It is unknown how sequential drug patterns convey information on a patient’s health status and treatment guidelines rarely account for this. Drug-agnostic longitudinal analyses of prescription trajectories in a population-wide setting are needed. In this cohort study, we used 24 years of data (1.1 billion prescriptions) from the Danish prescription registry to model the risk of sequentially redeeming a drug after another. Drug pairs were used to build multistep longitudinal prescription trajectories. These were subsequently used to stratify patients and calculate survival hazard ratios between the stratified groups. The similarity between prescription histories was used to determine individuals’ best treatment option. Over the course of 122 million person-years of observation, we identified 9 million common prescription trajectories and demonstrated their predictive power using hypertension as a case. Among patients treated with agents acting on the renin-angiotensin system we identified four groups: patients prescribed angiotensin converting enzyme (ACE) inhibitor without change, angiotensin receptor blockers (ARBs) without change, ACE with posterior change to ARB, and ARB posteriorly changed to ACE. In an adjusted time-to-event analysis, individuals treated with ACE compared to those treated with ARB had lower survival probability (hazard ratio, 0.73 [95% CI, 0.64–0.82]; P < 1 × 10⁻¹⁶). Replication in UK Biobank data showed the same trends. Prescription trajectories can provide novel insights into how individuals’ drug use change over time, identify suboptimal or futile prescriptions and suggest initial treatments different from first line therapies. Observations of this kind may also be important when updating treatment guidelines.

目前尚不清楚顺序药物模式如何传达有关患者健康状况的信息，治疗指南很少考虑到这一点。需要在人群范围内对处方轨迹进行与药物无关的纵向分析。在这项队列研究中，我们使用来自丹麦处方登记处的 24 年数据（11 亿张处方）来模拟按顺序兑换一种药物的风险。药物对用于建立多步纵向处方轨迹。这些随后被用于对患者进行分层并计算分层组之间的生存风险比。处方史之间的相似性用于确定个人的最佳治疗方案。在 1.22 亿人年的观测过程中，我们确定了 900 万个常见的处方轨迹，并以高血压为例证明了它们的预测能力。在接受作用于肾素-血管紧张素系统的药物治疗的患者中，我们确定了四组：患者开出的血管紧张素转换酶 (ACE) 抑制剂没有变化，血管紧张素受体阻滞剂 (ARBs) 没有变化，ACE 后变为 ARB，ARB 后变为高手。在调整后的事件发生时间分析中，与接受 ARB 治疗的个体相比，接受 ACE 治疗的个体具有较低的生存概率（风险比，0.73 [95% CI，0.64–0.82]；血管紧张素受体阻滞剂 (ARB) 无变化，ACE 后变为 ARB，ARB 后变为 ACE。在调整后的事件发生时间分析中，与接受 ARB 治疗的个体相比，接受 ACE 治疗的个体具有较低的生存概率（风险比，0.73 [95% CI，0.64–0.82]；血管紧张素受体阻滞剂 (ARB) 无变化，ACE 后变为 ARB，ARB 后变为 ACE。在调整后的事件发生时间分析中，与接受 ARB 治疗的个体相比，接受 ACE 治疗的个体具有较低的生存概率（风险比，0.73 [95% CI，0.64–0.82]；P  < 1 × 10 ^-16）。英国生物银行数据的复制显示出相同的趋势。处方轨迹可以提供有关个人药物使用如何随时间变化的新见解，识别次优或无效的处方，并建议与一线疗法不同的初始治疗。在更新治疗指南时，此类观察也可能很重要。