Opioids are commonly prescribed to patients on dialysis for pain or the treatment of opioid use disorder; however, practitioners lack basic outcome data on the safety of these medications in end-stage renal disease patients where the risk of sudden cardiac arrest is 30 times higher than the population average. For example, both methadone and oxycodone have been implicated in the prolongation of the QTc interval, which can precipitate fatal arrhythmias such as torsade de pointes. Similarly, propoxyphene has type 1A antidysrhythmic properties with QRS prolongation and potential fatal arrhythmias. Taken all together, the interaction between a proarrhythmic drug and patients with high cardiovascular burden may unknowingly place dialysis patients at excess risk for sudden cardiac arrest. We have preliminary data suggesting that patients seeking methadone therapy from a licensed opioid treatment program are more than twice as likely to die from sudden cardiac arrest when compared patients receiving buprenorphine for opioid use disorder. The intent of this proposal is to investigate the cardiovascular safety between opioid drug classes in a larger dataset through the linkage of external claims with substance abuse data to 15 years of electronic health record data. We will compare the rate of sudden cardiac arrest by drug class in dialysis patients receiving opioids for pain control or opioid use disorder. We believe this exploratory R21 mechanism will permit a collaborative team of addiction, renal, and biostatical investigators to address an important gap in clinical knowledge for physicians who care for patients with ESRD. This proposal has the potential to lead to changes in the practice of pain management and opioid use disorder in patients on dialysis.

Public Health Relevance

Opioids are commonly prescribed to patients on dialysis, but there is little outcome data that compares the safety of these drugs by class. Specifically, methadone, oxycodone, and propoxyphene are opioids that have proarrhythmic properties which may enhance the risk of sudden cardiac arrest. The risk of sudden cardiac arrest among dialysis patients is 30 times higher than the population average. As such, we hypothesize prescription of methadone, oxycodone, and propoxyphene is prohibitively dangerous in populations with inherently high cardiovascular burden as demonstrated by patients on dialysis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DA041682-01A1
Application #
9242924
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Duffy, Sarah Q
Project Start
2017-03-15
Project End
2019-02-28
Budget Start
2017-03-15
Budget End
2018-02-28
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114