Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, UT, United States of America.
Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, United States of America.
PLoS One. 2020 Dec 3;15(12):e0243371. doi: 10.1371/journal.pone.0243371. eCollection 2020.
Lisinopril and losartan manufacturer labels recommend twice-daily dosing (BID) if once-daily (QDay) is insufficient to lower blood pressure (BP).
Retrospective cohort study of patients taking QDay lisinopril and losartan who experienced a dose-doubling (index date). A text-processing tool categorized BID and QDay groups at the index date based on administration instructions. We excluded: pregnant/hospice, regimens other than BID/QDay, and without BP measurements -6 months/+12 months of the index date. The most proximal BP measurements -6 months and +2 weeks to 12 months of the index date were used to evaluate BP differences. Propensity scores were generated, and differences in BP and adverse events (angioedema, acute kidney injury, hyperkalemia) between BID/QDay groups were analyzed within dosing cohorts using inverse propensity of treatment-weighted regression models. Of 11,210 and 6,051 patients who met all criteria for lisinopril and losartan, 784 (7.0%) and 453 (7.5%) were taking BID, respectively. BID patients were older and had higher comorbidity and medication burdens. There were no differences in systolic/diastolic BP between BID and QDay, with absolute differences in mean systolic BP ranging from -1.8 to 0.7 mmHg and diastolic BP ranging from -1.1 to 0.1 mmHg (all 95% confidence intervals [CI] cross 0). Lisinopril 10mg BID was associated with an increased odds of angioedema compared to lisinopril 20mg QDay (odds ratio 2.27, 95%CI 1.13-4.58).
Adjusted models do not support improved effectiveness or safety of BID lisinopril and losartan.
赖诺普利和氯沙坦的制造商标签建议，如果每日一次（QD）不足以降低血压（BP），则应每日两次（BID）给药。
对接受 QD 赖诺普利和氯沙坦治疗且剂量加倍（索引日期）的患者进行回顾性队列研究。基于给药说明，使用文本处理工具在索引日期对 BID 和 QD 组进行分类。我们排除了：孕妇/临终关怀、非 BID/QD 方案以及无 BP 测量值-索引日期前 6 个月/后 12 个月。使用最接近的 BP 测量值-索引日期前 6 个月和后 2 周至 12 个月，评估 BP 差异。生成倾向评分，并使用逆处理倾向加权回归模型分析 BID/QD 组之间在剂量组内的 BP 和不良事件（血管性水肿、急性肾损伤、高钾血症）的差异。符合赖诺普利和氯沙坦所有标准的 11210 例和 6051 例患者中，分别有 784 例（7.0%）和 453 例（7.5%）接受 BID。BID 患者年龄较大，合并症和药物负担较高。BID 和 QD 之间的收缩压/舒张压无差异，平均收缩压的绝对差异范围为-1.8 至 0.7mmHg，舒张压的绝对差异范围为-1.1 至 0.1mmHg（所有 95%置信区间 [CI] 均跨越 0）。与赖诺普利 20mg QD 相比，赖诺普利 10mg BID 与血管性水肿的发生几率增加相关（比值比 2.27，95%CI 1.13-4.58）。
调整后的模型不支持 BID 赖诺普利和氯沙坦的有效性或安全性提高。
