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.

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.

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.

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).

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.

[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).

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.

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.

Impact of time from symptom onset to drug administration on outcome in patients undergoing glycoprotein IIb-IIIa facilitated primary angioplasty (from the EGYPT cooperation).

Contrasting data have been so far reported on facilitation with glycoprotein IIb-IIIa inhibitors (GpIIbIIIa) in patients who underwent primary percutaneous coronary intervention. However, it has been demonstrated a time-dependent composition of coronary thrombus in ST-segment elevation myocardial infarction, with more platelets in the first hours. Subsequently, the benefits of early administration of GpIIbIIIa may be affected by the time from symptoms onset to GpIIbIIIa, that therefore is the aim of this study. Our population is represented by 814 patients who underwent GpIIbIIIa facilitated primary angioplasty included in the Early glycoprotein IIb-IIIa inhibitors in primary angioplasty database. Patients were divided according to quartiles of time from symptom onset to GpIIbIIIa administration (≤65 minutes; 65 to 100 minutes; 101 to 178 minutes; and >178 minutes). Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Time from symptoms onset to GpIIbIIIa was linearly associated with hypertension, diabetes, hypercholesterolemia, and previous myocardial infarction but inversely associated with smoking. Abciximab was more often administrated later from symptoms onset. Time from symptoms onset to GpIIbIIIa was significantly associated with the rate of preprocedural recanalization (thrombolysis in myocardial infarction [TIMI] 2 to 3; p <0.001), postprocedural TIMI 3 flow (p <0.001), the rate of complete ST-segment resolution (p <0.001), and the rate of myocardial blush grade 2 to 3 (p <0.001) and inversely associated with the occurrence of distal embolization (p <0.001). Follow-up data were collected at a median (twenty-fifth to seventy-fifth) of 360 (30 to 1,095) days. A total of 52 patients had died. Time to GpIIbIIIa had a significant impact on mortality (hazard ratio [95% confidence interval] 1.46 [1.11 to 1.92], p = 0.007) that was confirmed after correction for baseline confounding factors (adjusted hazard ratio [95% confidence interval] 1.41 [1.02 to 2.21], p = 0.042). In conclusion, this study showed that in patients who underwent primary angioplasty with upstream GpIIbIIIa, time from symptoms onset to GpIIbIIIa strongly impacts on preprocedural recanalization, distal embolization, myocardial perfusion, and long-term survival.

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.

Relationship between inflammation and benefits of early high-dose rosuvastatin on contrast-induced nephropathy in patients with acute coronary syndrome: the pathophysiological link in the PRATO-ACS study (Protective Effect of Rosuvastatin and Antiplatelet Therapy on Contrast-Induced Nephropathy and Myocardial Damage in Patients With Acute Coronary Syndrome Undergoing Coronary Intervention).

OBJECTIVES: This study sought to investigate whether the beneficial impact of high-dose rosuvastatin against contrast-induced acute kidney injury (CI-AKI) in acute coronary syndrome (ACS) patients varied in relation to baseline high-sensitivity C-reactive protein (hs-CRP) levels. BACKGROUND: High-dose rosuvastatin administered on admission has been shown to prevent CI-AKI and improve short- and mid-term clinical outcome in ACS patients. METHODS: All 504 statin-naïve ACS patients enrolled in the PRATO-ACS (Protective Effect of Rosuvastatin and Antiplatelet Therapy on Contrast-Induced Acute Kidney Injury and Myocardial Damage in ACS Patients) study were stratified into baseline hs-CRP tertiles: <2.7 mg/l, ≥2.7 to <7.5 mg/l, and ≥7.5 mg/l. The primary endpoint was CI-AKI occurrence (creatinine ≥0.5 mg/dl or ≥25% above baseline within 72 h). Logistic regression models were used to evaluate the relationship between hs-CRP levels and effects of rosuvastatin. RESULTS: Patients with higher baseline hs-CRP values presented a significantly higher incidence of CI-AKI (5.4%, 8.7%, and 18.3% in the first, second, and third tertiles, respectively; p = 0.0001). The beneficial effect of rosuvastatin was markedly significant in the third hs-CRP tertile (odds ratio: 0.20; 95% confidence interval: 0.07 to 0.54; p = 0.002). Statin-treated patients in the third tertile presented a significantly lower rate of adverse events at 30 days (7.2% vs. 17.4%, p = 0.043) with a trend toward better outcome at 6 months (6.02% vs. 13.04%, p = 0.12). CONCLUSIONS: High-dose rosuvastatin administered on admission appears to exert more effective kidney protection in ACS subjects with higher baseline hs-CRP levels resulting in better short- and mid-term clinical outcome. (Protective Effect of Rosuvastatin and Antiplatelet Therapy on Contrast-Induced Nephropathy and Myocardial Damage in Patients With Acute Coronary Syndrome Undergoing Coronary Intervention [PRATO-ACS]; NCT01185938).

Pre-procedural bioimpedance vectorial analysis of fluid status and prediction of contrast-induced acute kidney injury.

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.

Early high-dose rosuvastatin for contrast-induced nephropathy prevention in acute coronary syndrome: Results from the PRATO-ACS Study (Protective Effect of Rosuvastatin and Antiplatelet Therapy On contrast-induced acute kidney injury and myocardial damage in patients with Acute Coronary Syndrome).

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).

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.

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.

Pharmacologic Prophylaxis for Contrast-Induced Acute Kidney Injury.

In the effort to prevent contrast-induced acute kidney injury (CI-AKI), several pharmacologic agents have been tested for their single or combined nephroprotective properties. To date, however, no drug has been officially approved for this aim. This article focuses on the three agents that have been most extensively studied: statins, N-acetylcysteine, and ascorbic acid. Particular attention is paid to the impact of these drugs on the CI-AKI prevention and improved prognosis.

[Statin and clopidogrel pharmacological interaction]. / Interazione farmacologica fra statine e clopidogrel.

Antiplatelet therapy with clopidogrel should be administered to patients with acute coronary syndromes and those submitted to percutaneous coronary intervention (PCI) (secondary prevention). Clopidogrel is a pro-drug which requires hepatic cytochrome P450 (CYP) metabolic activation to produce the active metabolite that inhibits platelet aggregation. CYP2C19 and CYP3A4/5 are the principal contributors in the two-step hepatic oxidation of clopidgrel. However, the response to clopidogrel is not uniform; it varies from patients platelet reactivity on standard-dose clopidogrel are at increased risk of recurrence of adverse cardiovascular events. Also drug-drug interactions that influence the function of CYP isoenzymes may affect the response to clopidogrel. Lipophilic statins, such as atorvastatin, are predominantly metabolized by CYP3A4 and may interfere with CYP activation of clopidogrel, contrary to what happens with hydrophilic statins, such as rosuvastin or pravastatin. Recently, it has been shown that in patients who presented post-PCI high on-treatment platelet reactivity on standard-dose clopidogrel during chronic treatment with clopidogrel and low-dose atorvastatin (10 mg), switching to a non-CYP3A4-metabolized statin, such as rosuvastatin or pravastatin, resulted in a significant decrease in platelet reactivity. The clinical benefit of statins is attributed to mulitple mechanisms which go beyond their lipid-lowering effects and include also antithrombotic properties. In particular, atorvastatin inhibits adenosine diphospate and thrombin-induced platelet aggregation. Moreover, pharmacodynamic studies appear to show some synergy between clopidogrel and atorvastatin: the enhancement of clopidogrel effects due to atorvastatin seems to be dose-related and independent of LDL cholesterol reduction. A recent study shows that the addition of high-dose atorvastatin (80mg) for 30 days significantly improves the pharmacodynamic effects of double-dose clopidogrel, reducing platelet reactivity and improving optimal clopidogrel response in statin naïve patients with high-on treatment platelet reactivity on standard-dose clopidogrel. These pharmacodynamic studies suggest that switching to a no CYP3A4-metabolized statin in patients with high on-treatment platelet reactivity on standard-dose clopidogre on chronic treatment with low-dose atorvastatin or administration of high-dose atorvastatin maybe two alternative strategies to avoid possible negative drug-drug interactions and to improve individual patient response to clopidogrel.

Impact of hypertension on distal embolization, myocardial perfusion, and mortality in patients with ST segment elevation myocardial infarction undergoing primary angioplasty.

Hypertension is a well-known risk factor for atherosclerosis. However, data on the impact of hypertension in patients with ST elevation myocardial infarction (STEMI) are inconsistent and mainly related to studies performed in the thrombolytic era, with very few data on patients undergoing primary angioplasty. The aim of the present study was to evaluate the impact of hypertension on distal embolization, myocardial perfusion, and mortality in patients with STEMI undergoing primary percutaneous coronary intervention. Our population is represented by 1,662 patients undergoing primary angioplasty for STEMI included in the Early Glycoprotein IIb-IIIa inhibitors in Primary angioplasty database. Myocardial perfusion was evaluated by myocardial blush grade and ST segment resolution. Follow-up data were collected within 1 year after primary angioplasty. Hypertension was observed in 700 patients (42.1%). Hypertension was associated with more advanced age (p <0.001), female gender (p <0.001), diabetes (p <0.001), hypercholesterolemia (p <0.001), previous revascularization (p <0.001), anterior myocardial infarction (p = 0.006), longer ischemia time (p = 0.03), more extensive coronary artery disease (p = 0.002), more often treated with abciximab (p <0.001), and less often smokers (p <0.001). Hypertension was associated with impaired postprocedural myocardial blush grade 2 to 3 (68.2% vs 74.2%, p = 0.019) and complete ST segment resolution (51.7% vs 61.1%, p = 0.001). By a mean follow-up of 206 ± 158 days, 70 patients (4.3%) had died. Hypertension was associated with a greater mortality (6.2% vs 2.9%, hazard ratio 2.31, 95% confidence interval 1.42 to 3.73, p <0.001), confirmed after correction for baseline confounding factors (hazard ratio 1.82, 95% confidence interval 1.03 to 3.22, p <0.001). In conclusion, this study showed that among patients with STEMI undergoing primary angioplasty, hypertension is associated with impaired reperfusion and independently predicts 1-year mortality.