Systolic Blood Pressure Intervention Trial (SPRINT-BioLINCC)

<u>Available Data</u><br>The available data include all elements of the previously released SPRINT Primary Outcome Paper (SPRINT-POP) data, the full SPRINT clinical data including the MRI and MIND data, and select ancillary study data (Ambulatory Blood Pressure Monitoring, APOL1, Acute Kidney Injury, ASK, Heart, FAST, PWV, Renal Resistance, Biomarkers, Plasma AD).

<u>Objective</u><br>The Systolic Blood Pressure Trial (SPRINT) was conducted to test the hypothesis that treating systolic blood pressure to a target of less than 120 mm Hg, as compared to a target of less than 140 mm Hg, would reduce the incidence of cardiovascular disease.

<u>Background</u><br>Hypertension is a highly prevalent condition among adults and is a leading risk factor for myocardial infarction and stroke. Further, isolated systolic hypertension is the most common form of hypertension in adults over 50 years of age. Observational studies have shown a monotonic increase in cardiovascular risk with systolic blood pressures above 115 mm Hg; however, general population clinical trials have only documented the benefits of lowering systolic blood pressure to a target of 150 mm Hg. A 2007 expert panel sponsored by the National Heart, Lung, and Blood Institute designated the hypothesis that lowering the systolic blood pressure goal to a level <120 mm Hg as the most important hypothesis to test in reducing hypertension related complications in those without diabetes.

<u>Subjects</u><br>A total of 9361 participants were enrolled, with 4,678 randomized to the intensive-treatment group and 4,683 randomized to the standard-treatment group.

<u>Design</u><br>SPRINT was a randomized, single blinded (outcome adjudicators were blinded to treatment assignment) treatment trial with participants randomized to a systolic blood-pressure target of either less than 140 mm Hg (the standard-treatment group) or less than 120 mm Hg (the intensive-treatment group). Following randomization, baseline hypertensive regimens were adjusted in accordance with study treatment algorithms established for each group. The study formulary included all major classes of antihypertensive agents. Investigators could prescribe other antihypertensive medications, but the use of drug classes with the strongest evidence for reduction in cardiovascular outcomes was encouraged. This included thiazide-type diuretics as the first-line agent, loop diuretics for participants with advanced chronic kidney disease, and beta-adrenergic blockers for participants with coronary artery disease. Medications for participants in the intensive-treatment group were adjusted on a monthly basis to target a systolic blood pressure of less than 120 mm Hg. Medications for participants in the standard-treatment group were adjusted to target a systolic blood pressure of 135 to 139 mm Hg, and the dose was reduced if systolic blood pressure was less than 130 mm Hg on a single visit or less than 135 mm Hg on two consecutive visits. Lifestyle modification was encouraged as part of the management strategy.

Participants were seen monthly for the first 3 months and every 3 months thereafter. Demographic data were collected at baseline. Clinical and laboratory data were obtained at baseline and every 3 months thereafter. A structured interview was used in both groups every 3 months to obtain self-reported cardiovascular disease outcomes. Medical records and electrocardiograms were obtained for documentation of events. Incidences of hypotension, syncope, injurious falls, electrolyte abnormalities, and bradycardia that were evaluated in an emergency department were included in adverse event reporting. Occurrences of acute kidney injury or acute renal failure requiring hospitalization were also monitored. <br>The primary outcome was a composite outcome of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.

<u>Conclusions</u><br>The blood pressure intervention was stopped in August of 2015 (median follow-up of 3.26 years) after the cardiovascular outcome results exceeded the boundary for efficacy at two consecutive time points. Compared with a systolic blood pressure target of less than 140 mm Hg, an intensive systolic blood pressure target of 120 mm Hg resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause. Significantly higher rates of some adverse events were observed in the intensive-treatment group.

可用数据
本数据集涵盖此前发布的SPRINT主要结局论文（SPRINT Primary Outcome Paper, SPRINT-POP）数据集的全部内容、完整的SPRINT临床数据（含磁共振成像（Magnetic Resonance Imaging, MRI）与MIND数据），以及精选的辅助研究数据：动态血压监测（Ambulatory Blood Pressure Monitoring）、APOL1基因、急性肾损伤（Acute Kidney Injury）、ASK、心脏相关研究、FAST、脉搏波速度（Pulse Wave Velocity, PWV）、肾脏阻力、生物标志物、血浆AD等。

研究目标
收缩压干预试验（Systolic Blood Pressure Trial, SPRINT）旨在验证如下假说：与将收缩压控制于<140 mmHg的标准目标相比，将收缩压控制于<120 mmHg的强化目标，可降低心血管疾病的发生率。

研究背景
高血压在成人中患病率极高，是心肌梗死与脑卒中的首要危险因素。此外，单纯收缩期高血压是50岁以上成人最常见的高血压类型。观察性研究表明，当收缩压高于115 mmHg时，心血管风险呈单调递增趋势；但此前的普通人群临床试验仅证实了将收缩压降至150 mmHg以下的获益。2007年，由美国国家心肺血液研究所（National Heart, Lung, and Blood Institute）资助的专家小组将“将收缩压控制目标降至<120 mmHg”列为针对非糖尿病患者、用于降低高血压相关并发症的最重要待验证假说。

研究对象
本研究共纳入9361名参与者，其中4678名被随机分配至强化治疗组，4683名被分配至标准治疗组。

研究设计
SPRINT是一项随机、单盲（结局判定者对治疗分配设盲）的治疗性临床试验，参与者被随机分配至两个收缩压控制目标组：<140 mmHg组（标准治疗组）与<120 mmHg组（强化治疗组）。随机分组后，研究人员根据针对两组制定的治疗方案算法，调整参与者的基线降压治疗方案。本研究的处方集涵盖所有主要类别降压药物，研究人员可开具其他降压药物，但鼓励使用被证实可最有效降低心血管结局风险的药物类别，包括：噻嗪类利尿剂作为一线用药，伴晚期慢性肾脏病的参与者使用袢利尿剂，合并冠状动脉疾病的参与者使用β肾上腺素能阻滞剂（beta-adrenergic blockers）。强化治疗组参与者的用药方案每月调整一次，目标为将收缩压控制至<120 mmHg；标准治疗组参与者的用药方案调整目标为将收缩压控制于135~139 mmHg，若单次随访收缩压<130 mmHg，或连续两次随访收缩压<135 mmHg，则需减少药物剂量。研究同时鼓励参与者通过生活方式干预辅助血压管理。

参与者在最初3个月内每月随访1次，此后每3个月随访1次。研究人员在基线时收集参与者的人口统计学数据，并在基线及后续每3个月采集临床与实验室数据。两组均每3个月开展一次结构化访谈，以获取参与者自我报告的心血管疾病结局事件。研究人员还会收集参与者的医疗记录与心电图（Electrocardiogram, ECG）以核实事件发生情况。不良事件报告涵盖在急诊科就诊的低血压、晕厥、跌倒致伤、电解质异常与心动过缓（bradycardia）事件；同时监测需住院治疗的急性肾损伤或急性肾衰竭发生情况。本研究的主要结局为复合终点，包括心肌梗死、其他急性冠状动脉综合征、脑卒中、心力衰竭或心血管原因死亡。

研究结论
2015年8月，因心血管结局结果在连续两个时间点均达到疗效界值，血压干预试验提前终止，中位随访时间为3.26年。与收缩压控制目标<140 mmHg的标准治疗相比，将收缩压强化控制至<120 mmHg可降低致命与非致命性主要心血管事件发生率及全因死亡率，但强化治疗组的部分不良事件发生率显著升高。