1. No category

結論
5-Step Evidence-Based Medicine Process
平成26年度 病院薬学コース事前教育
Journal Club
Define
Retrieve
Evaluate
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Clinical!
Question
Patient!
Information
薬物治療学 小川竜一
限界の認識
Categorize Develop
Literature
Quality of!
Evidence
Conclusion &!
Recommendation
Journal Club
Bryant PJ & Pace HA, “The Pharmacist’s Guide to Evidence Based Medicine for Clinical Decision Making,”
American Society of Health-System Pharmacists (2009)
結果の正しい解釈
論文の方法論の評価
(BACKGROUND)
Y or N
METHODS
Y or N
The new england
journal of medicine
Y or N
Y or N
established in 1812
Y or N
Y or N
Y or N
Y or N
Bryant PJ & Pace HA, “The Pharmacist’s Guide to Evidence Based Medicine for Clinical Decision Making,”
American Society of Health-System Pharmacists (2009)
vol. 370
Outcomes!
Statistical Analysis
no. 15
Spironolactone for Heart Failure with Preserved Ejection Fraction
RESULTS
Bertram Pitt, M.D., Marc A. Pfeffer, M.D., Ph.D., Susan F. Assmann, Ph.D., Robin Boineau, M.D., Inder S. Anand, M.D.,
Brian Claggett, Ph.D., Nadine Clausell, M.D., Ph.D., Akshay S. Desai, M.D., M.P.H., Rafael Diaz, M.D.,
Jerome L. Fleg, M.D., Ivan Gordeev, M.D., Ph.D., Brian Harty, M.A., John F. Heitner, M.D., Christopher T. Kenwood, M.S.,
Eldrin F. Lewis, M.D., M.P.H., Eileen O’Meara, M.D., Jeffrey L. Probstfield, M.D., Tamaz Shaburishvili, M.D., Ph.D.,
Sanjiv J. Shah, M.D., Scott D. Solomon, M.D., Nancy K. Sweitzer, M.D., Ph.D., Song Yang, Ph.D.,
and Sonja M. McKinlay, Ph.D., for the TOPCAT Investigators*
Y or N
Y or N
april 10, 2014
A BS T R AC T
Methods
In this randomized, double-blind trial, we assigned 3445 patients with symptomatic
heart failure and a left ventricular ejection fraction of 45% or more to receive either
spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite
of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for
the management of heart failure.
Results
With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of
1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in
the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77
to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization
for heart failure had a significantly lower incidence in the spironolactone group
than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard
ratio, 0.83; 95% CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations
for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of
the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the
incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter
(265 µmol per liter) or higher, or dialysis.
Conclusions
In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite
outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung,
and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.)
From the University of Michigan School
of Medicine, Ann Arbor (B.P.); the Cardiovascular Division, Brigham and Women’s
Hospital, Boston (M.A.P., B.C., A.S.D.,
E.F.L., S.D.S.); New England Research Institutes, Watertown, MA (S.F.A., B.H., C.T.K.,
S.M.M.); National Heart, Lung, and Blood
Institute, Bethesda, MD (R.B., J.L.F., S.Y.);
Veterans Affairs Medical Center and University of Minnesota, Minneapolis (I.S.A.);
Hospital de Clinicas de Porto Alegre, Porto
Alegre, Brazil (N.C.); Estudios Clinicos
Latinoamerica, Rosario, Argentina (R.D.);
Pirogov Russian National Research Medical University, Moscow (I.G.); New York
Methodist Hospital, Brooklyn (J.F.H.);
Montreal Heart Institute, Montreal (E.O.);
University of Washington Medical Center, Seattle (J.L.P.); Diagnostic Services
Clinic, Tbilisi, Georgia (T.S.); Northwestern University, Chicago (S.J.S.); and the
University of Wisconsin, Madison (N.K.S.).
Address reprint requests to Dr. Pfeffer at
the Cardiovascular Division, Brigham
and Women’s Hospital, 75 Francis St.,
Boston, MA 02115, or at mpfeffer@rics
.bwh.harvard.edu.
Drs. Pitt, Pfeffer, and McKinlay contributed equally to this article.
* A complete list of investigators and committees in the Treatment of Preserved
Cardiac Function Heart Failure with an
Aldosterone Antagonist (TOPCAT) trial
is provided in the Supplementary Appendix, available at NEJM.org.
This article was updated on April 10, 2014,
at NEJM.org.
N Engl J Med 2014;370:1383-92.
DOI: 10.1056/NEJMoa1313731
Copyright © 2014 Massachusetts Medical Society.
n engl j med 370;15
nejm.org
Study Patients & Follow-up!
Study Drug Administration!
Primary-Outcome & Component Events!
Secondary Outcomes!
Adverse Events
2 Tables & 3 Figures
Background
Mineralocorticoid-receptor antagonists improve the prognosis for patients with
heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular
ejection fraction.
Study Design & Oversight!
Study Patients!
Randomization & Study Drug!
april 10, 2014
The New England Journal of Medicine
Downloaded from nejm.org by Ryuichi Ogawa on April 9, 2014. For personal use only. No other uses without permission.
Copyright © 2014 Massachusetts Medical Society. All rights reserved.
1383
DISCUSSION
Outcomes
日本循環器学会「慢性心不全治療ガイドライン（2010年改訂版）」2010/9/13更新版
http://www.j-circ.or.jp/guideline/pdf/JCS2010_matsuzaki_h.pdf
Population data !
from EFFECT study
1-Yr readmission for HF
22.2%
13.5%
1-Yr mortality !
or readmission for HF
31.1%
1-Yr mortality
Bhatia RS, et al. N Engl J Med. 2006;355:260-9.
Age ≥ 50 yr
LVEF ≥ 45%
BP controlled
K < 5.0 mEq/L
連続尺度
順序尺度
分類尺度
•
ANCOVA
•
ANCOVA ranks
•
Chi-square test!
•
ANOVA!
•
ANOVA ranks
•
Cochrane’s Q test
•
Pearson correlation
•
Friedman ANOVA
•
Fischer’s exact test!
coefficient!
•
Kendall rank correlation
•
Logistic Regression!
Mantel-Haenstzel
McNemar’s test
•
coefficient
•
Student’s t-test
•
Kruskal-Wallis ANOVA!
•
•
Mann-Whitney U test!
•
Spearman Rank
correlation coefficient!
•
HFpEF (NYHA II/III)
N = 3447
Wilcoxon Rank Sum test
20.4% primary outcome rate (placebo)!
671 participants with primary outcomes
Hyperkalemia
AEs
SpironoPlacebo P-value
lactone
ARI! = 0.187 – 0.091!
(Absolute Risk Increase)
Hyperkalemia
18.7%
9.1%
!
<0.05
= 0.096 (9.6%)
NNH!= 1 / 0.096!
(Number Needed to Harm)
SCr 2xUNL
10.2%
7.0%
<0.05
!
= 10.4 (10人)
ARR (ARI)の95%信頼区間
+
Y
Y or N
PA – PB
Y
+
+
Y
± 1.96 x
PA x (1–PA)!
NA
+
PB x (1–PB)!
Y
NB
PA: A群のイベント発生率
PB: B群のイベント発生率
治療法の推奨
+
Y
+
Y
+
Bryant PJ & Pace HA, “The Pharmacist’s Guide to Evidence Based Medicine for Clinical Decision Making,”
American Society of Health-System Pharmacists (2009)
NB: B群の症例数
論文の質
論理的な理由
臨床判断
＋）
+
Y
Y
NA: A群の症例数
Strength
&
Limitation
Y
Strength
Limitation
低用量での検討
試験
開始用量
目標用量
平均用量
TOPCAT
RALES
15 mg/day
25 mg/day
45 mg/day
50 mg/day
25 mg/day
26 mg/day
試験薬中止例：590名（34.3%）