PowerPoint プレゼンテーション

Journal Club
Zoungas S, Chalmers J, Neal B, Billot L, Li Q, Hirakawa Y, Arima H, Monaghan H, Joshi R, Colagiuri
S, Cooper ME, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Lisheng L, Mancia G, Marre M,
Matthews DR, Mogensen CE, Perkovic V, Poulter N, Rodgers A, Williams B, MacMahon S, Patel A,
Woodward M; the ADVANCE-ON Collaborative Group.
Follow-up of Blood-Pressure Lowering and Glucose Control in Type 2 Diabetes.
N Engl J Med. 2014 Sep 19. DOI: 10.1056/NEJMoa1407963
Ikramuddin S, Blackstone RP, Brancatisano A, Toouli J, Shah SN, Wolfe BM, Fujioka K, Maher JW,
Swain J, Que FG, Morton JM, Leslie DB, Brancatisano R, Kow L, O'Rourke RW, Deveney C, Takata M,
Miller CJ, Knudson MB, Tweden KS, Shikora SA, Sarr MG, Billington CJ.
Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the
ReCharge randomized clinical trial.
JAMA. 2014 Sep 3;312(9):915-22. doi: 10.1001/jama.2014.10540.
2014年10月2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
ACCORD
HbA1Cの推移
9.0
主要評価項目
25
中央値
バーは四分位範囲
ハザード比
95%
信頼区間
p値
0.90
0.78, 1.04
0.16
9.5
通常療法
累積イベント発症率（%）
9.0
HbA1C（%）
8.5
8.0
7.5
7.0
6.5
6.0
20
通常療法
15
5
強化療法
0
0
1
症例数
通常療法
強化療法
強化療法
10
0.0
良い
差がない！
2
3
4
5
6
観察期間（年）
5,109
5,119
4,774
4,768
4,588
4,585
3,186
3,165
1,744
1,706
良い
0
1
2
436
471
強化療法
通常療法
4
5
6
475
440
448
395
観察期間（年）
症例数
455
476
3
5,128
5,123
4,843
4,827
4,390
4,262
2,839
2,702
1,337
1,186
VADT
HbA1Cの推移
非致死性イベント
10.5
中央値
10.0
通常療法（8.4%）
100
良い
9.5
差がない！
80
強化療法
60
通常療法
8.5
非発症率（%）
HbA1C（%）
9.0
8.0
7.5
7.0
40
6.5
強化療法（6.9%）
6.0
20
5.5
0.0
登録時
良い
95%
信頼区間
ハザード比
0.845
p値
0.704, 1.016 0.0725
0
1
2
3
4
観察期間（年）
5
6
0
1
2
3
4
観察期間（年）
5
6
7
ADVANCE
HbA1Cの推移
大血管症+細小血管症への影響
差があったが10%程度！
10.0
25
P<0.001
通常療法
9.5
平均HbA1C（%）
8.5
8.0
7.5
強化療法
7.0
6.5
6.0
5.5
累積イベント発症率（%）
9.0
20
15
10
通常療法
5.0
0.0
良い
5
ハザード比
95%
信頼区間
p値
0.90
0.82, 0.98
0.01
0
0
6 12 18 24 30 36 42 48 54 60 66
HbA1C値
通常療法
強化療法
強化療法
観察期間（ヵ月）
7.32 7.30
7.01 6.93
7.29
6.70
7.29
6.53
良い
症例数
7.31
6.50
7.33 7.29
6.52 6.53
0
6 12 18 24 30 36 42 48 54 60 66
観察期間（ヵ月）
強化療法 5,570 5,457 5,369 5,256 5,100 4,957 4,867 4,756 4,599 4,044 1,883 447
通常療法 5,569 5,448 5,342 5,240 5,065 4,903 4,808 4,703 4,545 3,992 1,921 470
ADVANCE Collaborative Group.
Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010;363:1410-8.
N Engl J Med. 2014 Sep 19. DOI: 10.1056/NEJMoa1407963
Background
In the Action in Diabetes and Vascular Disease:
Preterax and Diamicron Modified Release
Controlled Evaluation (ADVANCE) factorial trial,
the combination of perindopril and indapamide
reduced mortality among patients with type 2
diabetes, but intensive glucose control, targeting
a glycated hemoglobin level of less than 6.5%,
did not. We now report results of the 6-year posttrial follow-up.
Methods
We invited surviving participants, who had
previously been assigned to perindopril–
indapamide or placebo and to intensive or
standard glucose control (with the glucose-control
comparison extending for an additional 6 months),
to participate in a post-trial follow-up evaluation.
The primary end points were death from any
cause and major macrovascular events.
Figure 1. Cumulative Incidence of
Events, According to BloodPressure–Lowering Study Group.
Shown is the percentage of patients
who had events at any time after the
start of randomized treatment in the
Action in Diabetes and Vascular
Disease: Preterax and Diamicron
Modified Release Controlled
Evaluation (ADVANCE) trial,
according to assignment to the
active-drug (perindopril–indapamide)
group or the placebo group.
Cumulative hazard ratios (active-drug
group vs. placebo group) and P
values are shown for a 12-year
period from the start of randomized
treatment to the end of the post-trial
follow-up in the ADVANCE–
Observational Study (ADVANCE-ON).
The insets in Panels A and C (which
show outcomes that were reduced
significantly with the active drug)
display the same data on an enlarged
y axis.
Figure 2. Hazard Ratios for Events,
According to Blood-Pressure–
Lowering Study Group.
Hazard ratios are shown for events
that occurred from the start of
randomized treatment to the end of
the blood-pressuring–lowering
comparison (2007), to the end of the
glucose-control comparison (2008),
and to the end of each year of posttrial follow-up (2010 through 2013).
The hazard ratios are for the activedrug (perindopril–indapamide) group
versus the placebo group. P values
are for the between-group
comparison at the final visit for the
randomized trial in 2007 and at the
end of the post-trial follow-up period.
The data for 2013 include those
obtained in the first 2 months of
2014, when follow-up was
terminated. T1 indicates the final visit
for the blood-pressure-comparison
cohort, and T2 the final visit for the
glucose-comparison cohort. Vertical
lines indicate 95% confidence
intervals.
Figure 3. Cumulative Incidence of
Events, According to GlucoseControl Study Group.
Shown is the percentage of patients
who had events at any time after the
start of randomized treatment,
according to assignment to the
intensive-glucose-control group or
the standard-glucose-control group.
Hazard ratios (intensive control vs.
standard control) and P values are
shown for the 12-year period from
the start of randomized treatment to
the end of the post-trial follow-up.
The inset in Panel E (which shows an
outcome that was reduced
significantly with intensive glucose
control) displays the same data on an
enlarged y axis.
Figure 4. Hazard Ratios for Events,
According to Glucose-Control
Study Group.
Hazard ratios are shown for events
that occurred from the start of
randomized treatment to the end of
the glucose-control comparison
(2008) and to the end of each year of
post-trial follow-up (2010 through
2013). The hazard ratios are for the
intensive-control group versus the
standard-control group; values less
than 1.00 represent better outcomes
in the intensive-control group. P
values are for the between-group
comparison at the final visit for the
randomized trial in 2008 and at the
end of the post-trial follow-up period.
The data for 2013 include those
obtained in the first 2 months of 2014,
when follow-up was terminated.
Vertical lines indicate 95%
confidence intervals.
Results
The baseline characteristics were similar among the 11,140
patients who originally underwent randomization and the 8494
patients who participated in the post-trial follow-up for a median of
5.9 years (blood-pressure–lowering comparison) or 5.4 years
(glucose-control comparison). Between-group differences in blood
pressure and glycated hemoglobin levels during the trial were no
longer evident by the first post-trial visit. The reductions in the risk
of death from any cause and of death from cardiovascular causes
that had been observed in the group receiving active bloodpressure–lowering treatment during the trial were attenuated but
significant at the end of the post-trial follow-up; the hazard ratios
were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and
0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences
were observed during follow-up in the risk of death from any
cause or major macrovascular events between the intensiveglucose-control group and the standard-glucose-control group; the
hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI,
0.92 to 1.08), respectively.
Conclusions
The benefits with respect to mortality that had
been observed among patients originally
assigned to blood-pressure–lowering therapy
were attenuated but still evident at the end of
follow-up. There was no evidence that intensive
glucose control during the trial led to long-term
benefits with respect to mortality or
macrovascular events.
(Funded by the National Health and Medical Research Council of Australia and
others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286.)
Message
2型糖尿病への降圧療法と血糖降下強化療法を評
価したADVANCE試験の参加者8494人の試験後6年
追跡結果を報告（ADVANCE-ON試験）。降圧療法
による全死因死亡/心血管死抑制効果は減弱した
が、依然有意だった（ハザード比0.91、0.88）。
血糖降下の強化療法と標準療法では、全死因死
亡/大血管イベントリスクに差はなかった。
1Department
of Surgery, University of Minnesota, Minneapolis
of Minnesota, Minneapolis; Scottsdale Healthcare Bariatric Center, Scottsdale, Arizona
3Institute of Weight Control, Sydney, Australia
4Adelaide Bariatric Centre, Adelaide, Australia
5Department of Surgery, Tufts Medical Center, Boston, Massachusetts
6Department of Surgery, Oregon Health & Science University, Portland
7Scripps Clinic, San Diego, California
8Division of General Surgery, Virginia Commonwealth University, Richmond
9Department of Gastroenterologic and General Surgery, Mayo Clinic Rochester, Rochester, Minnesota
10Division of General Surgery, Stanford University School of Medicine, Stanford, California
11Department of Surgery, University of Michigan and Ann Arbor VA Hospital
12North American Science Associates, Minneapolis, Minnesota
13EnteroMedics Inc, St Paul, Minnesota
14Division of General and Gastrointestinal Surgery, Brigham and Women’s Hospital, Boston, Massachusetts
15Division of Endocrinology and Diabetes, Minneapolis VA Medical Center and University of Minnesota, Minneapolis
2University
JAMA. 2014 Sep 3;312(9):915-22. doi: 10.1001/jama.2014.10540.
Importance Although conventional bariatric
surgery results in weight loss, it does so with
potential short-term and long-term morbidity.
Objective To evaluate the effectiveness and
safety of intermittent, reversible vagal nerve
blockade therapy for obesity treatment.
Design, Setting, and Participants A randomized, double-blind,
sham-controlled clinical trial involving 239 participants who had a
body mass index of 40 to 45 or 35 to 40 and 1 or more obesityrelated condition was conducted at 10 sites in the United States
and Australia between May and December 2011. The 12-month
blinded portion of the 5-year study was completed in January
2013.
Interventions One hundred sixty-two patients received an active
vagal nerve block device and 77 received a sham device. All
participants received weight management education.
Main Outcomes and Measures The coprimary efficacy
objectives were to determine whether the vagal nerve block was
superior in mean percentage excess weight loss to sham by a 10point margin with at least 55% of patients in the vagal block group
achieving a 20% loss and 45% achieving a 25% loss. The primary
safety objective was to determine whether the rate of serious
adverse events related to device, procedure, or therapy in the
vagal block group was less than 15%.
VBLOC is a surgically implanted device
that uses electrical pulses to target the
multiple digestive functions under
control of the vagus nerves and to
affect the perception of hunger and
fullness. Unlike pacemakers, patients
power the EnteroMedics' VBLOC device
on and off with a control belt worn
around their waist. When VBLOC is on,
patients are supposed to feel less
hungry, eat less and therefore lose
weight.
According to the company, VBLOC is
potentially less invasive and reversible,
unlike gastric bypass surgery. But
EnteroMedics is also developing
VBLOC at a time when the obese have
far easier treatment options. Recently
approved pills from Vivus
(NASDAQ:VVUS) and Arena
Pharmaceuticals (NASDAQ:ARNA) are
some of the examples.
http://seekingalpha.com/article/1168571-enteromedics-vbloc-obesity-device-fails?page=2
BMI indicates body mass index.
Abbreviation: LOCF, last observation carried forward.
Error bars indicate 95%CIs. BMI indicates body mass index.
Only adverse events attributed by the investigator to the device, procedure, or therapy that
occurred in at least 3%of vagal nerve block group participants are displayed.
Results In the intent-to-treat analysis, the vagal nerve block group
had a mean 24.4% excess weight loss (9.2% of their initial body
weight loss) vs 15.9% excess weight loss (6.0% initial body weight
loss) in the sham group. The mean difference in the percentage of
the excess weight loss between groups was 8.5 percentage points
(95% CI, 3.1-13.9), which did not meet the 10-point target
(P = .71), although weight loss was statistically greater in the vagal
nerve block group (P = .002 for treatment difference in a post hoc
analysis). At 12 months, 52% of patients in the vagal nerve block
group achieved 20% or more excess weight loss and 38%
achieved 25% or more excess weight loss vs 32% in the sham
group who achieved 20% or more loss and 23% who achieved
25% or more loss. The device, procedure, or therapy–related
serious adverse event rate in the vagal nerve block group was
3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal.
The adverse events more frequent in the vagal nerve block group
were heartburn or dyspepsia and abdominal pain attributed to
therapy; all were reported as mild or moderate in severity.
Conclusion and Relevance Among patients with
morbid obesity, the use of vagal nerve block
therapy compared with a sham control device did
not meet either of the prespecified coprimary
efficacy objectives, although weight loss in the
vagal block group was statistically greater than in
the sham device group. The treatment was well
tolerated, having met the primary safety objective.
Trial Registration clinicaltrials.gov Identifier:
NCT01327976
Message
病的肥満患者239人を対象に、間欠的可逆的な迷
走神経ブロック療法の効果と安全性を無作為化
臨床試験で検証（ReCharge試験）。平均過剰体
重減少率はブロック群24.4％、偽治療群15.9％
と、偽治療との差は当初の目標であった10ポイ
ントを下回った。12カ月時の20％減量達成率は
それぞれ52％、32％、25％達成率は38％、23％
だった。
間欠的可逆的な迷走神経ブロック療法は一応減
量の効果はありそうだが．．．

Download Report