Diabetes Research Centre, University of Leicester, Gwendolen Rd, Leicester, LE5 4PW, UK.
Novo Nordisk A/S, Vandtårnsvej a08, b860, Søborg, Denmark.
Nutr Metab Cardiovasc Dis. 2019 May;29(5):481-488. doi: 10.1016/j.numecd.2019.01.006. Epub 2019 Feb 16.
The association of beta-blockers and their selectivity with mortality and cardiovascular events in patients with and without hypoglycaemia is unknown.
Insulin-treated patients with diabetes were identified within the UK CPRD database. All-cause deaths, cardiovascular events, and hypoglycaemic episodes were captured to assess the interaction between beta-blocker therapy and selectivity with hypoglycaemia. 13,682 patients, of which 2036 (14.9%) with at least one hypoglycaemic episode, were included; 3148 deaths and 1235 cardiovascular events were recorded during a median of 2.3 and 4.7 years in patients with and without incident hypoglycaemia, respectively. Treatment with any beta-blocker was not associated with risk of death in both patients with and without hypoglycaemia, without significant interaction. Compared to no therapy, non-selective beta-blockers were associated with higher risk of death in patients without hypoglycaemia (hazard ratio (HR) 2.93 [1.26-6.83] in the fully adjusted model) but not in those with hypoglycaemia; interactions was not significant. For beta1-selective beta-blockers, there was no association with mortality in both patients with and without hypoglycaemia, without significant interaction. After missing data imputation, results were consistent for non-selective beta-blockers (HR in patients without hypoglycaemia 1.59 [1.22-2.08]) while indicated a reduced risk of death for beta1-selective beta-blockers in patients with hypoglycaemia (HR 0.76 [0.61-0.94]). Due to few cardiovascular events, complete-case analysis compared only any vs no beta-blocker therapy and indicated no associations with therapy or interaction by hypoglycaemia.
In patients with hypoglycaemic episodes, treatment with beta1-selective beta-blockers may potentially reduce the risk of death. These explorative findings and the potential role of confounding by indication need to be evaluated in other studies.
β受体阻滞剂及其选择性与低血糖患者和非低血糖患者的死亡率和心血管事件的关系尚不清楚。
在英国 CPRD 数据库中确定了接受胰岛素治疗的糖尿病患者。记录所有原因的死亡、心血管事件和低血糖发作,以评估β受体阻滞剂治疗与低血糖之间的相互作用。共纳入 13682 例患者,其中 2036 例(14.9%)至少发生过一次低血糖发作;在有低血糖和无低血糖的患者中,分别记录到中位时间为 2.3 年和 4.7 年时发生 3148 例死亡和 1235 例心血管事件。在有低血糖和无低血糖的患者中,任何β受体阻滞剂的治疗均与死亡风险无关,且无显著交互作用。与无治疗相比,非选择性β受体阻滞剂与无低血糖患者的死亡风险增加相关(完全调整模型中的 HR 为 2.93[1.26-6.83]),但与低血糖患者无关;交互作用不显著。对于β1-选择性β受体阻滞剂,在有低血糖和无低血糖的患者中,与死亡率均无关联,且无显著交互作用。在缺失数据插补后,非选择性β受体阻滞剂的结果保持一致(无低血糖患者的 HR 为 1.59[1.22-2.08]),而在低血糖患者中,β1-选择性β受体阻滞剂的死亡风险降低(HR 为 0.76[0.61-0.94])。由于心血管事件较少,全分析集仅比较了任何β受体阻滞剂治疗与无β受体阻滞剂治疗,且与治疗或低血糖无交互作用。
在发生低血糖的患者中,β1-选择性β受体阻滞剂的治疗可能潜在降低死亡风险。这些探索性发现和潜在的指示性混杂作用需要在其他研究中进行评估。