Drug-use-associated infective endocarditis in Denmark

Abstract Introduction Infective endocarditis (IE) has high mortality and the incidence is rising. Intravenous drug use is a risk factor for IE and poses challenges in clinical care. Amid the opioid crisis in many countries, rates of drug-use-associated IE (DU-IE) are increasing. While drug use in Denmark has remained stable the last decade, little is understood about the features and prognostic impact of DU-IE in developed nations not facing a current opioid crisis. Further, with multiple preventive measures deployed in local Danish regions, data on the evolution of DU-IE are warranted. Purpose To examine the temporal evolution, baseline characteristics, and long-term rates of all-cause mortality and IE recurrence in patients with DU-IE compared with patients with non-DU-IE. Methods This nationwide cohort study identified all first-time IE-patients (1999-2018) and categorized them in 1) patients with DU-IE, and 2) patients with non-DU-IE. Drug use was defined using ICD-8/10 codes or treatment for opioid use disorder. Patients were followed from the date of discharge, and absolute one-year rates of mortality and IE recurrence were examined with Kaplan-Meier estimates and the cumulative incidence function, respectively. Outcomes were compared with a multivariable adjusted Cox model. Results We identified 8,843 patients with IE: 407 (4.6%) with DU-IE (61% male, median age 44 years) and 8,436 (95.4%) with non-DU-IE (66% male, median age 72 years). While the absolute number of DU-IE increased, the proportion of DU-IE decreased from 5.9% in 1999-2003 (n=87) to 3.8% in 2014-2018 (n=114). Patients with DU-IE had a higher proportion of bloodstream infection with Staphylococcus aureus (49.4% vs 26.7%, p<0.001); conversely, they had a lower proportion of bloodstream infections with Streptococcusspecies (14.4% vs. 26.2%, p<0.011). Patient with DU-IE had lower in-hospital mortality compared with non-DU-IE (15.5% vs. 20.9%, p<0.001). Among those surviving admission, the one-year cumulative incidence of all-cause mortality was 16.9% in DU-IE and 17.3% in non-DU-IE (p=0.82), yet in adjusted analysis, DU-IE was associated with a higher one-year mortality rate (HR 1.64 [95% CI:1.23-2.21]) (Figure). The one-year cumulative incidence of IE recurrence was 12.8% in DU-IE and 4.3% in non-DU-IE, which corresponded to an adjusted HR of 3.39 (95% CI:2.35-4.88) in DU-IE. Conclusion While an increase in the absolute number of patients with DU-IE was observed, the proportion among all IE-patients was on the decline in Denmark until 2018—which contrasts with other countries where physicians currently battle collateral damage of the opioid crisis. Although drug use was associated with lower in-hospital mortality, it was striking that even though patient with DU-IE was almost 30 years younger, they still had higher rates of all-cause mortality and a more than three-fold increase in IE recurrence one year following discharge.