1. 吴永健 中国医学科学院 北京协和医学院 心血管病研究所 阜外心血管医院
The Combination Lipid Therapy and Blood Pressure Control in ACCORD Study —ACCORD降脂和降压研究
吴永健
中国医学科学院 北京协和医学院
心血管病研究所 阜外心血管医院

2. About ACCORD Trial
ACCORD was a randomized trial conducted at 77 clinical sites organized into seven networks in the United States and Canada
The trial enrolled 10,251 high-risk participants with type 2 diabetes mellitus. All participants were randomly assigned to either intensive or standard glycemic control (the ACCORD glycemia trial). In addition, 5518 of the ACCORD participants were also randomly assigned (in a 2-by-2 factorial design) to either simvastatin plus fenofibrate or simvastatin plus placebo (ACCORD lipid trial), and the remaining 4733 participants were also randomly assigned (in a 2-by-2 factorial design) to either intensive or standard blood-pressure control (ACCORD blood-pressure trial).
Supported by contracts from the National Heart, Lung, and Blood Institute. Other components of the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute, contributed funding

3. N Engl J Med 2010;362:

4. 无论收缩压如何，糖尿病患者增加心血管发病率2-3倍

6. BMJ. 2000; 321(7258):412-9

7. "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount

8. There is, however, a paucity of evidence from randomized
clinical trials to support these recommendations

9. 研 究 方 法
The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Prespecified secondary outcomes included the combination of the primary outcome plus revascularization or hospitalization for congestive heart failure (termed the “expanded macrovascular outcome”); the combination of a fatal coronary event, nonfatal myocardial infarction, or unstable angina (termed “major coronary disease events”); nonfatal myocardial infarction; fatal or nonfatal stroke; nonfatal stroke; death from any cause; death from cardiovascular causes; and hospitalization or death due to heart failure

10. 研 究 结 果

11. 研 究 结 果

12. 研 究 结 果

13. 研 究 结 果

14. 研 究 结 果

15. 研 究 结 果

16. 研 究 结 果

17. Limitations
First, the trial had an open-label design, a design that was not likely to have affected bloodpressure goals or measurement or the blinded ascertainment of the outcomes but may have affected the reporting of adverse events
Second, the rate of cardiovascular events was lower than the expected rate in the standard-therapy group
Third, patients younger than 40 years of age were not included in the study and patients older than 79 years of age were not included after the vanguard phase

18. 讨 论 强化降压没有优于标准降压组： 可能影响因素 强化降压组严重不良事件发生率高 强化降压组影响肾小球滤过率和蛋白尿 讨论
讨 论
强化降压没有优于标准降压组：
可能影响因素
强化降压组严重不良事件发生率高
强化降压组影响肾小球滤过率和蛋白尿 讨论
糖尿病患者降压治疗收缩压小于140mmHg就够了?
随访时间不够长?
需要更低的收缩压才能获益？

19. N Engl J Med 2010;362:

23. 他汀治疗是糖尿病合并高脂血症患者的基石，但是对于糖尿病
高危的患者仅仅他汀治疗就足够吗？
Although statins are efficacious in patients with type 2 diabetes, rates of cardiovascular events remain elevated in such patients even after statin treatment—上述3篇文献

24. Arch Intern Med. 2002;162:

25. 研 究 方 法
The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Prespecified secondary outcomes included the combination of the primary outcome plus revascularization or hospitalization for congestive heart failure (termed the “expanded macrovascular outcome”); the combination of a fatal coronary event, nonfatal myocardial infarction, or unstable angina (termed “major coronary disease events”); nonfatal myocardial infarction; fatal or nonfatal stroke; nonfatal stroke; death from any cause; death from cardiovascular causes; and hospitalization or death due to heart failure

26. 研 究 结 果

27. 研 究 结 果

28. 研 究 结 果

29. 研 究 结 果

30. 研 究 结 果

31. 研 究 结 果

32. 研 究 结 果

33. 讨 论
影响因素
One possibility is that the addition of fenofibrate to statin therapy benefited only certain subgroups of patients and that other subgroups that did not benefit diluted the overall effect
A second possibility is that the trial might have had fewer events than anticipated
Another possibility is poor adherence to the experimental protocol（80%）
A fourth possibility is that fenofibrate is not as effective as gemfibrozil

34. ACCORD研究：
一个把看似“简单问题”变成“复杂问题”的研究
敬请杨文英教授和郭静萱教授点评

35. 谢谢！