Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART)

摘要/摘要 撒哈拉以南非洲(SSA)的中风患病率出现了前所未有的上升，与 高收入国家(HIC)的中风特征是发病年龄更小，病死率更高，以及更多 幸存者的严重残疾。SSA(与HIC相比)的卒中幸存者特别容易复发血管事件或 因血管风险因素未确诊或控制不足、后勤困难、健康素养低和缺乏护理而死亡 可负担性。虽然国际专家一致认为二级预防指南建议抗高血压、他汀类药物 和抗血小板治疗，在缺血性中风后迅速启动并坚持不懈地坚持，以达到最佳 降低血管风险，这些目标在SSA的常规临床护理环境中很少实现。一种相对简单、低成本、 以证据为基础的策略，可以很大程度上统一应用于中低收入的中风幸存者 迫切需要包括SSA国家在内的国家(LMIC)。固定剂量的联合药丸，也被称为“复方药”， 包含仿制药，即阿司匹林、他汀类药物和降血压药物(S)可能是一种可行的途径 改善用药依从性，从而降低中风患者进一步残疾或死亡的风险 在资源有限的地区遇到的幸存者。通过加法实现行程最小化的总体目标 常规治疗中的抗动脉粥样硬化剂(SMAART)试验是为了确定一种保心丸(PolyCap)的初步影响 DS®)，含有固定剂量的抗高血压药物、他汀类药物和抗血小板治疗，每天口服一次，以减少未来 加纳库马西一家医院120名近期中风患者在准备接受治疗时的血管风险与常规护理的比较 未来进行大规模、多中心的务实试验，建设本地研究能力。在SMAART中，我们将1)评估一个 与平时相比，基于多药的治疗策略将导致颈动脉内膜-中层厚度稳定/回落 近期卒中患者在指标性缺血性卒中后一年的护理；2)评估以多效药为基础的治疗是否 策略改善血管风险降低药物依从性和耐受性，以及血压和血清总胆固醇 控制目标，比较最近中风患者在指数缺血性中风后一年的常规护理；以及3) 提高开展临床研究的能力，并为早期职业研究人员提供持续的指导 加纳，并促进他们向能够计划和执行严格随机调查的独立调查人员过渡 在资源有限的情况下，控制二级中风预防和降低血管风险。一个初步可行和 疗效-建议SMAART试验将为未来多中心、双盲、安慰剂对照、 在非洲地区进行随机试验，比较波利匹林策略与“常规治疗”的临床疗效，以期在当地得出结论 相关的高质量证据表明，在卒中患者中常规应用Polipill策略来缓解血管风险 LMIC中的幸存者。

SUMMARY/ABSTRACT There has been unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA), which when compared to stroke profiles in high-income countries (HIC) is characterized by a younger age of onset, higher case fatality rates, and more severe disability among survivors. Stroke survivors in SSA (vs. HIC) are especially at high risk for recurrent vascular events or death due to undiagnosed or under-controlled vascular risk factors, logistical challenges, low health literacy, and lack of care affordability. While international expert consensus secondary prevention guidelines recommend that antihypertensive, statin and anti-platelet therapy, be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular risk reduction, these goals are seldom realized in routine clinical care settings in SSA. A relatively simple, low-cost, evidence-based strategy that could be largely applied in a uniform manner to stroke survivors in low- to –middle income countries (LMICs), including the nations of SSA, is sorely needed. Fixed-dose combination pills, also known as “polypills”, containing generic drugs, i.e. Aspirin, a statin, and blood pressure (BP) lowering medication(s) may be a viable avenue to improve medication adherence and consequently reduce risk of further disability or death on a large scale among stroke survivors encountered in resource-constrained regions. The overarching objective of the Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART) trial is to determine the preliminary impact of a polypill (Polycap DS ®) containing fixed doses of antihypertensives, a statin, and antiplatelet therapy taken once daily orally in reducing future vascular risk compared to usual care in 120 recent stroke patients seen at a hospital in Kumasi, Ghana, while preparing for a future large, multicenter pragmatic trial and building local research capacity. In SMAART, we will 1) evaluate whether a polypill-based treatment strategy would result in carotid intimal media thickness stabilization/regression compared with usual care among recent stroke patients at one year after an index ischemic stroke; 2) assess whether a polypill-based treatment strategy improves vascular risk reduction drug adherence and tolerability, as well as blood pressure and serum holesterol control targets, compared with usual care among recent stroke patients at one year after an index ischemic stroke; and 3) provide increased capacity for conducting clinical research and continuous mentorship to early stage career investigators in Ghana, and facilitate their transition to independent investigators capable of planning and executing rigorous randomized controlled for secondary stroke prevention and vascular risk reduction in a resource-limited setting. A preliminarily feasible and efficacy-suggesting SMAART trial will inform the design of a future multi-center, double-blinded, placebo-controlled, randomized trial comparing the clinical efficacy of the polypill strategy vs `usual care' in the African context to derive locally relevant, high-quality evidence for routine deployment of the polypill strategy for vascular risk moderation among stroke survivors in LMICs.