 2018 [recurso eletrônico] / Ministério da Saúde,
Secretaria de Ciência, Tecnologia e Insumos Estratégicos, Departamento de Assistência Farmacêutica e Insumos Estratégicos. – Brasília:
Ministério da Saúde, 2018. 218 p.
21. Forman DE, Rich MW, Alexander KP, Zieman S, Maurer MS, Najjar SS, et al. Cardiac care for older adults. Time for a new paradigm.
J Am Coll Cardiol. 2011. 57, 1801–1810. doi:10.1016/j.jacc.2011.02.014.
22. Omboni S, Caserini M. Effectiveness of pharmacist’s intervention in the management of cardiovascular diseases. Open Heart. 2018.
5(1), e000687. doi:10.1136/openhrt-2017-000687
23. Gray SL, Hart LA, Perera S, Semla TP, Schmader KE, Hanlon JT. Meta-analysis of interventions to reduce adverse drug reactions. J
Am Geriatr Soc. 2017. 66, 282–288. doi: 10.1111/jgs.15195
24. Lea M, Rognan SE, Koristovic R, Wyller TB, Molden E. Severity and management of drug–drug interactions in acute geriatric
patients. Drugs Aging. 2013. 30(9), 721-727. doi: 10.1007/s40266-013-0091-y.
25. Marusic S, Bacic-Vrca V, Neto PRO, Franic M, Erdeljic V, Gojo-Tomic N. Actual drug–drug interactions in elderly patients discharged
from internal medicine clinic: a prospective observational study. Eur J Clin Pharmacol. 2013. 69(9), 1717-1724. doi: 10.1007/s00228-
013-1531-7
