Comparative risk of fracture in community‐dwelling older adults initiating suvorexant versus Z‐drugs: Results from LIFE study

Abstract

Background An increased risk of fracture has been reported in older adults taking hypnotics. However, few studies have reported the comparative safety of hypnotics with different mechanisms of action. We examined the risk of fracture in older adults initiating suvorexant compared to those initiating Z‐drugs. Methods We conducted a retrospective cohort study using a claims database within a longevity improvement and fair evidence (LIFE) study in Japan (1.5 million beneficiaries). People aged ≥65 years were included in this study. Exposure was defined as the initiation of either suvorexant or Z‐drugs (eszopiclone, zolpidem, or zopiclone). The evaluated outcomes were hip fracture and all‐cause fracture requiring hospitalization. We used inverse probability of treatment weights to adjust for confounding and followed the incidence of the outcome for three different periods: 30, 90, and 365 days. Cox proportional hazards models were fitted to the weighted population to estimate hazard ratios (HRs). Sensitivity analyses were performed with narrowed outcome definitions and inverse probability of censoring weights. Results We identified 16,148 suvorexant new users and 54,327 Z‐drugs new users. During the 30‐day follow‐up, 21 (16.6 events per 1000 person‐years) and 53 hip fractures (12.2 events per 1000 person‐years) were identified among suvorexant and Z‐drugs new users, respectively (HR: 1.01, 95% confidence interval [CI]: 0.58–1.76). The analysis for all‐cause fracture showed an HR of 1.03 (95% CI: 0.78–1.36). Extended follow‐up (90 and 365 days) showed similar results for both outcomes. Sensitivity analyses showed consistent results except for an increased risk of all‐cause fracture requiring surgery (HR: 1.41, 95% CI: 0.87–2.29) during the 30‐day follow‐up. Conclusions This is the first study to show that suvorexant has a generally comparable risk of fracture as compared to Z‐drugs. Further research is needed to investigate the potential short‐term increased risk of all‐cause fracture requiring surgery among suvorexant initiators.

Association between the type of hypnotic drug and in‐hospital fractures in older patients with neurocognitive disorders: A case–control study using a nationwide database

“…A previous study reported a comparable risk of fractures between new users of suvorexant and Z‐drugs among community‐dwelling older people 8 . The results might have differed between the present study and the previous study, because inpatients with comorbidities experienced stronger adverse effects of Z‐drugs than did community‐dwelling outpatients.…”

“…A recent study using a claims database in Japan reported that new users of suvorexant among community-dwelling outpatients aged ≥65 years had a comparable risk of hip fracture or all-cause fracture compared with those who started Z-drugs. 8 In-hospital hip fractures lead to a higher mortality at 30 days and 1 year compared with those occurring in the community. 9 Therefore, it is important to clarify whether orexin receptor antagonists increase the risk of fractures among inpatients.…”

“…However, there is limited evidence regarding the safety of orexin receptor antagonists in older patients with neurocognitive disorders. A recent study using a claims database in Japan reported that new users of suvorexant among community‐dwelling outpatients aged ≥65 years had a comparable risk of hip fracture or all‐cause fracture compared with those who started Z‐drugs 8 …”

Effectiveness of suvorexant versus benzodiazepine receptor agonist sleep drugs in reducing the risk of hip fracture: Findings from a regional population-based cohort study

“…To our knowledge, this study is the first to compare suvorexant with BZRA sleep drugs. A similar study that compared Z-drugs with suvorexant showed no difference in fracture risk between suvorexant and Z-drugs [ 31 ]. Unlike our study, only Z-drugs were compared; therefore, a simple comparison cannot be made [ 31 ].…”

“…A similar study that compared Z-drugs with suvorexant showed no difference in fracture risk between suvorexant and Z-drugs [ 31 ]. Unlike our study, only Z-drugs were compared; therefore, a simple comparison cannot be made [ 31 ]. In this study, suvorexant was prescribed more frequently than BZRAs to patients of advanced age and patients with physical comorbidities ( Table 1 ).…”