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NUMBER of PATIENTS 21 MILLION adults worldwide are living with heart failure This number is expected to rise.1,2 REHOSPITALISATION Heart failure is the NUMBER 1 cause of hospitalisati

The war on heart failure

The not-so-good news – challenges

Heart failure is common

North America Canada

1,3%

~1%

Malaysia 6.7

% Singapore 4.5

%

Middle East Oman 0,5%

H

Australia 0,5%

H

Proportions of HF hospital admissions as the primary diagnosis

North America (2 countries) 1.8 – 3.0%

Europe (22countries) 0.3 – 3.7%

Asia (3countries) 0.8 – 1.2%

Australasia (2countries) 1,4 – 1.5%

Middle East (2ountries) 1.3%

Africa (1country) 0,7%

Latin America (3 countries) 1.6-2.1%

1 Mozaffarian D et al Circulation 2015;131(4):e29-e322

2 Mosterd A et al Heart 2007;93(9):1137-1146.

3 http://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/Chronic-Conditions/Downloads/2012Chartbook.pdf

4 Cowie MR et al Oxford PharmaGenesis; 2014 http://www.oxfordhealthpolicyforum.org/AHFreport Accessed February 18, 2015.

5 Fauci AS et al Harrison's Principles of Internal Medicine 17th ed New York: McGraw-Hill; 2008.

6 Cook C et al Int J Cardiol 2014;171(3):368-376.

NUMBER of PATIENTS

21 MILLION adults worldwide

are living with heart failure

This number is expected to

rise.1,2

REHOSPITALISATION

Heart failure is the NUMBER 1

cause of hospitalisation for

patients aged >65 years.4

*median follow-up 349 days [252-365]

Maggioni AP, et al Eur J Heart Fail 2013;15:808–817.

Heart failure patients suffer from recurrent hospitalization

1. Gheorghiade M et al Am J Cardiol.

With each hospitalization, there

on, downwa rd

leading to an

inevitable spiral 1

278,307 patients in the USA with ≥1 hospitalization with

a HF claim were followed from first

HF hospitalization for 24 months or until disenrollment

or end of data availability

Korves et al Presented at the American Heart Association Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke

2010 Scientific Sessions, Washington, D.C., May 19–21, 2010

Meanlength of hospital stay increases with each rehospitalization forHF

Length of hospital stay following hospitalization for HF

Desai AS and Stevenson LW Circulation 2012;126:501-506

Three-phase terrain of lifetime readmission risk after Heart

Elevated heart rate at hospital discharge predicts one-year mortality (OFICA)

1. Logeart D et al Raised heart rate at discharge after acute heart failure is an independent predictor of one-year mortality Eur Heart J

P = 0.01

N=1658 (170 hospitals); Mean HR at discharge:71 bpm; 1 year mortality: 33%

Time (days)

Kitai et al., Curr Treat Options Cardio 2016;18:13

HR Reduction as aTherapeutic

Target

• Reduce myocardial oxygenconsumption

• Improve contractileperformance

• Improve diastolic filling

• Reduce risk of VF and sudden death

• Promote reverseremodeling

Optimization of treatment before discharge

Pharmacological treatment in CHF recommended in the 2016 ESC guidelines

McMurray J et al European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 Eur

Heart J 2012;33:1787-1847.

1.

.

1

Effect of ivabradine on readmissions in the vulnerable phase afterhospitalisation

for worsening systolic HF:

a post hoc analysisof

Main findings:population

1186 of the 6505 randomised patients experienced at least

one HF hospitalisation during the study

➢ 28% were rehospitalized within 3 months

➢ The reasons for rehospitalizations was cardiovascular in 86% of patients, including worsening HF in 61% of patients

Komajda M et al Eur J Heart Fail 2016; doi: 10.1002/ejhf.582

75

P=0.0 3

IRR=0.

79

P=0.04

Placeb o

Ivabradine

Effect of ivabradine on all-cause hospitalizations over the 3 months after a first hospital admission for HF

1 Time (months) after hospital admission for heart failure

Vulnerable phase

ETHIC-AHF: effects of the early co-administration of ivabradine

and beta-blockers in patients with acute heart failure

P=0.02

Hidalgo FJ et al Int J Cardiol (2016)

Risk reduction of death/HF hospitalization

HF hospitalizations

BB – 31%

BB/IVABRADINE – 11%

Lopatin YM et al Int J Cardiol 2018;260:113-7

Optimization of management in patients hospitalized with HF

OPTIMIZE HEART FAILURE CARE PROGRAMME (www.optimize-hf.com)

370 patients hospitalized with HF; LVEF < 40%, SR, HR≥ 70 bpm

Therapy initiated in-hospital (with post-discharge follow-up): BB versus BB + IVABRADINE

After 12 months:

Deaths

BB – 10%

BB/IVABRADINE – 3%

How ivabradine may improve cardiac function in

patients with CHF (acute and long-term)

acute

long-term

Management of patients with chronic heart failure:

Real world experience

Data from ESC HF Registry on 9134 HF patients

Chioncel O et al Eur J Heart Fail 2017 ;19:1574-85

M Komajda

Komajda M, et al Eur J Heart Fail 2017;19(11):1414-1423.

M Komajda

Komajda M, et al Eur J Heart Fail 2017;19(11):1414-1423.

Guidelines that aren’t implemented don’t work

“The thrombocardiologist of the 20 th century will be replaced by the diabetocardiologist

of the 21 st century.”

Eugene Braunwald personal communication

Biguanides

centralα-2 agonists

Ca2+channel blockersperipheralα-1 blockersβ-blockers

α-glucosidase inhibitorsbiguanides

SGLT-2inhibitors dopamine agonists

renin inhibitors

bile acid sequestrantsDPP-4inhibitors

Lịch sử các thuốc đường huyết

G Fulcher, Presented at American Diabetes Association 2017

EMPA-REG Outcome Trial

N Engl J Med 2015;373:2117

EMPA-REG OUTCOME ®

Trial design

Randomized &treatet (n=7020)

Empagliflozin 10mg

(n=2345)

Placebo (n=2333)

Screening

(n=11531)

Empagliflozin 25 mg

• Study medication was given in addition to standard of care.

• Primary outcome: 3-point MACE

• Analysis: Placebo vs pooled empagliflozin groups

• Key inclusion criteria:

– Adults with type 2 diabetes and established CVD

– BMI ≤45 kg/m 2 ; HbA1c 7–10%; eGFR ≥30 mL/min/1.73m 2 (MDRD)

Zinman B et al N Engl J Med 2015;373:2117-28

Hospitalization for heart failure

Hospitalization for HF

in patients with vs without HF at baseline

0

14 12 10

HR, hazard ratio; CI, confidence interval.

Inzucchi SE, AHA Scientific Sessions, Orlando, FL, November 2015

HR0.75 (95% CI 0.48,1.19)

12.3

10.4

N=706 (10.1%

ofcohort)

HR0.59 (95% CI 0.43,0.82)

N=631

4 (89.9%

ofcohort)

3.1

1.8

P(interaction)=NS

1198 1135 ACEis/ARBs No

Yes

889 3798

465 1868

Yes

2640 2047

1345 988 Loop diuretics No

Yes

3962 725

1969 364 β-blockers No

Yes

1631 3056

835 1498 Mineralocorticoid receptor

antagonists

No Yes

4382 305

2197 136

• Cox regression analysis; All patients treated with at least one dose of study drug

Empagliflozin is not indicated for CV risk reduction or treatment of HF

ACEi, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blocker;

CI, confidence interval; CV, cardiovascular; eGFR, estimated glomerular filtration rate;

HHF, hospitalisation for heart failure; HR, hazard ratio

Fitchett D et al Eur Heart J 2016; doi:10.1093/eurheartj/ehv728

Favours empagliflozin Favours placebo

với HbA1c ban đầu

Empagliflozin is not indicated in all countries for CV risk reduction, and is not indicated for the treatment of HF

Cox regression analysis in patients treated with ≥1 dose of study drug

Fitchett D et al ESC-HF 2017 Poster presentation

HR (95% CI) Treatment by subgroup

interaction

p=0.69

Empagliflozin Placebo HR (95%CI)

n withevent/N analysed (%) All patients 265/4687 (5.7) 198/2333 (8.5) 0.66 (0.55,0.79)

empagliflozin

0.25 1

HR (95% CI) Hospitalisation for HF

2

Favours placebo

Wanner C et al ERA-EDTA 2016; oral presentation

N Engl J Med 2016;375:323

CONCLUSIONS

In patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care

N Engl J Med 2017;377:644

B Neal, presented at American Diabetes Association, 2017

Các khuyến cáo gần đây công nhận empagliflozin cho phòng

2016 ESC

guidelines

Empagliflozin should be considered in patients with T2D in order to

delay the onset of heart failure and prolong life Class IIa Level B

Empagliflozin is not indicated for the treatment of heart failure

Ponikowski P et al Eur Heart J 2016;37:2129

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