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Systematic assessment of prescribed medications and short-term risk of myocardial infarction - a pharmacopeia-wide association study from Norway and Sweden.
Sci Rep 2019; 9(1):8257SR

Abstract

Wholesale, unbiased assessment of Scandinavian electronic health-care databases offer a unique opportunity to reveal potentially important undiscovered drug side effects. We examined the short-term risk of acute myocardial infarction (AMI) associated with drugs prescribed in Norway or Sweden. We identified 24,584 and 97,068 AMI patients via the patient- and the cause-of-death registers and linked to prescription databases in Norway (2004-2014) and Sweden (2005-2014), respectively. A case-crossover design was used to compare the drugs dispensed 1-7 days before the date of AMI diagnosis with 15-21 days' time -window for all the drug individually while controlling the receipt of other drugs. A BOLASSO approach was used to select drugs that acutely either increase or decrease the apparent risk of AMI. We found 48 drugs to be associated with AMI in both countries. Some antithrombotics, antibiotics, opioid analgesics, adrenergics, proton-pump inhibitors, nitroglycerin, diazepam, metoclopramide, acetylcysteine were associated with higher risk for AMI; whereas angiotensin-II-antagonists, calcium-channel blockers, angiotensin-converting-enzyme inhibitors, serotonin-specific reuptake inhibitors, allopurinol, mometasone, metformin, simvastatin, levothyroxine were inversely associated. The results were generally robust in different sensitivity analyses. This study confirms previous findings for certain drugs. Based on the known effects or indications, some other associations could be anticipated. However, inverse associations of hydroxocobalamin, levothyroxine and mometasone were unexpected and needs further investigation. This pharmacopeia-wide association study demonstrates the feasibility of a systematic, unbiased approach to pharmacological triggers of AMI and other diseases with acute, identifiable onsets.

Authors+Show Affiliations

Department of Public health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway. abhijit.sen@ntnu.no. Center for Oral Health Services and Research (TkMidt), Trondheim, Norway. abhijit.sen@ntnu.no.Department of Mathematical Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway.Department of Mathematical Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway.Department of Thoracic Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, 7491, Trondheim, Norway. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.Department of Public health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway.Centre for Fertility and Health (CeFH), Norwegian Institute of Public Health, Oslo, Norway.Department of Public health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway.Department of Public health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway.Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE 171 77, Solna, Stockholm, Sweden.Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States.Department of Public health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway. Regional Center for Health Care Improvement, St Olav's Hospital, Trondheim, Norway.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31164670

Citation

Sen, Abhijit, et al. "Systematic Assessment of Prescribed Medications and Short-term Risk of Myocardial Infarction - a Pharmacopeia-wide Association Study From Norway and Sweden." Scientific Reports, vol. 9, no. 1, 2019, p. 8257.
Sen A, Vardaxis I, Lindqvist BH, et al. Systematic assessment of prescribed medications and short-term risk of myocardial infarction - a pharmacopeia-wide association study from Norway and Sweden. Sci Rep. 2019;9(1):8257.
Sen, A., Vardaxis, I., Lindqvist, B. H., Brumpton, B. M., Strand, L. B., Bakken, I. J., ... Janszky, I. (2019). Systematic assessment of prescribed medications and short-term risk of myocardial infarction - a pharmacopeia-wide association study from Norway and Sweden. Scientific Reports, 9(1), p. 8257. doi:10.1038/s41598-019-44641-1.
Sen A, et al. Systematic Assessment of Prescribed Medications and Short-term Risk of Myocardial Infarction - a Pharmacopeia-wide Association Study From Norway and Sweden. Sci Rep. 2019 Jun 4;9(1):8257. PubMed PMID: 31164670.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systematic assessment of prescribed medications and short-term risk of myocardial infarction - a pharmacopeia-wide association study from Norway and Sweden. AU - Sen,Abhijit, AU - Vardaxis,Ioannis, AU - Lindqvist,Bo Henry, AU - Brumpton,Ben Michael, AU - Strand,Linn Beate, AU - Bakken,Inger Johanne, AU - Vatten,Lars Johan, AU - Romundstad,Pål Richard, AU - Ljung,Rickard, AU - Mukamal,Kenneth Jay, AU - Janszky,Imre, Y1 - 2019/06/04/ PY - 2018/11/29/received PY - 2019/05/14/accepted PY - 2019/6/6/entrez PY - 2019/6/6/pubmed PY - 2019/6/6/medline SP - 8257 EP - 8257 JF - Scientific reports JO - Sci Rep VL - 9 IS - 1 N2 - Wholesale, unbiased assessment of Scandinavian electronic health-care databases offer a unique opportunity to reveal potentially important undiscovered drug side effects. We examined the short-term risk of acute myocardial infarction (AMI) associated with drugs prescribed in Norway or Sweden. We identified 24,584 and 97,068 AMI patients via the patient- and the cause-of-death registers and linked to prescription databases in Norway (2004-2014) and Sweden (2005-2014), respectively. A case-crossover design was used to compare the drugs dispensed 1-7 days before the date of AMI diagnosis with 15-21 days' time -window for all the drug individually while controlling the receipt of other drugs. A BOLASSO approach was used to select drugs that acutely either increase or decrease the apparent risk of AMI. We found 48 drugs to be associated with AMI in both countries. Some antithrombotics, antibiotics, opioid analgesics, adrenergics, proton-pump inhibitors, nitroglycerin, diazepam, metoclopramide, acetylcysteine were associated with higher risk for AMI; whereas angiotensin-II-antagonists, calcium-channel blockers, angiotensin-converting-enzyme inhibitors, serotonin-specific reuptake inhibitors, allopurinol, mometasone, metformin, simvastatin, levothyroxine were inversely associated. The results were generally robust in different sensitivity analyses. This study confirms previous findings for certain drugs. Based on the known effects or indications, some other associations could be anticipated. However, inverse associations of hydroxocobalamin, levothyroxine and mometasone were unexpected and needs further investigation. This pharmacopeia-wide association study demonstrates the feasibility of a systematic, unbiased approach to pharmacological triggers of AMI and other diseases with acute, identifiable onsets. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/31164670/Systematic_assessment_of_prescribed_medications_and_short-term_risk_of_myocardial_infarction_-_a_pharmacopeia-wide_association_study_from_Norway_and_Sweden L2 - http://dx.doi.org/10.1038/s41598-019-44641-1 DB - PRIME DP - Unbound Medicine ER -