Early high-dose rosuvastatin and cardioprotection in the protective effect of rosuvastatin and antiplatelet therapy on contrast-induced acute kidney injury and myocardial damage in patients with acute coronary syndrome (PRATO-ACS) study.

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.

Pharmacodynamic effects of adjunctive high dose atorvastatin on double dose clopidogrel in patients with high on-treatment platelet reactivity depending on diabetes mellitus status.

Diabetes mellitus (DM) is associated with impaired platelet response to clopidogrel. In patients with high on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel, high-dose atorvastatin enhances the pharmacodynamic (PD) effects of double-dose clopidogrel. It is unknown if similar effects are achieved in patients with DM. This study compare the PD effects of high-dose atorvastatin associated with double dose clopidogrel in HTPR patients with and without DM undergoing elective percutaneous coronary intervention (PCI). This is a post hoc analysis of a prospective randomized PD study that compared double-dose (150 mg) clopidogrel associated with high-dose (80 mg) atorvastatin to double-dose clopidogrel alone in statin naïve patients with HTPR undergoing elective PCI. In this analysis, patients were divided in two groups according to DM (n = 27) and non-DM (n = 49) status. Platelet reactivity was evaluated immediately before PCI and at 30 days using the VerifyNow P2Y12 assay. HTPR was defined as P2Y12 reaction units (PRU) ≥235. Administering high-dose atorvastatin in addition to high-dose clipodogrel, the 30 days absolute PRU changes (106 ± 75 vs 100 ± 42, p = 0.7) and optimal response rates (83 vs 84%; p = 0.9) were similar in DM and non-DM patients. The baseline variables significantly associated with 30-day optimal response to high-dose clopidogrel were: atorvastatin treatment (OR = 7.5 [95% CI 1.19-47]; p = 0.032) in DM patients; PRU values (OR = 0.9 [95% CI 0.95-0.99]; p = 0.031) and creatinine clearance (OR = 1.07 [95% CI 1.008-1.13]; p = 0.025) in non-DM patients. High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in DM patients with HTPR undergoing elective PCI.

Impact of advanced age on myocardial perfusion, distal embolization, and mortality patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb-IIIa inhibitors.

Despite mechanical reperfusion, the outcome is still unsatisfactory in elderly patients with ST-segment elevation myocardial infarction (STEMI). The vast majority of studies have been conducted without extensive use of glycoprotein (Gp) IIb-IIIa inhibitors, which have been associated with improved perfusion and survival. Thus the aim of the current study was to evaluate the impact of age on the angiographic and clinical outcome patients with STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors. Our population is represented by a total of 1,662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials comparing early versus late administration of Gp IIb-IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. A total of 231 (13.9 %) patients were older than 75 years. Elderly patients showed a larger prevalence of female gender, hypertension, and diabetes, more advanced Killip class at presentation and longer time to treatment, but a smaller prevalence of smoking. All patients were treated with GP IIb-IIIa inhibitors. Elderly patients showed a significantly impaired postprocedural thrombolysis in myocardial infarction (TIMI) flow (TIMI 0-2: 17.7 vs 10.3 %, P = 0.002) and myocardial perfusion (myocardial blush grade 0-1: 38.3 vs 26.5 %, P = 0.001), and higher prevalence of distal embolization (19.2 vs 9.8 %, P < 0.001), whereas no difference was observed in terms of ST-segment resolution. At follow-up, elderly patients showed a significantly higher mortality (3.2 vs 11.0 %, hazard ratio (HR) (95 % confidence interval (CI)) = 3.78 (2.31-6.16), P < 0.001), which was confirmed after adjustment for baseline confounding factors (HR (95 % CI) = 5.01 (2.63-9.55), P < 0.0001). This study showed that among patients with STEMI undergoing primary angioplasty, advanced age is an independent predictor of mortality after primary angioplasty. Higher rates of distal embolization and poor myocardial perfusion, in addition to the worse risk profile, contribute toward explaining the impact of aging on mortality.

Persistent renal damage after contrast-induced acute kidney injury: incidence, evolution, risk factors, and prognosis.

BACKGROUND: The temporal evolution of renal function in patients with acute kidney injury after contrast medium (CI-AKI) is not well known. The aim of this observational study was to evaluate the incidence, risk factors, and prognostic implications of persistent renal damage (RD) in patients with preexistent moderate-to-severe renal dysfunction. METHODS AND RESULTS: From June 2003 to March 2008, 3986 patients underwent coronary angiography at our institution; 1490 of 3986 had an estimated creatinine clearance of <60 mL/min and were enrolled. CI-AKI was defined as an absolute increase ≥ 0.5 mg/dL over baseline serum creatinine within 3 days after the administration of contrast medium (iodixanol). In patients who developed CI-AKI, persistent RD was defined as a relative decrease of creatinine clearance ≥ 25% over baseline at 3 months. Patients whose creatinine clearance returned to baseline (or nearly) were classified as transient RD. The overall incidence of CI-AKI was 12.1%, and persistent RD occurred in 18.6% of CI-AKI patients. At Cox regression analysis, nephropathy risk score ≥ 17, left ventricular ejection fraction ≤ 30%, and increased value of serum creatinine ≥ 1.5-fold from baseline within 5 days were found to be significant risk factors for persistent RD. At 5 years, the incidence of death was significantly higher in patients with persistent RD than in both patients with transient RD (P=0.015) and those without CI-AKI (P=0.0001). A similar trend was observed for the combined end point of death, dialysis and cardiovascular events. CONCLUSIONS: These results suggest that CI-AKI is not always a transient, benign creatininopathy, but rather a direct cause of worsening renal function. The occurrence of CI-AKI can identify patients at increased risk of cardiovascular events.

Rationale and design of COLchicine On-admission to Reduce inflammation in Acute Coronary Syndrome (COLOR-ACS) study.

AIMS: The aim of the colchicine on-admission to reduce inflammation in acute coronary syndrome (COLOR-ACS) study is to evaluate the effects of the addition of short-term, low-dose colchicine to high-dose atorvastatin in limiting levels of inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: The COLOR-ACS study is a multicenter, randomized, open-label, two-arm trial. Statin-naive patients with NSTE-ACS, scheduled for an early invasive strategy, are randomized on admission to receive standard treatment of atorvastatin 80 mg or standard treatment plus colchicine (1 mg loading dose followed by 0.5 mg/day until discharge). The main exclusion criteria are prior statin and/or colchicine treatment, current treatment with potent inhibitors of CYP3A4, P-glycoprotein or immunosuppressive drugs, known active malignancy, severe kidney, cardiac, liver disease. There is clinical and biochemical follow-up at 30 days after discharge and telephone interview at 6 months. The primary end point is the change in hs-CRP from admission to discharge. Secondary end points include: incidence of acute kidney injury; MB fraction of creatine kinase peak value; glomerular filtration rate change from baseline to 30 days; persistence of hs-CRP ≥2 mg/dl at 30 days; adverse clinical events within 30 days; tolerance to colchicine. CONCLUSION: The COLOR-ACS study will provide evidence on the efficacy of early short-term treatment with colchicine in addition to high-dose atorvastatin compared to atorvastatin alone in ACS patients. The potential anti-inflammatory action of colchicine plus atorvastatin is expected to limit hs-CRP increase with resultant clinical benefits. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05250596.

[Contrast-induced nephropathy: the VIKISAFE study group statement]. / Nefropatia da mezzo di contrasto: risoluzioni del gruppo di studio VIKISAFE (VIsipaque KIdney SAfety efFEct).

Contrast-induced nephropathy (CIN) has undergone a significant evolution over the years in terms of epidemiology and diagnostic criteria. At present it is defined as CI-AKI (contrast-induced acute kidney injury) and represents a pathologically relevant event for different disciplines. Thus, a multidisciplinary approach is needed to propose and deploy a common strategy to reduce the incidence of CI-AKI. It seems that the use of isoosmolar non-ionic contrast media such as iodixanol can reduce the nephrotoxic effects. However, since these - still controversial - results have been obtained using various diagnostic criteria, they are difficult to compare and pool together. Common criteria are therefore required. The term acute renal failure has been replaced by acute kidney injury (AKI). Thanks to consensus groups such as ADQI (Acute Dialysis Quality Initiative) and AKIN (Acute Kidney Injury Network) and the development of guidelines by KDIGO, the diagnostic criteria for AKI are well defined. Nevertheless, the possibility to utilize new biomarkers of structural kidney damage such as neutrophil gelatinase-associated lipocalin (NGAL) or cystatin C has introduced the concept that AKI may be diagnosed even in the absence of creatinine elevation or decreased urine output. A re-evaluation of the epidemiology of CI-AKI based on new diagnostic criteria is required. In this paper the results of a collaborative multidisciplinary study group are reported from the perspective of different disciplines including nephrology, cardiology, radiology and pharmacology. The findings in a cohort of cardiac patients undergoing imaging procedures using exclusively the isoosmolar non-ionic contrast medium iodixanol are evaluated according to the RIFLE/AKIN criteria.

Tailored Versus Standard Hydration to Prevent Acute Kidney Injury After Percutaneous Coronary Intervention: Network Meta-Analysis.

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.

Feasibility of an accurate assessment of myocardial salvage by comparing functional and perfusion abnormalities in post-reperfusion gated SPECT.

BACKGROUND: Because of persistent stunning, post-treatment functional abnormalities could identify the initial risk area. The study aims to detect myocardial salvage using post-revascularization gated SPECT in acute myocardial infarction (AMI) treated by reperfusion therapy. METHODS: In 36 AMI patients, we performed a first gated SPECT injecting (99m)Tc-sestamibi before primary percutaneous coronary intervention (PCI), and a second 5 days later. The salvage index defined by the two perfusion images was compared with the value obtained by subtracting in the second gated SPECT the extent of perfusion defect from the extent of wall thickening abnormalities. RESULTS: The wall thickening salvage index correlated with the reference perfusion salvage index (Spearman's ρ = .92, P < .0001), with a 95% limit of agreement = ±.25. The agreement between the classifications in salvage index tertiles of the reference and of the wall thickening salvage index was good (kappa = .75). All patients with optimal PCI result and 18/24 of those with intermediate or poor outcome were correctly classified. CONCLUSIONS: Comparing function and perfusion in a single post-PCI (99m)Tc-sestamibi gated SPECT it is possible to estimate myocardial salvage. This could have useful implications in studies comparing different treatment strategies for AMI.

Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb-IIIa inhibitors: insights from the EGYPT cooperation.

Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ''cutoff'' in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2-3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 +/- 356 U/l vs. 259 +/- 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2-3 (adjusted OR [95% CI] = 3.14 [2.06-4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84-1.92], P = 0.26). At 208 +/- 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73-6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1-4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb-IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.

Gender-related differences in outcome after ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb-IIIa inhibitors: insights from the EGYPT cooperation.

Several studies have found that among patients with ST-elevation myocardial infarction (STEMI) treated by thrombolysis, female sex is associated with a worse outcome. The aim of this study was to investigate sex-related differences in clinical and angiographic findings in patients with STEMI treated with primary angioplasty and Gp IIb-IIIa inhibitors. Our population is represented by 1662 patients undergoing primary angioplasty included in the EGYPT database. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Among 1662 patients, 379 were women (22.8%). Female sex was associated with more advanced age, higher prevalence of diabetes, hypertension, more advanced Killip class, longer ischemia time, less often smokers, with higher prevalence of preprocedural recenalization. No difference was observed in terms of postprocedural TIMI flow, myocardial perfusion and distal embolization. Similar findings were observed in terms of enzymatic infarct size and preprocedural ejection fraction. Female gender was associated with higher mortality (6.4% vs. 3.6%, HR = 1.83 [1.12-3.0], P = 0.015). However, the difference disappeared after correction for baseline confounding factors (HR = 1.01 [0.56-1.83], P = 0.98). This study shows that in patients with STEMI treated by primary angioplasty, female gender is associated with higher mortality rate in comparison with men, and this is mainly due to their higher clinical and angiographic risk profiles. In fact, female sex did not emerge as an independent predictor of mortality.

Pharmacologic Prophylaxis of Contrast-Induced Nephropathy.

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.

A Prospective, Randomized, Open-Label Trial of Atorvastatin versus Rosuvastatin in the Prevention of Contrast-Induced Acute Kidney Injury, Worsened Renal Function at 30 Days, and Clinical Events After Acute Coronary Angiography: the PRATO-ACS-2 Study.

BACKGROUND/AIMS: Both high-dose atorvastatin and rosuvastatin have been shown to reduce contrast-induced acute kidney injury (AKI) occurrence and improve clinical outcomes in high-risk coronary patients undergoing angiographic procedures. However, there is a lack of head-to-head comparative studies on the effects of atorvastatin or rosuvastatin administered upon hospital admission in statin-naive patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS). METHODS: In this open-label, noninferiority study, we compared changes in renal function in 709 NSTE-ACS patients randomized to atorvastatin (80 mg upon admission followed by 40 mg/day) or rosuvastatin (40 mg upon admission followed by 20 mg/day). The primary end point was AKI (increase in serum creatinine ≥0.5 mg/dL or ≥25% above baseline within 72 h). Worsening renal function (WRF) (decrease of ≥25% in the glomerular filtration rate from baseline to 30 days), 30-day major adverse cardiovascular events, and 12-month myocardial infarction (MI) or death were also evaluated. RESULTS: The AKI incidence was similar in the 2 groups (i.e., 8.2% with rosuvastatin and 7.6% with atorvastatin; absolute risk difference = 0.54; 90% CI -3.9 to 2.8), satisfying the noninferiority criteria. WRF occurred in 53 (7.5%) patients, 19 (34%) of whom had developed AKI. The rates of WRF and adverse events at 30 days and at 12 months did not differ significantly between the 2 groups. Both AKI and WRF were found to be closely associated with the 12-month cardiovascular outcome irrespectively of statin choice. CONCLUSIONS: High-dose rosuvastatin or atorvastatin started upon hospital admission led to similar rates of AKI, 30-day renal function changes, and 12-month death or MI in NSTE-ACS patients who underwent an early invasive strategy (clinical trial registration: https://www.clinicaltrials.gov; unique identifier: NCT01870804).

IntravaScular Lithotripsy for the Management of UndILatable Coronary StEnt: The SMILE Registry.

BACKGROUND: Intravascular lithotripsy (IVL) showed to be effective in dilating heavily calcified de novo coronary lesions but little is known about its performance in under-expanded stents management. Aim of this study was to assess the feasibility, effectiveness and safety of IVL for the treatment of stent underexpansion refractory to balloon dilatation. METHODS: A multicentre, retrospective cohort analysis was performed in patients undergoing IVL to treat under-expanded stents following non-compliant balloon expansion failure. Primary endpoint was successful IVL dilatation defined as IVL balloon delivery and application at the target site followed by an increase of at least 1 mm2 in minimal stent cross-sectional area (MSA) on intracoronary imaging or an increase of at least 20% in minimal stent diameter (MSD) by quantitative coronary analysis (QCA). RESULTS: Thirty-nine under-expanded stents (34 patients) were included. Two cases (5.1%) of multiple stent layers and one (2.5%) acutely under-expanded stent were treated. The median IVL balloon diameter was 3.1 mm (IQR: 2.5-3.5 mm) while the number of pulses emitted was 56.7 (IQR: 30-80). IVL was successful in 34 cases (87.1%), with significant improvement in MSD (post: 3.23 mm [IQR: 3-3.5 mm] vs. pre: 0.81 mm [IQR: 0.35-1.2], p < 0.00001) and MSA (post: 7.61mm2 [IQR: 6.43-7.79mm2] vs. pre: 3.35 [IQR: 2.8-4 mm2], p < 0.00001). Non-fatal peri-procedural ST-elevation myocardial infarction occurred in one case (2.5%) due to IVL balloon rupture. No cardiac death, target lesion revascularization and stent thrombosis occurred in-hospital and at 30-day follow-up. CONCLUSIONS: Bailout IVL was feasible, efficacious and safe to improve refractory stent under-expansion.

Association between advanced Killip class at presentation and impaired myocardial perfusion among patients with ST-segment elevation myocardial infarction treated with primary angioplasty and adjunctive glycoprotein IIb-IIIa inhibitors.

BACKGROUND: Although primary angioplasty has been shown to improve survival as compared with thrombolysis, the outcome is still unsatisfactory in subsets of patients such as those with signs of heart failure at presentation. In fact, although primary angioplasty is able to restore TIMI 3 flow in most patients, suboptimal myocardial reperfusion is observed in a relatively large proportion of patients. The aim of this study was to investigate among patients with ST-segment elevation myocardial infarction undergoing primary angioplasty the association between heart failure at presentation and myocardial perfusion and its implications in terms of survival. METHODS: Our population is represented by patients undergoing primary angioplasty who are included in the EGYPT database. Congestive heart failure was defined as Killip class >1 at admission. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. RESULTS: Detailed data on Killip class at presentation were available in 1,427 of 1,662 patients (86% of the initial population) who represent the final population of this study. Killip class was associated with myocardial perfusion, distal embolization, enzymatic infarct size, predischarge ejection fraction, and 1-year mortality rate. Myocardial blush was an independent predictor of 1-year mortality (hazard ratio 7.44, 95% CI 1.82-30.4, P = .005) in patients with advanced Killip class at presentation. CONCLUSIONS: Our study shows that patients with heart failure complicating ST-segment elevation myocardial infarction have impaired myocardial perfusion, which accounts for the poor outcome observed in these patients. Further efforts should be aimed at improving myocardial perfusion, beyond epicardial recanalization, to further improve the outcome of these high-risk patients.

Benefits of pharmacological facilitation with glycoprotein IIb-IIIa inhibitors in diabetic patients undergoing primary angioplasty for STEMI. A subanalysis of the EGYPT cooperation.

The Early Glycoprotein IIb-IIIa inhibitors in Primary angioplasty (EGYPT) cooperation aimed at evaluating, by pooling individual patient's data of randomized trials, the benefits of pharmacological facilitation with Gp IIb-IIIa inhibitors among STEMI patients undergoing primary angioplasty. In the current study we analyze the benefits of early Gp IIb-IIIa inhibitors in diabetic patients. The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. We examined all randomized trials on facilitation by early administration of Gp IIb-IIIa inhibitors in STEMI. No language restrictions were enforced. Individual patients' data were obtained from 11 out of 13 trials, including 1,662 patients. Diabetes was present in 281 (16.9%). Early Gp IIb-IIIa inhibitors were associated with improved preprocedural TIMI 3 flow (26.0% vs. 13.1%, P = 0.006), postprocedural TIMI 3 flow (90.1% vs. 75.0%, P = 0.18), MBG 3 (40.8% vs. 30.4%, P = 0.004), and less distal embolization (11.6% vs. 20.8%, P = 0.05). However, early Gp IIb-IIIa inhibitors did not significantly reduce mortality (8.3% vs. 9.5%, P = 0.64). This meta-analysis shows that pharmacological facilitation with early administration of Gp IIb-IIIa inhibitors in STEMI patients with diabetes undergoing primary angioplasty, is associated with significant benefits in terms of preprocedural and postprocedural TIMI flow, improved myocardial perfusion, without significant benefits in mortality.

[SICI-GISE/SIN Consensus document: Contrast-induced acute kidney injury in interventional cardiology]. / Documento di consenso SICI-GISE/SIN: Danno renale acuto da mezzo di contrasto in cardiologia interventistica.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication that can affect outcome and prognosis of patients undergoing percutaneous diagnostic and interventional procedures. The Italian Society of Interventional Cardiology (SICI-GISE) has promoted a consensus project on the subject of CI-AKI in order to disseminate and implement nephroprotection strategies in interventional cardiology. The initiative was conducted in partnership with the Italian Society of Nephrology (SIN).

Bioimpedance-Guided Hydration for the Prevention of Contrast-Induced Kidney Injury: The HYDRA Study.

BACKGROUND: Intravascular volume expansion plays a major role in the prevention of contrast-induced acute kidney injury (CI-AKI). Recommended standard amounts of fluid infusion before procedures do not produce homogeneous responses in subjects with different initial hydration status. OBJECTIVES: The goal of this study was to compare the effect of standard and double intravenous (IV) infusion volumes in patients with low body fluid level, assessed by using bioimpedance vector analysis (BIVA), on the incidence of CI-AKI after elective coronary angiographic procedures. METHODS: A total of 303 patients with low BIVA level on admission were randomized to receive standard volume saline (1 ml/kg/h for 12 h before and after the procedure) or double volume saline (2 ml/kg/h). Patients (n = 715) with an optimal BIVA level received standard volume saline and were included in a prospective registry. The saline infusion was halved in all patients with an ejection fraction <40%. BIVA was repeated immediately before the angiographic procedure in all patients. CI-AKI was defined as an increase in levels of cystatin C ≥10% above baseline at 24 h after contrast administration. RESULTS: The incidence of CI-AKI was significantly lower (11.5% vs. 22.3%; p = 0.015) in patients receiving double volume saline than in those receiving standard volume saline, respectively. Before the angiographic procedure, 50% of the double volume patients achieved the optimal BIVA level compared with only 27.7% in the standard group (p = 0.0001). The findings were consistent in all the pre-specified subgroups excluding patients with a left ventricular ejection fraction <40% (p for interaction = 0.01). CONCLUSIONS: Evaluation of BIVA levels on admission in patients with stable coronary artery disease allows adjustment of intravascular volume expansion, resulting in lower CI-AKI occurrence after angiographic procedures. (Personalized Versus Standard Hydration for Prevention of CI-AKI: A Randomized Trial With Bioimpedance Analysis; NCT02225431).

Early abciximab administration in acute myocardial infarction treated with primary coronary intervention.

BACKGROUND: Glycoprotein IIb/IIIa inhibitors improve myocardial reperfusion and clinical outcomes of patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. In this prospective randomized trial, we evaluated the impact of early abciximab administration on angiographic findings, myocardial salvage and left ventricular function. METHODS AND RESULTS: Fifty-five consecutive patients with first AMI, undergoing primary PCI, were randomized to abciximab administration either in the emergency room (early group: 27 patients) or in the catheterization laboratory after coronary angiography (late group: 28 patients). The primary outcome measures were initial Thrombolysis In Myocardial Infraction (TIMI) grade flow, corrected TIMI frame count and myocardial blush grade as well as salvage index and left ventricular function recovery as assessed by serial scintigraphic scans performed at admission, and 7 days and 1 month after PCI. Angiographic analysis showed a significant difference in initial TIMI grade 3 flow, corrected TIMI frame count and myocardial blush grade favouring early group. Moreover, salvage index and left ventricular function recovery were significantly greater in the early group (P=0.007; and P=0.043, respectively). CONCLUSIONS: In patients with AMI, treated with primary PCI, early abciximab administration improves myocardial salvage and left ventricular function recovery probably by starting early recanalization of the infarct-related artery.

Impact of Rosuvastatin in Contrast-Induced Acute Kidney Injury in the Elderly: Post Hoc Analysis of the PRATO-ACS Trial.

BACKGROUND: Age is a major predictor of contrast-induced acute kidney injury (CI-AKI). Few studies have focused on CI-AKI in elderly patients with acute coronary syndrome (ACS). METHODS: We compare the incidence of CI-AKI in patients <75 and ≥75 years enrolled in the Protective effect of Rosuvastatin and Antiplatelet Therapy On contrast-induced acute kidney injury and myocardial damage in patients with ACS (PRATO-ACS) study and explore the impact of high-dose rosuvastatin on CI-AKI and clinical outcomes in the 2 age-groups. Statin-naive patients with non-ST-segment elevation ACS scheduled for early invasive strategy (total 504) were randomized to rosuvastatin (40 mg on admission followed by 20 mg/day) or no statin treatment. Contrast-induced acute kidney injury was defined as creatinine increase ≥0.5 mg/dL or ≥25% above baseline within 72 hours after contrast administration. All patients were stratified in tertiles according to baseline high-sensitivity C-reactive protein (hs-CRP). RESULTS: Rate of CI-AKI was significantly higher in patients ≥75 years (15.9% vs 8.7%, odds ratio: 2.001; 95% confidence interval: 1.14-3.53, P = .015). No significant interaction was observed between age and statin treatment (P = .17). Pretreatment with rosuvastatin was associated with 65% relative reduction in CI-AKI rate (22/170 [12.9%] vs 8/177 [4.5%], P = .007) in younger patients and 38% (16/82 [19.5%] vs 9/75 [12%], P = .20) in the elderly individuals. The greatest protective effect of statin treatment was achieved in patients with the highest hs-CRP values in both age-groups. CONCLUSION: Patients ≥75 years with ACS had a higher risk of developing CI-AKI. Early high-dose rosuvastatin is efficacious in reducing kidney injury in all patients, especially those with the highest baseline hs-CRP values.

Meta-Analysis of Individual Patient Data of Sodium Bicarbonate and Sodium Chloride for All-Cause Mortality After Coronary Angiography.

We sought to examine the relation between sodium bicarbonate prophylaxis for contrast-associated nephropathy (CAN) and mortality. We conducted an individual patient data meta-analysis from multiple randomized controlled trials. We obtained individual patient data sets for 7 of 10 eligible trials (2,292 of 2,764 participants). For the remaining 3 trials, time-to-event data were imputed based on follow-up periods described in their original reports. We included all trials that compared periprocedural intravenous sodium bicarbonate to periprocedural intravenous sodium chloride in patients undergoing coronary angiography or other intra-arterial interventions. Included trials were determined by consensus according to predefined eligibility criteria. The primary outcome was all-cause mortality hazard, defined as time from randomization to death. In 10 trials with a total of 2,764 participants, sodium bicarbonate was associated with lower mortality hazard than sodium chloride at 1 year (hazard ratio 0.61, 95% confidence interval [CI] 0.41 to 0.89, p = 0.011). Although periprocedural sodium bicarbonate was associated with a reduction in the incidence of CAN (relative risk 0.75, 95% CI 0.62 to 0.91, p = 0.003), there exists a statistically significant interaction between the effect on mortality and the occurrence of CAN (hazard ratio 5.65, 95% CI 3.58 to 8.92, p <0.001) for up to 1-year mortality. Periprocedural intravenous sodium bicarbonate seems to be associated with a reduction in long-term mortality in patients undergoing coronary angiography or other intra-arterial interventions.