Alberto Menozzi

A Randomized Multicenter Study Comparing a Paclitaxel Drug-Eluting Balloon With a Paclitaxel-Eluting Stent in Small Coronary Vessels: The BELLO (Balloon Elution and Late Loss Optimization) Study

OBJECTIVES The aim of this study was to evaluate the efficacy of drug-eluting balloons (DEB) compared with paclitaxel-eluting stents (PES) for the reduction of restenosis in small vessels. BACKGROUND DEB have been shown to be effective in the treatment of coronary in-stent restenosis, but data are limited regarding their efficacy in de novo disease. METHODS BELLO (Balloon Elution and Late Loss Optimization) is a prospective, multicenter trial that randomized 182 patients with lesions located in small vessels (reference diameter <2.8 mm) to treatment with paclitaxel DEB and provisional bare-metal stenting (n = 90) or PES implantation (n = 92). The primary endpoint was noninferiority of angiographic in-stent (in-balloon) late loss with a delta of 0.25 mm. Secondary endpoints were angiographic restenosis, target lesion revascularization, and major adverse cardiac events (MACE; death, myocardial infarction, target vessel revascularization) at 6 months. RESULTS Baseline characteristics were well matched, except for a smaller vessel size in the DEB group (2.15 ± 0.27 mm vs. 2.25 ± 0.24 mm; p = 0.003). The majority (89%) of lesions involved vessels with a diameter <2.5 mm. Bailout stenting was required in 20% of lesions in the DEB group. The primary endpoint of in-stent (in-balloon) late loss was significantly less with DEB compared with PES (0.08 ± 0.38 mm vs. 0.29 ± 0.44 mm; difference -0.21; 95% CI: -0.34 to -0.09; p(noninferiority) < 0.001; p(superiority) = 0.001). At 6 months, DEB and PES were associated with similar rates of angiographic restenosis (10% vs. 14.6%; p = 0.35), [corrected] target lesion revascularization (4.4% vs. 7.6%; p = 0.37), and MACE (10% vs. 16.3%; p = 0.21). [corrected]. CONCLUSIONS Treatment of small-vessel disease with a paclitaxel DEB was associated with less angiographic late loss and similar rates of restenosis and revascularization as a PES. (Balloon Elution and Late Loss Optimization [BELLO]; Study NCT01086579).

Thrombocytopenia Caused by Abciximab or Tirofiban and Its Association With Clinical Outcome in Patients Undergoing Coronary Stenting

Background—Thrombocytopenia is a possible complication of treatment with glycoprotein (GP) IIb/IIIa antagonists during percutaneous coronary interventions, but it is not clear whether different GP IIb/IIIa inhibitors carry a different risk of thrombocytopenia, and its relation to clinical outcome is unknown. Methods and Results—We analyzed data from the Do Tirofiban and Reopro Give Similar Efficacy Outcomes (TARGET) study, which compared the safety and efficacy of abciximab and tirofiban in patients undergoing coronary stenting. Platelets were measured at baseline and 6 and 24 hours after the beginning of treatment. Thrombocytopenia (nadir platelet count <100×109 cells/L) developed in 2.4% of patients treated with abciximab and 0.5% of those treated with tirofiban (P <0.001). The variables independently associated with thrombocytopenia were treatment with abciximab within the previous 6 months (OR, 4.4; 95% CI, 1.7 to 11.2), baseline creatinine levels of ≥0.8 mg/dL (OR, 3.8; 95% CI, 1.7 to 8.8), previous transient ischemic attack (OR, 3.2; 95% CI, 1.4 to 7.6), female gender (OR, 1.9; 95% CI, 1.2 to 3.1), and history of peripheral vascular disease (OR, 1.78; 95% CI, 1.0 to 3.1). Severe bleeding occurred more frequently in patients with thrombocytopenia (5.1% versus 0.7%, P = 0.001), who also more frequently received blood transfusions (6.1% versus 1.4%, P = 0.001). At the 30-day follow-up, 2.0% of patients with thrombocytopenia and 0.4% of those without (P = 0.022) had died; myocardial infarction occurred in 9.13% versus 6.11% (P = NS); and target vessel revascularization occurred in 6.07% versus 0.60% (P <0.001). Conclusions—During coronary stenting, abciximab and other risk factors are independently associated with thrombocytopenia. Regardless of the cause, thrombocytopenia is associated with more ischemic events, bleedings, and transfusions.

A prospective, randomized trial of intravascular-ultrasound guided compared to angiography guided stent implantation in complex coronary lesions: The AVIO trial

BACKGROUND No randomized studies have thus far evaluated intravascular ultrasound (IVUS) guidance in the drug-eluting stent (DES) era. The aim was to evaluate if IVUS optimized DES implantation was superior to angiographic guidance alone in complex lesions. METHODS Randomized, multicentre, international, open label, investigator-driven study evaluating IVUS vs angiographically guided DES implantation in patients with complex lesions (defined as bifurcations, long lesions, chronic total occlusions or small vessels). Primary study endpoint was post-procedure in lesion minimal lumen diameter. Secondary end points were combined major adverse cardiac events (MACE), target lesion revascularization, target vessel revascularization, myocardial infarction (MI), and stent thrombosis at 1, 6, 9, 12, and 24 months. RESULTS The study included 284 patients. No significant differences were observed in baseline characteristics. The primary study end point showed a statistically significant difference in favor of the IVUS group (2.70 mm ± 0.46 mm vs. 2.51 ± 0.46 mm; P = .0002). During hospitalization, no patient died, had repeated revascularization, or a Q-wave MI. No difference was observed in the occurrence of non-Q wave MI (6.3% in IVUS vs. 7.0% in angio-guided group). At 24-months clinical follow-up, no differences were still observed in cumulative MACE (16.9%vs. 23.2 %), cardiac death (0%vs. 1.4%), MI (7.0%vs. 8.5%), target lesion revascularization (9.2% vs. 11.9%) or target vessel revascularization (9.8% vs. 15.5%), respectively in the IVUS vs. angio-guided groups. In total, only one definite subacute stent thrombosis occurred in the IVUS group. CONCLUSIONS A benefit of IVUS optimized DES implantation was observed in complex lesions in the post-procedure minimal lumen diameter. No statistically significant difference was found in MACE up to 24 months.

Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial

BACKGROUND Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. We assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen. METHODS TRILOGY ACS (ClinicalTrials.gov number NCT00699998) was a randomised controlled trial, done at more than 800 sites worldwide. Patients with non-ST-elevation acute coronary syndrome who were selected for management without [corrected] revascularisation were randomly assigned to clopidogrel or prasugrel.The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 months. In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not. FINDINGS 7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis. 3085 (43%) had angiography at baseline, 4158 (57%) had not. Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography, according to Kaplan-Meier analysis (281/3085 [12·8%] vs 480/4158 [16·5%], adjusted hazard ratio [HR] 0·63, 95% CI 0·53-0·75; p<0·0001). The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography (122/1524 [10·7%] vs 159/1561 [14·9%], HR 0·77, 95% CI 0·61-0·98; p=0·032) but did not differ between groups in patients who did not have angiography (242/2096 [16·3%] vs 238/2062 [16·7%], HR 1·01, 0·84-1·20; p=0·94; pinteraction=0·08). Overall, TIMI major bleeding and GUSTO severe bleeding were rare. Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort. INTERPRETATION Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths, myocardial infarctions, or strokes than in those who took clopidogrel. This result needs to be corroborated, but it is consistent with previous trials of more versus less intensive antiplatelet treatment. When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed, the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention. FUNDING Daiichi Sankyo, Eli Lilly.

Transradial Versus Transfemoral Intervention for Acute Myocardial Infarction: A Propensity Score-Adjusted and -Matched Analysis From the REAL (REgistro regionale AngiopLastiche dell'Emilia-Romagna) Multicenter Registry

OBJECTIVES This study sought to assess whether transradial intervention, by minimizing access-site bleeding and vascular events, improves outcomes in patients with ST-segment elevation myocardial infarction compared with the transfemoral approach. BACKGROUND Bleeding and consequent blood product transfusions have been causally associated with a higher mortality rate in patients with myocardial infarction undergoing coronary angioplasty. METHODS We identified all adults undergoing percutaneous intervention for acute myocardial infarction in Emilia-Romagna, a region in the north of Italy of 4 million residents, between January 1, 2003, and July 30, 2009, at 12 referral hospitals using a region-mandated database of percutaneous coronary intervention procedures. Differences in the risk of death at 2 years between patients undergoing transfemoral versus transradial intervention, assessed on an intention-to-treat basis, were determined from vital statistics records and compared based on propensity score adjustment and matching. RESULTS A total of 11,068 patients were treated for acute myocardial infarction (8,000 via transfemoral and 3,068 via transradial route). According to analysis of matched pairs, the 2-year, risk-adjusted mortality rates were lower for the transradial than for the transfemoral group (8.8% vs. 11.4%; p = 0.0250). The rate of vascular complications requiring surgery or need for blood transfusion were also significantly decreased in the transradial group (1.1% vs. 2.5%, p = 0.0052). CONCLUSIONS In patients undergoing angioplasty for acute myocardial infarction, transradial treatment is associated with decreased 2-year mortality rates and a reduction in the need for vascular surgery and/or blood transfusion compared with transfemoral intervention.

Long-Term Outcomes With Drug-Eluting Stents Versus Bare Metal Stents in the Treatment of Saphenous Vein Graft Disease (Results from the REgistro Regionale AngiopLastiche Emilia-Romagna Registry)

Percutaneous revascularization of saphenous vein grafts (SVGs) remains a challenging task. Drug-eluting stents (DESs) have been shown to decrease the incidence of restenosis in de novo native coronary artery lesions. However, their clinical value in SVGs remains to be established. We compared long-term clinical outcomes of percutaneous coronary intervention with DESs and bare metal stents (BMSs) for de novo lesions in SVGs. In a large prospective, multicenter registry, 360 patients underwent stenting of a de novo lesion in SVGs using BMSs (288 patients) or DESs (72 patients). Incidence of major adverse cardiac events (MACEs), including all-cause mortality, reinfarction, and target vessel revascularization, was recorded at a 12-month follow-up. Compared with the DES group, patients receiving BMSs were more likely to be men, to have chronic renal insufficiency or higher Charlson scores, but less likely to have undergone previous percutaneous coronary intervention. Incidence of MACEs at 12-month follow-up was similar in the 2 groups (17.8% in DES group vs 20.3% in BMS group, respectively, p = 0.460). Cox regression analysis identified age, chronic renal failure, cardiogenic shock at presentation, and ostial location of stenosis as independent predictors of long-term MACEs. In conclusion, our data suggest that rates of 12-month MACEs associated with the use of DESs and BMSs are similar in patients undergoing treatment of de novo lesions in SVGs.

Diagnostic accuracy of 64-slice computed tomography coronary angiography in patients with low-to-intermediate risk

PurposeOur aim was to evaluate the diagnostic accuracy of 64-slice computed tomography coronary angiography (MSCT-CA) for detecting significant stenosis (≥50% lumen reduction) in a population of patients at low to intermediate risk.Materials and methodsWe studied 72 patients (38 men, 34 women, mean age 53.9±8.0 years) with atypical or typical chest pain and stratified in the low-to intermediate risk category. MSCT-CA (Sensation 64 Cardiac, Siemens, Germany) was performed after IV administration of 100 ml of iodinated contrast material (Iomeprol 400 mgI/ml, Bracco, Italy). Two observers, blinded to the results of conventional coronary angiography (CAG), assessed the MSCT-CA scans in consensus. Diagnostic accuracy for detecting significant stenosis was calculated.ResultsCAG demonstrated the absence of significant disease in 70.1% of patients (51/72). No patient was excluded from MSCT-CA. There were 37 significant lesions on 1,098 available coronary segments. Sensitivity, specificity and positive and negative predictive value of MSCT-CA for detecting significant coronary artery on a per-segment basis were 100%, 98.6%, 71.2% and 100%, respectively. All patients with at least one significant lesion were correctly identified by MSCT-CA. MSCT-CA scored 15 false positives on a per-segment base, which affected only marginally the per-p.atient performance (only one false positive).ConclusionsWe concluded that 64-slice CT-CA is a diagnostic modality with high sensitivity and negative predictive value in patients at low to intermediate risk.RiassuntoObiettivoValutare l’accuratezza diagnostica dell’angiografia coronarica non invasiva con tomografia computerizzata (AC-TC) a 64 strati nell’individuazione delle stenosi coronariche significative (riduzione del lume coronarico ≥ 50%) in una popolazione di pazienti a basso-intermedio rischio cardiovascolare.Materiali e metodiSono stati studiati 72 pazienti (38 maschi, 34 donne, età media 53,9±8,0 anni) che presentavano dolore toracico atipico o angina pectoris stabile e che venivano stratificati nella categoria del rischio basso-intermedio. Per la scansione AC-TC sono stati iniettati endovena 100 ml di mezzo di contrasto (Iomeprolo 400 mgI/ml, Bracco, Italia). Due osservatori, in cieco rispetto alla coronarografia convenzionale CAG), hanno valutato in consenso le immagini dell’AC-TC. Sono stati quindi calcolati i valori di accuratezza diagnostica per la rilevazione di stenosi significative.RisultatiL’angiografia coronarica invasiva ha dimostrato l’assenza di malattia o la presenza di malattia non critica nel 70,1% dei pazienti (51/72). Nessun paziente è stato escluso dalla popolazione studiata. Sono state individuate 37 lesioni significative su 1098 segmenti disponibili. Sensibilità, specificità, valore predittivo positivo e negativo dell’AC-TC nella determinazione delle stenosi significative utilizzando un’analisi per segmenti sono risultate, rispettivamente, del 100%, 98,6%, 71,2% e 100%. Tutti i pazienti con almeno una lesione significativa sono stati correttamente identificati anche nella valutazione con AC-TC. L’AC-TC ha generato 15 falsi postivi su base segmentale che però si riducono a un solo falso positivo nell’analisi per paziente.ConclusioniL’AC-TC a 64 strati rappresenta una metodica diagnostica ad elevata sensibilità e valore predittivo negativo nei pazienti con rischio basso o intermedio.

Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention?: A Pre-Specified Analysis From the ZEUS Trial.

OBJECTIVES This study sought to investigate the ischemic and bleeding outcomes of patients fulfilling high bleeding risk (HBR) criteria who were randomized to zotarolimus-eluting Endeavor Sprint stent (E-ZES) or bare-metal stent (BMS) implantation followed by an abbreviated dual antiplatelet therapy (DAPT) duration for stable or unstable coronary artery disease. BACKGROUND DES instead of BMS use remains controversial in HBR patients, in whom long-term DAPT poses safety concerns. METHODS The ZEUS (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates) is a multinational, randomized single-blinded trial that randomized among others, in a stratified manner, 828 patients fulfilling pre-defined clinical or biochemical HBR criteria-including advanced age, indication to oral anticoagulants or other pro-hemorrhagic medications, history of bleeding and known anemia-to receive E-ZES or BMS followed by a protocol-mandated 30-day DAPT regimen. The primary endpoint of the study was the 12-month major adverse cardiovascular event rate, consisting of death, myocardial infarction, or target vessel revascularization. RESULTS Compared with patients without, those with 1 or more HBR criteria had worse outcomes, owing to higher ischemic and bleeding risks. Among HBR patients, major adverse cardiovascular events occurred in 22.6% of the E-ZES and 29% of the BMS patients (hazard ratio: 0.75; 95% confidence interval: 0.57 to 0.98; p = 0.033), driven by lower myocardial infarction (3.5% vs. 10.4%; p < 0.001) and target vessel revascularization (5.9% vs. 11.4%; p = 0.005) rates in the E-ZES arm. The composite of definite or probable stent thrombosis was significantly reduced in E-ZES recipients, whereas bleeding events did not differ between stent groups. CONCLUSIONS Among HBR patients with stable or unstable coronary artery disease, E-ZES implantation provides superior efficacy and safety as compared with conventional BMS. (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS]; NCT01385319).

Computed Tomography Coronary Angiography in Patients With Acute Myocardial Infarction Without Significant Coronary Stenosis

Background— It is known that a significant number of patients experiencing an acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at coronary angiography (CA). Computed tomography coronary angiography (CTCA) can identify the presence of plaques, even in the absence of significant coronary stenosis. This study evaluated the role of 64-slice CTCA in detecting and characterizing coronary atherosclerosis in these patients. Methods and Results— Consecutive patients with documented acute myocardial infarction but without significant coronary stenosis at CA underwent late gadolinium-enhanced magnetic resonance and CTCA. Only the 50 patients with an area of myocardial infarction identified by late gadolinium-enhanced magnetic resonance were included in the study. All of the coronary segments were assessed for the presence of plaques. CTCA identified 101 plaques against the 41 identified by CA: 61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs. In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non-IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified (P=0.005). Mean plaque area was greater in the IRAs than in the non-IRAs (6.1±5.4 mm2 versus 4.2±2.1 mm2; P=0.03); there was no significant difference in mean percentage stenosis (33.5%±14.6 versus 31.7%±12.2; P=0.59), but the mean remodeling index was significantly different (1.25±0.41 versus 1.08±0.21; P=0.01). Conclusions— CTCA detects coronary plaques in nonstenotic coronary arteries that are underestimated by CA, and identifies a different distribution of plaque types in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary atherosclerosis in acute myocardial infarction patients without significant coronary stenosis.

64-slice computed tomography coronary angiography: diagnostic accuracy in the real world

PurposeThis study was done to evaluate the diagnostic accuracy of 64-slice computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis in the real clinical world.Materials and methodFrom the CTCA database of our institution, we enrolled 145 patients (92 men, 52 women, mean age 63.4 ± 10.2 years) with suspected coronary artery disease. All patients presented with atypical or typical chest pain and underwent CTCA and conventional coronary angiography (CA). For the CTCA scan (Sensation 64, Siemens, Germany), we administered an IV bolus of 100 ml of iodinated contrast material (Iomeprol 400 mgI/ml, Bracco, Italy). The CTCA and CA reports used to evaluate diagnostic accuracy adopted ≥50% and ≥70%, respectively, as thresholds for significant stenosis.ResultEleven patients were excluded from the analysis because of the nondiagnostic quality of CTCA. The prevalence of disease demonstrated at CA was 63% (84/134). Sensitivity, specificity and positive and negative predictive values for CTCA on a per-segment, per-vessel, and per-patient basis were 75.6%, 85.1%, 97.6%; 86.9%, 81.8%, 58.0%; 48.2%, 68.1%, 79.6%; and 95.7%, 92.3%, 93.5%, respectively. Only two out of 134 eligible patients were false negative. Heart rate did not significantly influence diagnostic accuracy, whereas the absence or minimal presence of coronary calcification improved diagnostic accuracy. The positive and negative likelihood ratios at the per-patient level were 2.32 and 0.041, respectively.ConclusionCTCA in the real clinical world shows a diagnostic performance lower than reported in previous validation studies. The excellent negative predictive value and negative likelihood ratio make CTCA a noninvasive gold standard for exclusion of significant coronary artery disease.RiassuntoObiettivoValutare l’accuratezza diagnostica dell’angiografia coronarica non invasiva con tomografia computerizzata (CT-CA) a 64 strati nell’individuazione delle stenosi coronariche significative (riduzione del lume coronarico ≥50%) basando la valutazione sulla refertazione clinica.Materiali e metodiDal database della CT-CA sono stati arruolati nello studio 145 pazienti (92 maschi, 52 femmine, età media 63,4±10,2 anni) con sospetta malattia coronarica. I pazienti si presentavano con dolore toracico atipico o angina pectoris stabile e hanno poi eseguito CT-CA e coronarografia convenzionale (CAG). Per la scansione CT-CA (Sensation 64, Siemens, Germania) sono stati iniettati endovena 100 ml di mezzo di contrasto. (Iomeprol 400 mgI/ml, Bracco, Italia). I referti della CT-CA e della CAG sono utilizzati per la valutazione dell’accuratezza diagnostica utilizzano la definizione di stenosi ≥50% per la CT-CA e ≥70% per la CAG.RisultatiUndici pazienti sono stati esclusi dall’analisi per CT-CA di qualità insufficiente. La prevalenza di malattia dimostrata alla CAG era del 63% (84/134). Sensibilità, specificità, valore predittivo positivo e negativo della CT-CA nella determinazione delle stenosi significative utilizzando un’analisi per segmento, per vaso e per paziente sono risultate del 75,6%, 85,1%, 97,6%; 86,9%, 81,8%, 58,0%; 48,2%, 68,1%, 79,6%; e 95,7%, 92,3%, 93,5%, rispettivamente. Solo due pazienti su 134 eleggibili per lo studio sono risultati falsi negativi. La frequenza cardiaca non ha mostrato influenzare significativamente l’accuratezza diagnostica, mentre la presenza di scarse o assenti calcificazioni coronariche ha determinato un incremento dei valori di accuratezza diagnostica. I likelihood ratio positivo e negativo nell’analisi per paziente sono risultati 2,32 e 0,041, rispettivamente.ConclusioniLa CT-CA nel mondo reale mostra una performance diagnostica inferiore rispetto agli studi di validazione pubblicati in letteratura. I valori ottimali di valore predittivo negativo e likelihood ratio negativo collocano la CT-CA tra le metodiche non invasive gold standard per l’esclusione di malattia coronarica critica.