In type 2 diabetes, intensive glucose control for 5.6 years did not differ from usual care for major CV events at 14 years
In type 2 diabetes, intensive glucose control for 5.6 years did not differ from usual care for major CV events at 14 years
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DOI：
10.7326/acpj201909170-031
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发表时间：
2019-09
影响因子：
39.2
通讯作者：
G. Santulli
中科院分区：
文献类型：
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作者：
G. Santulli
在2型糖尿病患者中，与常规治疗相比，强化血糖控制中位数为5.6年是否可以减少15年以上的主要心血管（CV）事件？方法设计一项随机对照试验（退伍军人事务部糖尿病试验随访[VADT-F]研究）的长期观察随访。ClinicalTrials.gov NCT 00032487。分配不明确的分配隐藏。*设盲设盲 *（患者报告的截肢和CV事件的结局裁定者）。CV事件的中位随访期为13.6年;全因死亡的中位随访期为15年。在美国设立20个中心。患者1791名退伍军人>40岁（平均年龄60岁，97%为男性，平均糖尿病病程12年），患有2型糖尿病，对最大剂量的1种口服药物或胰岛素反应不足（血红蛋白[HbA 1c]水平7.5%）。干预强化血糖控制的目标是HbA 1c水平正常，中位水平比常规护理组（n =892）低1.5%，或常规护理的目标是HbA 1c水平为8%至9%（n =899）。患者接受随机治疗的中位时间为5.6年。主要结局是主要CV事件（非致死性心肌梗死或卒中、CV死亡、新发或恶化的充血性心力衰竭或因缺血性坏疽截肢）的复合终点。次要结局包括全因和CV死亡率以及主要糖尿病结局（主要复合结局、终末期肾病或非创伤性截肢）。92%的患者通过与国家登记处（退伍军人事务部中央医疗和死亡文件，医疗保险和医疗补助服务中心索赔文件和国家死亡指数）的联系进行随访，78%的患者通过年度调查和图表审查（意向治疗分析）提供额外数据。主要结果见表。结论：在2型糖尿病患者中，强化血糖控制中位数为5.6年，与常规治疗13.6年的主要心血管事件或15年的全因死亡率没有差异。2型糖尿病患者强化血糖控制（中位时间5.6年）与常规治疗结果每1000例患者-年的事件RR（95% CI）（中位时间13.6年）强化血糖控制住院治疗主要心血管事件47 52 6.5%（4 - 17）主要糖尿病结局50 56 7.1%（3 - 16）心血管死亡率12 13 5.5%（18至25）中位15年全因死亡率时的RRI（CI）37 36 1.5%（9至13）术语表中定义的缩写。根据文献中的常规护理事件发生率和风险比计算RRR、RRI和CI。非致死性心肌梗死或卒中、心血管死亡、新发或恶化的充血性心力衰竭或因缺血性坏疽而截肢。重大心血管事件、终末期肾病或非创伤性截肢。评论强化血糖控制的益处是否超出强化管理的有限时间（所谓的遗留效应）仍有争议（1-3）。尽管在UKPDS（英国前瞻性糖尿病研究）中发现了血糖遗传效应（3），但VADT-F研究未发现对晚期2型糖尿病患者主要CV事件的长期发生率有此类影响。2项干预后研究在干预时的糖尿病分期不同（UKPDS中新发，VADT中晚期），这可能部分解释了不同的结局，并表明在疾病早期阶段严格血糖控制的关键作用（1，3）。对医生来说，主要的带回家的信息是什么？这些研究的结果支持随着时间的推移保持血糖控制的重要性，并建议我们应该促进强化饮食和生活方式的方法，这有望长期缓解（2）。我们还需要考虑有效的心脏保护策略的可用性，包括他汀类药物、血管紧张素转换酶抑制剂和抗血小板药物，这些在UKPDS时都不是标准做法。此外，胰高血糖素样肽-1受体激动剂和钠-葡萄糖协同转运蛋白2抑制剂最近被证明可以独立于血糖控制改善CV结局（1，4）。2型糖尿病的心血管益处的证据仍在不断发展;因此，我们永远不应该放松警惕！
Question In patients with type 2 diabetes, does intensive glucose control for a median 5.6 years reduce major cardiovascular (CV) events over 15 years compared with usual care? Methods Design Long-term observational follow-up of a randomized controlled trial (Veterans Affairs Diabetes Trial Follow-up [VADT-F] study). ClinicalTrials.gov NCT00032487. Allocation Unclear allocation concealment.* Blinding Blinded* (outcome adjudicators for patient-reported amputations and CV events). Follow-up period Median 13.6 years for CV events; median 15 years for all-cause mortality. Setting 20 centers in the USA. Patients 1791 military veterans >40 years of age (mean age 60 y, 97% men, mean diabetes duration 12 y) who had type 2 diabetes mellitus and an inadequate response (hemoglobin [HbA1c] level 7.5%) to maximum doses of 1 oral drug or insulin. Intervention Intensive glucose control targeted to a normal HbA1c level and median level >1.5% lower than the usual care group (n =892) or usual care targeted to an HbA1c level of 8% to 9% (n =899). Patients received randomized treatments for a median 5.6 years. Outcomes Primary outcome was a composite of major CV events (nonfatal myocardial infarction or stroke, CV death, new or worsening congestive heart failure, or amputation for ischemic gangrene). Secondary outcomes included all-cause and CV mortality and major diabetes outcomes (primary composite outcome, end-stage renal disease, or nontraumatic amputation). Patient follow-up 92% of patients were followed through linkage to national registries (Veterans Affairs central medical and death files, Centers for Medicare & Medicaid Services claims files, and National Death Index), and 78% provided additional data through annual surveys and chart reviews (intention-to-treat analysis). Main results The main results are in the Table. Conclusion In type 2 diabetes, intensive glucose control for a median 5.6 years did not differ from usual care for major cardiovascular events at 13.6 years or all-cause mortality at 15 years. Intensive glucose control for a median 5.6 y vs usual care in type 2 diabetes Outcomes Events per 1000 patient-y RRR (95% CI) at a median 13.6 y Intensive glucose control Usual care Major cardiovascular event 47 52 6.5% (4 to 17) Major diabetes outcome 50 56 7.1% (3 to 16) Cardiovascular mortality 12 13 5.5% (18 to 25) RRI (CI) at a median 15 y All-cause mortality 37 36 1.5% (9 to 13) Abbreviations defined in Glossary. RRR, RRI, and CI calculated from usual care event rates and hazard ratios in article. Nonfatal myocardial infarction or stroke, cardiovascular death, new or worsening congestive heart failure, or amputation for ischemic gangrene. Major cardiovascular event, end-stage renal disease, or nontraumatic amputation. Commentary Whether the benefits of intensive blood glucose control extend beyond a finite period of intensive management (the so-called legacy effect) continues to be debated (1-3). Although a glycemic legacy effect was found in UKPDS (United Kingdom Prospective Diabetes Study) (3), the VADT-F study found no such effect for long-term rates of major CV events in patients with advanced type 2 diabetes. The 2 postintervention studies differed in diabetes stage at the time of intervention (new onset in UKPDS, advanced in VADT), which might partly explain the dissimilar outcomes and suggest a crucial role for tight glycemic control in the early phases of the disease (1, 3). What is the main take-home message for physicians? The findings of these studies support the importance of maintaining glycemic control over time and suggest that we should promote intensive dietary and lifestyle approaches, which hold promise for long-term remission (2). We also need to consider the availability of effective cardioprotective strategies, including statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents, none of which were standard practice at the time of UKPDS. Moreover, glucagon-like peptide-1 receptor agonists and sodiumglucose cotransporter 2 inhibitors have recently been shown to improve CV outcomes independently of glycemic control (1, 4). Evidence for CV benefit in type 2 diabetes continues to evolve; hence, we should never lower our guard!