Original Article

Potential Drug-Drug Interactions in a Cardiac Center: Development of Simple Software for Pattern Identification


Background: Patients with cardiovascular disorders (CVD) are at higher risk for potential drug-drug interactions (pDDIs) due to complex treatment regimens. This study aimed to evaluate pDDI patterns in physicians’ prescriptions in a specialized heart center using simple software.

Methods: This cross-sectional study identified severe and related interactions during a 2-stage survey of experts. The data collected included age, sex, the date of admission and discharge, the length of hospital stay, drug names, inpatient wards, and the final diagnosis. The extracted drug interactions were used as a source of software knowledge. The software was designed using the SQL Server and the C # programming language.

Results: Of 24 875 patients included in the study, 14 695 (59.1%) were male. The average age was 62 years. Based on the survey of experts, only 57 pairs of severe pDDIs were identified. The designed software evaluated 185 516 prescriptions. The incidence of pDDIs was 10.5%. The average number of prescriptions per patient was 7.5. The highest frequency of pDDIs was detected in patients with diseases of the lymphatic system (15.0%). Aspirin with heparin (14.3%) and heparin with clopidogrel (11.7%) were the most common documented pDDIs.

Conclusion: This study reports the prevalence of pDDIs in a cardiac center. Patients with lymphatic system disorders, male patients, and older patients were at higher risk of pDDIs. This study shows that pDDIs are common among CVD patients and highlights the need to use computer software to screen patients’ prescriptions to assist in detection and prevention.

1. Diksis N, Melaku T, Assefa D, Tesfaye A. Potential drug-drug interactions and associated factors among hospitalized cardiac patients at Jimma University Medical Center, Southwest Ethiopia. SAGE Open Med 2019;7:2050312119857353.
2. Moura CS, Acurcio FA, Belo NO. Drug-drug interactions associated with length of stay and cost of hospitalization. J Pharm Pharm Sci 2009;12:266-272.
3. Monteith S, Glenn T. A comparison of potential psychiatric drug interactions from six drug interaction database programs. Psychiatry Res 2019;275:366-372.
4. Janchawee B, Wongpoowarak W, Owatranporn T, Chongsuvivatwong V. Pharmacoepidemiologic study of potential drug interactions in outpatients of a university hospital in Thailand. J Clin Pharm Ther 2005;30:13-20.
5. Krähenbühl-Melcher A, Schlienger R, Lampert M, Haschke M, Drewe J, Krähenbühl S. Drug-related problems in hospitals: a review of the recent literature. Drug Saf 2007;30:379-407.
6. Nabovati E, Vakili-Arki H, Taherzadeh Z, Hasibian MR, Abu-Hanna A, Eslami S. Drug-drug interactions in inpatient and outpatient settings in Iran: a systematic review of the literature. Daru 2014;22:52.
7. Sharma S, Chhetri HP, Alam K. A study of potential drug-drug interactions among hospitalized cardiac patients in a teaching hospital in Western Nepal. Indian J Pharmacol 2014;46:152-156.
8. Cruciol-Souza JM, Thomson JC. Prevalence of potential drug-drug interactions and its associated factors in a Brazilian teaching hospital. J Pharm Pharm Sci 2006;9:427-433.
9. Haji Aghajani M, Sistanizad M, Abbasinazari M, Abiar Ghamsari M, Ayazkhoo L, Safi O, Kazemi K, Kouchek M. Potential Drug-drug Interactions in Post-CCU of a Teaching Hospital. Iran J Pharm Res 2013;12:243-248.
10. Murtaza G, Khan MY, Azhar S, Khan SA, Khan TM. Assessment of potential drug-drug interactions and its associated factors in the hospitalized cardiac patients. Saudi Pharm J 2016;24:220-225.
11. Kovačević M, Vezmar Kovačević S, Radovanović S, Stevanović P, Miljković B. Adverse drug reactions caused by drug-drug interactions in cardiovascular disease patients: introduction of a simple prediction tool using electronic screening database items. Curr Med Res Opin 2019;35:1873-1883.
12. Kovačević M, Vezmar Kovačević S, Miljković B, Radovanović S, Stevanović P. The prevalence and preventability of potentially relevant drug-drug interactions in patients admitted for cardiovascular diseases: A cross-sectional study. Int J Clin Pract 2017;71:1-9.
13. Shakeel F, Khan JA, Aamir M, Hannan PA, Zehra S, Ullah I. Risk of potential drug-drug interactions in the cardiac intensive care units. A comparative analysis between 2 tertiary care hospitals. Saudi Med J 2018;39:1207-1212.
14. Reis AM, Cassiani SH. Prevalence of potential drug interactions in patients in an intensive care unit of a university hospital in Brazil. Clinics (Sao Paulo) 2011;66:9-15.
15. Sepehri G, Khazaelli P, Dahooie FA, Sepehri E, Dehghani MR. Prevalence of potential drug interactions in an Iranian general hospital. Indian J Pharm Sci 2012;74:75-79.
16. Akbar Z, Rehman S, Khan A, Khan A, Atif M, Ahmad N. Potential drug-drug interactions in patients with cardiovascular diseases: findings from a prospective observational study. J Pharm Policy Pract 2021;14:63.
17. Kruse CS, Goetz K. Summary and frequency of barriers to adoption of CPOE in the U.S. J Med Syst 2015;39:15.
18. Gandhi TK, Weingart SN, Seger AC, Borus J, Burdick E, Poon EG, Leape LL, Bates DW. Outpatient prescribing errors and the impact of computerized prescribing. J Gen Intern Med 2005;20:837-841.
19. Nabovati E, Vakili-Arki H, Taherzadeh Z, Saberi MR, Medlock S, Abu-Hanna A, Eslami S. Information Technology-Based Interventions to Improve Drug-Drug Interaction Outcomes: A Systematic Review on Features and Effects. J Med Syst 2017;41:12.
20. Paterno MD, Maviglia SM, Gorman PN, Seger DL, Yoshida E, Seger AC, Bates DW, Gandhi TK. Tiering drug-drug interaction alerts by severity increases compliance rates. J Am Med Inform Assoc 2009;16:40-46.
21. van der Sijs H, Aarts J, Vulto A, Berg M. Overriding of drug safety alerts in computerized physician order entry. J Am Med Inform Assoc 2006;13:138-147.
22. Teka F, Teklay G, Ayalew E, Teshome T. Potential drug-drug interactions among elderly patients admitted to medical ward of Ayder Referral Hospital, Northern Ethiopia: a cross sectional study. BMC Res Notes 2016;9:431.
23. Khan MZ, Sridhar SB, Gupta PK. Assessment of Potential Drug-Drug Interactions in Hospitalized Cardiac Patients of a Secondary Care Hospital in the United Arab Emirates. J Res Pharm Pract 2019;8:20-24.
24. Mousavi S, Ghanbari G. Potential drug-drug interactions among hospitalized patients in a developing country. Caspian J Intern Med 2017;8:282-288.
25. Ahmadizar F, Soleymani F, Abdollahi M. Study of drug-drug interactions in prescriptions of general practitioners and specialists in iran 2007-2009. Iran J Pharm Res 2011;10:921-931.
26. Smithburger PL, Kane-Gill SL, Benedict NJ, Falcione BA, Seybert AL. Grading the severity of drug-drug interactions in the intensive care unit: a comparison between clinician assessment and proprietary database severity rankings. Ann Pharmacother 2010;44:1718-1724.
27. Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag 2015;11:1061-1075.
28. Miano TA, Yang W, Shashaty MGS, Zuppa A, Brown JR, Hennessy S. The Magnitude of the Warfarin-Amiodarone Drug-Drug Interaction Varies With Renal Function: A Propensity-Matched Cohort Study. Clin Pharmacol Ther 2020;107:1446-1456.
29. Askari M, Eslami S, Louws M, Wierenga PC, Dongelmans DA, Kuiper RA, Abu-Hanna A. Frequency and nature of drug-drug interactions in the intensive care unit. Pharmacoepidemiol Drug Saf 2013;22:430-437.
30. Magro L, Conforti A, Del Zotti F, Leone R, Iorio ML, Meneghelli I, Massignani D, Visonà E, Moretti U. Identification of severe potential drug-drug interactions using an Italian general-practitioner database. Eur J Clin Pharmacol 2008;64:303-309.
31. Vonbach P, Dubied A, Krähenbühl S, Beer JH. Prevalence of drug-drug interactions at hospital entry and during hospital stay of patients in internal medicine. Eur J Intern Med 2008;19:413-420.
32. Aleksic DZ, Jankovic SM, Mlosavljevic MN, Toncev GL, Miletic Drakulic SD, Stefanovic SM. Potential Drug-drug Interactions in Acute Ischemic Stroke Patients at the Neurological Intensive Care Unit. Open Med (Wars) 2019;14:813-826.
33. Kellick KA, Bottorff M, Toth PP, The National Lipid Association's Safety Task Force. A clinician's guide to statin drug-drug interactions. J Clin Lipidol 2014;8(3 Suppl):S30-46.
34. Anderson JR, Nawarskas JJ. Cardiovascular drug-drug interactions. Cardiol Clin 2001;19:215-234, v.
35. Mendell J, Zahir H, Matsushima N, Noveck R, Lee F, Chen S, Zhang G, Shi M. Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor. Am J Cardiovasc Drugs 2013;13:331-342.
36. Becker RC, Corrao JM, Bovill EG, Gore JM, Baker SP, Miller ML, Lucas FV, Alpert JA. Intravenous nitroglycerin-induced heparin resistance: a qualitative antithrombin III abnormality. Am Heart J 1990;119:1254-1261.
37. Gomes T, Mamdani MM, Juurlink DN. Macrolide-induced digoxin toxicity: a population-based study. Clin Pharmacol Ther 2009;86:383-386.
38. Edrees H, Amato MG, Wong A, Seger DL, Bates DW. High-priority drug-drug interaction clinical decision support overrides in a newly implemented commercial computerized provider order-entry system: Override appropriateness and adverse drug events. J Am Med Inform Assoc 2020;27:893-900.
39. Assefa YA, Kedir A, Kahaliw W. Survey on Polypharmacy and Drug-Drug Interactions Among Elderly People with Cardiovascular Diseases at Yekatit 12 Hospital, Addis Ababa, Ethiopia. Integr Pharm Res Pract 2020;9:1-9.
40. Jain S, Jain P, Sharma K, Saraswat P. A Prospective Analysis of Drug Interactions in Patients of Intensive Cardiac Care Unit. J Clin Diagn Res 2017;11:FC01-FC04.
41. Rodgers JL, Jones J, Bolleddu SI, Vanthenapalli S, Rodgers LE, Shah K, Karia K, Panguluri SK. Cardiovascular Risks Associated with Gender and Aging. J Cardiovasc Dev Dis 2019;6:19.
42. Fettah H, Moutaouakkil Y, Sefrioui MR, Moukafih B, Bousliman Y, Bennana A, Lamsaouri J, Makram S, Cherrah Y. Detection and analysis of drug-drug interactions among hospitalized cardiac patients in the Mohammed V Military Teaching Hospital in Morocco. Pan Afr Med J 2018;29:225.
43. Patel VK, Acharya LD, Rajakannan T, Surulivelrajan M, Guddattu V, Padmakumar R. Potential drug interactions in patients admitted to cardiology wards of a south Indian teaching hospital. Australas Med J 2011;4:9-14.
44. Smithburger PL, Kane-Gill SL, Seybert AL. Drug-drug interactions in cardiac and cardiothoracic intensive care units: an analysis of patients in an academic medical centre in the US. Drug Saf 2010;33:879-888.
IssueVol 17 No 4 (2022): J Teh Univ Heart Ctr QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/jthc.v17i4.11610
Drug interactions Cardiovascular diseases Prevalence Adverse effects Software

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How to Cite
Rangraz Jeddi F, Nabovati E, Peykani F, Anvari S, Bagheri Toolaroud P. Potential Drug-Drug Interactions in a Cardiac Center: Development of Simple Software for Pattern Identification. J Tehran Heart Cent. 2022;17(4):215-222.