Dapagliflozin Effects on Mayor Adverse Cardiovascular Events in Patients With Acute Myocardial Infarction (DAPA-AMI) (DAPA-AMI)

June 22, 2023 updated by: Hilda Elizabeth Macías Cervantes, Instituto Mexicano del Seguro Social

Dapagliflozin Effects on Mayor Adverse Cardiovascular Events in Patients With Acute Myocardial Infarction (DAPA-AMI). Randomized Clinical Trial

The actual evidence is solid about the use of de SGLT2-inhibitors in wide spectrum of cardiorenal targets, which has been shown in a great amount of randomized clinical trials compared with placebo. At present it must be taken into account as first line treatment in patients with DM2, even their security profile has allowed the use in patients without diagnosis of DM2, since they have be shown a beneficial cardioprotect effects. Most studies support they use in patients with high cardiovascular risk, nevertheless, their use in patients with recent diagnosis of ischemic hearth disease its limited, being the latter entity the most frequent etiology found in patients who develop chronic hearth failure either as part of heart attack or unstable angina.

Study Overview

Detailed Description

According with the World Health Organization, cardiovascular disease is the leading cause of mortality in the world, estimating 17.9 millions of deaths a year. The cardiovascular disease are a group of disorders of the hearth and the blood vessels including coronary artery disease, cerebrovascular disease, rheumatic hearth disease and other conditions. Four out of five deaths attributed to cardiovascular cause are related to acute myocardial infarction and cerebrovascular disease and one third of this deaths occur in persons younger than 70 years.

The concept of acute coronary syndrome includes the ST elevation myocardial infarction who presents a ST elevation in two contiguous leads or complete left branch bundle block instead patients who presents without ST elevation in the electrocardiogram they are usually classified as Non ST elevation acute myocardial infarction.

The optimum treatment of the STEMI must be based in the utilization of networks between hospitals with different technology levels connected by an efficient y prioritized ambulance system. The objective of this networks is to provide an efficient medical attention, reduce the lag time and to get better the clinical results. The percutaneous coronary intervention is the preferred treatment of reperfusion for the patients with acute myocardial infarction on the first 12 hours after the development of symptoms, provided it can be done quickly (120 minutes since the diagnosis). In some circumstances, the PCI is not an option, then the fibrinolysis could be started immediately.

Most patients with ischemic heart disease are carriers of DM2. The DM2 is associated to an increase 3 times the risk of cardiovascular disease being this the principal cause of morbidity and mortality in this patients. Further, more than 40% of the patient with DM2 develops diabetic nephropathy and this increase strongly the risk of poor cardiovascular outcomes.

Improve the glycemic control in patients with DM2 has been a major objective in the clinical practice for decades, abreast to a reduction of the multifactorial cardiovascular risk. On randomized trials, controlled with placebo, the sodium-glucose linked transported inhibitors type 2 have shown convincingly improve the cardiovascular results, including a reduction in cardiovascular death and particularly, the reduction in the occurrence of heart failure leading to hospitalization . The consistent evidence of the beneficial cardiovascular effects of SGLT-2 inhibitors has led to recommend it in international papers for patients with DM2 and cardiovascular disease in addition to metformin, regardless of their basal levels of glycated hemoglobin.

The clinical trial EMPAREG OUTCOME in patients with DM2 and cardiovascular disease who receive a standard medical treatment shown a reduce in risk of MACE with empagliflozin compared with placebo, conferred mainly by a reduction in cardiovascular death. Mortality from all causes fell as well the risk of hospitalization associated to hearth failure. The CANVAS PROGRAM in patients with DM2 and high cardiovascular risk (66% had cardiovascular disease) shown also a reduction of risk of MACE with the use of canagiflozin compared against placebo, though the reduction on the risk of cardiovascular death and mortality by all causes didn't reach statistical significance.

The clinical trial DAPAHF included patients with LVEF of 45% and DM2 diagnosis. During the follow up (18.2 months) the patients aleatory assigned to receive dapagliflozin (in addition to standard medical therapy) had a significant reduction of 26% in risk of death from cardiovascular cause or deterioration of heart failure compared with placebo group, with a reduction of 18% of cardiovascular death. The amount of the effect were similar between patients with or without DM2, indicating a new beneficial mechanism that goes beyond glycemic control.

The SGLT-2 inhibitors effectively increase glycosuria, improve glycemic control and reduce the corporal mass index due to calorie loss. In addition, promote sodium excretion trough urine early (with a reduction in the plasmatic volume and increase in hematocrit), reduce the systemic blood pressure, and reduce the glomerular hyperfiltation and albuminuria. It is uncertain which of this mechanisms underlies the cardiovascular and renal benefits that had been shown in the big clinical trials but probably the sodium excretion trough urine early followed by a change in tisular sodium give a back up to protect against the decompensation against heart failure and the studies support this includes in patients without diagnosis of DM2. Other beneficial mechanisms includes a reduction in the inflammation mediated by adipose tissue and production of pro inflammatory cytokines, reduction in oxidative stress, inhibition of the exchanger Na+ / H+ of the myocardium and reduced levels of serum uric acid.

Study Type

Interventional

Enrollment (Actual)

188

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Guanajuato
      • Leon, Guanajuato, Mexico, 37260,
        • Unidad Medica de Alta Especialidad No. 1, Bajío

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male and female IMSS eligible patients over 18 years of age
  • Meet the criteria of the fourth definition of ST-segment elevation myocardial infarction
  • Known with diabetes mellitus 2 or newly diagnosed diabetes according to ADA criteria

Exclusion Criteria:

  • Patients diagnosed with Type 1 Diabetes Mellitus
  • Patients on chronic replacement therapy for renal function through peritoneal dialysis or hemodialysis
  • Patients who have recently undergone immunosuppressive therapy
  • Patients with a history of recurrent urinary tract infection
  • Patients known to be allergic to SGLT-2 inhibitors
  • Patients presenting as sudden aborted death
  • Patients who after percutaneous coronary intervention require orotracheal intubation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention Group
Dapagliflozin 10 mg every 24 hours for 12 months
patients who meet the inclusion criteria will be randomized to receive dapagliflozin 10 mg every 24 hours for 12 months
Placebo Comparator: Control Group
1 placebo tablet every 24 hours for 12 months
patients meeting the inclusion criteria will be randomized to receive a placebo solution every 24 hours for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mayor adverse cardiovascular effects
Time Frame: 12 months
To assess the presence of myocardial infarction, stroke and death from cardiovascular causes in post-infarction patients during the study follow-up
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular ejection fraction
Time Frame: 12 months
Evaluate baseline left ventricular ejection fraction in post-infarct patients and 12 months of treatment
12 months
Chronic heart failure
Time Frame: 12 months
Evaluate the effect of Dapagliflozin on the development of chronic heart failure that deserves hospitalization
12 months
Post infarction angina
Time Frame: 12 months
Evaluate the effect of Dapagliflozin on the development of post infarction angina
12 months
Mortality due to cardiovascular cause
Time Frame: 12 months
Assess the presence of mortality due to cardiovascular causes during the study follow-up.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Hilda E Macias Cervantes, Master in Clinical Research, Unidad Médica de Alta Especialidad No. 1 Bajío, Boulevard Adolfo López Mateos esquina Insurgentes S/N, colonia Los Paraísos, Leon, Guanajuato, Mexico, 37260
  • Study Director: German R Bautista Lopez, Cardiology, Unidad Médica de Alta Especialidad No. 1 Bajío, Boulevard Adolfo López Mateos esquina Insurgentes S/N, colonia Los Paraísos, Leon, Guanajuato, Mexico, 37260
  • Study Chair: Luis J Gonzalez, Cardiology Resident, Unidad Médica de Alta Especialidad No. 1 Bajío, Boulevard Adolfo López Mateos esquina Insurgentes S/N, colonia Los Paraísos, Leon, Guanajuato, Mexico, 37260
  • Study Director: Rodolfo Guardado Mendoza, Endocrinologist, Unidad de Investigación Metabólica, Universidad de Guanajuato, Boulevard Cañaveral 1001, fracciones de los Aguirre, CP 37672, León, Guanajuato, México
  • Study Chair: Gabriel Fernandez Yañez, Cardiology Resident, Unidad Médica de Alta Especialidad No. 1 Bajío, Boulevard Adolfo López Mateos esquina Insurgentes S/N, colonia Los Paraísos, Leon, Guanajuato, Mexico, 37260

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 26, 2021

Primary Completion (Actual)

June 30, 2022

Study Completion (Actual)

June 20, 2023

Study Registration Dates

First Submitted

January 17, 2021

First Submitted That Met QC Criteria

January 17, 2021

First Posted (Actual)

January 22, 2021

Study Record Updates

Last Update Posted (Actual)

June 26, 2023

Last Update Submitted That Met QC Criteria

June 22, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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