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

Overview

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.

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.