What is the mechanism of action of this treatment?

Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, such as Dapagliflozin, work by blocking the reabsorption of glucose in the kidneys, leading to increased glucose excretion and lower blood glucose levels. This class of drugs has been shown to reduce myocardial infarct size, improve cardiac function, and enhance vascular function, which are critical for patients with Myocardial Ischemia. By improving endothelial function and reducing cardiac stress, SGLT2 inhibitors help protect the heart from further ischemic damage and improve overall cardiovascular outcomes. These benefits are particularly important for Myocardial Ischemia patients as they help mitigate the risk of heart failure and other cardiovascular events.

What side effects are associated with this type of intervention?

Common treatments for myocardial ischemia, particularly SGLT2 inhibitors like dapagliflozin, can cause side effects such as urinary tract infections, genital infections, increased urination, dehydration, hypotension, and, rarely, diabetic ketoacidosis. Other treatments, such as ACE inhibitors, ARBs, and beta-blockers, may cause cough, hyperkalemia, and bradycardia, respectively.

What prior FDA approvals exist?

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, have been approved by the FDA primarily for the treatment of type 2 diabetes mellitus. However, they have also demonstrated cardiovascular benefits, including in patients with heart failure and those at risk of myocardial ischemia. Dapagliflozin, in particular, has shown promise in improving cardiovascular outcomes, including reducing the risk of hospitalization for heart failure and potentially improving microvascular function in patients with ischemic heart disease. Other SGLT2 inhibitors like empagliflozin and canagliflozin have also been noted for their cardiovascular benefits, making them relevant in the context of myocardial ischemia treatment.

What other types of research exist?

Promising alternatives to dapagliflozin for myocardial ischemia patients include GLP-1 receptor agonists such as liraglutide, semaglutide, and dulaglutide, as well as DPP-4 inhibitors like linagliptin. These drugs have demonstrated cardiovascular benefits and are considered effective and safe options.

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Sodium-Glucose Cotransporter 2 Inhibitor

Dapagliflozin for Coronary Artery Disease (SMILE Trial)

Phase 1

Recruiting

Led By Caroline L Flournoy, MD

Research Sponsored by University of Virginia

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Estimated glomerular filtration rate ≥30ml/min/1.73m2 at enrollment

Be older than 18 years old

Must not have

Severe Valvular disease

Symptomatic hypotension or systolic blood pressure <95 mmHg on 2 consecutive measurements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and after 12 weeks of treatment

Summary

This trial is testing whether dapagliflozin, a drug that lowers blood sugar, can improve heart blood flow in women who have heart disease symptoms but no blocked arteries. Participants will take the drug for a few months, and their heart blood flow will be measured at the start and end of the study. Dapagliflozin has been shown to help manage blood sugar levels and improve heart health in patients with type 2 diabetes.

Who is the study for?

This trial is for women with symptoms of ischemic heart disease but no major blockages in their heart arteries. They must have suspected ischemia, a decent kidney function, and if diabetic, approval from their diabetes doctor. It's not for those with severe heart failure, recent acute coronary syndrome or stroke, certain chronic diseases, low blood pressure, frequent urinary infections, type 1 diabetes or active cancer.

What is being tested?

The study tests whether Dapagliflozin improves blood flow in the heart compared to a placebo over 12 weeks. Women will be randomly given either the drug or placebo and monitored using stress cardiac MRI at the start and end of the trial to measure any changes in heart blood flow.

What are the potential side effects?

While specific side effects are not listed here, drugs like Dapagliflozin can typically cause urinary tract infections, dehydration leading to low blood pressure (hypotension), potential kidney issues and an increased risk of diabetic ketoacidosis in diabetics.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function is at a safe level for the trial.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious heart valve condition.

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I often feel faint due to low blood pressure below 95 mmHg.

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I have type 2 diabetes and have had diabetic ketoacidosis.

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My kidney disease is severe, unstable, or getting worse quickly.

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I have not had a stroke or brain bleed in the last 6 months.

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I am currently receiving treatment for an active cancer.

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I have had multiple urinary or kidney infections.

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My doctor expects I have less than 3 years to live due to a non-heart related condition.

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I have Type 1 diabetes.

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I have a history of heart failure, severe lung or liver disease.

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I have a heart condition with weak pumping or thickened heart muscle.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and after 12 weeks of treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and after 12 weeks of treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and after 12 weeks of treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in myocardial perfusion reserve

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: DapagliflozinExperimental Treatment1 Intervention

Dapagliflozin 10mg oral tablet.

Group II: PlaceboPlacebo Group1 Intervention

Placebo matching tablet.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dapagliflozin 10mg Tab

2022

Completed Phase 4

~1070

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, such as Dapagliflozin, work by blocking the reabsorption of glucose in the kidneys, leading to increased glucose excretion and lower blood glucose levels. This class of drugs has been shown to reduce myocardial infarct size, improve cardiac function, and enhance vascular function, which are critical for patients with Myocardial Ischemia. By improving endothelial function and reducing cardiac stress, SGLT2 inhibitors help protect the heart from further ischemic damage and improve overall cardiovascular outcomes. These benefits are particularly important for Myocardial Ischemia patients as they help mitigate the risk of heart failure and other cardiovascular events.

Acute canagliflozin treatment protects against in vivo myocardial ischemia-reperfusion injury in non-diabetic male rats and enhances endothelium-dependent vasorelaxation.Load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction.