Cardioprotective Effect of Fimasartan, a New Angiotensin Receptor Blocker, in a Porcine Model of Acute Myocardial Infarction

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Effects of ACE inhibition on endothelial progenitor cell mobilization and prognosis after acute myocardial infarction in type 2 diabetic patients

OBJECTIVE: We aimed to assess the chemotactic response of endothelial progenitor cells to angiotensin-converting enzyme inhibitors in T2DM patients after acute myocardial infarction, as well as the associated prognosis. METHODS: Sixty-eight T2DM patients with acute myocardial infarction were randomized to either receive or not receive daily oral perindopril 4 mg, and 36 non-diabetic patients with acute myocardial infarction were enrolled as controls. The numbers of circulating CD45−/low+CD34+CD133+KDR+ endothelial progenitor cells, as well as the stromal cell-derived factor-α and high-sensitivity C reactive protein levels, were measured before acute percutaneous coronary intervention and on days 1, 3, 5, 7, 14, and 28 after percutaneous coronary intervention. Patients were followed up for 6 months. Chinese Clinical Trial Registry: ChiCTR-TRC-12002599. RESULTS: T2DM patients had lower circulating endothelial progenitor cell counts, decreased plasma vascular endothelial growth factor and α levels, and higher plasma high-sensitivity C reactive protein levels compared with non-diabetic controls. After receiving perindopril, the number of circulating endothelial progenitor cells increased from day 3 to 7, as did the plasma levels of vascular endothelial growth factor and stromal cell-derived factor-α, compared with the levels in T2DM controls. Plasma high-sensitivity C reactive protein levels in the treated group decreased to the same levels as those in non-diabetic controls. Furthermore, compared with T2DM controls, the perindopril-treated T2DM patients had lower cardiovascular mortality and occurrence of heart failure symptoms (p<0.05) and better left ventricle function (p<0.01). CONCLUSIONS: The use of angiotensin-converting enzyme inhibitors represents a novel approach for improving cardiovascular repair after acute myocardial infarction in T2DM patients. .

Assessment of perindopril's efficacy on arterial distensibility in mild to moderate hypertension.

OBJECTIVE: Angiotensin Converting Enzyme Inhibitors (ACEIs) have been clearly proven to be effective in blood pressure control and haemodynamic control in heart failure patients. Moreover, there is evidence that ACEIs, both in animal models and in humans, also possess the ability to reduce remodeling in cardiovascular structures. Therefore, the reduction of the occurrence of arterial stiffness, leading to an increase in distensibility, is also anticipated. METHOD: Other than physically measuring arterial wall, the assessment of Pulse Wave Velocity (PWV) is also a widely used index of arterial distensibility, which deteriorates through the course of remodeling. To determine the efficacy of a particular ACEI, perindopril, in increasing arterial distensibility, thus reducing PWV, a 6-month multi-center study was conducted in 146 patients with mild to moderate hypertension. The study population consisted of 70 men and 76 women, aged 56.36 (SD 9.4, range 28-73) years. 73 patients were newly diagnosed, 65 were treated patients but the blood pressure was not controlled, and 8 were treated patients with their blood pressure controlled but with adverse effects in need of switching treatment regimens. RESULTS: Mean blood pressure at the beginning of the study was 164.25/97.49 mmHg and 11.71 m/s (SD 2.29 range 7.35-20.12 m/s) in mean PWV. Perindopril was prescribed tritrating from 4 mg/day to 8 mg/day and adding a diuretic. 106 patients completed the study with 76.4 per cent of patients having their blood pressure controlled (Mean Blood pressure 138.6/85.18 mmHg, SD 11.34 and 7.10 Range 110-170/70-110 mmHg) (p<0.05). Mean PWV reduced to 10.56 m/s (-9.89%) (SD 1.84 range 7.27-15.96 m/s) (p<0.05). CONCLUSION: Anti-hypertensive treatment with perindopril for 6 months was effective in controlling blood pressure and reducing Pulse Wave Velocity reflecting the increase of arterial distensibility.