Vincenzo Pasceri - Academia.edu (original) (raw)

Papers by Vincenzo Pasceri

Research paper thumbnail of Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of Myocardial Damage during Angioplasty) Study

ACC Current Journal Review, 2005

Background-Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardia... more Background-Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. Although observational data have suggested that pretreatment with a high loading dose of clopidogrel may be more effective than a conventional dose, this hypothesis has never been tested in a randomized trial. Methods and Results-A total of 255 patients scheduled to undergo percutaneous coronary intervention were randomized to a 600-mg (nϭ126) or 300-mg (nϭ129) loading regimen of clopidogrel given 4 to 8 hours before the procedure. Creatine kinase MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI), or target vessel revascularization. The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group (Pϭ0.041) and was due entirely to periprocedural MI. Peak values of all markers were significantly lower in patients treated with the 600-mg regimen (PՅ0.038). Safety end points were similar in the 2 arms. At multivariable analysis, the high loading regimen was associated with a 50% risk reduction of MI (OR 0.48, 95% CI 0.15 to 0.97, Pϭ0.044). An incremental benefit was observed in patients randomized to the 600-mg dose who were receiving statins, with an 80% risk reduction. Conclusions-Pretreatment with a 600-mg loading dose of clopidogrel 4 to 8 hours before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduced periprocedural MI in patients undergoing percutaneous coronary intervention. These results may influence practice patterns with regard to antiplatelet therapy before percutaneous revascularization.

Research paper thumbnail of Outcome Comparison of 600- and 300-mg Loading Doses of Clopidogrel in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction

Journal of the American College of Cardiology, 2011

The purpose of this study was to compare 600-and 300-mg clopidogrel loading doses in patients wit... more The purpose of this study was to compare 600-and 300-mg clopidogrel loading doses in patients with STsegment elevation myocardial infarction (STEMI). Background Given the high thrombotic risk of patients with STEMI, greater platelet inhibition may improve outcome in those patients receiving percutaneous coronary intervention (PCI). Although observational data suggest that pretreatment with a 600-mg clopidogrel loading dose may be more effective than the 300-mg regimen in primary PCI, this hypothesis has never been tested in a randomized study. Methods A total of 201 patients undergoing primary PCI for STEMI randomly received a 600-mg (n ϭ 103) or 300-mg (n ϭ 98) clopidogrel loading dose before the procedure. The primary endpoint was the evaluation of the infarct size, defined as the area under the curve of cardiac markers. Results Infarct size was significantly lower in the high-dose regimen: median creatine kinase-myocardial band 2,070 ng/ml (interquartile range [IQR]: 815 to 2,847 ng/ml) versus 3,049 ng/ml (IQR: 1,050 to 7,031 ng/ml) in the 300-mg group, p ϭ 0.0001; troponin-I 255 ng/ml (IQR: 130 to 461 ng/ml) versus 380 ng/ml (IQR: 134 to 1,406 ng/ml), p Ͻ 0.0001. In the 600-mg arm, Thrombolysis In Myocardial Infarction flow grade Ͻ3 after PCI was less frequent (5.8% vs. 16.3%, p ϭ 0.031), left ventricular ejection fraction at discharge was improved (52.1 Ϯ 9.5% vs. 48.8 Ϯ 11.3%, p ϭ 0.026), 30-day major adverse cardiovascular events were fewer (5.8% vs. 15%, p ϭ 0.049), and bleeding/entry site complications were not increased (secondary endpoints). Conclusions In STEMI patients, pre-treatment with a 600-mg clopidogrel loading dose before primary PCI was associated with a reduction of the infarct size compared with a 300-mg loading dose, as well as with improvement of angiographic results, residual cardiac function, and 30-day major adverse cardiovascular events; further studies are warranted to evaluate impact of such strategy on survival.

Research paper thumbnail of Effectiveness of In-Laboratory High-Dose Clopidogrel Loading Versus Routine Pre-Load in Patients Undergoing Percutaneous Coronary Intervention

Journal of the American College of Cardiology, 2010

This study sought to evaluate safety and effectiveness of in-laboratory (in-lab) 600-mg clopidogr... more This study sought to evaluate safety and effectiveness of in-laboratory (in-lab) 600-mg clopidogrel loading prepercutaneous coronary intervention (PCI) versus routine 6-h pre-load.

Research paper thumbnail of High Versus Standard Clopidogrel Maintenance Dose After Percutaneous Coronary Intervention and Effects on Platelet Inhibition, Endothelial Function, and Inflammation

Journal of the American College of Cardiology, 2011

This study was done to compare effects of high versus standard clopidogrel maintenance doses on p... more This study was done to compare effects of high versus standard clopidogrel maintenance doses on platelet inhibition, inflammation, and endothelial function in patients undergoing percutaneous coronary intervention. Background Previous data suggested that clopidogrel has various biological actions in addition to antiplatelet effects. Methods Fifty patients were randomly assigned 1 month after intervention (T-0) to receive standard (75 mg/day; n ϭ 25) or high (150 mg/day; n ϭ 25) clopidogrel maintenance dose for 30 days (until T-1); at this time-point, cross-over was performed, and the assigned clopidogrel maintenance regimen was switched and continued for a further 30 days (until T-2). Platelet reactivity (expressed as P2Y 12 reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]), endothelial function (evaluated by flow-mediated vasodilation), and highsensitivity C-reactive protein levels were measured at T-0, T-1, and T-2. Results Patients in the 150-mg/day arm had higher platelet inhibition (50 Ϯ 20% vs. 31 Ϯ 20% in the 75-mg/day group; p Ͻ 0.0001), better flow-mediated vasodilation (16.9 Ϯ 12.6% vs. 7.9 Ϯ 7.5%; p ϭ 0.0001), and lower high-sensitivity C-reactive protein levels (3.6 Ϯ 3.0 mg/l vs. 7.0 Ϯ 8.6 mg/l; p ϭ 0.016). Higher clopidogrel dose was associated with decreased proportion of patients with P2Y 12 reaction units Ն240 (12% vs. 32%; p ϭ 0.001), flow-mediated vasodilation Ͻ7% (16% vs. 58%; p ϭ 0.0003), and high-sensitivity C-reactive protein levels Ͼ3 mg/l (46% vs. 64%; p ϭ 0.07). Conclusions For patients undergoing percutaneous coronary intervention, the 150-mg/day clopidogrel maintenance dose is associated with stronger platelet inhibition, improvement of endothelial function, and reduction of inflammation, compared with the currently recommended 75-mg/day regimen; those effects might have a role in the clinical benefit observed with clopidogrel and may provide the rationale for using the higher maintenance regimen in selected patients.

Research paper thumbnail of Efficacy of Atorvastatin Reload in Patients on Chronic Statin Therapy Undergoing Percutaneous Coronary Intervention

Journal of the American College of Cardiology, 2009

Research paper thumbnail of 1008-189 Atorvastatin therapy reduces markers of myocardial damage after percutaneous coronary interventions? Preliminary data from a randomized study

Journal of the American College of Cardiology, 2004

S-Vascular Disease, Hypertension, and Prevention 447A Vascular Disease, Hypertension, and Prevent... more S-Vascular Disease, Hypertension, and Prevention 447A Vascular Disease, Hypertension, and Prevention elderly (>/= 75 years of age) were consistently less likely to receive statins on discharge. Conclusions: Statin use was low irrespective of CAD status and total cholesterol levels in older patients with heart failure. These results emphasize the importance of continued efforts to improve secondary prevention in older patients with HF and ischemic heart disease.

Research paper thumbnail of Evidence of Cocaine-Related Coronary Atherosclerosis in Young Patients With Myocardial Infarction

Journal of the American College of Cardiology, 2006

To the Editor: Cocaine use has increased in the last years reaching in 1999 in the U.S. 30% of al... more To the Editor: Cocaine use has increased in the last years reaching in 1999 in the U.S. 30% of all drug-related visits to the emergency department, exceeding morphine and representing the most frequent cause of drug-related deaths (1). One of every four myocardial infarctions (MIs) in people aged 18 to 45 years can be linked to cocaine use (2). Several reports (3) implicated coronary vaso

Research paper thumbnail of Role of Endothelial Progenitor Cells in Restenosis and Progression of Coronary Atherosclerosis After Percutaneous Coronary Intervention

JACC: Cardiovascular Interventions, 2010

Objectives We prospectively investigated the relationship of circulating endothelial progenitor c... more Objectives We prospectively investigated the relationship of circulating endothelial progenitor cells at time of percutaneous coronary intervention to the subsequent development of in-stent restenosis or progression of coronary atherosclerosis. Background Endothelial progenitor cells provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a pathogenic role in coronary atherosclerosis. Methods We studied 155 consecutive stable angina patients (92 men, age 60 Ϯ 11 years). All patients had flow cytometry the day before elective percutaneous coronary intervention in order to derive subpopulations of endothelial progenitor cells. A control group of 20 normal subjects was considered for comparison. Results At 8-month control angiography, 30 patients showed in-stent restenosis (restenosis group), 22 patients showed progression of coronary atherosclerosis (progression group), whereas the remaining 103 patients had neither in-stent restenosis nor progression of coronary atherosclerosis (stable group). Comparison of the 3 groups did not show any difference in risk factors, cardiac morphology and function, extension of coronary artery disease, and treatment. Absolute numbers of CD34ϩ/KDRϩ/CD45-cells (i.e., progenitors of endothelial lineage) measured in the restenosis group (1.41 Ϯ 0.64 cells/l) were significantly higher than in the progression, stable, and control groups (1.03 Ϯ 0.53 cells/l, 1.07 Ϯ 0.46 cells/l, and 0.95 Ϯ 0.44 cells/l, respectively, p Ͻ 0.05). Similarly, CD133ϩ/KDRϩ/CD45-cells (i.e., progenitors of endothelial cells at an earlier stage) were significantly higher in the restenosis (0.63 Ϯ 0.23 cells/l) compared with progression, stable, and control groups (0.33 Ϯ 0.19 cells/l, 0.41 Ϯ 0.32 cells/l, and 0.36 Ϯ 0.15 cells/l, respectively, p Ͻ 0.001). Also, numbers of CD14ϩ/CD45ϩ cells (i.e., which have a role in angiogenesis via a paracrine effect) were significantly different among the restenosis, progression, stable, and control groups (0.72 Ϯ 0.56 cells/l vs. 0.51 Ϯ 0.52 cells/l vs. 0.28 Ϯ 0.54 cells/l vs. 0.62 Ϯ 0.67 cells/l, respectively, p Ͻ 0.05), whereas CD105ϩ/CD45-/CD34-cells (i.e., which have a receptor for transforming growth factor-beta) were similar among groups. Conclusions Patients with restenosis have higher numbers of subpopulations of endothelial progenitor cells that incorporate into endothelial cells or play a role in arteriogenesis compared with controls and patients with either progression of coronary atherosclerosis or stable disease.

Research paper thumbnail of Statins and percutaneous coronary intervention

European Heart Journal, 2005

Research paper thumbnail of Clopidogrel reloading in patients undergoing percutaneous coronary intervention on chronic clopidogrel therapy: results of the ARMYDA-4 RELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) randomized trial

European Heart Journal, 2010

Aims To evaluate safety and effectiveness of clopidogrel reloading in patients on chronic clopido... more Aims To evaluate safety and effectiveness of clopidogrel reloading in patients on chronic clopidogrel therapy undergoing percutaneous coronary intervention (PCI). Methods and results Five hundred and three patients on .10 days clopidogrel therapy (41% with non-ST-segment elevation acute coronary syndrome, ACS) randomly received 600 mg clopidogrel loading 4-8 h before PCI (n ¼ 252) or placebo (n ¼ 251). Primary endpoint was 30-day incidence of major adverse cardiac events (MACE). In the overall population primary endpoint occurred in 6.7% of patients in the reload vs. 8.8% in the placebo arm [odds ratios (OR) 0.75, 95% confidence intervals (CI) 0.37-1.52; P ¼ 0.50]. In stable angina patients, 1-month MACE were not significantly different (7.0 vs. 3.9%; OR 1.84, 0.60-5.88; P ¼ 0.36), whereas ACS patients had significant clinical benefit with reloading (6.4 vs. 16.3%; OR 0.34, 95% CI 0.32-0.90, P ¼ 0.033 at multivariable analysis; interaction test: P ¼ 0.01). There was no excess bleeding in the reload arm (6% in both groups). Conclusion ARMYDA-4 RELOAD reveals no overall benefit from reloading patients on chronic clopidogrel therapy prior to PCI; the benefit observed in ACS patients is a hypothesis-generating finding that needs to be confirmed by larger studies.

Research paper thumbnail of Interleukin-1 receptor antagonist levels correlate with extent of myocardial loss in patients with acute myocardial infarction

Clinical Cardiology, 2005

Research paper thumbnail of Pharmacodynamic Comparison of Pitavastatin Versus Atorvastatin on Platelet Reactivity in Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy

Circulation Journal, 2014

Research paper thumbnail of Endothelial Progenitor Cells Predict Long-Term Prognosis in Patients With Stable Angina Treated With Percutaneous Coronary Intervention

Circulation Journal, 2013

Research paper thumbnail of Letters Regarding Article by Patti et al, "Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty...

Circulation, 2005

al recently investigated the effect of pretreating patients undergoing percutaneous coronary inte... more al recently investigated the effect of pretreating patients undergoing percutaneous coronary intervention (PCI) with 600 mg of clopidogrel versus the conventional 300-mg dose. 1 Their results showed that the 600-mg dose reduces the composite of death, myocardial infarction, or target vessel revascularization up to 30 days after the procedure. The authors concluded that the study "demonstrated that the higher loading dose was more effective than the conventional dose in preventing ischemic complication." These findings were immediately accepted with enthusiasm. 2 Although this investigation is an important step in understanding the optimal loading dose for clopidogrel, we are concerned about a methodological limitation in the study. The trial randomized 329 patients scheduled for coronary angiography who actually received a loading dose of either 600 mg or 300 mg clopidogrel. The authors reported only a perprotocol analysis in patients who actually underwent PCI. No safety or efficacy data were reported based on the intention-totreat principle, which would be the most relevant information, because in clinical practice when the decision is made to pretreat with clopidogrel, the coronary anatomy is frequently unknown. Therefore, the decision to undertake clopidogrel pretreatment would be better understood based on the efficacy/safety data in the overall population, including CABG and medically managed patients. Thus, it would be of utmost interest to know the adjusted odds ratio for the primary end point. The trial presents other methodological issues as the sample size calculated on the expected rate of any periprocedural CK-MB elevation instead of the major adverse cardiovascular events, which is referred to as the primary end point throughout the article and the fact that the logistic regression model "assessing the risk of the primary end point according to potential confounding" announced in the Methods is not shown anywhere in the article. Finally, the results presented cannot be conclusive because the 95% CI of the unadjusted OR is wide and entails a marginal potential advantage of the 600-mg dose (OR 0.31, 95% CI 0.09 to 0.95) If the evidence of the efficacy of clopidogrel pretreatment is weak overall, mainly based on a post-hoc analysis, then the evidence that 600 mg is the optimal dose is negligible. The results of the ARMYDA-2 trial support the need of a welldesigned and properly powered trial to answer the question whether 600 mg of clopidogrel as the loading dose is indicated in clinical practice.

Research paper thumbnail of Clinical Benefit of Statin Pretreatment in Patients Undergoing Percutaneous Coronary Intervention

Circulation, 2011

Background— Previous studies suggested that statin pretreatment reduces cardiac events in patient... more Background— Previous studies suggested that statin pretreatment reduces cardiac events in patients undergoing percutaneous coronary intervention. However, most data were observational, and single randomized trials included limited numbers of patients. Methods and Results— We performed a collaborative meta-analysis using individual patient data from 13 randomized studies in which 3341 patients received either high-dose statin (n=1692) or no statin/low-dose statin (n=1649) before percutaneous coronary intervention, with all patients receiving statin therapy after intervention. Occurrence of periprocedural myocardial infarction, defined as postintervention creatine kinase–MB increase ≥3 times the upper limit of normal, and 30-day major adverse cardiac events (death, myocardial infarction, target-vessel revascularization) was evaluated. Incidence of periprocedural myocardial infarction was 7.0% in the high-dose statin versus 11.9% in the control group, which corresponds to a 44% risk re...

Research paper thumbnail of Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention

Circulation, 2005

Background— Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardi... more Background— Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. Although observational data have suggested that pretreatment with a high loading dose of clopidogrel may be more effective than a conventional dose, this hypothesis has never been tested in a randomized trial. Methods and Results— A total of 255 patients scheduled to undergo percutaneous coronary intervention were randomized to a 600-mg (n=126) or 300-mg (n=129) loading regimen of clopidogrel given 4 to 8 hours before the procedure. Creatine kinase MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI), or target vessel revascularization. The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group ( P =0.041) and was due entirely to periprocedur...

Research paper thumbnail of Impaired Flow-Mediated Dilation and Risk of Restenosis in Patients Undergoing Coronary Stent Implantation

Circulation, 2005

Background— Impaired endothelial function is a key event in the atherosclerosis process and predi... more Background— Impaired endothelial function is a key event in the atherosclerosis process and predicts future cardiovascular events in subjects with and without coronary artery disease (CAD). We performed the first prospective study evaluating whether early measurement of brachial artery endothelium-dependent dilation (flow-mediated dilation [FMD]) after coronary stenting could predict occurrence of in-stent-restenosis. Methods and Results— The study population included 136 patients with single-vessel CAD undergoing percutaneous coronary intervention (PCI) with stenting and at least 6 months of follow-up. All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI; FMD was investigated before and after 5 minutes of occlusion of the brachial artery, and nitroglycerin-mediated dilation was investigated before and after administration of sublingual nitrates. Clinical in-stent restenosis was demonstrated in 20 patients (15%), whereas 116 patients (85%) rema...

Research paper thumbnail of C-Reactive Protein: Linking Inflammation to Cardiovascular Complications

Research paper thumbnail of A Tale of Two Diseases : Atherosclerosis and Rheumatoid Arthritis

Research paper thumbnail of Association of Virulent Helicobacter pylori Strains With Ischemic Heart Disease

Circulation, 1998

Background —Previous studies have reported an association between chronic Helicobacter pylori inf... more Background —Previous studies have reported an association between chronic Helicobacter pylori infection and ischemic heart disease. However, it is not clear whether this association is really due to the virulence of the bacterium or is merely the result of confounding factors (in particular, age and social class). Methods and Results —We assessed the prevalence of infection by Helicobacter pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, in 88 patients with ischemic heart disease (age, 57±8 years; 74 men) and in 88 age- and sex-matched controls (age, 57±8 years; 74 men) with similar social background. Prevalence of Helicobacter infection was significantly higher in patients than in controls (62% versus 40%; P =.004), with an odds ratio of 2.8 (95% CI, 1.3 to 7.4; P <.001) adjusted for age, sex, main cardiovascular risk factors, and social class. Patients with ischemic heart disease also had a higher prevalence of CagA-positive strai...

Research paper thumbnail of Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of Myocardial Damage during Angioplasty) Study

ACC Current Journal Review, 2005

Background-Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardia... more Background-Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. Although observational data have suggested that pretreatment with a high loading dose of clopidogrel may be more effective than a conventional dose, this hypothesis has never been tested in a randomized trial. Methods and Results-A total of 255 patients scheduled to undergo percutaneous coronary intervention were randomized to a 600-mg (nϭ126) or 300-mg (nϭ129) loading regimen of clopidogrel given 4 to 8 hours before the procedure. Creatine kinase MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI), or target vessel revascularization. The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group (Pϭ0.041) and was due entirely to periprocedural MI. Peak values of all markers were significantly lower in patients treated with the 600-mg regimen (PՅ0.038). Safety end points were similar in the 2 arms. At multivariable analysis, the high loading regimen was associated with a 50% risk reduction of MI (OR 0.48, 95% CI 0.15 to 0.97, Pϭ0.044). An incremental benefit was observed in patients randomized to the 600-mg dose who were receiving statins, with an 80% risk reduction. Conclusions-Pretreatment with a 600-mg loading dose of clopidogrel 4 to 8 hours before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduced periprocedural MI in patients undergoing percutaneous coronary intervention. These results may influence practice patterns with regard to antiplatelet therapy before percutaneous revascularization.

Research paper thumbnail of Outcome Comparison of 600- and 300-mg Loading Doses of Clopidogrel in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction

Journal of the American College of Cardiology, 2011

The purpose of this study was to compare 600-and 300-mg clopidogrel loading doses in patients wit... more The purpose of this study was to compare 600-and 300-mg clopidogrel loading doses in patients with STsegment elevation myocardial infarction (STEMI). Background Given the high thrombotic risk of patients with STEMI, greater platelet inhibition may improve outcome in those patients receiving percutaneous coronary intervention (PCI). Although observational data suggest that pretreatment with a 600-mg clopidogrel loading dose may be more effective than the 300-mg regimen in primary PCI, this hypothesis has never been tested in a randomized study. Methods A total of 201 patients undergoing primary PCI for STEMI randomly received a 600-mg (n ϭ 103) or 300-mg (n ϭ 98) clopidogrel loading dose before the procedure. The primary endpoint was the evaluation of the infarct size, defined as the area under the curve of cardiac markers. Results Infarct size was significantly lower in the high-dose regimen: median creatine kinase-myocardial band 2,070 ng/ml (interquartile range [IQR]: 815 to 2,847 ng/ml) versus 3,049 ng/ml (IQR: 1,050 to 7,031 ng/ml) in the 300-mg group, p ϭ 0.0001; troponin-I 255 ng/ml (IQR: 130 to 461 ng/ml) versus 380 ng/ml (IQR: 134 to 1,406 ng/ml), p Ͻ 0.0001. In the 600-mg arm, Thrombolysis In Myocardial Infarction flow grade Ͻ3 after PCI was less frequent (5.8% vs. 16.3%, p ϭ 0.031), left ventricular ejection fraction at discharge was improved (52.1 Ϯ 9.5% vs. 48.8 Ϯ 11.3%, p ϭ 0.026), 30-day major adverse cardiovascular events were fewer (5.8% vs. 15%, p ϭ 0.049), and bleeding/entry site complications were not increased (secondary endpoints). Conclusions In STEMI patients, pre-treatment with a 600-mg clopidogrel loading dose before primary PCI was associated with a reduction of the infarct size compared with a 300-mg loading dose, as well as with improvement of angiographic results, residual cardiac function, and 30-day major adverse cardiovascular events; further studies are warranted to evaluate impact of such strategy on survival.

Research paper thumbnail of Effectiveness of In-Laboratory High-Dose Clopidogrel Loading Versus Routine Pre-Load in Patients Undergoing Percutaneous Coronary Intervention

Journal of the American College of Cardiology, 2010

This study sought to evaluate safety and effectiveness of in-laboratory (in-lab) 600-mg clopidogr... more This study sought to evaluate safety and effectiveness of in-laboratory (in-lab) 600-mg clopidogrel loading prepercutaneous coronary intervention (PCI) versus routine 6-h pre-load.

Research paper thumbnail of High Versus Standard Clopidogrel Maintenance Dose After Percutaneous Coronary Intervention and Effects on Platelet Inhibition, Endothelial Function, and Inflammation

Journal of the American College of Cardiology, 2011

This study was done to compare effects of high versus standard clopidogrel maintenance doses on p... more This study was done to compare effects of high versus standard clopidogrel maintenance doses on platelet inhibition, inflammation, and endothelial function in patients undergoing percutaneous coronary intervention. Background Previous data suggested that clopidogrel has various biological actions in addition to antiplatelet effects. Methods Fifty patients were randomly assigned 1 month after intervention (T-0) to receive standard (75 mg/day; n ϭ 25) or high (150 mg/day; n ϭ 25) clopidogrel maintenance dose for 30 days (until T-1); at this time-point, cross-over was performed, and the assigned clopidogrel maintenance regimen was switched and continued for a further 30 days (until T-2). Platelet reactivity (expressed as P2Y 12 reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]), endothelial function (evaluated by flow-mediated vasodilation), and highsensitivity C-reactive protein levels were measured at T-0, T-1, and T-2. Results Patients in the 150-mg/day arm had higher platelet inhibition (50 Ϯ 20% vs. 31 Ϯ 20% in the 75-mg/day group; p Ͻ 0.0001), better flow-mediated vasodilation (16.9 Ϯ 12.6% vs. 7.9 Ϯ 7.5%; p ϭ 0.0001), and lower high-sensitivity C-reactive protein levels (3.6 Ϯ 3.0 mg/l vs. 7.0 Ϯ 8.6 mg/l; p ϭ 0.016). Higher clopidogrel dose was associated with decreased proportion of patients with P2Y 12 reaction units Ն240 (12% vs. 32%; p ϭ 0.001), flow-mediated vasodilation Ͻ7% (16% vs. 58%; p ϭ 0.0003), and high-sensitivity C-reactive protein levels Ͼ3 mg/l (46% vs. 64%; p ϭ 0.07). Conclusions For patients undergoing percutaneous coronary intervention, the 150-mg/day clopidogrel maintenance dose is associated with stronger platelet inhibition, improvement of endothelial function, and reduction of inflammation, compared with the currently recommended 75-mg/day regimen; those effects might have a role in the clinical benefit observed with clopidogrel and may provide the rationale for using the higher maintenance regimen in selected patients.

Research paper thumbnail of Efficacy of Atorvastatin Reload in Patients on Chronic Statin Therapy Undergoing Percutaneous Coronary Intervention

Journal of the American College of Cardiology, 2009

Research paper thumbnail of 1008-189 Atorvastatin therapy reduces markers of myocardial damage after percutaneous coronary interventions? Preliminary data from a randomized study

Journal of the American College of Cardiology, 2004

S-Vascular Disease, Hypertension, and Prevention 447A Vascular Disease, Hypertension, and Prevent... more S-Vascular Disease, Hypertension, and Prevention 447A Vascular Disease, Hypertension, and Prevention elderly (>/= 75 years of age) were consistently less likely to receive statins on discharge. Conclusions: Statin use was low irrespective of CAD status and total cholesterol levels in older patients with heart failure. These results emphasize the importance of continued efforts to improve secondary prevention in older patients with HF and ischemic heart disease.

Research paper thumbnail of Evidence of Cocaine-Related Coronary Atherosclerosis in Young Patients With Myocardial Infarction

Journal of the American College of Cardiology, 2006

To the Editor: Cocaine use has increased in the last years reaching in 1999 in the U.S. 30% of al... more To the Editor: Cocaine use has increased in the last years reaching in 1999 in the U.S. 30% of all drug-related visits to the emergency department, exceeding morphine and representing the most frequent cause of drug-related deaths (1). One of every four myocardial infarctions (MIs) in people aged 18 to 45 years can be linked to cocaine use (2). Several reports (3) implicated coronary vaso

Research paper thumbnail of Role of Endothelial Progenitor Cells in Restenosis and Progression of Coronary Atherosclerosis After Percutaneous Coronary Intervention

JACC: Cardiovascular Interventions, 2010

Objectives We prospectively investigated the relationship of circulating endothelial progenitor c... more Objectives We prospectively investigated the relationship of circulating endothelial progenitor cells at time of percutaneous coronary intervention to the subsequent development of in-stent restenosis or progression of coronary atherosclerosis. Background Endothelial progenitor cells provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a pathogenic role in coronary atherosclerosis. Methods We studied 155 consecutive stable angina patients (92 men, age 60 Ϯ 11 years). All patients had flow cytometry the day before elective percutaneous coronary intervention in order to derive subpopulations of endothelial progenitor cells. A control group of 20 normal subjects was considered for comparison. Results At 8-month control angiography, 30 patients showed in-stent restenosis (restenosis group), 22 patients showed progression of coronary atherosclerosis (progression group), whereas the remaining 103 patients had neither in-stent restenosis nor progression of coronary atherosclerosis (stable group). Comparison of the 3 groups did not show any difference in risk factors, cardiac morphology and function, extension of coronary artery disease, and treatment. Absolute numbers of CD34ϩ/KDRϩ/CD45-cells (i.e., progenitors of endothelial lineage) measured in the restenosis group (1.41 Ϯ 0.64 cells/l) were significantly higher than in the progression, stable, and control groups (1.03 Ϯ 0.53 cells/l, 1.07 Ϯ 0.46 cells/l, and 0.95 Ϯ 0.44 cells/l, respectively, p Ͻ 0.05). Similarly, CD133ϩ/KDRϩ/CD45-cells (i.e., progenitors of endothelial cells at an earlier stage) were significantly higher in the restenosis (0.63 Ϯ 0.23 cells/l) compared with progression, stable, and control groups (0.33 Ϯ 0.19 cells/l, 0.41 Ϯ 0.32 cells/l, and 0.36 Ϯ 0.15 cells/l, respectively, p Ͻ 0.001). Also, numbers of CD14ϩ/CD45ϩ cells (i.e., which have a role in angiogenesis via a paracrine effect) were significantly different among the restenosis, progression, stable, and control groups (0.72 Ϯ 0.56 cells/l vs. 0.51 Ϯ 0.52 cells/l vs. 0.28 Ϯ 0.54 cells/l vs. 0.62 Ϯ 0.67 cells/l, respectively, p Ͻ 0.05), whereas CD105ϩ/CD45-/CD34-cells (i.e., which have a receptor for transforming growth factor-beta) were similar among groups. Conclusions Patients with restenosis have higher numbers of subpopulations of endothelial progenitor cells that incorporate into endothelial cells or play a role in arteriogenesis compared with controls and patients with either progression of coronary atherosclerosis or stable disease.

Research paper thumbnail of Statins and percutaneous coronary intervention

European Heart Journal, 2005

Research paper thumbnail of Clopidogrel reloading in patients undergoing percutaneous coronary intervention on chronic clopidogrel therapy: results of the ARMYDA-4 RELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) randomized trial

European Heart Journal, 2010

Aims To evaluate safety and effectiveness of clopidogrel reloading in patients on chronic clopido... more Aims To evaluate safety and effectiveness of clopidogrel reloading in patients on chronic clopidogrel therapy undergoing percutaneous coronary intervention (PCI). Methods and results Five hundred and three patients on .10 days clopidogrel therapy (41% with non-ST-segment elevation acute coronary syndrome, ACS) randomly received 600 mg clopidogrel loading 4-8 h before PCI (n ¼ 252) or placebo (n ¼ 251). Primary endpoint was 30-day incidence of major adverse cardiac events (MACE). In the overall population primary endpoint occurred in 6.7% of patients in the reload vs. 8.8% in the placebo arm [odds ratios (OR) 0.75, 95% confidence intervals (CI) 0.37-1.52; P ¼ 0.50]. In stable angina patients, 1-month MACE were not significantly different (7.0 vs. 3.9%; OR 1.84, 0.60-5.88; P ¼ 0.36), whereas ACS patients had significant clinical benefit with reloading (6.4 vs. 16.3%; OR 0.34, 95% CI 0.32-0.90, P ¼ 0.033 at multivariable analysis; interaction test: P ¼ 0.01). There was no excess bleeding in the reload arm (6% in both groups). Conclusion ARMYDA-4 RELOAD reveals no overall benefit from reloading patients on chronic clopidogrel therapy prior to PCI; the benefit observed in ACS patients is a hypothesis-generating finding that needs to be confirmed by larger studies.

Research paper thumbnail of Interleukin-1 receptor antagonist levels correlate with extent of myocardial loss in patients with acute myocardial infarction

Clinical Cardiology, 2005

Research paper thumbnail of Pharmacodynamic Comparison of Pitavastatin Versus Atorvastatin on Platelet Reactivity in Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy

Circulation Journal, 2014

Research paper thumbnail of Endothelial Progenitor Cells Predict Long-Term Prognosis in Patients With Stable Angina Treated With Percutaneous Coronary Intervention

Circulation Journal, 2013

Research paper thumbnail of Letters Regarding Article by Patti et al, "Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty...

Circulation, 2005

al recently investigated the effect of pretreating patients undergoing percutaneous coronary inte... more al recently investigated the effect of pretreating patients undergoing percutaneous coronary intervention (PCI) with 600 mg of clopidogrel versus the conventional 300-mg dose. 1 Their results showed that the 600-mg dose reduces the composite of death, myocardial infarction, or target vessel revascularization up to 30 days after the procedure. The authors concluded that the study "demonstrated that the higher loading dose was more effective than the conventional dose in preventing ischemic complication." These findings were immediately accepted with enthusiasm. 2 Although this investigation is an important step in understanding the optimal loading dose for clopidogrel, we are concerned about a methodological limitation in the study. The trial randomized 329 patients scheduled for coronary angiography who actually received a loading dose of either 600 mg or 300 mg clopidogrel. The authors reported only a perprotocol analysis in patients who actually underwent PCI. No safety or efficacy data were reported based on the intention-totreat principle, which would be the most relevant information, because in clinical practice when the decision is made to pretreat with clopidogrel, the coronary anatomy is frequently unknown. Therefore, the decision to undertake clopidogrel pretreatment would be better understood based on the efficacy/safety data in the overall population, including CABG and medically managed patients. Thus, it would be of utmost interest to know the adjusted odds ratio for the primary end point. The trial presents other methodological issues as the sample size calculated on the expected rate of any periprocedural CK-MB elevation instead of the major adverse cardiovascular events, which is referred to as the primary end point throughout the article and the fact that the logistic regression model "assessing the risk of the primary end point according to potential confounding" announced in the Methods is not shown anywhere in the article. Finally, the results presented cannot be conclusive because the 95% CI of the unadjusted OR is wide and entails a marginal potential advantage of the 600-mg dose (OR 0.31, 95% CI 0.09 to 0.95) If the evidence of the efficacy of clopidogrel pretreatment is weak overall, mainly based on a post-hoc analysis, then the evidence that 600 mg is the optimal dose is negligible. The results of the ARMYDA-2 trial support the need of a welldesigned and properly powered trial to answer the question whether 600 mg of clopidogrel as the loading dose is indicated in clinical practice.

Research paper thumbnail of Clinical Benefit of Statin Pretreatment in Patients Undergoing Percutaneous Coronary Intervention

Circulation, 2011

Background— Previous studies suggested that statin pretreatment reduces cardiac events in patient... more Background— Previous studies suggested that statin pretreatment reduces cardiac events in patients undergoing percutaneous coronary intervention. However, most data were observational, and single randomized trials included limited numbers of patients. Methods and Results— We performed a collaborative meta-analysis using individual patient data from 13 randomized studies in which 3341 patients received either high-dose statin (n=1692) or no statin/low-dose statin (n=1649) before percutaneous coronary intervention, with all patients receiving statin therapy after intervention. Occurrence of periprocedural myocardial infarction, defined as postintervention creatine kinase–MB increase ≥3 times the upper limit of normal, and 30-day major adverse cardiac events (death, myocardial infarction, target-vessel revascularization) was evaluated. Incidence of periprocedural myocardial infarction was 7.0% in the high-dose statin versus 11.9% in the control group, which corresponds to a 44% risk re...

Research paper thumbnail of Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention

Circulation, 2005

Background— Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardi... more Background— Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. Although observational data have suggested that pretreatment with a high loading dose of clopidogrel may be more effective than a conventional dose, this hypothesis has never been tested in a randomized trial. Methods and Results— A total of 255 patients scheduled to undergo percutaneous coronary intervention were randomized to a 600-mg (n=126) or 300-mg (n=129) loading regimen of clopidogrel given 4 to 8 hours before the procedure. Creatine kinase MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI), or target vessel revascularization. The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group ( P =0.041) and was due entirely to periprocedur...

Research paper thumbnail of Impaired Flow-Mediated Dilation and Risk of Restenosis in Patients Undergoing Coronary Stent Implantation

Circulation, 2005

Background— Impaired endothelial function is a key event in the atherosclerosis process and predi... more Background— Impaired endothelial function is a key event in the atherosclerosis process and predicts future cardiovascular events in subjects with and without coronary artery disease (CAD). We performed the first prospective study evaluating whether early measurement of brachial artery endothelium-dependent dilation (flow-mediated dilation [FMD]) after coronary stenting could predict occurrence of in-stent-restenosis. Methods and Results— The study population included 136 patients with single-vessel CAD undergoing percutaneous coronary intervention (PCI) with stenting and at least 6 months of follow-up. All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI; FMD was investigated before and after 5 minutes of occlusion of the brachial artery, and nitroglycerin-mediated dilation was investigated before and after administration of sublingual nitrates. Clinical in-stent restenosis was demonstrated in 20 patients (15%), whereas 116 patients (85%) rema...

Research paper thumbnail of C-Reactive Protein: Linking Inflammation to Cardiovascular Complications

Research paper thumbnail of A Tale of Two Diseases : Atherosclerosis and Rheumatoid Arthritis

Research paper thumbnail of Association of Virulent Helicobacter pylori Strains With Ischemic Heart Disease

Circulation, 1998

Background —Previous studies have reported an association between chronic Helicobacter pylori inf... more Background —Previous studies have reported an association between chronic Helicobacter pylori infection and ischemic heart disease. However, it is not clear whether this association is really due to the virulence of the bacterium or is merely the result of confounding factors (in particular, age and social class). Methods and Results —We assessed the prevalence of infection by Helicobacter pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, in 88 patients with ischemic heart disease (age, 57±8 years; 74 men) and in 88 age- and sex-matched controls (age, 57±8 years; 74 men) with similar social background. Prevalence of Helicobacter infection was significantly higher in patients than in controls (62% versus 40%; P =.004), with an odds ratio of 2.8 (95% CI, 1.3 to 7.4; P <.001) adjusted for age, sex, main cardiovascular risk factors, and social class. Patients with ischemic heart disease also had a higher prevalence of CagA-positive strai...