Objectives This study sought to determine if in addition to standard preventive measures on-admission, high-dose rosuvastatin exerts a protective effect against contrast-induced acute kidney injury ...(CI-AKI). Background Patients with acute coronary syndrome (ACS) are at high risk for CI-AKI, and the role of statin pre-treatment in preventing renal damage remains uncertain. Methods Consecutive statin-naïve non-ST elevation ACS patients scheduled to undergo early invasive strategy were randomly assigned to receive rosuvastatin (40 mg on admission, followed by 20 mg/day; statin group n = 252) or no statin treatment (control group n = 252). CI-AKI was defined as an increase in creatinine concentration of ≥0.5 mg/dl or ≥25% above baseline within 72 h after contrast administration. Results The incidence of CI-AKI was significantly lower in the statin group than in controls (6.7% vs. 15.1%; adjusted odds ratio: 0.38; 95% confidence interval CI: 0.20 to 0.71; p = 0.003). The benefits against CI-AKI were consistent, even applying different CI-AKI definition criteria and in all the pre-specified risk categories. The 30-day incidence of adverse cardiovascular and renal events (death, dialysis, myocardial infarction, stroke, or persistent renal damage) was significantly lower in the statin group (3.6% vs. 7.9%, respectively; p = 0.036). Moreover, statin treatment given on admission was associated with a lower rate of death or nonfatal myocardial infarction at 6 month follow-up (3.6% vs. 7.2%, respectively; p = 0.07). Conclusions High-dose rosuvastatin given on admission to statin-naïve patients with ACS who are scheduled for an early invasive procedure can prevent CI-AKI and improve short-term clinical outcome. (Statin Contrast Induced Nephropathy Prevention PRATO-ACS; NCT01185938 )
Introduction
The action of environmental steroids on the human glucocorticoid receptor (hGR) has been pointed out with the risk to impair physiological immune and metabolic processes regulated by ...this nuclear receptor. However, there is still a lack of mechanistic information regarding their ability to interact with GR in aquatic species.
Methods
To investigate ligand activation differences between hGR and zebrafish GR (zfGR), we tested several natural and synthetic steroids using reporter cell lines expressing hGR or zfGR.
Results and discussion
Almost all the glucocorticoids tested (dexamethasone, cortisol, bimedrazol, medrol, cortivazol and fluticasone) are agonists of the two receptors with similar potencies. The dissociated glucocorticoids, RU24782 and RU24858 are agonists of both zfGR and hGR but with a better potency for the latter. On the other hand, the synthetic glucocorticoid forbimenol and the mineralocorticoid aldosterone are agonist on hGR but antagonist on zfGR. The other steroids tested, androgens and progestins, are all antagonists of both GRs with equal or lower potency on zfGR than on hGR. Surprisingly, the lower efficacy and potency on zfGR of aldosterone, forbimenol and the dissociated glucocorticoids is not related to their affinity for the receptors which would suggest that it could be related to less efficacious recruitment of coactivators by zfGR compared to hGR.
Sodium Bicarbonate Versus Saline for the Prevention of Contrast-Induced Nephropathy in Patients With Renal Dysfunction Undergoing Coronary Angiography or Intervention Mauro Maioli, Anna Toso, Mario ...Leoncini, Michela Gallopin, Delio Tedeschi, Carlo Micheletti, Francesco Bellandi This randomized study shows that, in addition to oral N -acetylcysteine, the hydration with sodium bicarbonate is not more effective than isotonic saline for prophylaxis of contrast-induced nephropathy in patients with moderate-to-severe renal dysfunction undergoing planned coronary angiography or intervention.
Objectives The aim of this study was to evaluate the relationship between pre-procedural fluid status assessed by bioimpedance vector analysis (BIVA) and development of contrast-induced acute kidney ...injury (CI-AKI). Background Accurate fluid management in patients undergoing angiographic procedures is of critical importance in limiting the risk of CI-AKI. Therefore, establishing peri-procedural fluid volume related to increased risk of CI-AKI development is essential. Methods We evaluated the fluid status by BIVA of 900 consecutive patients with stable coronary artery disease (CAD) immediately before coronary angiography, measuring the resistance/height (R/H) ratio and impedance/height (Z/H) vector. CI-AKI was defined as an increase in serum creatinine ≥0.5 mg/dl above baseline within 3 days after contrast administration (iodixanol). Results CI-AKI occurred in 54 patients (6.0%). Pre-procedural R/H ratios were significantly higher in patients with CI-AKI than without CI-AKI (395 ± 71 Ohm/m vs. 352 ± 58 Ohm/m, p = 0.001 for women; 303 ± 59 Ohm/m vs. 279 ± 45 Ohm/m, p = 0.009 for men), indicating lower fluid volume in the patients with CI-AKI. When patients were stratified according to R/H ratio, there was an almost 3-fold higher risk in patients with higher values (odds ratio OR: 2.9; 95% confidence interval CI: 1.5 to 5.5; p = 0.002). The optimal receiver-operating characteristic curve analysis threshold values of R/H ratio for predicting CI-AKI were 380 Ohm/m for women and 315 Ohm/m for men. R/H ratio above these thresholds was found to be a significant and independent predictor of CI-AKI (OR: 3.1; 95% CI: 1.8 to 5.5; p = 0.001). Conclusions Lower fluid status evaluated by BIVA immediately before contrast medium administration resulted in a significant and independent predictor of CI-AKI in patients with stable CAD. This simple noninvasive analysis should be tested in guiding tailored volume repletion.
We investigated the efficacy of short-term high-dose atorvastatin in decreasing the risk of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) subjected to coronary ...angiography and/or angioplasty. CIN occurs in up to 15% of patients with pre-existing CKD and affects clinical outcome. The protective effect of statin therapy against CIN is still controversial. A prospective, single-center study of 304 patients with baseline estimated creatinine clearance <60 ml/min were randomized to receive atorvastatin 80 mg/day or placebo for 48 hours before and 48 hours after contrast medium administration. All patients received intravenous saline hydration and oral N -acetylcysteine 1,200 mg 2 times/day. Iso-osmolar contrast medium was used. CIN was defined as an absolute increase of serum creatinine ≥0.5 mg/dl within 5 days after the procedure. CIN occurred in 31 patients (10%), 16 (11%) in the placebo group and 15 (10%) in the atorvastatin group (p = 0.86). Mean increase in creatinine was not significantly different in the 2 groups (0.59 ± 0.17 in placebo group vs 0.72 ± 0.26 mg/dl in atorvastatin group, p = 0.31). Persistent kidney injury, defined as 1-month increase from baseline creatinine value ≥25%, was observed in 30% in the placebo group and in 31% in the atorvastatin group (p = 0.58). In conclusion, a short-term administration of high doses of atorvastatin before and after contrast exposure, in addition to standard intravenous hydration and oral N -acetylcysteine, does not decrease CIN occurrence in patients with pre-existing CKD.
Different pharmacologic agents have been tested in the effort to prevent contrast-induced acute kidney injury (AKI) in the last two decades. To date, however, no individual drug has received ...unanimous approval for this aim. Since 2014 statins have been included as preventive treatment in the European guidelines for revascularization procedures in cardiac patients. The present update presents the latest findings in this field focusing on the changing paradigms in the definition and consequently the approach to nephroprotection that considers clinical prognosis as the major issue. We note the current shift from attention to contrast-induced AKI to contrast-associated AKI.
Background Contrast‐induced acute kidney injury (CI‐AKI) is a serious complication after percutaneous coronary intervention. The mainstay of CI‐AKI prevention is represented by intravenous hydration. ...Tailoring infusion rate to patient volume status has emerged as advantageous over fixed infusion‐rate hydration strategies. Methods and Results A systematic review and network meta‐analysis with a frequentist approach were conducted. A total of 8 randomized controlled trials comprising 2312 patients comparing fixed versus tailored hydration strategies to prevent CI‐AKI after percutaneous coronary intervention were included in the final analysis. Tailored hydration strategies included urine flow rate–guided, central venous pressure–guided, left ventricular end‐diastolic pressure–guided, and bioimpedance vector analysis–guided hydration. Primary endpoint was CI‐AKI incidence. Safety endpoint was incidence of pulmonary edema. Urine flow rate–guided and central venous pressure–guided hydration were associated with a lower incidence of CI‐AKI compared with fixed‐rate hydration (odds ratio OR, 0.32 95% CI, 0.19–0.54 and OR, 0.45 95% CI, 0.21–0.97). No significant difference in pulmonary edema incidence was observed between the different hydration strategies. P score analysis showed that urine flow rate–guided hydration is advantageous in terms of both CI‐AKI prevention and pulmonary edema incidence when compared with other approaches. Conclusions Currently available hydration strategies tailored on patients' volume status appear to offer an advantage over guideline‐supported fixed‐rate hydration for CI‐AKI prevention after percutaneous coronary intervention. Current evidence suggests that urine flow rate–guided hydration as the most convenient strategy in terms of effectiveness and safety.
Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to ...characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3 days), subacute (4-30 days), and late (31-365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( P
<0.001) without a difference in ADBRs ( P
=0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( P
<0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( P
<0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.
Randomized Early Versus Late Abciximab in Acute Myocardial Infarction Treated With Primary Coronary Intervention (RELAx-AMI Trial) Mauro Maioli, Francesco Bellandi, Mario Leoncini, Anna Toso, Roberto ...Piero Dabizzi This prospective randomized trial, comparing early (in the emergency room) versus late (in the catheterization laboratory) abciximab administration in patients with acute myocardial infarction treated with primary percutaneous coronary intervention, demonstrates that early abciximab administration significantly improves preprocedural angiographic findings at epicardial and tissue level (Thrombolysis In Myocardial Infarction TIMI flow grade 3, corrected TIMI frame count, and myocardial blush grade 2 or 3), as well as postprocedural perfusion parameters (60-min ST-segment resolution >70% ST-segment and myocardial blush grade 2 or 3) and was accompanied by greater improvement in global and regional left ventricular function.
Background There is a strong correlation between adverse clinical events and peak values of myocardial necrosis markers in non–ST-elevation acute coronary syndrome patients. In this clinical setting, ...high-dose statin treatment exerts acute beneficial effects against renal and myocardial damage. The aim of this report was to evaluate if, on admission, high-dose rosuvastatin can exert cardioprotective effects when administered in addition to high-dose clopidogrel. Methods In the PRATO-ACS trial, 504 consecutive statin-naïve non–ST-elevation acute coronary syndrome patients scheduled for early invasive strategy and pretreated with high-dose clopidogrel were randomly assigned to rosuvastatin (40 mg on admission followed by 20 mg/d; statin group, n = 252) or no statin treatment (control group, n = 252). Serial myocardial biomarker samples were collected before and after angiography and/or percutaneous coronary intervention. The primary end point was the peak level of cardiac troponin I (cTnI) during the index event. Results Statin-treated patients presented median cTnI peak values similar to controls (3.9 0.6-12.8 vs 3.5 1.2-11.9 ng/mL, respectively; P = .60; no differences were found between the 2 groups in cTnI and creatine kinase–MB values at any time point, in either preangiography and postangiography peak values or their cumulative release. In patients submitted to percutaneous coronary intervention, periprocedural myocardial infarction occurred in 8 (4.7%) of 171 statin-treated and 7 (4.3%) of 162 control patients ( P = .87). Conclusion In the PRATO-ACS trial, early high-dose rosuvastatin did not show cardioprotective effects when administered in addition to high-dose clopidogrel.
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