Systolic Blood Pressure Intervention Trial (SPRINT-Imaging)

Available Data

Systolic Blood Pressure Intervention Trial, SPRINT-Imaging, provides access to ECG signals data from the SPRINT clinical trial. The clinical phenotyping and outcomes data from the trial are associated with SPRINT-BioLINCC, phs003483.

Objective

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.

Background

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.

Subjects

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.

Design

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.

The primary outcome was a composite outcome of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.

Conclusions

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
收缩压干预试验（Systolic Blood Pressure Intervention Trial，SPRINT）影像数据集（SPRINT-Imaging）可获取SPRINT临床试验的心电图（Electrocardiogram, ECG）信号数据。该试验的临床表型与结局数据关联于SPRINT-BioLINCC（phs003483）。

试验目标
本收缩压试验（SPRINT）旨在验证如下假说：将收缩压控制在120mmHg以下的强化治疗方案，相较于140mmHg以下的标准治疗方案，可降低心血管疾病的发病率。

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。观察性研究显示，当收缩压高于115mmHg时，心血管风险呈单调递增趋势；但目前的普通人群临床试验仅证实了将收缩压降至150mmHg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, NHLBI）资助的专家小组提出，将收缩压目标值降至<120mmHg的假说，是针对非糖尿病高血压患者降低其并发症的最重要待验证假说。

受试者
本试验共纳入9361名受试者，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。

试验设计
SPRINT为一项随机、单盲（结局判定者对治疗分配设盲）治疗试验，受试者被随机分配至收缩压靶目标为<140mmHg的标准治疗组，或<120mmHg的强化治疗组。随机分组后，根据各组预设的研究治疗算法调整基线降压治疗方案。研究处方涵盖所有主要类别降压药物。研究者可开具其他降压药物，但鼓励优先使用被证实可显著降低心血管结局的药物类别，包括：噻嗪类利尿剂作为一线用药；伴晚期慢性肾脏病的受试者使用袢利尿剂；伴冠状动脉疾病的受试者使用β肾上腺素能受体阻滞剂。强化治疗组受试者的药物调整需每月进行，以将收缩压控制在<120mmHg。标准治疗组受试者的药物调整目标为将收缩压控制在135~139mmHg，若单次随访收缩压<130mmHg或连续两次随访收缩压<135mmHg，则需降低药物剂量。研究同时鼓励受试者进行生活方式干预作为治疗策略的一部分。

受试者在入组后前3个月每月随访1次，此后每3个月随访1次。入组基线时收集人口统计学资料，基线及此后每3个月采集临床与实验室检测数据。两组每3个月采用结构化访谈获取受试者自我报告的心血管疾病结局事件。通过医疗记录与心电图结果确认事件发生情况。不良事件报告涵盖于急诊科评估的低血压、晕厥、创伤性跌倒、电解质异常及心动过缓。同时监测需住院治疗的急性肾损伤与急性肾衰竭的发生情况。

本试验的主要结局为复合终点，涵盖心肌梗死、其他急性冠状动脉综合征、脑卒中、心力衰竭及心血管原因死亡。

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超出疗效界值，本血压干预试验提前终止，中位随访时间为3.26年。相较于收缩压靶目标<140mmHg的标准治疗，将收缩压强化控制至<120mmHg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。但强化治疗组部分不良事件的发生率显著升高。