1) The document summarizes findings from the CHART studies on heart failure management in Japan, showing improved outcomes over time with increased use of evidence-based neurohormonal therapies like RAS inhibitors and beta-blockers. 2) A randomized controlled trial called the SUPPORT trial found that adding olmesartan did not improve outcomes for hypertensive heart failure patients already receiving guideline-directed medical therapy and instead increased risk of renal dysfunction. 3) Overall guideline-directed medical therapies like RAS inhibitors and beta-blockers have improved long-term prognosis of heart failure in Japan, though opportunities remain to optimize treatment.

1. Current status and future perspective of
management of heart failure in Japan
Hiroaki Shimokawa, MD, PhD.
Heart Failure 2015 (May 23 – 26, 2015 , Seville, Spain)
Joint Session with HFSA and JHFS
- Controversial issues in drug therapy -
Chair, Department of Cardiovascular Medicine
Tohoku University Graduate School of Medicine

2. COI disclosure
Department of Evidenced-based Medicine
Research grants: Daiichi Sankyo, Bayer Yakuhin,
Kyowa Hakko Kirin, Kowa Pharmaceutical Co. ,
Novartis Pharma, Dainippon Sumitomo Pharma,
Nippon Boehringer Ingelheim Co.
Hiroaki Shimokawa, MD, PhD.
Lecture fees: Daiichi Sankyo, Bayer Yakuhin, Novartis Pharma.

3. Paradigm Shift in HF Management
- From Treatment to Prevention -
Adopted from AHA/ACCF guideline 2013
Prevention Treatment
Stage-A
At high risk for
HF but without
structural hearat
disease of
symptoms of HF
Stage-B
Structural heart
disease but
without signs or
symptoms of HF
Stage-C
Structural heart
disease with
prior or current
symptoms of HF
Stage-D
Refractory HF
requiring
specialized
interventions
Neurohormonal Activation
1) Renin-angiotensin-aldosterone system 4) Inflammation
2) Sympathetic nervous system 5) Arginine vasopressin
3) Oxidative stress 6) Endothelin

4. Chronic Heart Failure Analysis and Registry in the
Tohoku District (CHART) Studies
Tohoku Heart Failure Association
Founded in 1999
ü CHART-1 (N=1,258)
Study focus: Prognosis
Registration:2000-2004
Follow-up: 2000-2005
ü CHART-2 (N=10,219)
Study focus: Prevention, Prognosis
Registration:2006-2010
Follow-up: 2006- present
Aomori
Akita
Iwate
Yamagata
Miyagi
Fukushima
●
Sendai

5. 80
60
40
20
0
(%)
P<0.001
P<0.001
P<0.001
P<0.001
P<0.001
P<0.001
Epidemiologic Transition in Asia
CAD HT DM CAD HT DM
Japan China
2000-2004 (CHART-1)
2006-2010 (CHART-2)
1993-1998
2003-2007
(Sakata, Shimokawa. Circ J. 2014;78:428-435.)

6. 0
10
20
30
40
50
LVEF < 40%
LVEF > 40%
Ischemic heart disease Cardiomyopathy
50
40
30
20
10
0
P < 0.001
CHART-2 (2006-present, N=3,676)
CHART-1 (2000-2005, N=1,006)
Temporal Trends in HF Etiologies
(%)
P < 0.001
(Ushigome, Shimokawa, et al. Circ J. 2015, in press)

7. 80
70
60
50
40
30
20
10
0
P = 0.006
P < 0.001
P < 0.001
P < 0.001
P < 0.001
RAS-I β-blockers
Loop
diuretics
Digitalis
Aldosterone
antagonists
80
70
60
50
40
30
20
10
0
ICD/CRT-D
P = 0.031
(%)
CHART-2 (2006-present, N=3,676)
CHART-1 (2000-2005, N=1,006)
Temporal Trends in Treatments for Symptomatic HF
(Ushigome, Shimokawa, et al. Circ J. 2015, in press)

8. All-cause death Hospitalization for HFCardiovascular death
(yrs.)
756
3.141
599
2,549
442
1,771
1,006
3,676
(yrs.)
Cumulativeincidence(%)
1,006
3,676
884
3,448
739
2,893
568
2,003
No. at risk
CHART-1
CHART-2
(yrs.)
884
3,448
739
2,893
568
2,893
1,006
3,676
Cumulativeincidence(%)
Cumulativeincidence(%)
CHART-2 (N=3,676)
CHART-1 (N=1,006)
CHART-2 (N=3,676)
CHART-1 (N=1,006)
CHART-2 (N=3,676)
CHART-1 (N=1,006)
HR 0.59, 95%CI 0.50-0.69; P< 0.001
HR※ 0.73, 95%CI 0.59-0.88; P= 0.001
HR 0.38, 95%CI 0.31-0.46; P< 0.001
HR ※ 0.45, 95%CI 0.34-0.58; P< 0.001
HR 0.51, 95%CI 0.44-0.58; P< 0.001
HR ※ 0.57, 95%CI 0.47-0.68; P< 0.001
A B C
Temporal Trends in Long-term Prognosis of
Symptomatic HF Patients
※： Adjusted with age, sex, hypertension, diabetes, dyslipidemia, AF, and VT
(Ushigome, Shimokawa, et al. Circ J. 2015, in press)

9. 1086420
CHART2
CHART1
100%80%60%40%20%0%
Stroke death
Other cardiovascular death
Heart failure death
Sudden cardiac death
(%)0 2 4 6 8 10
P= 0.189
P= 0.285
P= 0.543
0 20 40 60 80 100 (%)
P< 0.001
AMI death
Cardiovascular death
Non-cardiovascular death
Unknown death
P< 0.001
CHART-1
(2000-2005)
CHART-2
(20006-present)
74%
48%
23%
36%
CHART-2 (2006-Present, N = 3,676)
CHART-1 (2000-2005, N = 1,006)
A
Temporal Trends in Mode of Death in Symptomatic HF
(Ushigome, Shimokawa, et al. Circ J. 2015, in press)

10. •RAS inhibitors
•Beta blockers
•Statins

11. Prescription Rates of RAS inhibitors by Age
Subjects: 4,733 patients in Stage C/D patients in the CHART-2 Study

12.
Kaplan-Meier Curves for Composite Endpoints
in the CHART-2 Study (Stage C/D)
*composite endpoints: all-cause death, HF admission, myocardial infarction and stroke.
(+) RAS inhibitors n=3,421
(-) RAS inhibitors n=1,312
Adjusted HR 1.08 (0.93-1.25), P=0.32

13.
LVEF<40% LVEF40-50% LVEF>50%
Adjusted HR 1.10, P=0.56 Adjusted HR 1.31, P=0.13 Adjusted HR 0.98, P=0.83
β遮断薬あり n=383
β遮断薬なし n=213
β遮断薬あり n=1,161
β遮断薬なし n=1,485
β遮断薬あり n=465
β遮断薬なし n=202
Kaplan-Meier Curves for Composite Endpoints
in the CHART-2 study (Stage C/D)
(+) RAS inhibitors n=563
(-) RAS inhibitors n=134
(+) RAS inhibitors n=152
(-) RAS inhibitors n=58
(+) RAS inhibitors n=2,166
(-) RAS inhibitors n=957

14. The SUPPORT Trial
(Sakata, Shimokawa, et al. Eur Heart J. 2015;36:915-923.)

15. Study Flow
Hypertensive patients with Stage C/D HF
(n = 1147)
Randomization
Control group
(n = 569)
Olmesartan group
(n = 578)
Excluded (n=1)
・lack of information
(n=1)
Excluded (n=0)
Control group
(n = 568)
Olmesartan group
(n = 578)
Enrollment : 2006.10.1 – 2010.3.31
Annual follow-up ( 2013.3.31)~
The SUPPORT Trial
993 (87%) at out-patient clinics.
Titrated
up to 40mg/day.
（clinicaltrials.gov-NCT00417222） (Sakata, Shimokawa, et al. Eur Heart J. 2015;36:915-923.)

16.
Control
(n=569)
Olmesartan (n=578) P-value
Age, years 65.5 ± 10.1 65.8 ± 10.4 0.445
Males, % 427 (75.2%) 429 (74.2%) 0.71
Body mass index, kg/m2 24.6 ± 4.1 24.2 ± 4.1 0.185
NYHA functional class 0.564
II 530 (93.5%) 535 (92.6%)
III 37 (6.5%) 43 (7.4%)
Baseline cardiovascular disease
Ischemic heart disease 262 (46.1%) 283 (49%) 0.337
Dilated cardiomyopathy 132 (23.2%) 110 (19%) 0.081
Diabetes mellitus 292 (51.4%) 283 (49%) 0.408
Hemodynamics and LV function
Systolic BP, mmHg 127.1 ± 18.0 128.7 ± 18.2 0.081
Diastolic BP, mmHg 73.9 ± 11.7 74.8 ± 12.2 0.311
Heart rate, bpm 71.5 ± 14.6 71.2 ± 13.8 0.808
LVDd, mm 54.0 ± 8.7 53.3 ± 9.0 0.113
LVEF, % 53.7 ± 14.5 54.5 ± 14.9 0.277
Patient Characteristics
The SUPPORT Trial
Control
(n=569)
Olmesartan
(n=578)
P-value
Laboratory findings
Hemoglobin (g/dL) 13.7 ± 1.9 13.8 ± 1.7 0.279
Blood urea nitrogen (mg/dL) 18.0 ± 6.9 18.3 ± 7.5 0.556
Creatinine (mg/dL) 0.95 ± 0.36 0.94 ± 0.33 0.956
Albumin (mg/dL) 4.2 ± 0.4 4.2 ± 0.4 0.28
LDL-C (mg/dL) 107.3 ± 30.0 108.2 ± 30.8 0.775
eGFR (mL/min/1.73 m2) 70.4 ± 24.4 70.0 ± 22.6 0.887
BNP (pg/mL) 78.2 (37.8, 173.0) 84.2 (36.7, 188.8) 0.63
Baseline medication
Beta-blocker 416 (73.2%) 405 (70.1%) 0.234
ACE inhibitor 460 (81.0%) 469 (81.1%) 0.946
Diuretics 322 (56.7%) 328 (56.7%) 0.984
Calcium channel blocker 212 (37.3%) 222 (38.4%) 0.705
Statin 274 (48.2%) 287 (49.7%) 0.632
(Sakata, Shimokawa, et al. Eur Heart J. 2015;36:915-923.)

17. Control 568 513 483 449 317 134 28
Olmesartan 578 517 474 436 293 118 47
Cumulativeeventrate
29.2% vs.33.2%
HR 1.18 (0.96-1.46), P=0.112
Control
Olmesartan
No. at risk
(%)
Primary Endpoint
The SUPPORT Trial
(Sakata, Shimokawa, et al. Eur Heart J. 2015;36:915-923.)

18. Primary and Other Endpoints
The SUPPORT Trial
Control
(n=568)
Olmesartan
(n=578) Hazard
ratio
95% C.I.
P-value
events, n (%) events, n (%) lower upper
Primary endpoint 166 ( 29.2 ) 192 ( 33.2 ) 1.183 0.961 1.457 0.112
all-cause death 85 ( 15.0 ) 98 ( 17.0 ) 1.152 0.862 1.541 0.338
non-fatal AMI 8 ( 1.4 ) 12 ( 2.1 ) 1.479 0.604 3.617 0.391
non-fatal stroke 26 ( 4.6 ) 34 ( 5.9 ) 1.313 0.788 2.188 0.296
hospitalization for HF 99 ( 17.4 ) 113 ( 19.6 ) 1.148 0.877 1.504 0.316
Secondary endpoints
CV death 38 ( 6.7 ) 48 ( 8.3 ) 1.258 0.822 1.926 0.290
HF death 18 ( 3.2 ) 10 ( 1.7 ) 0.556 0.257 1.205 0.137
sudden death 8 ( 1.4 ) 18 ( 3.1 ) 2.238 0.973 5.148 0.058
fatal arrythmia 29 ( 5.1 ) 30 ( 5.2 ) 1.017 0.611 1.695 0.947
new-onset DM 60 ( 10.6 ) 70 ( 12.1 ) 1.169 0.828 1.650 0.376
renal dysfunction 61 ( 10.7 ) 97 ( 16.8 ) 1.638 1.189 2.257 0.003
new-onset AF 31 ( 5.5 ) 21 ( 3.6 ) 0.665 0.382 1.157 0.149
Additive use of olmesartan did not improve
clinical outcomes but worsened renal
function in hypertensive CHF patients treated
with evidence-based medications.
(Sakata, Shimokawa, et al. Eur Heart J. 2015;36:915-923.)

19. P=0.588
HR=1.12(0.75, 1.66)
Control 104 95 88 80 59 37 8
Olmesartan 106 101 96 90 65 43 43
P=0.118
HR=0.66(0.39, 1.12)
C. (+)ACEI, (+)BBA. (+)ACEI, (-)BB B. (-)ACEI, (+)BB
Control
Olmesartan
Cumulativeeventrate
Cumulativeeventrate
Cumulativeeventrate
Control
Olmesartan
Control
Olmesartan
(%)(%) (%)
Control 312 286 270 251 168 68 45
Olmesartan 299 261 233 211 140 93 30
P=0.006
HR=1.47(1.11, 1.95)
Control 148 130 124 117 96 55 7
Olmesartan 170 154 144 135 92 37 37
Number
at risk
Number
at risk
Number
at risk
Baseline Medications and the Primary Endpoint
The SUPPORT Trial
(Sakata, Shimokawa, et al. Eur Heart J. 2015;36:915-923.)

20. Primary Endpoint
Overall
(+) ACEI, (-) BB
(-) ACEI, (+) BB
(+) ACEI, (+) BB
Olmesartanbetter worse
HR 4.03.53.02.52.01.51.00.50.0
All-cause Death
Overall
(+) ACEI, (-) BB
(-) ACEI, (+) BB
(+) ACEI, (+) BB
Olmesartanbetter worse
HR
3.02.52.01.51.00.50.0
Renal Dysfunction
Overall
(+) ACEI, (-) BB
(-) ACEI, (+) BB
(+) ACEI, (+) BB
Olmesartanbetter worse
HR 4.03.53.02.52.01.51.00.50.0
ACEI: ACE inhibitors
BB: Beta blockers
Triple Combination and Adverse Cardiac Events
The SUPPORT Trial
(Sakata, Shimokawa, et al. Eur Heart J. 2015;36:915-923.)

21. •RAS inhibitors
•Beta blockers
•Statins

22. Prescription of Beta-blockers in the CHART-2 Study
Carvedilol 67.5%
Bisoprolol 9.0%
Metoprolol 5.1%
Unknown 18.4%
Subjects: 4,733 patients in Stage C/D patients in the CHART-2 Study

23. 30歳未満 40歳以上50歳未満60歳以上70歳未満 80歳以上
0
20
40
60
80
100
30歳未満 40歳以上50歳未満60歳以上70歳未満 80歳以上
0
20
40
60
80
100
Prescription Rates of Beta-blockers by Age
0
20
40
60
80
100
(%)
0
20
40
60
80
100
(%)
CHART-1 (N=1,006) CHART-2 (N=3,673)
<30 30-39 40-49 50-59 60-69 70-79 80< <30 30-39 40-49 50-59 60-69 70-79 80<
Age Age

24. Dose of Carvedilol in the CHART-2 Study
30歳未満30歳以上40歳未満40歳以上50歳未満50歳以上60歳未満60歳以上70歳未満70歳以上80歳未満80歳以上
0
2
4
6
8
10
12
0
2
4
6
8
10
(mg)
12
全体 男性 女性
0
2
4
6
8
10
12
0
2
4
6
8
10
(mg)
12
All Male Female <30 30-39 40-49 50-59 60-69 70-79 80<
Age
Subjects: 1,817 patients in Stage C/D patients in the CHART-2 Study

25.
(+) Beta blockers n=2,009
(-) Beta blockers n=1,900
(%)
Time (Year)
0 1 2 3 4
Kaplan-Meier Curves for All-cause Death
in the CHART-2 Study (Stage C/D)
Adjusted HR 0.80 (0.72-0.90), P<0.001
100
60
80
20
40
0
Survivalrate

26.
LVEF<40% LVEF40-50% LVEF>50%
Adjusted HR 0.48, P<0.001 Adjusted HR 0.80, P=0.15 Adjusted HR 1.01, P=0.86
(%)
100
80
60
40
20
0
(%)
100
80
60
40
20
0
(%)
100
80
60
40
20
0
β遮断薬あり n=383
β遮断薬なし n=213
β遮断薬あり n=1,161
β遮断薬なし n=1,485
β遮断薬あり n=465
β遮断薬なし n=202
0 1 2 3 4 0 1 2 3 4 0 1 2 3 4
Kaplan-Meier Curves for All-cause Death
in the CHART-2 study (Stage C/D)
(+) Beta-blockers n=465
(-) Beta-blockers n=202
Time (Year)
Survivalrate
Time (Year) Time (Year)
(+) Beta-blockers n=383
(-) Beta-blockers n=213
(+) Beta-blockers n=1,161
(-) Beta-blockers n=1,485

27. Prognostic Impacts of Beta-blockers in Stage
C/D Patients with Sinus Rhythm
HFrEF
(N=885)
HFpEF
(N=1,803)
(Takada, Shimokawa, et al. Eur J Heart Fail. 2014;16:309-316.)
Beta-blockers
better worse
HR
Beta-blockers
better worse
HR

28. All-cause death Hospitalization for HF
CHART-1 (n=306)
Log-rank P= 0.010
CHART-2 (n=710)
(years)
Log-rank P= 0.015
(years)
CHART-1 (n=306)
CHART-2 (n=710)
(%) (%)
Survivalrate
Hospitalization-freerate
306
710
281
666
247
570
189
406
306
710
245
611
209
496
156
346
HR 0.60, 95%CI 0.49-0.81;
P= 0.011
HR 0.69, 95%CI 0.51-0.93;
P= 0.015
No. at risk
CHART-1
CHART-2
No. at risk
CHART-1
CHART-2
DCM: Kaplan-Meier Survival Curves
(Ushigome R, Shimokawa H, et al. Circ J. 2015;79:1332-1341.)

29. 6
Stroke death
Other death
Heart failure death
Sudden cardiac death
Non-cardiovascular death
100%80%60%40%20%0%
51.6
84.1
37.1
11.4
（%）
CHART-1
CHART-2
Cardiovascular death
Non-cardiovascular death
Unknown death
CHART-1
CHART-2
0 1 2 3 4 5
P= 0.526
P= 0.107
P= 0.257
0 20 40 60 80 100 (%)
P< 0.001
P= 0.062
84%
52%
DCM: Mode of Death
(Ushigome R, Shimokawa H, et al. Circ J. 2015;79:1332-1341.)

30. (%)
Survivalrate
CHART-1 (n=147)
CHART-2 (n=567)
(years)
(%)
Survivalrate
Log-rank P= 0.851
CHART-1 (n=159)
CHART-2 (n=143)
HR 0.94, 95%CI 0.53-1.71;
P= 0.850
(years)
159
143
147
133
131
109
115
84
No. at risk
CHART-1
CHART-2
147
567
135
534
116
468
79
343
No. at risk
CHART-1
CHART-2
(+) Beta-blocker(-) Beta-blocker
Beta-blockers in DCM Patients
Log-rank P= 0.017
HR 0.53, 95%CI 0.31-0.90;
P= 0.019
(Ushigome R, Shimokawa H, et al. Circ J. 2015;79:1332-1341.)

31. •RAS inhibitors
•Beta blockers
•Statins

32. Selection of HFpEF Populations
Total cohort
Matched cohort
Required past or current
symptoms of HF
(Nochioka, Shimokawa, et al. Circ J. 2015;79:574-582.)

33. Kaplan-Meier Curves for All-cause Death in HFpEF
(Nochioka, Shimokawa, et al. Circ J. 2015;79:574-582.)

34. No. at risk
Matched cohort
No statin use
Statin use
Total cohort
No statin use
Statin use
207
207
555
863
CumulativeIncidence(%)
193
194
529
769
163
166
451
648
106
119
320
441
0
0
No statin use in total HFrEF cohort
No statin use in matched HFrEF cohort
Statin use in total HFrEF cohort
Statin use in matched HFrEF cohort
P=0.970 for matched HFrEF cohort
P=0.001 for total HFrEF cohort
10
20
30
1 2 3 Years
Kaplan-Meier Curves for All-cause Death in HFrEF
Statin use was not associated
with improved mortality in the PS
-matched HFrEF population.
(Nochioka, Shimokawa, et al. Circ J. 2015;79:574-582.)

35.
Statin use in the total cohort
P
Total Yes No
n=3,124 n=1,163 n=1,961 HR 95%CI
All-cause death 440 113 327 0.72 0.63-0.82 <0.001
Cardiovascular 210 64 146 1.01 0.83-1.22 0.960
Heart failure 97 28 69 1.16 0.88-1.53 0.288
Sudden death 40 12 28 0.59 0.36-0.98 0.041
Stroke 25 11 14 1.25 0.72-2.15 0.426
MI 11 3 8 0.61 0.27-1.38 0.234
Other cardiovascular 37 10 27 1.07 0.68-1.64 0.758
Non-cardiovascular 206 47 159 0.53 0.62-0.82 <0.001
Cancer 75 22 53 0.74 0.53-1.03 0.078
Infection 67 14 53 0.53 0.36-0.77 0.001
Renal failure 18 5 13 0.73 0.36-1.47 0.371
Gastrointestinal bleeding 4 0 4 0.00 - -
Other non-cardiovascular 42 6 36 0.21 0.11-0.39 <0.001
Unknown cause 24 2 22 0.17 0.01-0.42 <0.001
*P value is the results of the Cox hazard models adjusted by IPTW.
Mode of death in HFpEF
(Nochioka, Shimokawa, et al. Circ J. 2015;79:574-582.)

36. HR 95% CI P value
β-blockers
CHART-1 0.96 ( 0.63 - 1.44 ) 0.829
CHART-2 0.82 ( 0.68 - 1.00 ) 0.055
RAS-I
CHART-1 0.79 ( 0.55 - 1.14 ) 0.208
CHART-2 0.94 ( 0.76 - 1.15 ) 0.534
Aldosterone
antagonists
CHART-1 1.36 ( 0.89 - 2.07 ) 0.154
CHART-2 1.14 ( 0.93 - 1.39 ) 0.223
Loop diuretics
CHART-1 1.72 ( 1.03 - 2.87 ) 0.038
CHART-2 1.29 ( 1.05 - 1.59 ) 0.017
Digitalis
CHART-1 0.97 ( 0.69 - 1.38 ) 0.875
CHART-2 1.06 ( 0.87 - 1.31 ) 0.555
CCB
CHART-1 1.32 ( 0.92 - 1.90 ) 0.135
CHART-2 0.91 ( 0.75 - 1.12 ) 0.376
Statin
CHART-1 NA NA NA
CHART-2 0.81 ( 0.65 - 1.02 ) 0.068
Effects of Medications in Symptomatic HF Patients
All patients, All-cause death
※： Adjusted with age, sex, hypertension, diabetes, dyslipidemia, AF, and VT

37. HR 95% CI P value
β-blockers
CHART-1 0.87 ( 0.50 - 1.50 ) 0.610
CHART-2 0.59 ( 0.44 - 0.81 ) 0.001
RAS-I
CHART-1 0.67 ( 0.40 - 1.12 ) 0.128
CHART-2 0.83 ( 0.60 - 1.15 ) 0.252
Aldosterone
antagonists
CHART-1 1.39 ( 0.80 - 2.43 ) 0.247
CHART-2 1.23 ( 0.91 - 1.66 ) 0.172
Loop diuretics
CHART-1 1.63 ( 0.78 - 3.41 ) 0.192
CHART-2 1.30 ( 0.91 - 1.85 ) 0.147
Digitalis
CHART-1 0.99 ( 0.61 - 1.61 ) 0.978
CHART-2 1.10 ( 0.80 - 1.51 ) 0.558
CCB
CHART-1 1.40 ( 0.82 - 2.38 ) 0.213
CHART-2 1.09 ( 0.77 - 1.54 ) 0.618
Statin
CHART-1 NA NA NA
CHART-2 0.84 ( 0.60 - 1.17 ) 0.299
Effects of Medications in Symptomatic HFrEF Patients
HFrEF, All-cause death
※： Adjusted with age, sex, hypertension, diabetes, dyslipidemia, AF, and VT

38. HR 95% CI P value
β-blockers
CHART-1 0.89 ( 0.45 - 1.75 ) 0.734
CHART-2 0.94 ( 0.73 - 1.22 ) 0.654
RAS-I
CHART-1 0.86 ( 0.51 - 1.47 ) 0.592
CHART-2 1.01 ( 0.77 - 1.32 ) 0.924
Aldosterone
antagonists
CHART-1 1.32 ( 0.67 - 2.61 ) 0.423
CHART-2 0.96 ( 0.72 - 1.29 ) 0.808
Loop diuretics
CHART-1 1.50 ( 0.72 - 3.11 ) 0.281
CHART-2 1.17 ( 0.90 - 1.52 ) 0.251
Digitalis
CHART-1 0.92 ( 0.55 - 1.54 ) 0.764
CHART-2 1.07 ( 0.81 - 1.41 ) 0.632
CCB
CHART-1 1.31 ( 0.77 - 2.24 ) 0.321
CHART-2 0.84 ( 0.65 - 1.08 ) 0.173
Statin
CHART-1 NA NA NA
CHART-2 0.72 ( 0.53 - 0.98 ) 0.035
HFpEF, All-cause death
Effects of Medications in Symptomatic HFpEF Patients
※： Adjusted with age, sex, hypertension, diabetes, dyslipidemia, AF, and VT

39. Conclusions
1. Along with implementation of evidence-based
medications, 3-year incidences of all-cause death,
cardiovascular death and HF admission have been
decreased in patients with HF in Japan.
2. Better implementation of beta-blockers and statins
appears to have contributed to this prognostic
improvement in patients with HFrEF and those with
HFpEF, respectively.

40. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
Acknowledgements
Tohoku Heart Failure Society