Dapagliflozin for Coronary Artery Disease

(SMILE Trial)

Overseen By Nicole J Sprouse, RN

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Virginia

Disqualifiers: Cardiomyopathy, Heart failure, Stroke, others

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is dapagliflozin generally safe for humans?

Dapagliflozin, also known as Farxiga, is generally well tolerated in humans. It has been used safely in treating conditions like heart failure and type 2 diabetes, although it may cause some side effects like genital infections, especially in women, and is not recommended for people with moderate or severe kidney problems. ^{1 2 3 4 5}

How does the drug Dapagliflozin differ from other treatments for coronary artery disease?

Dapagliflozin is unique because it is primarily used for managing type 2 diabetes by helping the kidneys remove glucose from the bloodstream, which is different from traditional coronary artery disease treatments like beta-blockers or nitrates that focus on reducing heart workload and improving blood flow. ^{6 7 8 9 10}

What evidence supports the effectiveness of the drug dapagliflozin for coronary artery disease?

Dapagliflozin has shown benefits in reducing the risk of cardiovascular death and hospitalization for heart failure in patients with heart failure and type 2 diabetes, as seen in the DECLARE-TIMI 58 and DAPA-HF trials. These cardiovascular benefits suggest potential effectiveness for coronary artery disease, although direct evidence for this specific condition is not provided. ^{1 2 3 11 12}

Who Is on the Research Team?

Patricia Rodriguez-Lozano, MD

Principal Investigator

University of Virginia Health System

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Willing to provide written informed consent

I was referred for a heart check-up due to suspected blockage signs within the last 2 years.

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

Exclusion Criteria

I have a serious heart valve condition.

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

I have type 2 diabetes and have had diabetic ketoacidosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 12-week course of dapagliflozin 10mg or placebo. Blood flow in the heart is assessed using stress cardiac magnetic resonance imaging at baseline and 12 weeks.

12 weeks

3 visits (in-person) at baseline, 6 weeks, and 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin 10mg Tab
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: Dapagliflozin Experimental Treatment 1 Intervention

Dapagliflozin 10mg oral tablet.

Group II: Placebo Placebo Group 1 Intervention

Placebo matching tablet.

Dapagliflozin 10mg Tab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Farxiga for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Farxiga for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Heart failure with preserved ejection fraction
• Heart failure with mildly reduced ejection fraction

Approved in Canada as Farxiga for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Farxiga for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin, an SGLT2 inhibitor, effectively improves glycemic control, reduces body weight, and lowers blood pressure in adults with type 2 diabetes, heart failure, and chronic kidney disease, starting at an estimated glomerular filtration rate of 25 mL/min/1.73 m².

In addition to its primary benefits, dapagliflozin positively affects cardiovascular health by improving arterial stiffness and lipid profiles, thereby reducing the risk of cardiovascular complications, although it is underused in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond the Glycaemic Control of Dapagliflozin: Impact on Arterial Stiffness and Macroangiopathy. González-Clemente, JM., García-Castillo, M., Gorgojo-Martínez, JJ., et al.[2022]

Dapagliflozin is an effective SGLT2 inhibitor for managing type 2 diabetes, showing consistent reductions in blood glucose levels and body weight over long-term follow-up periods of 1-4 years across various clinical trials.

It has a low risk of causing hypoglycemia and is generally well tolerated, although it can lead to genital infections, particularly in women, and is not recommended for patients with moderate to severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. Plosker, GL.[2022]

Dapagliflozin is an effective treatment for type 2 diabetes, showing noninferiority to metformin and glimepiride in clinical trials involving 9 studies, indicating it can be a reliable option for patients.

While generally safe, dapagliflozin is associated with an increased risk of urinary infections and other side effects, suggesting it may be best used as an add-on therapy for patients not adequately controlled on other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin for the Treatment of Type 2 Diabetes Mellitus. Aylsworth, A., Dean, Z., VanNorman, C., et al.[2019]

In a study involving 949 patients with type 2 diabetes and chronic stable angina, ranolazine significantly reduced the average weekly frequency of angina episodes compared to placebo (3.8 vs. 4.3 episodes), indicating its efficacy in managing angina in this high-risk population.

Ranolazine also decreased the use of sublingual nitroglycerin (1.7 doses vs. 2.1 doses), and it was well tolerated with no difference in serious adverse events compared to placebo, suggesting it is a safe option for patients who remain symptomatic despite other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina). Kosiborod, M., Arnold, SV., Spertus, JA., et al.[2022]

Beta-receptor blockers are the first-line therapy for treating coronary artery disease, effectively reducing symptoms and improving patient prognosis, while calcium channel blockers and nitrates are alternatives for those who cannot tolerate beta-blockers.

Aspirin is recommended for all patients with coronary artery disease to lower the risk of future cardiac events, with clopidogrel as an alternative for those who cannot take aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Risk management of coronary artery disease--pharmacological therapy]. Hofmann, T.[2019]

In a study involving 32 patients with stable angina and 17 with acute myocardial infarction, the esophageal electrostimulation test was found to effectively assess the efficiency of antianginal medications by measuring increases in anginal threshold.

The long-acting nitrate Isomak R (forte) demonstrated significant efficacy as an antianginal drug, improving physical stress tolerance and reducing angina attacks without major side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of transesophageal electrostimulation of the heart for evaluating the effectiveness of anti-anginal therapy]. Makolkin, VI., Petriĭ, VV.[2017]

Stable angina, a common symptom of coronary artery disease, is primarily managed through lifestyle changes and a combination of medications, including antianginal drugs and disease-modifying agents.

Recent advancements have introduced new treatment options like nicorandil, ivabradine, trimetazidine, and ranolazine, which are being used as second-line therapies, although their long-term effects are still being studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stable angina pectoris: current medical treatment. Siama, K., Tousoulis, D., Papageorgiou, N., et al.[2018]

Calcium antagonists, particularly 1,4-dihydropyridines like nifedipine, are effective in treating myocardial ischaemia by reducing afterload and inducing coronary vasodilation, but their short action can lead to reflex tachycardia, limiting their effectiveness.

Newer DHPs such as amlodipine and lacidipine offer longer-lasting effects with less impact on heart rate, and lacidipine also provides vascular protection and reduces atheroma plaque formation, likely due to its antioxidant properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent developments in the use of calcium antagonists in myocardial protection. Gaviraghi, G., Micheli, D., Trist, DG.[2019]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

3. Belgium pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Beyond the Glycaemic Control of Dapagliflozin: Impact on Arterial Stiffness and Macroangiopathy. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Dapagliflozin for the Treatment of Type 2 Diabetes Mellitus. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina). [2022]

9. Austria pubmed.ncbi.nlm.nih.gov

[Risk management of coronary artery disease--pharmacological therapy]. [2019]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Use of transesophageal electrostimulation of the heart for evaluating the effectiveness of anti-anginal therapy]. [2017]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Stable angina pectoris: current medical treatment. [2018]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Recent developments in the use of calcium antagonists in myocardial protection. [2019]