Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; Komfo Anokye Teaching Hospital, Kumasi, Ghana.
Medical University of South Carolina, Charleston, SC, USA.
Lancet Glob Health. 2023 Oct;11(10):e1619-e1628. doi: 10.1016/S2214-109X(23)00347-9.
A cardiovascular polypill containing generic drugs might facilitate sustained implementation of and adherence to evidence-based treatments, especially in resource-limited settings. However, the impact of a cardiovascular polypill in mitigating atherosclerotic risk among stroke survivors has not been assessed. We aimed to compare a polypill regimen with usual care on carotid intima-media thickness (CIMT) regression after ischaemic stroke.
In SMAART, a phase 2 parallel, open-label, assessor-masked, randomised clinical trial, we randomly allocated individuals (aged ≥18 years) who had an ischaemic stroke within the previous 2 months, using a computer-generated randomisation sequence (1:1), to either a polypill or usual care group at a tertiary centre in Ghana. The polypill regimen was a fixed-dose pill containing 5 mg ramipril, 50 mg atenolol, 12·5 mg hydrochlorothiazide, 20 mg simvastatin, and 100 mg aspirin administered as two capsules once per day for 12 months. Usual care was tailored guideline-recommended secondary prevention medications. The primary outcome was the change in CIMT over 12 months with adjustment for baseline values, compared using ANCOVA in all participants with complete data at month 12. Safety was analysed in all randomly assigned participants. This trial is registered at ClinicalTrials.gov, NCT03329599, and is completed.
Between Feb 12, 2019, and Dec 4, 2020, we randomly assigned 148 participants (74 to the usual care group and 74 to the polypill group), 74 (50%) of whom were male and 74 (50%) female. CIMT was assessed in 62 (84%) of 74 participants in the usual care group and 59 (80%) of 74 participants in the polypill group; the main reason for loss to follow-up was participants not completing the study. The mean CIMT change at month 12 was -0·092 mm (95% CI -0·130 to -0·051) in the usual care group versus -0·017 mm (-0·067 to 0·034) in the polypill group, with an adjusted mean difference of 0·049 (-0·008 to 0·109; p=0·11). Serious adverse events occurred among two (3%) participants in the usual care group, and eight (11%) participants in the polypill group (p=0·049).
The polypill regimen resulted in similar regression in subclinical atherosclerosis and many secondary and tertiary outcome measures as the tailored drug regimen, but with more serious adverse events. Larger, longer-term, event-based studies, including patients with stroke in primary care settings, are warranted.
US National Institutes of Health.
For the Akan (Twi) translation of the abstract see Supplementary Materials section.
含有仿制药的心血管复方药可能更有助于持续实施和坚持循证治疗，特别是在资源有限的环境中。然而，心血管复方药在减轻中风幸存者的动脉粥样硬化风险方面的影响尚未得到评估。我们旨在比较复方药方案与常规护理对缺血性中风后颈动脉内膜中层厚度（CIMT）的消退作用。
在一项 2 期平行、开放标签、评估者设盲、随机临床试验（SMAART）中，我们在加纳的一个三级中心，使用计算机生成的随机序列（1:1）将最近 2 个月内发生缺血性中风的年龄≥18 岁的个体（n=148）随机分配到复方药组或常规护理组。复方药方案是一种固定剂量的药丸，含有 5mg 雷米普利、50mg 阿替洛尔、12.5mg 氢氯噻嗪、20mg 辛伐他汀和 100mg 阿司匹林，每天服用两次，持续 12 个月。常规护理是根据指南推荐的二级预防药物。主要结局是在 12 个月时与基线值相比 CIMT 的变化，使用完全数据在第 12 个月时进行 ANCOVA 比较。所有随机分配的参与者均进行安全性分析。本试验在 ClinicalTrials.gov 注册，编号为 NCT03329599，现已完成。
2019 年 2 月 12 日至 2020 年 12 月 4 日，我们随机分配了 148 名参与者（常规护理组 74 名，复方药组 74 名），其中 74 名（50%）为男性，74 名（50%）为女性。在常规护理组中，有 74 名（50%）参与者和在复方药组中，有 59 名（80%）参与者完成了 12 个月的 CIMT 评估；主要的失访原因是参与者没有完成研究。常规护理组 12 个月时的平均 CIMT 变化为-0.092mm（95%CI -0.130 至 -0.051），复方药组为-0.017mm（-0.067 至 0.034），调整后的平均差异为 0.049（-0.008 至 0.109；p=0.11）。常规护理组有 2 名（3%）参与者发生严重不良事件，复方药组有 8 名（11%）参与者发生严重不良事件（p=0.049）。
复方药方案在亚临床动脉粥样硬化和许多二级和三级结局方面的消退作用与个体化药物方案相似，但不良事件更多。需要更大规模、更长时间、基于事件的研究，包括初级保健环境中的中风患者。
美国国立卫生研究院。
