Comparative risk of mortality in new users of prescription opioids for noncancer pain: results from the International Pharmacosurveillance Study.

Although opioids continue to be used internationally for noncancer pain, evidence to date on the comparative safety of different opioids is sparse and conflicting. The aim of this study was to examine the comparative risk of all-cause mortality in patients newly initiated on opioids for noncancer pain, across 3 jurisdictions in the United Kingdom (UK), United States, and Canada. A multicentre retrospective, population-based cohort study was conducted. Data sources included UK national primary care electronic health records (Clinical Practice Research Datalink), The Partners HealthCare Research Patient Data in Boston (US), and The Montreal Population Health Record data (Canada). New users of opioids aged ≥18 years without cancer were included. Patients with a diagnosis of a pain condition and with known back pain were analysed separately. Fully adjusted hazard ratios (HRs) were calculated using Cox-proportional models and adjusted for confounders. In total, 1,066,216 patients were included (UK: n = 993,294; Boston, US: n = 43,243; Montreal, Canada: n = 26,116). Compared with codeine, patients using morphine had a significantly higher adjusted risk in the UK {HR: 12.58 [95% confidence interval (CI), 11.87-13.32]}, US (HR: 8.62 [95% CI, 3.34-22.27]), and Canadian cohorts (HR: 6.69; [95% CI, 1.35-32.22]). In addition, other factors associated with higher mortality were being on combination opioids, fentanyl, buprenorphine, and oxycodone. Compared with those on <50 morphine milligram equivalents/day, patients on higher-doses experience an incremental increase in risk. In new users of opioids, compared with codeine, strong opioids, including morphine, fentanyl, buprenorphine, oxycodone, and combination opioids, and those on ≥50 morphine milligram equivalent/day were associated with a higher subsequent risk of all-cause mortality.