The Heart And The Evolving Role Of

Empaglifozin In Heart Failure

Management

DR SWALEH BREIK MISFAR

CONSULTANT PHYSICIAN / CARDIOLOGIST (MADRAS)
SPEACIAL INTEREST IN HF (PCHF LONDON)
FESC
Disclosure

 I am contracted by Boehringer Ingelheim to conduct this session.

 I have no financial interest in Boehringer Ingelheim
An Insidious Disease that Starts Before the

First Symptoms
Outcomes for HF Compared With the
General US Population
4 Pillars of HFrEF Therapy
Initiate Multiple Drugs Together
 Paradigm Shift in the Management of
Type 2 Diabetes
 Person-centric
 Gluco-centric
 A1C-lowering important,
 A1C-lowering primary but comorbidities and
consideration risks also considered

American Diabetes Association. Diabetes Care. 2020;43:S1-S212. Slide credit: clinicaloptions.com

 Adverse CV events led the FDA to require demonstration of
CV safety for new glucose-lowering drugs

1961 UGDP trial: tolbutamide discontinued due to increased CV

mortality vs other treatment groups1

Muraglitazar found to potentially increase CV risk • Sponsor withdrew

2005 application1
during FDA assessment2
Rosiglitazone associated with increased risk • Withdrawn in the EU1
2007
for MI and CV-related death3 • Use restricted in US1*
2008 ACCORD trial: intensive glucose lowering was *In 2013, FDA panel voted to reduce safety
associated with increased all-cause mortality 4 restrictions on rosiglitazone7

HR 1.22 (95% CI 1.01‒1.46); p = 0.04

2008 New FDA requirements5

2012 New EMA requirements6
New diabetes drugs should demonstrate CV safety with
meta-analysis and a CV outcome trial (CVOT)

1. Nissen. Ann Intern Med 2012;157:671–2. 2. Nissen et al. JAMA 2005;294:2581–6. 3. Nissen et al. N Engl J Med 2007;356:2457–71.
4. ACCORD Study Group. N Engl J Med 2008;358:2545–59.
5. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/%20guidances/ucm071627.pdf
6. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500129256.pdf
7.http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm376683.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

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SGLT2’s CVOT’s

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 ADA 2020: Using a Person-Centered
Approach
Lifestyle modification
plus metformin
If above A1C target, proceed below

High risk or established ASCVD, HF, or CKD?

Yes No

A1C irrelevant; Start

Add GLP-1 RA or SGLT-2 inhibitor A1C-based therapy

American Diabetes Association. Diabetes Care. 2020;43:S98. Slide credit: clinicaloptions.com

 ADA 2020: Using a Person-Centered
Approach
All patients: lifestyle modification
Most patients: metformin

High risk or established ASCVD, CKD, or HF,

regardless of A1C

ASCVD predominates HF or CKD predominates

SGLT2 with evidence of reducing HF and/or

GLP-1 RA with SGLT2 with proven CKD progression in CVOTs if eGFR adequate
EITHER/OR
proven CVD CVD benefit, OR
benefit if eGFR adequate If SGLT2 not tolerated or contraindicated or
if eGFR less than adequate, add GLP-1 RA with
proven CVD benefit

American Diabetes Association. Diabetes Care. 2020;43:S98. Slide credit: clinicaloptions.com

 SGLT2-Inhibition SGTL2
SGLT2 expression increased
SGLT2 inhibitor
Increased glucose reabsorption
Distal
tubule

Glomeruli Proximal
Increased tubule
glucose
filtration SGTL1

Increased urinary
sodium excretion
Increased urinary
After Marx et al. Eur Heart J 2016;37(42):3192-3200 glucose excretion
SGLT2 Inhibitors Trials – a rethink on Diabetes
to Cardiovascular Disease Pathways
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Several SGLT2 inhibitor mechanisms may have

beneficial effects on heart failure

Reduced preload, afterload

Natriuresis and reduction in LV wall stress
Na+
SGLT2i
SGLT2 and
prevention
inhibitors of
and HF
chronic
prevention
of HF
Improved kidney function and Reduction in
cardio–renal physiology interstitial oedema

LV, left FOR INTERNAL

ventricular; USE ONLY.
SGLT2, sodium-glucose STRICTLY CONFIDENTIAL.
co-transporter-2 DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY.
17 Adapted from Farkouh ME & Verma S. J Am Coll Cardiol. 2018;71:2507
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Benefit of SGLT2 Inhibition in HF

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Benefit of SGLT2 Inhibition in HF (cont)

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Benefit of SGLT2 Inhibition in HF (cont)

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Benefit of SGLT2 Inhibition in HF (cont)

FOR INTERNAL USE ONLY. STRICTLY CONFIDENTIAL. DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY.
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Benefit of SGLT2 Inhibition in HF (cont)

FOR INTERNAL USE ONLY. STRICTLY CONFIDENTIAL. DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY.
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Benefit of SGLT2 Inhibition in HF (cont)

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HFrEF Management in Primary Care

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73-Year-Old Man With HF With Cormorbidities

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73-Year-Old Man With HF With Cormorbidities:

Management Considerations

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73-Year-Old Man With HF With Cormorbidities:

Management Considerations (cont)

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73-Year-Old Man With HF With Cormorbidities:

Management Considerations (cont)

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73-Year-Old Man With HF With Cormorbidities:

Management Considerations (cont)

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HFpEF Trials
Ongoing HF Trials With SGLT2 Inhibitors
Benefit of SGLT2 Inhibition Across EF
Spectrum
SGLT2 Inhibitors Provide Benefit Across
EF Spectrum
HF Phenotypes Are Not Static
SGLT2 Inhibitors Trials – a rethink on Diabetes to
Cardiovascular Disease Pathways
THANK YOU