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. doi: 10.1038/s41598-019-44641-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / adverse effects
  • Adrenergic Agents / therapeutic use
  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / therapeutic use
  • Cause of Death*
  • Databases, Factual
  • Drug Prescriptions*
  • Electronic Health Records
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / mortality*
  • Myocardial Infarction / pathology
  • Nitroglycerin / adverse effects
  • Nitroglycerin / therapeutic use
  • Norway / epidemiology
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use
  • Risk Factors
  • Sweden / epidemiology

Substances

  • Adrenergic Agents
  • Adrenergic beta-Antagonists
  • Analgesics, Opioid
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Bacterial Agents
  • Calcium Channel Blockers
  • Fibrinolytic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Proton Pump Inhibitors
  • Nitroglycerin