Transcript 20110728ADDITIONEuro
Journal Club
Griffin SJ, Borch-Johnsen K, Davies MJ, Khunti K, Rutten GE, Sandbæk A, Sharp SJ, Simmons RK, van den Donk M, Wareham NJ, Lauritzen T.
Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial.
Lancet. 2011 Jul 9;378(9786):156-67. Epub 2011 Jun 24.
2011年7月28日 8:30-8:55 ８階 医局 埼玉医科大学 総合医療センター 内分泌・糖尿病内科
Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University
松田 昌文
Matsuda, Masafumi
J-DOIT3 2
型糖尿病患者を対象とした血管合併症抑制 のための強化療法と従来治療とのランダム化比較試験
2
型糖尿病（
45
歳以上
70
歳未満、
HbA1c
≧
6.5
％） ＋ 血圧 ≧
140/90(
内服なし
) or 130/80(1 or 2
剤内服
) or LDL
≧
120 or TG
≧
150 or HDL
＜
40(
内服なし
or 1
剤
)
ランダム割付
(
心血管病変既往の有無、性別、年齢、
HbA1c
で調整
)
強化治療群（目標値）
HbA1c
＜
5.8
％ 血圧＜
120/75 LDL
＜
80
，
HDL
≧
40
，
TG
＜
120 (
虚血性心疾患の既往例は
LDL
＜
70) (TG
≧
150
の場合は
nonHDL
で評価
,nonHDL<110) BMI
≦
22
従来治療群（目標値）
HbA1c
＜
6.5
％ 血圧＜
130/80 LDL
＜
120
，
TG
＜
150 (
虚血性心疾患の既往例は
LDL
＜
100) BMI
≦
24
〔
http://www.jdoit3.jp/index.html
〕
3
the Steno-2 Study 7.8 years follow-up to the Steno-2 Study + 5.5 years N Engl J Med 2008;358:580-91.
Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional-therapy group (hazard ratio, 0.54; 95% confidence interval [CI], 0.32 to 0.89; P = 0.02). Intensive therapy was associated with a lower risk of death from cardiovascular causes (hazard ratio, 0.43; 95% CI, 0.19 to 0.94; P = 0.04) and of cardiovascular events (hazard ratio, 0.41; 95% CI, 0.25 to 0.67; P<0.001).
MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK
(S J Griffi n DM, S J Sharp MSc, R K Simmons PhD, Prof N J Wareham PhD)
; Steno Diabetes Centre, Gentofte, Denmark
(Prof K Borch Johnsen DMSc)
; Institute of Public Health, Research Centre for Quality in Health Care, University of Southern Denmark, Odense, Denmark
(Prof K Borch-Johnsen)
; School of Public Health, Department of General Practice, University of Arhus, Arhus, Denmark
(Prof K Borch-Johnsen, Prof A Sandbak PhD, Prof T Lauritzen DMSc)
; Department of Cardiovascular Sciences
(Prof M J Davies MD)
and Department of Health Sciences
(Prof K Khunti MD)
, University of Leicester, Leicester, UK; and Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands
(Prof G E H M Rutten PhD, M van den Donk PhD)
Lancet 2011; 378: 156 –67
Background
Intensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes. We investigated the effect of early multifactorial treatment after diagnosis by screening.
Methods
In a pragmatic, cluster-randomised, parallel-group trial done in Denmark, the Netherlands, and the UK, 343 general practices were randomly assigned screening of registered patients aged 40 –69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors. The primary endpoint was first cardiovascular event, including cardiovascular mortality and morbidity, revascularisation, and non traumatic amputation within 5 years. Patients and staff assessing outcomes were unaware of the practice ’ s study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549.
T-chol 5 mmol/L = 193 mg/dl 4.5 mmol/L = 174 mg/dl 3.5 mmol/L = 135 mg/dl
Figure 1: Trial profile
81mg/dl
Figure 2: Cumulative incidence and relative risk of composite cardiovascular endpoint
(A) Cumulative incidence curves by treatment group. The p value was calculated with Cox ’ s regression and fixed-effects meta-analysis.
Figure 2: Cumulative incidence and relative risk of composite cardiovascular endpoint
(B) HRs of development of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and revascularisation as a first event (secondary endpoints), and these cardiovascular events combined (primary endpoint), by country and overall. HR=hazard ratio. CVD=cardiovascular disease.
Figure 3: Cumulative incidence and relative risk of all-cause mortality
(A) Kaplan-Meier survival estimates by treatment group.
Figure 3: Cumulative incidence and relative risk of all-cause mortality
(B) HRs of all-cause mortality, by country and overall. HR=hazard ratio. CVD=cardiovascular disease.
Figure 4: Proportion of patients for whom cardiovascular risk factor values were below the intensive treatment intervention target thresholds at baseline and after 5 years of follow-up
1 SE are shown. CVD=cardiovascular disease. HbA1c=glycated haemoglobin A1c.
Findings
Primary endpoint data were available for 3055 (99 ・ 9%) of 3057 screen-detected patients. The mean age was 60 ・ 3 (SD 6 ・ 9) years and the mean duration of follow-up was 5 ・ 3 (SD 1 ・ 6) years. Improvements in cardiovascular risk factors (HbA1c and cholesterol concentrations and blood pressure) were slightly but significantly better in the intensive treatment group. The incidence of first cardiovascular event was 7 ・ 2% (13 ・ 5 per 1000 person-years) in the intensive treatment group and 8 ・ 5% (15 ・ 9 per 1000 person-years) in the routine care group (hazard ratio 0 ・ 83, 95% CI 0 ・ 65 –1 ・ 05), and of all-cause mortality 6 ・ 2% (11 ・ 6 per 1000 person years) and 6 ・ 7% (12 ・ 5 per 1000 person-years; 0 ・ 91, 0 ・ 69 –1 ・ 21), respectively.
Interpretation
An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death.
Message/Comments 2
型糖尿病患者
3057
人
を
対象
に、
早期
の
多 元的強化療法
の
心血管疾患予防効果
を
無作 為化比較試験
で
調査
。リスク
因子
にわずか ながら
有意
な
改善
が
見
られ、
初発心血管
イ ベント
発生率
は
強化治療群
7.2％、ル
ー
チン
治療群
8.5％（ハザ
ー
ド
比
0.83）だった。
早 期強化治療
により
心血管
イベントは
有意
で はないものの、わずかに
減少
した。
有意差