瑞典卡罗莱纳研究所BjÖrn Pasternak小组取得一项新突破。他们分析了使用钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂与重大心血管事件和心力衰竭风险的关系：一项基于斯堪的纳维亚的注册队列研究。 该研究成果发表在2019年8月29日出版的《英国医学杂志》上。

2013年4月至2016年12月，研究团队在丹麦、挪威、瑞典招募受试者，其中20983人首次使用SGLT2抑制剂，20983人首次使用二肽基肽酶4（DPP4） 抑制剂，参与者平均年龄61岁，60%为男性，19%有重大心血管疾病史，两组参与者的年龄、性别、重大心血管疾病史和倾向评分无显著性差异。重大心血管事件包括心肌梗死、中风和心血管死亡，心力衰竭事件包括因心力衰竭住院或死亡。

在SGLT2抑制剂组共27416人年的随访中，22627名（83%）患者首次使用dapagliflozin，4521名（16%）患者首次使用empagliflozin，268名（1%）患者首次使用canagliflozin。随访期间，SGLT2抑制剂组中有467名（每1000人年17.0例）发生重大心血管事件，DPP4抑制剂组中有662名（18.0例）；SGLT2抑制剂组中有130名（4.7例）发生心力衰竭事件，DPP4抑制剂组中有265名（7.1例）。重大心血管事件和心力衰竭的风险比分别为0.94和0.66。

在伴或不伴重大心血管疾病史和心力衰竭史的亚组患者中，该风险比是一致的。SGLT2抑制剂与DPP4抑制剂相比，心肌梗死的风险比为0.99，中风为0.94，心血管死亡为0.84，全因死亡为0.80。经附加处理分析，重大心血管事件的风险比为0.84，心力衰竭为0.55，心肌梗死为0.93，中风为0.83，心血管死亡为0.67，全因死亡为0.75。

在这个斯堪的纳维亚大型队列中，与DPP4抑制剂相比，使用SGLT2抑制剂降低了心力衰竭和全因死亡的风险，但与重大心血管事件无关。 在附加处理分析中，SGLT2抑制剂与心力衰竭和全因死亡的相关性变得更大，且主要由心血管死亡因素驱动的重大心血管事件的风险降低。 这些数据有助于患者、医生和政府了解SGLT2抑制剂在常规临床实践中对心血管的影响。

Title: Use of sodium glucose cotransporter 2 inhibitors and risk of major cardiovascular events and heart failure: Scandinavian register based cohort study

Author: Bjorn Pasternak,Peter Ueda,et al

Issue&Volume: Volume 394 Number 10200,30 August 2019

Abstract: 

Objective To investigate the cardiovascular effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in routine clinical practice.

Design Cohort study using data from nationwide registers and an active-comparator new-user design.

Setting Denmark, Norway, and Sweden, from April 2013 to December 2016.

Participants 20 983 new users of SGLT2 inhibitors and 20 983 new users of dipeptidyl peptidase 4 (DPP4) inhibitors, aged 35-84, matched by age, sex, history of major cardiovascular disease, and propensity score.

Main outcome measures Primary outcomes were major cardiovascular events (composite of myocardial infarction, stroke, and cardiovascular death) and heart failure (hospital admission for heart failure or death due to heart failure). Secondary outcomes were the individual components of the cardiovascular composite and any cause death. In the primary analyses, patients were defined as exposed from treatment start throughout follow-up (analogous to intention to treat); additional analyses were conducted with an as-treated exposure definition. Cox regression was used to estimate hazard ratios.

Results Mean age of the study cohort was 61 years, 60% were men, and 19% had a history of major cardiovascular disease. Of the total 27 416 person years of follow-up in the SGLT2 inhibitor group, 22 627 (83%) was among patients who initiated dapagliflozin, 4521 (16%) among those who initiated empagliflozin, and 268 (1%) among those who initiated canagliflozin. During follow-up, 467 SGLT2 inhibitor users (incidence rate 17.0 events per 1000 person years) and 662 DPP4 inhibitor users (18.0) had a major cardiovascular event, whereas 130 (4.7) and 265 (7.1) had a heart failure event, respectively. Hazard ratios were 0.94 (95% confidence interval 0.84 to 1.06) for major cardiovascular events and 0.66 (0.53 to 0.81) for heart failure. Hazard ratios were consistent among subgroups of patients with and without history of major cardiovascular disease and with and without history of heart failure. Hazard ratios for secondary outcomes, comparing SGLT2 inhibitors with DPP4 inhibitors, were 0.99 (0.85 to 1.17) for myocardial infarction, 0.94 (0.77 to 1.15) for stroke, 0.84 (0.65 to 1.08) for cardiovascular death, and 0.80 (0.69 to 0.92) for any cause death. In the as-treated analyses, hazard ratios were 0.84 (0.72 to 0.98) for major cardiovascular events, 0.55 (0.42 to 0.73) for heart failure, 0.93 (0.76 to 1.14) for myocardial infarction, 0.83 (0.64 to 1.07) for stroke, 0.67 (0.49 to 0.93) for cardiovascular death, and 0.75 (0.61 to 0.91) for any cause death.

Conclusions In this large Scandinavian cohort, SGLT2 inhibitor use compared with DPP4 inhibitor use was associated with reduced risk of heart failure and any cause death, but not with major cardiovascular events in the primary intention-to-treat analysis. In the additional as-treated analyses, the magnitude of the association with heart failure and any cause death became larger, and a reduced risk of major cardiovascular events that was largely driven by the cardiovascular death component was observed. These data help inform patients, practitioners, and authorities regarding the cardiovascular effectiveness of SGLT2 inhibitors in routine clinical practice.

DOI: https://doi.org/10.1136/bmj.l4772

Source: https://www.bmj.com/content/366/bmj.l4772