Sodium-Glucose Transporter 2 Inhibitors

Updated guidelines for management of congestive heart failure rom the American College of Cardiology and the American Heart Association. James W. Mold, MD, MPH

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GUIDELINE TITLE 2022 American College of Cardiology
(ACC)/American Heart Association AHA)/Heart Failure
Society of America (HFSA) Guidelines for the Management
of Heart Failure
RELEASE DATE April 1, 2022
PRIOR VERSIONS 2017 ACC/AHA/HFSA Focused Update
of the 2013 ACCF/AHA Guideline for the Management of
Heart Failure and 2013 ACCF/AHA Guideline for the
Management of Heart Failure
DEVELOPER AND FUNDING SOURCE ACC/AHA Joint
Committee on Clinical Practice Guidelines
TARGET POPULATION Adult patients with a diagnosis of
or at risk for heart failure (HF)
MAJOR RECOMMENDATIONS
• Classifications for HF are separated into 4 categories based
on ejection fraction (EF) and disease history: HF with
reduced EF (EF 40%), HF with mildly reduced EF
(EF 41%-49%), HF with preserved EF (EF 50%), and HF
with improved EF (EF previously 40% with improvement
to >40%).
• In patients with chronic HF with reduced EF, angiotensin
receptor–neprilysin inhibitors (ARNIs) are preferred over
angiotensin-converting enzyme inhibitors (ACEIs) and
angiotensin II receptor blockers (ARBs). If ARNI use is not
feasible, ACEIs are preferred over ARBs, unless there is
significant cough or angioedema (class 1, level of
evidence [LOE] A).
• Sodium-glucose cotransporter 2 (SGLT2) inhibitors should
be included across all HF categories (symptomatic HF with
reduced EF [class 1, LOE A]; HF with mildly reduced EF and
HF with preserved EF [class 2a, LOE B-R]).
• Patients with HF with improved EF should continue to
receive medical therapy originally indicated for HF with
reduced EF (class 1, LOE B-R).
• Evidence-based treatment of HF with preserved EF
includes blood pressure control (class 1, LOE C-LD),
SGLT2 inhibitors (class 2a, LOE B-R), mineralocorticoid
antagonists, ARBs, and ARNIs (class 2b, LOE B-R).

Author/s:

Belkin, M. N., Cifu, A. S., Pinney, S.

GLP1Agonists and SGLT2 Inhibitors Table

Saige Blanchard — Thu, 10 Mar 2022 06:00:00 +0000

Date Added:

March 10, 2022

Publication Date:

February 6, 2022

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Poster

MeSH

diabetes mellitus, type 2

Sodium-Glucose Transporter 2 Inhibitors

Glucagon-Like Peptide-1 Receptor

Patient Selection

This table shows the relative risk reduction (RRR) and absolute risk reduction (ARR) as percentages for GLP1 agonists and SGLT2 Inhibitors, based upon RCTs of at least one year duration. In most cases, the participants were at high risk for adverse CV events, but the ARRs were still fairly small, with insufficient information about how these drugs perform vs. other, less expensive antihyperglycemic agents. James W. Mold, MD, MPH

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Based upon the following two meta-analyses:
1. Alexander JT, et al. The longer-term benefits and harms of glucagon-like peptide-1 receptor agonists: A Systematic review and meta-analysis. JGIM, 2021; 7(2): 415-43.
2. Alexander JT, et al. Longer-term benefits and risks of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes: A systematic review and meta-analysis. JGIM, 2021; 37(2): 439-44, plus Supplementary materials at https://doi.org/10.1007/s11606-021-07227-0.

Selection criteria for the RCTs was that the study period was at least 52 weeks in duration. I assume the average duration of the studies was at least 2 years. So, an absolute risk reduction of mortality of 0.5% would be per 2+ years.

Author/s:

Mold, J. W.

Using Insulin to Treat Poorly Controlled Type 2 Diabetes in 2020

John Bayhi — Tue, 26 May 2020 20:43:16 +0000

Date Added:

May 26, 2020

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

May 22, 2020

Volume:

Online ahead of print

URL:

Using Insulin to Treat Poorly Controlled Type 2 Diabetes in 2020

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2020.1303

Keywords

PMID (1):

32442246

MeSH

Sodium-Glucose Transporter 2 Inhibitors

hypoglycemic agents

insulin

glycated hemoglobin a

dipeptidyl-peptidase IV inhibitors

Metformin

diabetes mellitus, type 2

Glucagon-Like Peptide-1 Receptor

Thiazolidinediones

A potentially useful decision algorithm for management of patients with Type 2 diabetes, which includes early consideration of use of basal insulin in patients with A1c > 9%. James W. Mold, MD, MPH

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No abstract available

Author/s:

Hirsch, IB, Gaudiani, LM

Estimating Lifetime Benefits of Comprehensive Disease-Modifying Pharmacological Therapies in Patients With Heart Failure With Reduced Ejection Fraction: A Comparative Analysis of Three Randomised Controlled Trials

John Bayhi — Tue, 26 May 2020 20:29:33 +0000

Date Added:

May 26, 2020

Journal/Publication:

Lancet

Publisher:

Elsevier Ltd

Publication Date:

May 21, 2020

Volume:

Online ahead of print

URL:

Estimating Lifetime Benefits of Comprehensive Disease-Modifying Pharmacological Therapies in Patients With Heart Failure With Reduced Ejection Fraction: A Comparative Analysis of Three Randomised Controlled Trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/S0140-6736(20)30748-0

Keywords

CHF patients

heart failure

pharmacologic management

PMID (1):

32446323

MeSH

Humans

Angiotensin Receptor Antagonists

Mineralocorticoid Receptor Antagonists

Angiotensin-Converting Enzyme Inhibitors

Sodium-Glucose Transporter 2 Inhibitors

Peptidyl-Dipeptidase A

Neprilysin

heart failure

SLC5A2 protein, human

sodium-glucose transporter 2

Stroke Volume

Control Groups

Receptors, Drug

Progression-Free Survival

Receptors, Angiotensin

NR3C2 protein, human

For those of you who still initiate and manage CHF with reduced LV ejection fraction, this meta-analysis appears to support using combinations of the following five agents: 1) an ACEI or ARB, 2) a beta-blocker, 3) a mineralocorticoid receptor antagonist [MRA], 4) an angiotensin receptor–neprilysin inhibitor [ARNI], and 5) a sodium/glucose cotransporter 2 [SGLT2] inhibitor. They estimate that combined therapy could increase life expectancy for an 80-year-old 1.4 years and for a 55-year-old 6.3 years. If we are going to continue to manage these patients, it looks like we are going to have to develop specific CHF visits and protocols like those used in CHF clinics run by cardiology teams. James W. Mold, MD, MPH

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Background: Three drug classes (mineralocorticoid receptor antagonists [MRAs], angiotensin receptor-neprilysin inhibitors [ARNIs], and sodium/glucose cotransporter 2 [SGLT2] inhibitors) reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF) beyond conventional therapy consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and β blockers. Each class was previously studied with different background therapies and the expected treatment benefits with their combined use are not known. Here, we used data from three previously reported randomised controlled trials to estimate lifetime gains in event-free survival and overall survival with comprehensive therapy versus conventional therapy in patients with chronic HFrEF.

Methods: In this cross-trial analysis, we estimated treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, β blocker, MRA, and SGLT2 inhibitor) versus conventional therapy (ACE inhibitor or ARB and β blocker) in patients with chronic HFrEF by making indirect comparisons of three pivotal trials, EMPHASIS-HF (n=2737), PARADIGM-HF (n=8399), and DAPA-HF (n=4744). Our primary endpoint was a composite of cardiovascular death or first hospital admission for heart failure; we also assessed these endpoints individually and assessed all-cause mortality. Assuming these relative treatment effects are consistent over time, we then projected incremental long-term gains in event-free survival and overall survival with comprehensive disease-modifying therapy in the control group of the EMPHASIS-HF trial (ACE inhibitor or ARB and β blocker).

Findings: The hazard ratio (HR) for the imputed aggregate treatment effects of comprehensive disease-modifying therapy versus conventional therapy on the primary endpoint of cardiovascular death or hospital admission for heart failure was 0·38 (95% CI 0·30-0·47). HRs were also favourable for cardiovascular death alone (HR 0·50 [95% CI 0·37-0·67]), hospital admission for heart failure alone (0·32 [0·24-0·43]), and all-cause mortality (0·53 [0·40-0·70]). Treatment with comprehensive disease-modifying pharmacological therapy was estimated to afford 2·7 additional years (for an 80-year-old) to 8·3 additional years (for a 55-year-old) free from cardiovascular death or first hospital admission for heart failure and 1·4 additional years (for an 80-year-old) to 6·3 additional years (for a 55-year-old) of survival compared with conventional therapy.

Interpretation: Among patients with HFrEF, the anticipated aggregate treatment effects of early comprehensive disease-modifying pharmacological therapy are substantial and support the combination use of an ARNI, β blocker, MRA, and SGLT2 inhibitor as a new therapeutic standard.

Funding: None.

Author/s:

Vaduganathan, M., Claggett, BL, Jhund, PS, Cunningham, JW, Ferreira, JP, Zannad, F, Packer, M, Fonarow, GC, McMurray, JJV, Solomon, S.D.