Pharmacy-based predictors of non-adherence, non-persistence and reinitiation of antihypertensive drugs among patients on oral diabetes drugs in the Netherlands

Background
Adherence to antihypertensive drugs in patients with diabetes is important. To support adherence, attention should be paid to the dynamic process of implementation, persistence and reinitiation of these drugs. We assessed non-adherence, non-persistence and reinitiation patterns for antihypertensive drugs in patients on oral diabetes drugs and identified pharmacy-based predictors of these processes.
Methods
We conducted a cohort study in patients on oral diabetes drugs who initiated antihypertensive drugs between 1995–2015, as registered in the IADB.nl pharmacy database. Non-adherence was defined as a medication possession ratio < 80% and non-persistence as a gap > 180 days. We defined reinitiation as the dispensing of an antihypertensive drug within one year following discontinuation. We provide descriptive statistics for different time periods and applied logistic and Cox regressions to assess associations with sociodemographic and drug-related factors.
Results
Of 6,669 initiators, non-adherence rates in persistent patients decreased from 11.0% in the first year to 8.5% and 7.7% in the second and third years, respectively. Non-persistence rates decreased from 18.0% in the first year to 3.7% and 2.9% in the second and third years, respectively. Of the 1,201 patients who discontinued in the first year, 22.0% reinitiated treatment within one year. Non-adherence and non-persistence rates were lower in the more recent time period. Predictors of non-adherence were secondary prevention (OR: 1.45; 95% CI: 1.10–1.93) and diuretics as initial drug class (OR: 1.37; 95% CI: 1.08–1.74). Predictors of non-persistence were female gender (HR: 1.18; 95% CI: 1.05–1.32), older age (HR: 1.33; 95% CI: 1.08–1.63) and diuretics, beta-blocking agents or calcium channel blockers as initial drug class. Longer duration of persistence was a predictor of reinitiation.
Conclusions
Adherence to antihypertensive drugs in patients on oral diabetes drugs has improved over time. The first year after initiation is the most crucial with regard to non-adherence and non-persistence, and the risk groups are different for both processes. Early non-persistence is a risk factor for not reinitiating treatment.

研究背景
糖尿病患者服用降压药物（antihypertensive drugs）的依从性至关重要。为提升患者用药依从性，需关注此类药物启动、持续服用及重新启用的全动态流程。本研究针对口服降糖药（oral diabetes drugs）治疗的糖尿病患者的降压药物不依从（non-adherence）、不持续用药（non-persistence）及重新启用（reinitiation）模式进行评估，并明确了上述流程的药房源性预测因子。

研究方法
本研究基于IADB.nl药房数据库，针对1995年至2015年间启动降压药物治疗的口服降糖药治疗糖尿病患者开展队列研究（cohort study）。不依从性定义为药物持有率（Medication Possession Ratio, MPR）<80%，不持续用药定义为用药中断时长>180天。本研究将重新启用定义为停药后1年内再次配取降压药物。本研究对不同时间段进行描述性统计分析，并采用逻辑回归（logistic regression）与Cox回归（Cox regression）分析，评估患者社会人口学特征（sociodemographic characteristics）及药物相关因素与上述结局的关联。

研究结果
在6669名启动降压治疗的患者中，持续用药患者的不依从率从第1年的11.0%分别降至第2年的8.5%与第3年的7.7%。不持续用药率则从第1年的18.0%分别降至第2年的3.7%与第3年的2.9%。在第1年停药的1201名患者中，有22.0%在停药后1年内重新启动了治疗。较近时间段的不依从与不持续用药率更低。不依从性的预测因子包括二级预防（secondary prevention）（比值比（Odds Ratio, OR）：1.45；95%置信区间（95% Confidence Interval, 95%CI）：1.10~1.93）以及以利尿剂（diuretics）作为初始用药类别（OR：1.37；95%CI：1.08~1.74）。不持续用药的预测因子包括女性性别（风险比（Hazard Ratio, HR）：1.18；95%CI：1.05~1.32）、高龄（HR：1.33；95%CI：1.08~1.63）以及以利尿剂、β受体阻滞剂（beta-blocking agents）或钙通道阻滞剂（calcium channel blockers）作为初始用药类别。持续用药时长更长是重新启动治疗的预测因子。

研究结论
口服降糖药治疗的糖尿病患者的降压药物依从性随时间推移有所提升。治疗启动后的第1年是不依从与不持续用药的高风险阶段，且两种结局对应的风险人群存在差异。早期不持续用药是未能重新启动降压治疗的风险因素。