Simone Calcagno

Pharmacodynamic Effect of Switching Therapy in Patients With High On-Treatment Platelet Reactivity and Genotype Variation With High Clopidogrel Dose Versus Prasugrel The RESET GENE Trial

Background—High on-treatment platelet reactivity (HTPR) is associated with adverse outcomes. We aim to compare the novel thienopyridine prasugrel versus double-dose clopidogrel in patients with HTPR and explore the interaction between CYP2C19 genotype and both drugs. Methods and Results—Consecutive stable patients undergoing percutaneous coronary intervention were screened with the Multiplate Analyzer P2Y12 assay, defining HTPR as area under the curve >450. Those with HTPR were randomized to prasugrel (10 mg/day) or high-dose clopidogrel (150 mg/day) for 2 weeks and then crossed-over to, respectively, clopidogrel and prasugrel, repeating the P2Y12 assay at the end of each cycle. Clinical follow-up (until 3 months) and CYP2C19 genotyping was performed in all patients. The primary end point was platelet reactivity after 14 days of prasugrel versus high-dose clopidogrel. Thirty-two patients were randomized to prasugrel and then high-dose clopidogrel or to high-dose clopidogrel followed by prasugrel. Prasugrel was associated with a significantly lower platelet reactivity than high-dose clopidogrel was (325.8 versus 478.5 area under the curve, P=0.028). No patient treated with prasugrel exhibited HTPR, whereas 9 (28.1%) receiving high-dose clopidogrel still had prevalence of HTPR (P=0.001). Similar findings were obtained changing cutoffs or considering platelet reactivity as a continuous variable. Genotyping showed the same efficacy between high-dose clopidogrel and prasugrel in the 18 (56.3%) CYP2C19*2 noncarriers (HTPR in 12.5% versus 0, P=0.274), whereas it was significantly worse in the 14 (43.7%) carriers (HTPR in 43.7% versus 0, P=0.003). Conclusions—HTPR is successfully abolished by therapy with prasugrel irrespective of CYP2C19 genotype. Conversely, high-dose clopidogrel can address HTPR only in CYP2C19*2 noncarriers. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01465828.

Comparison of high reloading ROsuvastatin and Atorvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of MyocArdial periprocedural necrosis. the ROMA II trial

OBJECTIVES The objective of this study is to compare a reloading dose of Rosuvastatin and Atorvastatin administered within 24 h before coronary angioplasty (PCI) in reducing the rate of periprocedural myonecrosis and major cardiac and cerebrovascular events (MACCE) in patients on chronic statin treatment undergoing elective PCI. BACKGROUND Elective PCI may be complicated with elevation of cardiac biomarkers. Several studies suggested that pretreatment with statins may be associated with a reduction in periprocedural myocardial necrosis. METHODS Three hundred and fifty patients with stable angina who underwent elective PCI were randomly assigned to receive a pre-procedural reloading dose of Rosuvastatin (40 mg) (Rosuvastatin Group-RG n=175) or Atorvastatin (80 mg) (Atorvastatin Group-AG n=175) and a control group on chronic statin therapy without reloading (Control-Group-CG). The primary end-point was periprocedural myocardial necrosis and the occurrence of MACCE at 30-day,6-12 month follow-up. Also we evaluate the rise of periprocedural Troponin T serum levels >3× the upper limit of normal. RESULTS Twelve and 24-hour post-PCI Creatine Kinase Muscle and Brain (CK-MB) elevation >3× occurred more frequently in the CG than in the RG and in the AG (at 24-h: 25.0 vs 7.1; p=0.003 and 25.0 vs 6.1; p=0.001). At 30-day, 6-and 12-month follow-up the incidence of cumulative MACCE was higher in CG than in the RG or AG (at 12-month: 41.0% vs 11.4% vs 12.0%; p=0.001). There was no difference between the RG and AG in terms of myocardial post-procedural necrosis and MACCE occurrence at follow-up. CONCLUSIONS High-dose statin reloading improves procedural and long term clinical outcomes in stable patients on chronic statin therapy. Both Rosuvastatin and Atorvastatin showed similar beneficial effects on procedural and long-term outcomes.

Rosuvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of myocardial periprocedural necrosis: The ROMA trial

The aim of this study is to assess the efficacy of the high‐dose rosuvastatin preadministration in reducing periprocedural myocardial necrosis and major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing elective percutaneous coronary intervention (PCI).

Beneficial impact of prolonged dual antiplatelet therapy after drug-eluting stent implantation

BACKGROUND  Twelve-month dual antiplatelet therapy (DAT) with aspirin and clopidogrel after drug-eluting stent (DES) implantation is routinely recommended. It is unclear if prolonged (>12-month) DAT is also favorable. We compared the outcome of patients discontinuing DAT 12 months after off-label DES implantation versus those with DAT for >12 months. METHODS  Baseline, treatment, and outcome data of patients undergoing off-label DES implantation and free from events 11.5 months after index procedure were retrospectively retrieved. Those discontinuing DAT between 11.5 and 12.5 months (12-month DAT group) were compared to those discontinuing DAT after 12.5 months (>12-month DAT group). The primary end-point was the long-term (>24-month) rate of major adverse cerebro-cardiovascular events (MACCE). RESULTS Two hundred seventy-two patients met study inclusion criteria: 133 (48.9%) in the 12-month DAT group and 139 (51.1%) in the >12-month DAT group (who were on DAT for an average of 24 months). After an average of 36 months after DES implantation, 14 patients (5.1%) developed MACCE, with 6 (3.5%) cardiac deaths, 7 (2.2%) myocardial infarctions, no stroke, and 5 (1.8%) repeat revascularizations. The >12-month DAT group had a significantly lower risk of MACCE (1 [0.7%] vs. 13 [9.8%] in the 12-month DAT group, P < 0.001) and myocardial infarction (0 vs. 7 [5.3%], P = 0.006), with such differences confirmed at multivariable propensity-adjusted analyses. No significant differences in terms of minor or major bleedings occurred. CONCLUSIONS In this retrospective registry, patients with off-label DES implantation receiving prolonged (>12 months) DAT presented with lower rates of MACCE and myocardial infarction.

Effects of statins on plaque rupture assessed by optical coherence tomography in patients presenting with acute coronary syndromes: insights from the optical coherence tomography (OCT)-FORMIDABLE registry

Aims Chronic pre-treatment with statins may reduce mortality and morbidity in patients experiencing acute coronary syndromes (ACS), but mechanisms accounting for these findings are not completely understood. Methods and results The optical coherence tomography (OCT)-Formidable registry retrospectively enrolled 285 consecutive patients with ACS undergoing OCT in 9 European centres. Mean age was 60.4 ± 12.8 years, 148 (51.9%) patients had hyperlipemia, 45 (15.8%) diabetes mellitus and 142 (49.8%) presented with ST Segment Elevation Myocardial Infarction (STEMI). Patients were stratified according to statin prescription: 150 (52.6%) were on chronic pre-treatment with statins before ACS and were more likely to present with non-ST segment elevation acute coronary syndromes (NSTE-ACS) at admission (111, 74%) rather than STEMI, while the opposite was observed for patients not on statins. The primary end-point of ruptured plaque at OCT occurred significantly less frequently in the patients on chronic pre-treatment with statins [odds ratio (OR) 0.375, 95% confidence interval (CI) 0.185-0.759, P = 0.006]. The secondary end-point of thin-cap fibro-atheroma (TCFA) at any site was significantly less frequent in the statin group (OR 0.423, 95%CI 0.213-0.840, P = 0.014). No differences were observed for the secondary end-point of not-ruptured TCFA as the culprit lesion. Pre-specified sensitivity analysis was conducted according to the pattern of ACS: the reported differences were confirmed for NSTE-ACS patients, with a trend towards less plaque rupture and a significant reduction of TCFA at any site with statins, but not for STEMI. Conclusions Chronic pre-treatment with statins is associated with a reduced prevalence of ruptured plaques in patients presenting with ACS, particularly in those with NSTE-ACS. Statins bear hence the potential to reduce morbidity during the acute phase of ACS.

Comparison of therapy with Ticagrelor, Prasugrel or high Clopidogrel dose in PCI patients with high on treatment platelet reactivity and genotype variation. TRIPLETE RESET trial.

Comparison of therapy with Ticagrelor, Prasugrel or high Clopidogrel dose in PCI patients with high on treatment platelet reactivity and genotype variation. TRIPLETE RESET trial☆ Gennaro Sardella ⁎, Simone Calcagno , Massimo Mancone , Luigi Lucisano , Mauro Pennacchi , Rocco Edoardo Stio , Filippo Placentino , Angelo Di Roma , Erika Cavallo , Raffaele Palmirotta , Fiorella Guadagni , Francesco Fedele a

Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment

Platelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASA<1 month patients) and aspirinated patients who started the treatment more than two months ago (ASA>2 months patients). In platelets obtained from ASA>2 months patients, it was found a statistically significant MRP4 enhancement of both mRNA and protein expression compared to HV, CTR and ASA<1 month patients. Platelets obtained from ASA>2 months patients that present high levels of platelet MRP4, have higher serum TxB2 levels and collagen-induced platelet aggregation compared to patient with low levels of MRP4 in platelets. In addition collagen induced platelet aggregation is higher in in vitro aspirinated platelets obtained from patients with high levels of MRP4 patients compared to those obtained from patients with low MRP4 levels. We can assert that, in patients under chronic aspirin treatment, platelets that present high MRP4 levels have an increase of residual platelet reactivity, which is due in part to incomplete COX-1 inhibition, and in part to COX-1-independent mechanism.

Clinical outcomes with reservoir-based polymer-free amphilimus-eluting stents in real-world patients according to diabetes mellitus and complexity: The INVESTIG8 registry

Patients with diabetes mellitus (DM) remain at higher risk of restenosis after percutaneous coronary intervention despite the use of contemporary drug‐eluting stents. The Cre8 amphilimus‐eluting stent (AES) has shown promising results in DM patients. Whether this holds true irrespective of patients clinical and angiographic complexity is unknown.

Coronary artery bifurcation narrowing treated by Axxess stent implantation: The CARINAX registry

To compare the safety and efficacy of the Axxess™ biolimus‐eluting stent with the second‐generation drug‐eluting stent (DES) in the treatment of bifurcation lesions.

Different Prasugrel Administration in STEMI Patients*. Go Faster and No Fear to Crush!

The first goal in ST-segment elevation myocardial infarction (STEMI) patients is “speed”: to diagnose, to transfer to the catheterization laboratory, to pre-treat orally, to perform coronary angiography, and to open the culprit vessel. A delay of 1 of these steps could have a negative effect on