Transcript 3992576bytes - 埼玉医科大学総合医療センター 内分泌・糖尿病内科

Journal Club
2008年２月14日 8:20-8:50
B棟８階 カンファレンス室
亀田メディカルセンター 糖尿病内分泌内科
Diabetes and Endocrine Department,
Kameda Medical Center
松田 昌文
Matsuda, Masafumi
① NEJM Steno-2 paper
② ACCORD study and JDOIT3 study
③ 4月からの診療報酬改定
From the Steno Diabetes Center, Copenhagen (P.G., H.L.-A., O.P.);
Department of Ophthalmology, Glostrup University Hospital, Glostrup
(H.L.-A.); Department of Medical Endocrinology, Rigshospitalet
Copenhagen University Hospital, Copenhagen (H.-H.P.); and Faculty of
Health Sciences, University of Aarhus, Aarhus (H.-H.P., O.P.) — all in
Denmark. Address reprint requests to Dr. Pedersen at the Steno Diabetes
Center, 2820 Gentofte, Copenhagen, Denmark, or at [email protected].
N Engl J Med 2008;358:580-91.
Background
Intensified multifactorial intervention — with tight
glucose regulation and the use of renin–
angiotensin system blockers, aspirin, and lipidlowering agents — has been shown to reduce the
risk of nonfatal cardiovascular disease among
patients with type 2 diabetes mellitus and
microalbuminuria. We evaluated whether this
approach would have an effect on the rates of
death from any cause and from cardiovascular
causes.
Methods
In the Steno-2 Study, we randomly assigned
160 patients with type 2 diabetes and
persistent microalbuminuria to receive either
intensive therapy or conventional therapy;
the mean treatment period was 7.8 years.
Patients were subsequently followed
observationally for a mean of 5.5 years, until
December 31, 2006. The primary end point at
13.3 years of follow-up was the time to death
from any cause.
Summary of Results
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). One patient in the intensive-therapy
group had progression to end-stage renal disease, as
compared with six patients in the conventional-therapy
group (P = 0.04). Fewer patients in the intensive-therapy
group required retinal photocoagulation (relative risk,
0.45; 95% CI, 0.23 to 0.86; P = 0.02). Few major side
effects were reported.
Conclusions
In at-risk patients with type 2 diabetes,
intensive intervention with multiple drug
combinations and behavior modification
had sustained beneficial effects with
respect to vascular complications and
on rates of death from any cause and
from cardiovascular causes.
(ClinicalTrials.gov number, NCT00320008.)
Participants will be treated and followed for 4–8 years (approximate
mean, 5.6 years). The primary outcome measure for all 3 research
questions is the first occurrence of a major cardiovascular event,
specifically a composite outcome of nonfatal MI, nonfatal stroke, or
cardiovascular death. Secondary outcomes include other
cardiovascular outcomes, total mortality, diabetic microvascular
disease (retinopathy, nephropathy, and neuropathy), health-related
quality of life, and cost-effectiveness.
All participants were randomized to either intensive or standard
glycemic goals in the open-label glycemia trial. Participants
randomized to the intensive glycemia treatment group have an HbA1c
target of 6.0%. Participants randomized to the standard glycemia
treatment group have an HbA1c target of 7.0%–7.9%, with an
expectation that the median HbA1c level will be approximately 7.5%.
Treatment algorithms using metformin, sulfonylureas, meglitinides,
thiazolidinediones, -glucosidase inhibitors, insulin, and insulin
analogues, coupled with lifestyle intervention, have been developed
for the 2 groups. Exenatide was added to the available formulary in
April 2007. Details of the approaches to glycemia therapy are
presented elsewhere in this supplement.
Among the 10,251 randomized participants, 5,518 with moderate levels of
dyslipidemia were also randomized to either fenofibrate or matching
placebo in a double-masked fashion, in addition to open-label
background simvastatin therapy administered in accordance with current
guidelines (20–40 mg/day, depending on observed LDL cholesterol values
and whether the participant has had a clinical CVD event). This is the only
masked intervention in ACCORD. Details regarding the evolution of the
lipid protocol are also presented elsewhere in this supplement. Briefly, the
standard dose of the masked fenofibrate or identical placebo used in
ACCORD is 160 mg/day (or the bioequivalent doses of previous
formulations).
Finally, the other 4,733 participants in ACCORD were further randomized to
either an intensive or a standard systolic blood pressure target, 120 or 140
mm Hg, respectively. Most currently available antihypertensive drug
classes are available for use in the 2 groups, and they are administered in
an open-label fashion. Details regarding the blood pressure treatment
strategies are presented elsewhere in this supplement.
ACCORD study
DCCT：網膜症の累積発生率
The Diabetes Control and Complications Trial
一次予防
二次介入
（%）
（%）
60
60
従来療法群
従来療法群
50
50
強化療法群
累
積 40
発
生 30
率
累
積 40
発
生 30
率
20
20
強化療法群
10
10
p＜0.001
p＜0.001
0
0
0
1
2
3
4
5
調査年次
6
7
8
9 （年）
0
Mantel (log-rank) test
データ出典：DCCT Research Group: N Engl J Med, 329(14); 977-986, 1993
1
2
3
4
5
6
調査年次
7
8
9 （年）
Mantel (log-rank) test
For Safety, NHLBI Changes Intensive Blood Sugar Treatment Strategy in Clinical Trial of
Diabetes and Cardiovascular Disease
The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped
one treatment within a large, ongoing North American clinical trial of diabetes and cardiovascular
disease 18 months early due to safety concerns after review of available data, although the study will
continue.
In this trial of adults with type 2 diabetes at especially high risk for heart attack and stroke, the medical
strategy to intensively lower blood glucose (sugar) below current recommendations increased the risk
of death compared with a less-intensive standard treatment strategy. Study participants receiving
intensive blood glucose lowering treatment will now receive the less-intensive standard treatment.
The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study enrolled 10,251 participants. Of
these, 257 in the intensive treatment group have died, compared with 203 within the standard treatment
group. This is a difference of 54 deaths, or 3 per 1,000 participants each year, over an average of almost
four years of treatment. The death rates in both groups were lower than seen in similar populations in
other studies.
10,251 participants. 40-82 y.o., 2-7 years
Death in the intensive Tx group:
257/5128 (14 in 1000 persons per year)
Death in the standard Tx group:
203/5123 (11 in 1000 persons per year)
p=0.011 (not shown)
Statement from the American Diabetes Association
Related to ACCORD Trial Announcement
The American Diabetes Association continues to advise people with diabetes to strive for an A1C (a
measure of long-term blood glucose control) of less than 7 percent. Recent data indicates that more than
half of the population with diabetes in the U.S. have an A1C less than 7 percent and this overall level of
glucose control appears to be of great benefit rather than harm.
The importance of glucose control in diabetes is firmly established. Evidence from the landmark Diabetes
Control and Complications Trial (DCCT), and the U.K. Prospective Diabetes Study (UKPDS) show that
improved glucose control to a level of approximately 7 percent reduces the complications of diabetes
dramatically.
The Association’s treatment guidelines also state that treatment should be tailored to the individual
patient and that for some people with diabetes, intensive glucose control may not be warranted. Of note,
the American Diabetes Association (in its Standards of Medical Care) states: “Less stringent A1C goals
may be appropriate for patients with a history of severe hypoglycemia, patients with limited life
expectancies, children, individuals with comorbid conditions, and those with longstanding diabetes and
minimal or stable microvascular complications.”
This recent announcement by ACCORD investigators suggests that very intensive glucose lowering
treatment aimed at normalizing blood glucose (A1C<6%) may be detrimental, at least in middle-aged and
older adults with vascular disease or multiple risk factors for vascular disease. The exact reason for the
increased death rates with intensive treatment that occurred in ACCORD are not yet known. However, an
analysis of the ACCORD data indicates that the detrimental effect of intensive therapy was not due to
hypoglycemia or any specific combination of drug therapies.
The American Diabetes Association looks forward to more analysis of the data from ACCORD, as well as
other ongoing studies that may shed more light on this issue. However, at this time, the American
Diabetes Association advises people with diabetes who have existing cardiovascular disease (CVD), or
multiple CVD risk factors, to consult with their health care team about their treatment goals and to
ensure that their blood pressure and cholesterol are appropriately managed.
PRESENT Diabetes
http://presentdiabetes.com/
【J-DOIT3 新規登録一時停止等に伴うFAQ】
Q1．いつまで新規登録停止となるのか
A1．一斉調査に基づいた中間解析を早急に行い、安全性が確認されるまで停止となります。
Q2．現在、仮登録中の被験者はどうするのか
A2．本登録に進まず、登録再開の連絡があるまでお待ちください。
Q3．仮登録もできないのか
A3．はい。
Q4．新たな同意説明はしてもいいのか
A4．いいえ。登録再開になるまでは、新たな同意説明も行わないようお願いいたします。
Q5．血糖コントロールためのステップアップを行って良いか
A5．いいえ。血糖コントロールのためのステップアップは行わず、安全性が確認されるまでは現在のス
テップの維持をお願い致します。
Q6. 血糖コントロールのステップアップを行わないということは、いかなる変更もしないという意味でしょ
うか？血糖コントロールが悪化した場合は、担当医師の裁量で経口薬の変更等は行ってよいの
でしょうか？
A6. なるべく増量・追加はせずに過ごしてください。しかし、血糖値が悪化して、変更・追加をした方がい
いとわれる症例に対しては、ステップアップのルールに従って変更・追加を行ってください。
Q7．運動療法、食事療法はどうするのか
A7．現在行っている運動療法、食事療法を維持するようお願い致します。
Q8．従来治療群はそのままでいいのか
A8．はい。従来治療群については、そのまま試験を継続していただいて問題ございません。
Q9．今後はどうなるのか
A9．一斉調査に基づいた解析結果を受けての判断となります。
Q10．日本でもそのようなデータはあるのか
A10．ございません。
Q11．今回の件は、何か施設で手続きや報告がいるのか
Q11．貴施設の倫理審査委員会にご確認いただき、必要時はお手数ですが報告対応をお願い致します。
Q12．患者への再同意は必要か
A12．現時点では、不要です。今回の結果を受けて、同意説明文書の改訂が行われたときには、倫理審
査委員会への手続きおよび患者様からの再同意が必要となります。
Q13. 登録済みあるいは仮登録済の患者への説明はどのように行えばよいでしょうか？
ACCORD試験のように、中央から手紙の送付を考えていらっしゃるのでしょうか？
A13. 今回のACCORD試験の結果はこれまでの他の研究成果からしても予想外の結果であり、JDOIT3や一般の糖尿病の患者さんに敷衍できる結果かどうかは疑問もあります。
実際に米国糖尿病学会は血糖値のコントロール目標をこれまでどおり7%未満とすると発表していま
すし、さらに、先行する3つの危険因子に介入した試験であるSteno2では13.3年間の観察（介入期
間7.8年、観察期間5.5年）で、強化療法の患者さんの死亡率が46％減少したと最近報告されていま
す(NEJM、ただし、強化療法群の観察終了時平均HbA1c 7.7%)。
J-DOIT3では、現在これまでの本試験における死亡を含めた有害事象と治療の有効性の中間的な
検討を行っており、近日中に結果が出て再開するかどうか決定しますので、次回の外来時にはお知
らせできると思います。
中間解析の結果が出たあとに、参加していただいている患者さん宛に手紙は出したいと思います。
入院基本料等加算の新設
医師事務作業補助体制加算（入院初日）
１
２５対１補助体制加算 ３５５点
２
５０対１補助体制加算 １８５点
３
７５対１補助体制加算 １３０点
４
１００対１補助体制加算 １０５点
［医師事務作業補助者の業務範囲］
１ 診断書などの文書作成補助、診療記録への代行入力、医療の質
の向上に資する事務作業（診療に関するデータ整理、院内がん
登録等の統計・調査、医師の教育や臨床研修のカンファレンスの
ための準備作業等）並びに行政上の業務（救急医療情報システ
ムへの入力、感染症のサーベイランス事業等）への対応を医師
の指示の下に行う
２ 医師以外の職種の指示の下に行う業務、診療報酬の請求事務、
窓口・受付業務、医療機関の経営、運営のための基礎データ収
集業務、看護業務の補助並びに物品運搬業務等については行
わないこと