Dapagliflozin Effects on Mayor Adverse Cardiovascular Events in Patients With Acute Myocardial Infarction (DAPA-AMI)
Condition: Acute Myocardial Infarction; Cardiovascular Morbidity; Heart Failure; Angina, Unstable
MeSH terms: Myocardial Infarction; Angina, Unstable; Infarction
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Dapagliflozin 10Mg Tab; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): patients who meet the inclusion criteria will be randomized to receive dapagliflozin 10 mg 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
Intervention MeSH terms: Dapagliflozin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Asses the effect of Dapagliflozin on mayor adverse cardiovascular effects in patients with acute myocardial infarction compared against placebo.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Acute myocardial infarction; Dapagliflozin; mayor adverse cardiovascular events