Rosetta Melfi

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

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%) remained free of signs or symptoms of recurrent ischemia. FMD was significantly impaired in patients with restenosis versus those without restenosis (percent diameter variation 4.6±5.8% versus 9.5±6.6%, P=0.002); moreover, 4% of patients with FMD ≥7% (median value) developed in-stent restenosis versus 28% of those with FMD <7% (P=0.0001). On multivariate analysis, FMD was the strongest predictor of restenosis (OR 4.5, 95% CI 2.4 to 12.0); conversely, nitroglycerin-mediated dilation did not independently predict the risk of restenosis (OR 2.4, 95% CI 0.8 to 6.3). Conclusions—This is the first prospective study indicating that impaired FMD independently predicts occurrence of in-stent restenosis in patients undergoing PCI. Early evaluation of endothelial function after stenting may represent a useful screening tool to stratify patients according to future risk of restenosis.

Strategies of Clopidogrel Load and Atorvastatin Reload to Prevent Ischemic Cerebral Events in Patients Undergoing Protected Carotid Stenting: Results of the Randomized ARMYDA-9 CAROTID (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting) Study

OBJECTIVES This study sought to evaluate whether a strategy with a 600-mg clopidogrel load and a short-term, high-dose atorvastatin reload would improve outcomes in clopidogrel-naïve, statin-treated patients undergoing protected carotid stenting. BACKGROUND Optimal clopidogrel loading dose during carotid stenting has not been investigated; in addition, statin neuroprotection in this setting has not been described. METHODS A total of 156 patients were randomized using a 2 × 2 factorial design to receive either a 600-mg (n = 78) or 300-mg (n = 78) clopidogrel load given 6 h before intervention and either a atorvastatin reload (n = 76; 80 mg + 40 mg initiating 12 h before the procedure) or no statin reload (n = 80). The primary endpoint was the 30-day incidence of transient ischemic attack/stroke or new ischemic lesions on cerebral diffusion-weighted magnetic resonance imaging performed at 24 to 48 h. RESULTS Occurrence of the primary outcome measure was significantly lower in the 600-mg clopidogrel arm (18% vs. 35.9% in the 300-mg group; p = 0.019) and in the atorvastatin reload arm (18.4% vs. 35.0% in the no statin reload group; p = 0.031). High-dose clopidogrel also significantly reduced the transient ischemic attack/stroke rate at 30 days (0% vs. 9%, p = 0.02, secondary endpoint), without an increase in bleeding risk. CONCLUSIONS In patients undergoing carotid stenting, a strategy using both a 600-mg clopidogrel load and a short-term reload with high-dose atorvastatin protects against early ischemic cerebral events. These results, obtained along with routine mechanical neuroprotection, provide new evidence of the optimization of drug therapy before percutaneous carotid intervention. (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting [ARMYDA-9 CAROTID]; NCT01572623).

Statin loading for acute coronary syndromes.

Purpose of review This review discusses the role of statin therapy in patients with acute coronary syndromes. These drugs modulate endothelial function and stabilize atherosclerotic plaque by inhibiting oxidative stress and inflammation and may provide a relevant clinical benefit in unstable patients. Recent findings Conflicting data derive from randomized trials about early statin therapy in medically treated patients with acute coronary syndromes. Results of the ARMYDA studies demonstrate a clear benefit of statin pretreatment in patients with both stable and unstable syndromes undergoing percutaneous coronary revascularization. In the ARMYDA RECAPTURE, even an acute reload with high-dose atorvastatin in patients on top of chronic statin use was associated with a significant reduction of 30-day major adverse cardiac events, especially in those patients who presented with acute coronary syndromes. Summary All this evidence strongly supports an ‘upstream’ administration of high-dose statins in patients with acute coronary syndromes treated with an early invasive strategy.

Efficacy and Safety of Paclitaxel-Coated Balloon for the Treatment of In-Stent Restenosis in High-Risk Patients.

In-stent restenosis (ISR) is a major cause of failure of percutaneous coronary intervention. The efficacy and safety of drug-coated balloon (DCB) in patients with high-risk clinical features are largely unknown. We enrolled 82 consecutive patients at high risk of bleeding with angiographically significant (diameter stenosis ≥ 50%) ISR of bare metal stent (BMS) or drug-eluting stent (DES), treated with paclitaxel-coated balloon. All patients presented at least one of the following criteria: high bleeding risk, neoplasm, chronic inflammatory disease, and need for noncardiac surgery. Dual antiplatelet therapy was indicated for 4 weeks after the procedure. At angiographic follow-up, overall late lumen loss was 0.24 ± 0.32 mm, with no significant difference between BMS-ISR and DES-ISR (0.25 ± 0.35 vs 0.22 ± 0.30 mm, p = 0.714). The Kaplan-Meier estimate for major adverse clinical events-free survival at 3 years was 81.4% (82.3% in BMS-ISR vs 79.4% in DES-ISR, log-rank p = 0.866). No stent thrombosis has been recorded. In conclusion, the use of paclitaxel-coated balloon seems to be associated with favorable outcomes after percutaneous coronary intervention for BMS-ISR or DES-ISR in patients with high-risk clinical features and could be considered as a reasonable option in the presence of systemic co-morbidities and contraindications to long-term dual antiplatelet therapy.

Statins and Their Role in Pre-Percutaneous Coronary Intervention

Lipid-lowering therapy with statins reduces the risk of cardiovascular events in patients with coronary artery disease. Recent in vitro and in vivo studies demonstrated a low-density lipoprotein-independent action of this class of drugs, which appears to modulate endothelial function, inflammation, and thrombosis. Randomized studies showed a beneficial effect of short-term statin pretreatment in reducing periprocedural cardiac marker release in patients undergoing percutaneous coronary intervention (PCI). In particular, the ARMYDA (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) investigators—initially in stable angina patients, then in patients with acute coronary syndrome, and then in patients already on chronic statin therapy—demonstrated an improvement in 30-day major adverse cardiac event rates, which were driven by a reduced rate of periprocedural myocardial infarction. Moreover, statin therapy at the time of PCI significantly decreased the incidence of contrast-induced nephropathy. These observations support high-dose statin pretreatment in all patients who are candidates for PCI.

Review: Percutaneous coronary interventions and statins therapy

Statins exert a number of beneficial effects on endothelial function and atherosclerotic plaque, modulating oxidative stress and inflammation, with subsequent, well documented, primary and secondary prevention of coronary artery disease. Periprocedural myocardial infarction and contrast induced nephropathy, after percutaneous coronary intervention (PCI), are associated with a worse outcome on long term follow-up. In the ARMYDA study, pretreatment with statins before elective PCI reduces periprocedural myocardial infarction in patients with stable angina. Moreover, the ARMYDA ACS was the first randomized, prospective trial that demonstrated that an acute loading with a high dose of atorvastatin prevents myocardial damage in patients with unstable syndromes undergoing early (<48 hours) coronary angiography and consequent angioplasty. Statins could also have beneficial effects by reducing expression of adhesion molecules in endothelial cells (ICAM-1 and E-Selectin) as demonstrated in the ARMYDA-CAMS study. Furthermore, patients receiving statins at the time of procedure show a significantly reduced incidence of contrast-induced nephropathy. All this evidence may strongly influence the clinical practice of an interventional cardiologist.

Glycemic Variability Assessed by Continuous Glucose Monitoring and Short-Term Outcome in Diabetic Patients Undergoing Percutaneous Coronary Intervention: An Observational Pilot Study.

Poor glycemic control is associated with unfavorable outcome in patients undergoing percutaneous coronary intervention (PCI), irrespective of diabetes mellitus. However a complete assessment of glycemic status may not be fully described by glycated hemoglobin or fasting blood glucose levels, whereas daily glycemic fluctuations may influence cardiovascular risk and have even more deleterious effects than sustained hyperglycemia. Thus, this paper investigated the effectiveness of a continuous glucose monitoring (CGM), registering the mean level of glycemic values but also the extent of glucose excursions during coronary revascularization, in detecting periprocedural outcome such as renal or myocardial damage, assessed by serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and troponin I levels. High glycemic variability (GV) has been associated with worse postprocedural creatinine and NGAL variations. Moreover, GV, and predominantly hypoglycemic variations, has been observed to increase in patients with periprocedural myocardial infarction. Thus, our study investigated the usefulness of CGM in the setting of PCI where an optimal glycemic control should be achieved in order to prevent complications and improve outcome.

Relation of Platelet Indexes to Platelet Reactivity and Periprocedural Myocardial Infarction in Patients Who Underwent Percutaneous Coronary Angioplasty

No comprehensive data are available on the role of platelet indexes (PI) in the periprocedural risk stratification of patients who underwent percutaneous coronary intervention (PCI). The aim of this study was to investigate the relation of PI to platelet reactivity (PR) and periprocedural myocardial infarction (PMI) in patients receiving PCI. A total of 502 PCI patients had preprocedural measurement of PI and PR, the latter assessed by VerifyNow P2Y12 assay. Study end points were incidence of PMI and high platelet reactivity (HPR) according to tertiles of PI and evaluation of PI in HPR patients. Incidence of PMI in the overall population was 6.6%. Rates of PMI were not different in PI tertiles: platelet count (I: 6.0%, II: 7.1%, III: 6.5%; p = 0.74), mean platelet volume (MPV, I: 6.6%, II: 7.3%, III: 5.8%;p = 0.86), platelet distribution width (I: 7.2%, II: 7.2%, III: 5.8%;p = 0.74), and MPV/P ratio (I: 6.6%, II: 6.0%, III: 7.1%; p = 0.91). The occurrence of PMI was significantly different in PR tertiles (I: 3%, II: 5.4%, III: 11.4%; p = 0.006). Platelet count and MPV/P ratio were significantly different in patients with and without HPR (221.8 ± 58.6 × 103/µL vs207 ± 59.4 × 103/µL, p = 0.008; 51.73 ± 15.17 vs 56.7 ± 18.3, p = 0.002).In conclusion, this study showed no relation between PI and PMI in PCI patients but confirms the association of HPR with increased incidence of PMI; thus, PI seem to be not able to identify patients at higher periprocedural risk, but monitoring PR by a bedside assay remains a useful tool for risk stratification.

LDL-LOWERING INDEPENDENT EFFECTS OF EARLY PRE-TREATMENT WITH HIGH-DOSE STATINS IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTIONS

Statins exert beneficial effects on the endothelium, inflammation and the coagulation cascade that are independent of cholesterol lowering. The main mechanism underlying these effects is inhibi tion of isoprenoid synthesis, modulating the inflammatory cascade and the endothelial activation reliable of atherosclerosis. Different studies demonstrated that statins improve endothelial function in patients with stable atherosclerotic plaque and that this effect is dose-dependent. Statins may modulate endothelial expression of adhesion molecules, as demonstrated in the ARMYDA-CAMS, and may enhance mobilisation of endothelial progenitor cells. Elevated C-reactive protein levels, an inflammatory marker that also plays a direct pathogenetic role in the atherosclerotic process, have been correlated with worse outcome in patients with cardiovascular disease. Multiple studies demonstrated that statin attenuates the rise of inflammatory markers and improves clinical outcome in patients with stable angina, unstable angina and non-Q wave acute myocardial infarction. During percutaneous coronary intervention randomised trials showed a benefical effect of statin pre-treatment in reducing peri-procedural myocardial damage probably by plaque stabilisation and inhibition of microembolisation phenomena during stent implantation. The ARMYDA study and the NAPLES II trial demonstrated this beneficial effect in patients undergoing coronary revascularisation for stable angina. Also in patients with ACS, receiving invasive strategy, the role of statins in preventing peri-procedural damage was demonstrated in the ARMYDA-ACS study by the administration of an acute high loading-dose with atorvastatin. In patients already on chronic statin therapy at the time of the procedure, an acute drug reload before stenting would have cardioprotective effects, like demonstrated in the ARMYDA RECAPTURE study.

Clinical benefits of statin pretreatment in patients undergoing coronary revascularization

Abstract A large number of randomized trials have established the beneficial effects of statins for primary and secondary prevention of coronary artery disease. Statins may improve endothelial function and stabilize atherosclerotic plaques by inhibiting oxidative stress and inflammation. Pretreatment with statins before elective percutaneous coronary intervention reduces periprocedural myocardial infarction in patients with stable angina or acute coronary syndromes. Moreover, an acute reload of atorvastatin even in the context of chronic statin has been associated with a significant reduction within 30 days of major adverse cardiac events after percutaneous coronary intervention. Patients on statins at the time of percutaneous coronary intervention also had a lower incidence of contrast-induced nephropathy, as compared with those that were statin-naive. Finally, atorvastatin pretreatment may prevent the occurrence of atrial fibrillation in patients undergoing elective cardiac surgery. Overall, this evidence may strongly influence the clinical practice of interventional cardiologists and cardiac surgeons.