Mauro Pennacchi

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.

In-hospital and midterm clinical outcomes of rotational atherectomy followed by stent implantation: The ROTATE multicentre registry

AIMS The aim of this multicentre study was to investigate the in-hospital and midterm outcomes of rotational atherectomy (RA) followed by metallic stent implantation. METHODS AND RESULTS Between 2002 and 2013, 1,176 de novo lesions with calcified coronary lesions treated by RA and metallic stent implantation at nine institutions were assessed. Patients with ST-segment elevation myocardial infarction (STEMI) within 30 days, cardiogenic shock before the procedure, lesions with thrombus, and in-stent restenosis were excluded from the current analysis. In-hospital major adverse cardiac events (MACE) occurred in 8.3% of cases, mainly driven by periprocedural myocardial infarction. The incidence of MACE was 16.0% at one-year and 24.9% at two-year follow-up, both driven by target vessel revascularisation (13.5% at one year and 19.8% at two years). Multivariable analysis revealed that dialysis was an independent predictor for both in-hospital MACE (OR 2.33, 95% CI: 1.11-4.87, p=0.03) and follow-up MACE (HR 4.14, 95% CI: 2.87-5.96, p<0.001), whilst drug-eluting stent (DES) use was associated with a reduction in follow-up MACE (HR 0.42, 95% CI: 0.26-0.67, p<0.001). CONCLUSIONS RA appears to be safe and effective with acceptable in-hospital and follow-up MACE considering the severity of patient and lesion characteristics. DES implantation following RA was associated with a reduction in MACE during the follow-up period.

Rotational atherectomy in very long lesions: Results for the ROTATE registry.

Rotational atherectomy (RA) is relatively contraindicated in patients with lesions ≥25 mm of length. Aim of this study was to evaluate RA safety and efficacy in this subset of patients with new technology and devices.

RoTational AThErectomy in acute coronary syndrome: Early and midterm outcomes from a multicentre registry

AIMS The safety and efficacy of rotational atherectomy (RA) in patients presenting with non-ST-elevation myocardial infarction (NSTE-ACS) remain to be defined. The aim of our study was to assess the safety and efficacy of RA in NSTE-ACS patients with reference to both short- and long-term follow-up. METHODS AND RESULTS This was an observational retrospective registry which enrolled all consecutive patients undergoing RA, comparing patients with stable angina (SA) and NSTE-ACS. In addition, ACS patients were matched with those not undergoing RA. The primary endpoint was angiographic success. Procedural complications and in-hospital MACE were secondary endpoints along with MACE during follow-up. One thousand three hundred and eight patients were included: 37% (484) with an NSTE-ACS diagnosis and 63% (824) in the SA group. Angiographic success did not differ between the groups (98.8% vs. 99.2%, p=0.57). By univariate analysis procedural complications were more frequent in the NSTE-ACS group (11.3% vs. 8.0%, p=0.04). In-hospital MACE rates were comparable (5.7% vs. 5.8%, p=0.93); by multivariate analysis NSTE-ACS patients showed a non-significant trend towards a higher risk of adverse events (HR 2.39, CI: 0.96-5.96, p=0.061). MACE after a median of 27.9 months was significantly higher in the NSTE-ACS group compared with the SA group (32.4% vs. 24.2%, log-rank p<0.001), results confirmed by multivariate analysis. After propensity score matching, NSTE-ACS patients undergoing RA had similar outcomes to ACS patients who did not undergo RA (16% vs. 13%, log-rank p=0.14). CONCLUSIONS Rotational atherectomy has similar safety and angiographic outcome in patients with NSTE-ACS or SA. The higher rate of adverse cardiac events at follow-up in NSTE-ACS patients undergoing RA is comparable with a matched population of NSTE-ACS patients not undergoing RA.

Planned versus provisional rotational atherectomy for severe calcified coronary lesions: Insights From the ROTATE multi-center registry

We aimed to investigate procedural feasibility and outcomes associated with planned rotational atherectomy (RA) for severely calcified coronary lesions. Background: Limited data are available addressing the benefits of planned RA compared to provisional RA.

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

Evidence from the Resorbable-polymer stent versus Unresorbable-polymer stent Deployment for coronary Intervention: (RUDI-2) registry

Evidence from the Resorbable-polymer stent versus Unresorbable-polymer stent Deployment for coronary Intervention: (RUDI-2) registry Gennaro Sardella , Carlo Briguori , Roberto Garbo , Enrico Romagnoli , Mauro Pennacchi ⁎, Michael Donahue , Giacomo Boccuzzi , Francesco Summaria , Giulia Conti , Emanuele Canali , Filippo Placentino , Rocco Stio , Luigi Lucisano , Giuseppe Biondi-Zoccai , Massimo Mancone , Francesco Fedele a a Policlinico Umberto I, Sapienza University of Rome, Rome, Italy b Clinica Mediterranea, Naples, Italy c San Giovanni Bosco Hospital, Turin, Italy d Policlinico Casilino, Rome, Italy e Aurelia Hospital, Rome, Italy f Department of Medico-Surgical Science and Biotechnologies, Sapienza University of Rome, Latina, Italy

One-Year Outcome From an All-Comers Population of Patients With ST-Segment Elevation Myocardial Infarction Treated With Biolimus-Eluting Stent With Biodegradable Polymer

To evaluate the performance of biolimus‐eluting stent (BES) in patients with ST‐elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) in a real world clinical scenario.

Percutaneous coronary intervention in TAVI: The “proboscis” catheter

We report a case of an 81‐years‐old male, recently implanted with a Core Valve (CV) prosthesis and admitted to the ER for acute coronary syndrome. Coronary angiography revealed the patency of the coronary artery by‐pass grafts but was impossible to cannulate the left main “imprisoned” by the CV prosthesis struts. Aortography showed an excessive gap between the CV struts and the coronary ostium. To cross the CV struts, we developed a “proboscis” catheter by cutting away the proximal end of the 7F JL 4 catheter and putting inside the 5F Heartrail catheter. The following angiograms showed a critical stenosis in the proximal obtuse marginal (branch), successfully treated with a bare‐metal stent implantation.