Primary and secondary outcomes.

Background
The Danish cardiovascular screening (DANCAVAS) trial, a nationwide trial designed to investigate the impact of cardiovascular screening in men, did not decrease all-cause mortality, an outcome decided by the investigators. However, the target group may have varied preferences. In this study, we aimed to evaluate whether men aged 65 to 74 years requested a CT-based cardiovascular screening examination and to assess its impact on outcomes determined by their preferences.
Methods and findings
This is a post hoc study of the randomised DANCAVAS trial. All men 65 to 74 years of age residing in specific areas of Denmark were randomised (1:2) to invitation-to-screening (16,736 men, of which 10,471 underwent screening) or usual-care (29,790 men). The examination included among others a non-contrast CT scan (to assess the coronary artery calcium score and aortic aneurysms). Positive findings prompted preventive treatment with atorvastatin, aspirin, and surveillance/surgical evaluation. The usual-care group remained unaware of the trial and the assignments. The user-defined outcome was based on patient preferences and determined through a survey sent in January 2023 to a random sample of 9,095 men from the target group, with a 68.0% response rate (6,182 respondents). Safety outcomes included severe bleeding and mortality within 30 days after cardiovascular surgery. Analyses were performed on an intention-to-screen basis. Prevention of stroke and myocardial infarction was the primary motivation for participating in the screening examination. After a median follow-up of 6.4 years, 1,800 of 16,736 men (10.8%) in the invited-to-screening group and 3,420 of 29,790 (11.5%) in the usual-care group experienced an event (hazard ratio (HR), 0.93 (95% confidence interval (CI), 0.88 to 0.98; p = 0.010); number needed to invite at 6 years, 148 (95% CI, 80 to 986)). A total of 324 men (1.9%) in the invited-to-screening group and 491 (1.7%) in the usual-care group had an intracranial bleeding (HR, 1.17; 95% CI, 1.02 to 1.35; p = 0.029). Additionally, 994 (5.9%) in the invited-to-screening group and 1,722 (5.8%) in the usual-care group experienced severe gastrointestinal bleeding (HR, 1.02; 95% CI, 0.95 to 1.11; p = 0.583). No differences were found in mortality after cardiovascular surgery. The primary limitation of the study is that exclusive enrolment of men aged 65 to 74 renders the findings non-generalisable to women or men of other age groups.
Conclusion
In this comprehensive population-based cardiovascular screening and intervention program, we observed a reduction in the user-defined outcome, stroke and myocardial infarction, but entail a small increased risk of intracranial bleeding.
Trial registration
ISRCTN Registry number, ISRCTN12157806 https://www.isrctn.com/ISRCTN12157806.

背景
丹麦心血管筛查（DANCAVAS）试验是一项全国性随机对照试验，旨在探究心血管筛查对男性人群的健康影响，但未达成研究者预设的全因死亡率降低这一核心结局。不过目标人群可能存在异质性的健康偏好。本研究旨在评估65至74岁男性是否愿意接受基于计算机断层扫描（Computed Tomography, CT）的心血管筛查检查，并分析其对基于受试者自身偏好的研究结局的影响。

方法与结果
本研究为针对随机对照DANCAVAS试验的事后分析。所有居住在丹麦特定区域的65至74岁男性按照1:2的比例被随机分配至筛查邀请组（16736名男性，其中10471名实际接受了筛查）或常规护理组（29790名男性）。筛查检查内容包括非增强CT扫描（用于评估冠状动脉钙化评分（coronary artery calcium score）与主动脉瘤（aortic aneurysms））。若检出阳性结果，则需接受阿托伐他汀（atorvastatin）、阿司匹林（aspirin）的预防性治疗，以及随访或外科评估。常规护理组受试者对本试验及分组情况完全不知情。本研究的用户自定义结局基于患者健康偏好，通过2023年1月向目标人群中随机抽取的9095名男性发放调查问卷确定，最终有效回收率为68.0%（共6182名受访者）。安全性结局包括心血管手术后30天内的严重出血事件与死亡。所有分析均采用意向性筛查（intention-to-screen）原则开展。受试者参与筛查的主要动机为预防脑卒中（stroke）与心肌梗死（myocardial infarction）。中位随访时长为6.4年，筛查邀请组16736名男性中有1800例（10.8%）发生终点事件，常规护理组29790名男性中有3420例（11.5%）发生终点事件（风险比（Hazard Ratio, HR）=0.93，95%置信区间（Confidence Interval, CI）：0.88~0.98；P=0.010；6年时需筛查邀请人数为148，95%CI：80~986）。筛查邀请组中共324名男性（1.9%）发生颅内出血，常规护理组为491名（1.7%）（HR=1.17，95%CI：1.02~1.35；P=0.029）。此外，筛查邀请组有994名男性（5.9%）发生严重胃肠道出血，常规护理组为1722名（5.8%）（HR=1.02，95%CI：0.95~1.11；P=0.583）。两组心血管手术后的死亡率无显著差异。本研究的主要局限性在于仅纳入65至74岁男性群体，因此研究结果无法推广至女性或其他年龄段男性。

结论
在这项基于全人群的综合性心血管筛查与干预项目中，我们观察到用户自定义结局（脑卒中与心肌梗死）发生率显著降低，但同时存在颅内出血风险小幅升高的情况。

试验注册
ISRCTN注册编号：ISRCTN12157806，网址：https://www.isrctn.com/ISRCTN12157806。