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.

Association of statin pretreatment with presentation characteristics, infarct size and outcome in older patients with acute coronary syndrome: the Elderly ACS-2 trial.

BACKGROUND: prior statin treatment has been shown to have favourable effects on short- and long-term prognosis in patients with acute coronary syndrome (ACS). There are limited data in older patients. The aim of this study was to investigate the association of previous statin therapy and presentation characteristics, infarct size and clinical outcome in older patients, with or without atherosclerotic cardiovascular disease (ASCVD), included in the Elderly-ACS 2 trial. METHODS: data on statin use pre-admission were available for 1,192 of the 1,443 patients enrolled in the original trial. Of these, 531 (44.5%) were already taking statins. Patients were stratified based on established ASCVD and statin therapy. ACS was classified as non-ST elevation or ST elevation myocardial infarction (STEMI). Infarct size was measured by peak creatine kinase MB (CK-MB). All-cause death in-hospital and within 1 year were the major end points. RESULTS: there was a significantly lower frequency of STEMI in statin patients, in both ASCVD and No-ASCVD groups. Peak CK-MB levels were lower in statin users (10 versus 25 ng/ml, P < 0.0001). There was lower all-cause death in-hospital and within 1 year for subjects with ASCVD already on statins independent of other baseline variables. There were no differences in all-cause death for No-ASCVD patients whether or not on statins. CONCLUSIONS: statin pretreatment was associated with more favourable ACS presentation and lower myocardial damage in older ACS patients both ASCVD and No-ASCVD. The incidence of all-cause death (in-hospital and within 1 year) was significantly lower in the statin treated ASCVD patients.

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.

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).

Effects of statin therapy on platelet reactivity after percutaneous coronary revascularization in patients with acute coronary syndrome.

Statin use is associated with enhanced pharmacodynamic response to clopidogrel in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). However, the impact of statin therapy on clopidogrel response profiles in patients with acute coronary syndrome (ACS) undergoing PCI has not been established and represents the objective of this investigation. On-treatment P2Y12 platelet reactivity was measured using the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay before PCI, at hospital discharge, and at 1 month after PCI in ACS patients enrolled in the multicenter, prospective GEne polymorphisms, Platelet Reactivity, and Syntax Score (GEPRESS) study (n = 962). High platelet reactivity (HPR) was defined as platelet reactivity index ≥50%. Statins were prescribed at hospital discharge in 87% (n = 835) of patients. All patients were followed for 1 year. The 1-month HPR rate was lower in statin than in non-statin treated patients (39.6 vs 52%, respectively, p = 0.009). This finding was confirmed also among statin-treated patients with high Syntax score (≥15). After adjustment for differences in baseline characteristics, statin use at discharge was independently associated with 1-month HPR rate (odds ratio, 0.58, 95% confidence interval, 0.38-0.89; p = 0.015). In ACS patients undergoing PCI treated with clopidogrel the use of statins at discharge was associated with significantly lower 1-month HPR rates compared with patients not treated with statins.

The natural history of takotsubo syndrome: a two-year follow-up study with myocardial sympathetic and perfusion G-SPECT imaging.

PURPOSE: To investigate changes in sympathetic activity, perfusion, and left ventricular (LV) functionality in takotsubo cardiomyopathy (TTC) patients from onset (T0) to post-onset conditions at 1 month (T1), 1-2 years (T2, T3). METHODS: Twenty-two patients (70 ± 11 years) underwent serial gated single photon emission tomography (G-SPECT) studies with 123I-mIBG and 99mTc-Sestamibi. Statistics were performed using ANOVA/Sheffé post-hoc, correlation test, and receiver operating characteristic (ROC) curve analysis (p < 0.05). RESULTS: Patients presented at T0 with LV ballooning and reduced early-late mIBG uptake (95%, 100%), left ventricular ejection fraction (LVEF)G-SPECT (86%) and perfusion (77 %). Adrenergic dysfunction was greater in apex, it overlaps with contractile impairment, and both were more severe than perfusion defect. During follow-up, LVEFG-SPECT, contractility, and perfusion were normal, while 82% and 90% of patients at T1 and 50% at T2 and T3 continued to show a reduced apical early-late mIBG distribution. These patients presented at T0-T1 with greater impairment of adrenergic function, contractility, and perfusion. A relationship was present within innervation and both perfusion and contractile parameters at T0 and T1, and between the extent of adrenergic defect at T3 and both the defect extent and age at T0 (cut-off point 42.5%, 72 years). CONCLUSION: Outcome for TTC is not limited to a reversible contractile and perfusion abnormalities, but it includes residual adrenergic dysfunction, depending on the level of adrenergic impairment and age of patients at onset. The number of patients, as well as degree of perfusion abnormalities were found to be higher than those previously reported possibly depending on the time-interval between hospital admission and perfusion scan.

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.

Acute Kidney Injury in Elderly Patients With Non-ST Elevation Acute Coronary Syndrome: Insights From the Italian Elderly: ACS Study.

We examined the incidence and predictors of acute kidney injury (AKI) in elderly patients (≥75 years) enrolled in the prospective Italian Elderly acute coronary syndrome (ACS) study and explored the impact of AKI on clinical outcome. Acute kidney injury, defined according to the Acute Kidney Injury Network criteria, occurred in 128 (21%) of 615 patients. Patients submitted to coronary angiographic procedures did not present higher rate of AKI. The only baseline variables independently associated with AKI development were creatinine clearance (odds ratio [OR]: 0.98; 95% confidence interval [CI]: 0.97-0.99) and left ventricular ejection fraction (OR: 0.98; 95% CI: 0.96-0.99). Adverse clinical events were significantly higher in patients who developed AKI. After multivariable adjustment, AKI (hazard ratio: 2.73; 95% CI: 1.87-4.0) was an independent predictor of all-cause mortality within 1 year.

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.

Time course changes of cystatin C and inflammatory and biochemical markers in non-ST-elevation acute coronary syndromes.

BACKGROUND: Serum cystatin C (Cys-C), a good marker of renal function, predicts prognosis in non-ST-elevation acute coronary syndromes (NSTE-ACS). However, no data are available on the time course of Cys-C values after discharge. In this study, Cys-C was measured during admission (ACS sample) and 6 weeks after discharge, and was correlated with troponin (c-TNT), high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and the N-terminal portion of the pro-brain natriuretic peptide (proBNP) peptide (NT-proBNP) in a highly selected homogeneous group of NSTE-ACS patients. METHODS: In this prospective, multicentre study, patients with a first NSTE-ACS, single-vessel disease and successful percutaneous coronary interventions (PCIs) had their sera collected, aliquoted and stored at the enrolling site and then shipped for analysis to the clinical chemistry core laboratory. RESULTS: Cys-C values slightly, but significantly, increased from the ACS samples to the 6-week samples. In contrast, hsCRP, NT-proBNP and IL-6 values significantly decreased from the ACS to the 6-week sample. Patients with elevated c-TNT levels had higher hsCRP, NT-proBNP and IL-6 values than patients with normal c-TNT levels in the ACS sample, whereas Cys-C levels were similar in patients with and without elevated c-TNT. Cys-C was highly correlated with estimated glomerular filtration rate in both the ACS and 6-week samples. CONCLUSIONS: In contrast to inflammatory and biochemical stress markers, Cys-C is not affected by the occurrence of myocardial necrosis or by acute left-ventricular impairment, being a reliable marker of renal function during NSTE-ACS.

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).

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.

Statin treatment before percutaneous cononary intervention.

Treatment with 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improves short-and-long term prognosis in high-risk patients with stable coronary artery disease and in those with acute coronary syndrome and their use is strongly recommended for secondary prevention. Moreover, recent data suggest that statin pre-treatment is associated with a better short- and long-term outcome in patients undergoing percutaneous coronary intervention. Current guidelines for coronary revascularization recommend the use of high-dose of statins before percutaneous coronary intervention to reduce the risk of periprocedural myocardial infarction in statin naïve patients (class IIa A) and in those on chronic statin therapy (class IIa B). However, the beneficial clinical effects elicited by statins in patients undergoing coronary angioplasty may arise not only from a cardiac protection against periprocedural myocardial injury but also from a renal protection against acute kidney injury caused by iodinated contrast media. Actually, statins exert multiple non-lipid lowering (pleiotropic) effects, including improved endothelial function, reduced inflammatory and immuno-modulatory processes, oxidative stress and platelet adhesion, that may contribute to both cardio- and nephro-protection even in the short-term.