Journal ClubJournal Club

埼玉医科大学　総合医療センター　内分泌・糖尿病内科埼玉医科大学　総合医療センター　内分泌・糖尿病内科Department of Endocrinology and Diabetes, Department of Endocrinology and Diabetes,

Saitama Medical Center, Saitama Medical UniversitySaitama Medical Center, Saitama Medical University

松田　昌文松田　昌文Matsuda, MasafumiMatsuda, Masafumi

20102010年年 11 月月 2121日　日　 8:30-8:558:30-8:55８階　医局８階　医局

Cannon CP, Harrington RA, James S, Ardissino D, Becker RC, Emanuelsson H, Husted S, Katus H, Keltai M, Khurmi, NS, Kontny F, Lewis BS, Gabriel Steg P, Storey RF, Wojdyla D, Wallentin L for the PLATelet inhibition and patient Outcomes (PLATO) investigators Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind studyLancet Published online January 14, 2010 DOI:10.1016/S0140-6736(09)62191-7

Morrison JA, Glueck CJ, Horn PS, Wang P.Childhood predictors of adult type 2 diabetes at 9- and 26-year follow-ups. Arch Pediatr Adolesc Med. 2010 Jan;164(1):53-60.

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Original Article Ticagrelor versus Clopidogrel in Patients with

Acute Coronary Syndromes

Lars Wallentin, M.D., Ph.D., Richard C. Becker, M.D., Andrzej Budaj, M.D., Ph.D., Christopher P. Cannon, M.D., Håkan Emanuelsson, M.D., Ph.D., Claes Held, M.D., Ph.D., Jay Horrow, M.D., Steen Husted, M.D., D.Sc.,

Stefan James, M.D., Ph.D., Hugo Katus, M.D., Kenneth W. Mahaffey, M.D., Benjamin M. Scirica, M.D., M.P.H., Allan Skene, Ph.D., Philippe Gabriel

Steg, M.D., Robert F. Storey, M.D., D.M., Robert A. Harrington, M.D., for the PLATO Investigators

N Engl J MedVolume 361(11):1045-1057

September 10, 2009

ClinicalTrials.gov number, NCT00391872

Cumulative Kaplan-Meier Estimates of the Time to the First Adjudicated Occurrence of the Primary Efficacy End Point

Wallentin L et al. N Engl J Med 2009;361:1045-1057

• At 12 months, the primary end point of death from vascular causes, myocardial infarction, or stroke occurred less often with ticagrelor

Cumulative Kaplan-Meier Estimates of the Time to the First Major Bleeding End Point, According to the Study Criteria

Wallentin L et al. N Engl J Med 2009;361:1045-1057

• Ticagrelor was not associated with an increase in the risk of major bleeding

TIMI Study Group, Brigham and Women’s Hospital, Boston, MA, USA (C P Cannon MD); Duke Clinical Research Institute, Durham, NC, USA (Prof R A Harrington MD, Prof R C Becker MD, D Wojdyla MSc); Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala, Sweden (S James MD, Prof L Wallentin MD); Azienda Ospedaliero Universitaria di Parma, Parma, Italy (D Ardissino MD); AstraZeneca, Molndal, Sweden (H Emanuelsson MD); AstraZeneca, Wilmington, DE, USA (N S Khurmi MD); Arhus University Hospital, Arhus, Denmark (S Husted MD); Universitatsklinikum Heidelberg, Heidelberg, Germany (Prof H Katus MD); Hungarian Institute of Cardiology, Budapest, Hungary (Prof M Keltai MD); Volvat Medical Centre, Oslo, Norway (F Kontny MD); Lady Davis Carmel Medical Centre, Haifa, Israel (Prof B S Lewis MD); INSERM U-698, Assistance Publique–Hopitaux de Paris, and Universite Paris, Paris, France (Prof P G Steg MD); and University of Sheffi eld, Sheffield, UK (R F Storey MD)

In the PLATelet inhibition and patient Outcomes (PLATO) trial, reversible long-term P2Y12 inhibition with ticagrelor was better than that with clopidogrel for the prevention of cardiovascular and total death, myocardial infarction, and stent thrombosis, without an increase in the rates of major bleeding in a broad population of patients with acute coronary syndromes who were started on treatment as soon as possible after hospital admission. We therefore compared ticagrelor with clopidogrel in patients with acute coronary syndromes who were planned to undergo an invasive strategy.

Difference???

BackgroundVariation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients.

MethodAt randomisation, an invasive strategy was planned for 13 408 (72・ 0%) of 18 624 patients hospitalised for acute coronary syndromes (with or without ST elevation). In a double-blind, double-dummy study, patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300–600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6–12 months. All patients were given aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials. gov, number NCT00391872.

Table 2: Efficacy of ticagrelor versus clopidogrel

Figure 3: Cumulative Kaplan-Meier estimates of time to myocardial infarction (A) or cardiovascular death (B) in patients intended to undergo an invasive strategy

We defined major life-threatening bleeding as fatal bleeding, intracranial bleeding, intrapericardial bleeding with cardiac tamponade, hypovolemic shock or severe hypotension due to bleeding and requiring pressors or surgery, a decline in the hemoglobin level of 5.0 g per deciliter or more, or the need for transfusion of at least 4 units of red cells. We defined other major bleeding as bleeding that led to clinically significant disability (e.g., intraocular bleeding with permanent vision loss) or bleeding either associated with a drop in the hemoglobin level of at least 3.0 g per deciliter but less than 5.0 g per deciliter or requiring transfusion of 2 to 3 units of red cells. We defined minor bleeding as any bleeding requiring medical intervention but not meeting the criteria for major bleeding.

In Myocardial Infarction (TIMI) definition was recorded from the electronic case-report form, using a cutoff for haemoglobin of at least 50 g/L, but did not necessarily require clinical evidence of excessive bleeding after CABG. Severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries (GUSTO), was also established from specific questions on the electronic case-report form, and was defined as fatal, intracranial, or intrapericardial bleeding with cardiac tamponade, or development of hypovolaemic shock or severe hypotension caused by bleeding and requiring pressor support or surgery.

Results6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9・ 0%] vs 668 [10・ 7%], hazard ratio 0・ 84, 95% CI 0・ 75–0・ 94; p=0・ 0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11・ 6%] vs 689 [11・ 5%], 0・ 99 [0・ 89–1・ 10]; p=0・ 8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3・ 2%] vs 185 [2・ 9%], 0・ 91 [0・ 74–1・ 12]; p=0・ 3785).

ConclusionTicagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned.

Funding AstraZeneca.

Message世界的には Clopidgrelがよく売れているが、（売上　 Plavix $ 6,057,000,000 2006年世界 $ 3,796,221,000 2008年 USABristol-Myers Squibb/ Sanfi-Aventis）

これからは Ticagrelorが主流になるかもしれない。ところで、同じプロトコールで、若干の仮説の違いで NEJMと Lancetに掲載されているが、ありらしい。

ARCH PEDIATR ADOLESC MED/VOL 164 (NO. 1), JAN 2010

ObjectiveTo determine whether pediatric office measures (waist circumference, body mass index [BMI], systolic [SBP] and diastolic [DBP] blood pressure, and parental diabetes) and laboratory measures (glucose, triglyceride, high-density lipoprotein cholesterol, and insulin) predict risk of type 2 diabetes mellitus (T2DM) at ages 19 and 39 years.

MethodDesign: Nine- and 26-year prospective follow-ups of schoolchildren.

Setting: Urban and suburban schools.

Participants: One thousand sixty-seven girls starting at age 10 years in the National Growth and Health Study and 822 schoolchildren aged 6 to 18 years at entry from the Princeton Follow-up Study.

Outcome Measure: Development of T2DM.

ResultsIn the Princeton Follow-up Study, childhood SBP and BMI in the top fifth percentile and black race predicted T2DM at age 39 years (area under the receiver operator curve [AUC]=0.698). Adding a childhood glucose level of 100 mg/dL or higher, and high-density lipoprotein cholesterol in the bottom fifth percentile and triglyceride concentration in the top fifth percentile as explanatory variables increased AUC to 0.717 and 0.709, respectively. If childhood BMI, SBP, and DBP were all lower than the 75th percentile, likelihood of T2DM at age 39 years was 2%; the likelihood was 1% if the parents had no DM. In the National Growth and Heath Study, SBP in the top fifth percentile and parental diabetes predicted T2DM at age 19 years (AUC=0.699). Adding insulin in the top fifth percentile increased AUC to 0.764, with insulin being a significant variable. If childhood BMI, SBP, and DBP were all lower than the 75th percentile, the likelihood of T2DM at age 19 years was 0.2%, 0.2% if the parents were also free of DM, and 0.3% if childhood insulin was also less than the 75th percentile.

ConclusionOffice-based childhood measures predict the presence and absence of future T2DM 9 and 26 years after baseline. Childhood insulin measurement improves prediction, facilitating approaches to primary prevention of T2DM.

Message小児の身長、体重、血圧、若干の血液検査で将来２型糖尿病になるとわかるらしい。

来週の木曜日は学会予行

来週の木曜日は学会予行

第２会場　 9:40-10:30第１会場　 16:20-16:50