カテゴリー: 臓器別の問題

【文献名】

Adriana Buitrago-Lopez et al: Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis. BMJ 2011; 343:d4488



【要約】

＜Objective＞

To evaluate the association of chocolate consumption with the risk of developing cardiometabolic disorders.



＜Design＞

Systematic review and meta-analysis of randomised controlled trials and observational studies.



＜Data sources＞

Medline, Embase, Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, reference lists of relevant studies to October 2010, and email contact with authors.



＜Study selection＞

Randomised trials and cohort, case-control, and cross sectional studies carried out in human adults, in which the association between chocolate consumption and the risk of outcomes related to cardiometabolic disorders were reported.



＜Data extraction＞
Data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The primary outcome was cardiometabolic disorders, including cardiovascular disease (coronary heart disease and stroke), diabetes, and metabolic syndrome. A meta-analysis assessed the risk of developing cardiometabolic disorders by comparing the highest and lowest level of chocolate consumption.



＜Results＞

From 4576 references seven studies met the inclusion criteria (including 114 009 participants). None of the studies was a randomized trial, six were cohort studies, and one a cross sectional study. Large variation was observed between these seven studies for measurement of chocolate consumption, methods, and outcomes evaluated. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels.



＜Conclusions＞

Based on observational evidence, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders. Further experimental studies are required to confirm a potentially beneficial effect of chocolate consumption.



【開催日】

2011年9月7日

【文献名】

Julia Hippisley-Cox.Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: prospective cohort study.BMJ 2011;343:d4656 doi: 10.1136/bmj.d4656



【この文献を選んだ背景】

入院、もしくは外来診療の中でDVTなどの静脈血栓塞栓症を疑い、場合によっては診断に至るケースは少なくない。今回、DVTの発症リスクを予測するツールが開発されたので紹介したい。



【要約】

＜Objectives＞

静脈血栓塞栓症（深部）の将来の発症リスクを予測するアルゴリズムの開発と妥当性を確認するため。

（下肢腫脹などの有症状患者が血栓塞栓症に「現在」罹患しているかどうかのリスクではない。）



＜Design＞
Prospective open cohort study
　1年後と5年後の時点でのリスク計算式を導き出すためコホートでCox比例ハザードモデルを用いた。
  Calibration（較正）とdiscrimination（識別）を測定するため、validation cohortを用いた。
　患者をStataを用いて無作為に2/3をderivation（解析群）に、1/3をvalidation（検証群）に割り付けた。



＜Setting＞

QReserchデータベース上のイングランドとウェールズにある564か所の家庭医（general practices）



＜Participants＞
25～84歳で、過去12カ月で妊娠記録がなく、静脈血栓塞栓症の既往がなく、ベースラインで経口抗凝固薬の処方を受けていない患者。

＜Outcomes＞
　プライマリケア医のカルテもしくは死亡記録に記録されている静脈血栓塞栓症（DVTもしくは肺塞栓）の発生



＜Results＞
Derivation cohort（解析群）：
 
割り付け 2,598,829人－exclusion＝2,314,701人が対象。

14,746件/10,095,199人年（14.6/10,000人年）発生。
Validation cohort（検証群）：

割り付け 1,354,517人－exclusion＝1,240,602人が対象。
6,913件/4,632,694人年（14.9/10,000人年）発生した。
Baselineのcharacteristic　⇒　Table1参照
最終的なモデルにおいて独立予測因子に以下が含まれる。
男性・女性双方において、年齢、BMI、喫煙状況、静脈瘤、うっ血性心不全、慢性腎症、COPD、炎症性腸疾患、過去6カ月における入院歴、抗精神病薬の現在の処方歴

研究者らによって以下が含められた。
女性における経口避妊薬、タモキシフェン、ホルモン補充療法
   （以下の項目は有意差なし）

心房細動、心血管系疾患、喘息、静脈血栓塞栓症の家族歴

このモデルは良く較正されていると言える。（well calibrated）　⇒　Table3

5年時点で

R2 statistic：女性においては33%、男性においては34%

D statistic：女性では1.43、男性では1.45であった。
ROC statistic：両性別で0.75であった。



＜Conclusions＞

1年と5年の時点における血栓症の寄与危険度を定量化する新しいリスク予測モデルを開発し、妥当性を確認した。静脈血栓塞栓症を予防していくためにハイリスク患者を同定することに役立つ。このアルゴリズムは患者であれば知っている、もしくはカルテに一般的に記載されている単純な臨床上の変数から成り立っている。臨床上の一般的なコンピュータシステムと統合することができ、入院、もしくはリスクを上昇させてしまうような治療を開始する前のリスク評価に用いることができる。



QThrombosisR risk calculator

http://www.qthrombosis.org/index.php



【開催日】

2011年9月7日

【文献名】

Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials
 BMJ 2011;343:d4169 doi: 10.1136/bmj.d4169



【要約】

＜目的＞

2型糖尿病における厳密な血糖降下治療と、全死亡及び血管系死亡の関係をみる



＜研究デザイン＞

RCTのメタ解析



＜データ源＞

Medline、Embace、Cochraneデータベースのシステマティックレビュー、最近のメタアナリシスのリスト



＜選択された研究＞

１８歳以上の2型糖尿病で、心血管イベントと微小血管合併症における、厳密な血糖降下治療について評価されている13編のRCT（5つは二重盲検でJadad３点以上。8つは非盲検は３点以下）



＜データの抽出＞

一次エンドポイントは全死亡と心血管系死亡。二次エンドポイントは重症な低血糖と、大血管および微小血管イベント。



＜結果の統合＞

結果はrisk ratio(99％信頼区間)として報告した。統計学的異質性はカイ二乗検定など。fixed effect modelで統合した。厳密な血糖降下治療と通常のコントロールの比較は、fixed effect modelで評価した。かくRCTの質はJadad scoreで評価した。



＜結果＞

13の研究が採用された。34533人の患者のうち、18315人が厳密な血糖降下治療をうけ、16218人が通常の治療を受けた。厳密な血糖降下治療は全死亡に大きな影響はもたらさなかった(RR：1.04、99％信頼区間：0.91?1.19)。心血管系死亡も同様であった(1.11、0.86?1.43)。しかし、厳密な血糖降下治療は、非致死的なAMIを減少させた(0.85、0.74?0.96、P<0.001)。また微量アルブミン尿も減少させた(0.90、0.85?0.96、P<0.001)。しかし重症な低血糖が2倍だった(2.33、1.62?3.36、P<0.001)。５年間で、１人の心筋梗塞を防ぐために117人?150人の治療が必要。微量アルブミン尿も同様に32人?142人の治療が必要。しかしこれをすると、15人?52人に１人の割合で毎年重症な低血糖が起きる(NNH=15?52)。質の高い研究(Jadad scoreで3点以上)に限ると、うっ血性心不全の危険性が47％増加する。 

＜結論＞ 
メタ解析の結果からは、全死亡および心血管死亡における厳密な血糖降下治療の利益は限られている。研究者らは、全死亡の９％の減少および19％の増加は除外できなかった。同様に心血管死亡の14％の減少と43％の増加は除外できなかった。大血管および微小血管イベントにおける厳密な血糖降下治療の利益／不利益の比は、不明確なままである。重症な低血糖の害は、厳密な血糖降下治療にcounterbalanceしてしまうかもしれない。2型糖尿病患者への最前の治療アプローチを確立するには、さらなる二重盲検RCTが必要である。

 ＜限界＞
 出版バイアスがあるかもしれない。研究間に治療方法、治療目標、フォローの期間にばらつきがある。

 【開催日】 
2011年9月21日

【文献名】

Memantine Treatment in Patients With Moderate to Severe Alzheimer Disease Already Receiving Donepezil  A Randomized Controlled Trial　JAMA 2004 Jan 21;Vol291,No.3:317-324



【要約】

＜Context＞

Memantine is a low- to moderate-affinity, uncompetitive N-methyl-Daspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease(AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed.

Objective  To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil.



＜Design, Setting, and Participants＞

A randomized, double-blind, placebo controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial.



＜Interventions＞

Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n=203) or placebo (n=201) for 24 weeks.



＜Main Outcome Measures＞

Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study? Activities of Daily Living Inventory (ADCS-ADL19). Secondary outcomes included a Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale).



＜Results＞

The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs ?2.5 (0.69), respectively (P_.001); ADCS-ADL19 (possible score range, 0-54), ?2.0 (0.50) vs ?3.4 (0.51), respectively (P=.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P=.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively.



＜Conclusions＞

In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.



【開催日】

2011年8月24日

【文献名】

Leslee L. Subak, M.D.,　 Weight Loss to Treat Urinary Incontinence　in Overweight and Obese Women　N Engl J Med 2009 360;5 jan 29, 481-490



【要約】

＜Background＞

Obesity is an established and modifiable risk factor for urinary incontinence, but conclusive evidence for a beneficial effect of weight loss on urinary incontinence is lacking.



＜Methods＞

Researchers randomly assigned 338 overweight and obese women with at least 10 urinary incontinence episodes per week to an intensive 6-month weight-loss program that included diet, exercise, and behavior modification (226 patients) or to a structured education program (112 patients).



＜Results＞

The mean (±SD) age of the participants was 53±11 years. The body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) and the weekly number of incontinence episodes as recorded in a 7-day diary of voiding were similar in the intervention group and the control group at baseline (BMI, 36±6and 36±5, respectively; incontinence episodes, 24±18 and 24±16, respectively). The women in the intervention group had a mean weight loss of 8.0% (7.8 kg), as compared with 1.6% (1.5 kg) in the control group (P<0.001). After 6 months, the mean weekly number of incontinence episodes decreased by 47% in the intervention group, as compared with 28% in the control group (P = 0.01). As compared with the control group, the intervention group had a greater decrease in the frequency of stress incontinence episodes (P = 0.02), but not of urge-incontinence episodes (P = 0.14).A higher proportion of the intervention group than of the control group had a clinically relevant reduction of 70% or more in the frequency of all incontinence episodes (P<0.001), stress-incontinence episodes (P = 0.009), and urge-incontinence episodes(P = 0.04).

 ＜Conclusions＞
 A 6-month behavioral intervention targeting weight loss reduced the frequency of self-reported urinary-incontinence episodes among overweight and obese women as compared with a control group. A decrease in urinary incontinence may be another benefit among the extensive health improvements associated with moderate weight reduction. 

 【開催日】
 2011年8月17日

【文献名】

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. The Lancet, Volume 378, Issue 9789, Pages 403 – 411, 30 July 2011.



【要約】
うつ症状を示すアルツハイマー病患者に、選択的セロトニン再取り込み阻害薬（SSRI）のセルトラリン、ノルアドレナリン作動性・特異的セロトニン作動性抗うつ薬（NaSSA）のミルタザピン、偽薬のいずれかを投与した無作為化試験の結果が、Lancet誌2011年7月18日号に掲載された。英London King’s CollegeのSube Banerjee氏らによると、13週後と39週後のうつ症状の変化において、どちらの抗うつ薬にも偽薬を上回る利益は見られず、有害事象発生率は高かった。

認知症患者の多くはうつ症状を示すが、適切な薬物療法を示した質の高いエビデンスはない。



現状では、主要学会は抗うつ薬の認知症患者への適用を支持しており、セルトラリンなどが第1選択として処方されている。高齢化が進む先進国では、認知症患者のうつは臨床的に重要な領域であると考えた英National Institute of Health Research (NIHR)は、著者らに臨床試験の実施を依頼した。



そこで著者らは、英国で最もよく処方されているセルトラリンとミルタザピンの有効性と安全性を偽薬と比較する、二重盲検の無作為化試験HTA-SADDを実施した。

イングランドの高齢者精神医療施設9カ所で、07年1月から09年12月まで、患者登録を実施。NINCDS-ADRDA基準に基づいてアルツハイマー病疑いまたは可能性例と判定された患者の中から、4週間以上うつ状態が続いており、Cornell認知症抑うつ尺度（CSDD）のスコアが8以上の人々を選んだ。臨床的に危険な状態（自殺リスクが高いなど）の患者などは除外した。

登録患者は、1対1対1の割合で、セルトラリン（目標用量は150mg、107人、平均年齢80歳）、ミルタザピン（同45mg、108人、79歳）、偽薬（111人、79歳）のいずれかに無作為に割り付けた。4週と8週の時点でCSDDスコアを調べ、いずれも4以上なら増量するとした。

主要アウトカム評価指標は、13週時点のCSDDスコアに基づくうつ状態の軽減とし、2次評価指標として39週時点のCSDDスコアなどを評価した。

39週までの脱落は、セルトラリン群が35％、ミルタザピン群が29％、偽薬群が24％だった。1日用量の平均は、登録患者全体ではセルトラリンが70mg、ミルタザピンが24mgで、脱落患者を除くとそれぞれ95mgと30mgになった。



どのグループでも、うつ症状はベースラインに比べ軽快化していた。13週時点でCSDDスコアの低下が最も大きかったのは偽薬群で、-5.6ポイント。セルトラリン群では-3.9ポイント、ミルタザピン群では-5.0ポイントだった。39週時点では、それぞれ-4.8ポイント、-4.0ポイント、-5.0ポイントだった。



線形回帰混合モデルを利用し、ベースラインのCSDDスコア、時間、施設で調整して平均差を求めた。ベースラインから13週までのうつスコアの低下レベルに有意差はなかった。セルトラリン群の偽薬群との平均差は1.17（95％信頼区間-0.23から2.58、P＝0.10）、ミルタザピン群の偽薬群との平均差は0.01（-1.37から1.38、P＝0.99）で、セルトラリン群をミルタザピン群と比較した場合の平均差は1.16（-0.25から2.57、P＝0.11）だった。39週の時点でも結果は同様で、偽薬群との平均差は、セルトラリン群が0.37（-1.12から1.87、P＝0.62）、ミルタザピン群は-0.66（-2.12から0.79、P＝0.37）だった。



ベースラインのうつ病の程度で患者を層別化（CSDDのスコアが8～11か12以上か）して分析したが、やはりこれら2種類の抗うつ薬の有効性は認められなかった。

39週までの消化器症状、神経学的症状などの有害事象発生率を調べたところ、偽薬群は29人（26％）、セルトラリン群は46人(43％、P＝0.010)、ミルタザピン群は44人(41％、P＝0.031)だった。

この試験では、偽薬を上回る抗うつ薬の利益は見られず、有害事象のリスクは有意に高かった。著者らは、「得られた結果はネガティブだが臨床的には重要だ」という。この試験では、割り付けから13週時点で偽薬群のうつスコアにも改善が見られたことから、「うつ症状が見られてから3カ月程度は観察を継続し、変化が見られないケースにのみ抗うつ薬の使用を考慮した方が良いのではないか」と著者らは述べている。いずれにせよ、認知症患者のうつに対する第1選択としてこれらの薬剤を用いることについては、再考が必要だろう。



【開催日】

2011年8月10日

【文献名】

Julia Hippisley-Cox : Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database(¶1)  BMJ 2010;340:c2197



【要約】

＜Objective＞

To quantify the unintended effects of statins according to type, dose, and duration of use.



＜Design＞

Prospective open cohort study using routinely collected data. 



＜Setting＞
368 general practices in England and Wales supplying data to the QResearch database. 【Participants】 2 004 692 patients aged 30-84 years of whom 225 922 (10.7%) were new users of statins: 159 790 (70.7%) were prescribed simvastatin(訳注；リポバスR), 50 328 (22.3%) atorvastatin(訳注；リピトールR), 8103 (3.6%) pravastatin(訳注；メバロチンR), 4497 (1.9%) rosuvastatin(訳注；クレストールR), and 3204 (1.4%) fluvastatin(訳注；ローコール).



＜Methods＞

Cox proportional hazards models were used to estimate effects of statin type, dose, and duration of use. The number needed to treat (NNT) or number needed to harm (NNH) were calculated and numbers of additional or fewer cases estimated for 10 000 treated patients.



＜Main outcome measure＞

First recorded occurrence of cardiovascular disease, moderate or serious myopathic events, moderate or serious liver dysfunction, acute renal failure, venous thromboembolism, Parkinson’s disease,dementia, rheumatoid arthritis, cataract, osteoporotic fracture, gastric cancer, oesophageal cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer.



＜Results＞

(To help reading, I added the number to the original article.　See Table6 in original article.)

1.Individual statins were not significantly associated with risk of Parkinson’s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, gastric cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer. 

2.Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract. 

3. Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin. A dose-response effect was apparent for acute renal failure and liver dysfunction. All increased risks persisted during treatment and were highest in the first year. After stopping treatment the risk of cataract returned to normal within a year in men and women. Risk of oesophageal cancer returned to normal within a year in women and within 1-3 years in men. Risk of acute renal failure returned to normal within 1-3 years in men and women, and liver dysfunction within 1-3 years in women and from three years in men.

4. Based on the 20% threshold for cardiovascular risk, for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 (95% confidence interval 27 to 64) and for oesophageal cancer was 1266 (850 to 3460) and for men the respective values were 33 (24 to 57) and 1082 (711 to 2807).

5. In women the NNH for an additional case of acute renal failure over five years was 434 (284 to 783), of moderate or severe myopathy was 259 (186 to 375), of moderate or severe liver dysfunction was 136 (109 to 175), and of cataract was 33 (28 to 38). Overall, the NNHs and NNTs for men were similar to those for women, except for myopathy where the NNH was 91 (74 to 112).



＜Conclusions＞

Claims of unintended benefits of statins, except for oesophageal cancer, remain unsubstantiated, although potential adverse effects at population level were confirmed and quantified. Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely.

【開催日】

2011年8月3日

【文献名】

Shimoli V. Shah and Brian F. Gage. Cost-Effectiveness of Dabigatran for Stroke Prophylaxis in Atrial Fibrillation. (Circulation. 2011;123:2562-2570.)



【要約】

＜Background＞

Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation (AF), but whether these alternatives are cost-effective is unknown.



＜Methods and Results＞

On the basis of the results from Randomized Evaluation of Long Term Anticoagulation Therapy
(RE-LY) and other trials, we developed a decision-analysis model to compare the cost and quality-adjusted survival of various antithrombotic therapies. We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $50 000/quality-adjusted life-year. We estimated the cost of dabigatran as US $9 a day. For a patient with an average risk of major hemorrhage (3%/y), the most cost-effective therapy depended on stroke risk. For patients with the lowest stroke rate (CHADS 2 stroke score of 0), only aspirin was cost-effective. For patients with a moderate stroke rate (CHADS 2 score of 1 or 2), warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor (time in the therapeutic range 57.1%). For patients with a high stroke risk (CHADS 2 stroke score 3), dabigatran 150 mg (twice daily) was cost-effective unless international normalized ratio control was excellent (time in the therapeutic range  72.6%). Neither dabigatran 110 mg nor dual therapy (aspirin and clopidogrel) was cost-effective.



＜Conclusions＞

Dabigatran 150 mg (twice daily) was cost-effective in AF populations at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent. Warfarin was cost-effective in moderate-risk AF populations unless international normalized ratio control was poor.



【開催日】

2011年7月26日

【タイトル】

風邪に対するプラセボの効果～ランダム化比較試験～



【文献名】

Barret B. Brown R. et al. Placebo Effects and the Common Cold: A Randomized Controlled Trial. Ann Fam Med. 2011; 312-322.



【要約】

＜PURPOSE＞

 We wanted to determine whether the severity and duration of illness caused by the common cold are influenced by randomized assignment to open- label pills, compared with conventional double-blind allocation to active and placebo pills, compared with no pills at all.



＜METHODS＞

We undertook a randomized controlled trial among a population with new-onset common cold. Study participants were allocated to 4 parallel groups: (1) those receiving no pills, (2) those blinded to placebo, (3) those blinded to echina- cea, and (4) those given open-label echinacea. Primary outcomes were illness dura- tion and area-under-the-curve global severity. Secondary outcomes included neu- trophil count and interleukin 8 levels from nasal wash at intake and 2 days later.



＜RESULTS＞

Of 719 randomized study participants, 2 were lost and 4 exited early. Participants were 64% female, 88% white, and aged 12 to 80 years. Mean ill- ness duration for each group was 7.03 days for those in the no-pill group, 6.87 days for those blinded to placebo, 6.34 days for those blinded to echinacea, and 6.76 days for those in the open-label echinacea group. Mean global sever- ity scores for the 4 groups were no pills, 286; blinded to placebo, 264; blinded to echinacea, 236; and open-label echinacea, 258. Between-group differences were not statistically significant. Comparing the no-pill with blinded to placebo groups, differences (95% confidence interval [CI]) were ?0.16 days (95% CI, ?0.90 to 0.58 days) for illness duration and ?22 severity points (95% CI, ?70 to 26 points) for global severity. Comparing the group blinded to echinacea with the open-label echinacea group, differences were 0.42 days (95% CI, ?0.28 to 1.12 days) and 22 severity points (95% CI, ?19 to 63 points). Median change in interleukin 8 concentration and neutrophil cell count, respectively by group, were 30 pg/mL and 1 cell for the no-pill group, 39 pg/mL and 1 cell for the group binded to placebo, 58 pg/mL and 2 cells for the group blinded to echinacea, and 70 pg/mL and 1 cell for the group with open-label echinacea, also not statisti- cally significant. Among the 120 participants who at intake rated echinacea’s effectiveness as greater than 50 on a 100-point scale for which 100 is extremely effective, illness duration was 2.58 days shorter (95% CI, ?4.47 to ?0.68 days) in those blinded to placebo rather than no pill, and mean global severity score was 26% lower but not significantly different (?97.0, 95% CI, ?249.8 to 55.8 points). In this subgroup, neither duration nor severity differed significantly between the group blinded to echinacea and the open-label echinacea group.



＜CONCLUSIONS＞

Participants randomized to the no-pill group tended to have longer and more severe illnesses than those who received pills. For the subgroup who believed in echinacea and received pills, illnesses were substantively shorter and less severe, regardless of whether the pills contained echinacea. These findings sup- port the general idea that beliefs and feelings about treatments may be important and perhaps should be taken into consideration when making medical decisions.



【開催日】

2011年7月20日

【文献名】

Stuart J. Connolly, M.D. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-1151



【要約】

＜Background＞

Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.



＜Methods＞

In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran ? 110 mg or 150 mg twice daily ? or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary study outcome was stroke or systemic embolism.
  Systemic embolism was defined as an acute vascular occlusion of an extremity or organ,documented by means of imaging,surgery,or autopsy.
The primary safety outcome was major hemorrhage.



＜Results＞

Characteristics of the study patients was described table 1 in the original article. The three treatment groups were well balanced with respect to baseline characteristics
Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% CI, 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). 
The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051).

The only adverse effect that was significantly more common with dabigatran than with warfarin was dyspepsia（Table.4）Dyspepsia occurred in 348 patients (5.8%) in the warfarin group and in 707 patients (11.8%) and 688 patients (11.3%) in the 110-mg and 150-mg dabigatran groups, respectively (P<0.001 for both comparisons)



 
 ＜Conclusions＞

In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage.



【開催日】

2011年6月22日