Impact of early intervention with alogliptin on coronary plaque regression and stabilization in patients with acute coronary syndromes.

BACKGROUND AND AIMS: Anti-atherosclerotic effects of early intervention with dipeptidyl peptidase-4 inhibitors remain poorly defined. METHODS: In a prospective, single-center, randomized trial, 66 patients with acute coronary syndrome (ACS) and mild dysglycemia (HbA1c 6.0 (5.7, 6.3)%, 58% of impaired glucose tolerance) were randomly assigned to receive alogliptin (n = 33) or placebo (n = 33) in addition to standard treatments. Serial intravascular ultrasound (IVUS) was performed at baseline and 10 months to evaluate changes in coronary percent plaque volumes (%PV) and plaque tissue components of non-culprit lesions (NCLs). RESULTS: Baseline clinical and IVUS characteristics, as well as decreases in HbA1c and lipid variables during 10 months, did not differ significantly between the 2 groups. In contrast, with respect to vascular responses, the alogliptin group showed significantly greater decreases in plaque volumes (-0.3 ± 0.6 vs. -0.04 ± 0.7 mm3/mm, p = 0.03) and %PV (-0.9 ± 2.8 vs. 1.2 ± 3.6%, p = 0.01), with a tendency toward smaller lumen loss (-0.1 ± 0.7 vs. -0.4 ± 0.8 mm3/mm, p = 0.07) compared with the placebo group. Significantly decreased percent necrotic volumes (%NV) (-1.9 ± 3.8 vs. 0.3 ± 3.7%, p = 0.03) and increased fibrotic volumes (2.5 ± 5.0 vs. -0.3 ± 5.3%, p = 0.05) were or tended to be seen in alogliptin versus placebo groups at 10 months. In multiple regression analysis, alogliptin use was a statistically significant determinant of changes in %PV (ß = -0.33, p = 0.004) and %NV (ß = -0.28, p = 0.03) at 10 months. CONCLUSIONS: Alogliptin treatment, independently of glycemic and lipid status, resulted in significant plaque regression and stabilization in NCLs in patients with ACS and mild dysglycemia, suggesting the potential utility of early intervention with incretin-based treatments for this patients' subset.

Impact of Acute Kidney Injury on In-Hospital Outcomes of Patients With Acute Myocardial Infarction　- Results From the Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) Substudy.

BACKGROUND: Acute kidney injury (AKI) is associated with poor outcome after acute myocardial infarction (AMI), but whether hemodynamic status at presentation influences this prognostic significance is unknown.Methods and Results:A total of 2,798 AMI patients admitted within 48 h after symptom onset and who underwent urgent coronary angiography were enrolled in the present study. AKI was defined as an increase in serum creatinine ≥0.3 mg/dL or ≥50% within 48 h during hospitalization. Patients were classified into 3 groups according to Killip class on admission: Killip 1, n=2,164; Killip 2-3, n=366; and Killip 4, n=268. AKI occurred more frequently with increasing Killip class (Killip 1, 2-3, and 4: 6.3%, 15.3%, and 31.3%, respectively; P<0.001). AKI was associated with increased in-hospital mortality, regardless of Killip class (non-AKI and AKI patients: 1.1% vs. 6.6% in Killip 1; 5.2% vs. 35.7% in Killip 2-3, and 28.8% vs. 45.2% in Killip 4, P<0.01 for all). On multivariate analysis, the adjusted OR of AKI for in-hospital mortality in Killip 1, Killip 2-3, and Killip 4 were 3.79 (95% CI: 1.54-9.33, P=0.004), 5.35 (95% CI: 2.67-10.7, P<0.001), and 1.48 (95% CI: 0.94-2.35, P=0.093), respectively. CONCLUSIONS: In AMI patients undergoing urgent coronary angiography, AKI was significantly associated with increased in-hospital mortality in Killip 1 as well as Killip 2-3 at presentation, but not in Killip 4.

Combined impact of chronic kidney disease and contrast-induced nephropathy on long-term outcomes in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) and chronic kidney disease (CKD) are associated with poor outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI); however, its combined prognostic significance remains unclear. We enrolled 577 patients with AMI undergoing primary PCI within 12 h after symptom onset and measured serum creatinine on admission and the next 3 days. CKD was defined as admission estimated glomerular filtration rate <60 ml/min/1.73 m2, and CIN was defined as creatinine increase ≥0.5 mg/dl or ≥25 % from baseline within the first 72 h. Patients were stratified according to the presence or absence of CKD and CIN. In patients with no CKD and no CIN (n = 244), no CKD but CIN (n = 152), CKD but no CIN (n = 127), and both CKD and CIN (n = 54), the 3-year major adverse cardiovascular events (MACE: a combination of all-cause mortality, nonfatal reinfarction, or heart failure requiring rehospitalization) were 8, 9, 13, and 35 %, respectively (p < 0.001). Multivariate analysis showed that as compared with no CKD and no CIN, hazard ratios (95 % CI) for MACE associated with no CKD but CIN, CKD but no CIN, and both CKD and CIN were 0.91 (0.44-1.84; p = 0.79), 1.11 (0.5-2.23; p = 0.77), and 2.98 (1.48-6.04; p = 0.002), respectively. In patients with AMI undergoing primary PCI, the combination of CKD and CIN is significantly associated with adverse long-term outcomes.