Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial.

BACKGROUND: The optimal duration of dual-antiplatelet therapy and the risk-benefit ratio for long-term dual-antiplatelet therapy after coronary stenting remain poorly defined. We evaluated the impact of up to 6 versus 24 months of dual-antiplatelet therapy in a broad all-comers patient population receiving a balanced proportion of Food and Drug Administration-approved drug-eluting or bare-metal stents. METHODS AND RESULTS: We randomly assigned 2013 patients to receive bare-metal, zotarolimus-eluting, paclitaxel-eluting, or everolimus-eluting stent implantation. At 30 days, patients in each stent group were randomly allocated to receive up to 6 or 24 months of clopidogrel therapy in addition to aspirin. The primary end point was a composite of death of any cause, myocardial infarction, or cerebrovascular accident. The cumulative risk of the primary outcome at 2 years was 10.1% with 24-month dual-antiplatelet therapy compared with 10.0% with 6-month dual-antiplatelet therapy (hazard ratio, 0.98; 95% confidence interval, 0.74-1.29; P=0.91). The individual risks of death, myocardial infarction, cerebrovascular accident, or stent thrombosis did not differ between the study groups; however, there was a consistently greater risk of hemorrhage in the 24-month clopidogrel group according to all prespecified bleeding definitions, including the recently proposed Bleeding Academic Research Consortium classification. CONCLUSIONS: A regimen of 24 months of clopidogrel therapy in patients who had received a balanced mixture of drug-eluting or bare-metal stents was not significantly more effective than a 6-month clopidogrel regimen in reducing the composite of death due to any cause, myocardial infarction, or cerebrovascular accident. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00611286.

Different image integration modalities to guide AF ablation: impact on procedural and fluoroscopy times.

BACKGROUND: Different image integration modalities are available for atrial fibrillation (AF) ablation, but their impact on procedural and fluoroscopy times has not been evaluated yet. METHODS: Sixty patients (mean age 52.2 ± 12.0 years, 48.3% men, 75% paroxysmal AF) undergoing pulmonary vein (PV) encircling with PV disconnection for symptomatic drug-refractory AF were randomized to ablation with CARTO electroanatomical mapping (Biosense Webster, Diamond Bar, CA, USA) integrated with: (1) preprocedural magnetic resonance imaging (MRI; Group 1); (2) intracardiac echocardiography (ICE; Group 2); (3) preprocedural MRI and ICE (Group 3). RESULTS: PV disconnection was achieved in all patients. Total procedural time (Group 1: 124.7 ± 47.0; Group 2: 112.5 ± 30.4; Group 3: 108.6 ± 34.7 minutes) and total ablation time were similar between groups (P = ns). MRI integration alone required a higher fluoroscopy time (23.8 ± 6.9 in Group 1 vs 11.0 ± 2.3 and 13.9 ± 4.2 minutes in Groups 2 and 3, respectively; P < 0.005) and a longer time spent in the left atrium (109.0 ± 43.5 in Group 1 vs 78.2 ± 29.7 and 74.8 ± 34.3 minutes in Groups 2 and 3, respectively; P = 0.03) in comparison to ICE integration. Addition of MRI to ICE integration showed a tendency for a higher fluoroscopy time in comparison to ICE integration alone (P = 0.06). At a mean follow-up of 9.1 ± 2.2 months, there were no significant differences in AF recurrences among the groups (P = ns). CONCLUSION: ICE image integration significantly reduces the fluoroscopy time and the time spent in the left atrium in comparison to MRI integration alone. Addition of MRI to ICE integration does not reduce total procedural time and seems to lead to higher fluoroscopy time in comparison to ICE integration alone.

Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study.

BACKGROUND: Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown. METHODS AND RESULTS: We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups. CONCLUSIONS: In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention.

Randomized comparison of 6- versus 24-month clopidogrel therapy after balancing anti-intimal hyperplasia stent potency in all-comer patients undergoing percutaneous coronary intervention Design and rationale for the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia study (PRODIGY).

BACKGROUND: The optimal duration of clopidogrel therapy after coronary stenting is debated because of the scarcity of randomized controlled trials and inconsistencies arising from registry data. Although prolonged clopidogrel therapy after bare metal stenting is regarded as an effective secondary prevention measure, the safety profile of drug-eluting stents itself has been questioned in patients not receiving ≥ 12 months of dual-antiplatelet therapy. HYPOTHESIS: Twenty-four months of clopidogrel therapy after coronary stenting reduces the composite of death, myocardial infarction, or stroke compared with 6 months of treatment. STUDY DESIGN: PRODIGY is an unblinded, multicenter, 4-by-2 randomized trial. All-comer patients with indication to coronary stenting are randomly treated-balancing randomization-with bare metal stent (no active late loss inhibition), Endeavor Sprint zotarolimus-eluting stent (Medtronic, Santa Rosa, CA) (mild late loss inhibition), Taxus paclitaxel-eluting stent (Boston Scientific, Natick, MA) (moderate late loss inhibition), or Xience V everolimus-eluting stent (Abbott Vascular, Santa Clara, CA) (high late loss inhibition). At 30 days, patients in each stent group are randomly allocated to receive 24 or up to 6 months of clopidogrel therapy-primary end point randomization. With 1,700 individuals, this study will have >80% power to detect a 40% difference in the primary end point after sample size augmentation of 5% and a background event rate of 8%. SUMMARY: The PRODIGY trial aims to assess whether 24 months of clopidogrel therapy improves cardiovascular outcomes after coronary intervention in a broad all-comer patient population receiving a balanced mixture of stents with various anti-intimal hyperplasia potency.

Short and long-term benefits of sirolimus-eluting stent in ST-segment elevation myocardial infarction: a meta-analysis of randomized trials.

BACKGROUND: Recent concerns have emerged on the potential higher risk of stent thrombosis after DES implantation, that might be even more pronounced among STEMI patients. The aim of the current study was to perform a meta-analysis to evaluate the benefits and safety of Sirolimus-Eluting Stent (SES) as compared to BMS in patients undergoing primary angioplasty for STEMI. METHODS: The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following keywords were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. RESULTS: A total of 9 trials were included in the meta-analysis, involving 2,769 patients (1389 or 50.2% randomized to DES and 1,380 or 49.8% randomized to BMS). At 12 months follow-up, SES was associated with a significant reduction in TVR (4.9% vs. 13.6%, p < 0.0001), with a trend in benefits in mortality (2.9% vs. 4.2%, p = 0.08) and reinfarction (3.0% vs. 4.3%, p = 0.06), without any significant difference in stent thrombosis (1.9% vs. 2.5%, p = 0.36). Safety and efficacy of DES were confirmed at 2-3 years follow-up (data available from 4 trials including 569 patients). CONCLUSIONS: This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, SES as compared to BMS is safe and associated with a significant reduction in TVR at 1 and 2-3 years follow-up.

Clinical impact of an inter-hospital transfer strategy in patients with ST-elevation myocardial infarction undergoing primary angioplasty: the Emilia-Romagna ST-segment elevation acute myocardial infarction network.

AIMS: This study sought to evaluate the impact of an inter-hospital transfer strategy on treatment times and in-hospital and 1 year cardiac mortality of patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous intervention (p-PCI) in the Italian region of Emilia-Romagna, where an efficient region-wide system for reperfusion has been established. METHODS AND RESULTS: 3296 patients with STEMI, undergoing on-site p-PCI (2444 patients) (OS group) or p-PCI after inter-hospital transfer (852 patients) (T group) between 1 January 2004 and 30 June 2006 in the Italian region of Emilia-Romagna, were considered. During the study period, the number of patients undergoing p-PCI increased both for patients admitted to interventional centres and for those admitted to peripheral hospitals. At the same time, the proportion of patients with STEMI initially admitted to peripheral hospitals and not transferred and the door-to-balloon time delays of transfer patients decreased. In spite of longer door-to-balloon delay in the transfer group [112 min (86-147) vs. 71 min (46-104)], in-hospital cardiac mortality (OS 7.0 vs. T 5.4%, P = 0.10) did not significantly differ between the two groups. After multivariable adjustment, the transfer strategy was not associated with increased risk of in-hospital [odds ratio 0.956; 95% confidence interval (CI) 0.633-1.442] and 1 year (hazard ratio 0.817; 95% CI 0.617-1.085) cardiac mortality. CONCLUSION: This study, concerning an established STEMI regional network, suggests that a strategy of inter-hospital transfer for p-PCI, when supported by an organized system of care, may be applied with rapid reperfusion times and favourable short- and long-term clinical outcomes.

Long-term safety and efficacy of drug-eluting stents: two-year results of the REAL (REgistro AngiopLastiche dell'Emilia Romagna) multicenter registry.

BACKGROUND: The long-term safety and efficacy of drug-eluting stents (DES) have been questioned recently. METHODS AND RESULTS: Between July 2002 and June 2005, 10,629 patients undergoing elective percutaneous coronary intervention with either DES (n=3064) or bare-metal stents (BMS, n=7565) were enrolled in a prospective registry comprising 13 hospitals. We assessed the cumulative incidence of major adverse cardiac events (death, acute myocardial infarction, and target-vessel revascularization) and angiographic stent thrombosis during 2-year follow-up. A propensity score analysis to adjust for different baseline clinical, angiographic, and procedural characteristics was performed. The 2-year unadjusted cumulative incidence of major adverse cardiac events was 17.8% in the DES group and 21.0% in the BMS group (P=0.003 by log-rank test). Angiographic stent thrombosis was 1.0% in the DES group and 0.6% in the BMS group (P=0.09). After adjustment, the 2-year cumulative incidence of death was 6.8% in the DES group and 7.4% in the BMS group (P=0.35), whereas the rates were 5.3% in DES and 5.8% in BMS for acute myocardial infarction (P=0.46), 9.1% in DES and 12.9% in BMS for target-vessel revascularization (P<0.00001), and 16.9% in DES and 21.8% in BMS for major adverse cardiac events (P<0.0001). Independent predictors of target-vessel revascularization in the DES group were diabetes mellitus (hazard ratio 1.36, 95% confidence interval 1.06 to 1.76), renal failure (hazard ratio 1.69, 95% confidence interval 1.06 to 2.69), and reference vessel diameter (hazard ratio 0.64, 95% confidence interval 0.45 to 0.93). CONCLUSIONS: In this large real-world population, the beneficial effect of DES in reducing the need for new revascularization compared with BMS extends to 2 years without evidence of a worse safety profile.

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.

Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial.

CONTEXT: Abciximab infusion and uncoated-stent implantation is a complementary treatment strategy to reduce major adverse cardiac events in patients undergoing angioplasty for ST-segment elevation myocardial infarction (STEMI). It is uncertain whether there may be similar benefits in replacing abciximab with high-dose bolus tirofiban. Similarly, the use of drug-eluting stents in this patient population is currently discouraged because of conflicting results on efficacy reported in randomized trials and safety concerns reported by registries. OBJECTIVE: To evaluate the effect of high-dose bolus tirofiban and of sirolimus-eluting stents as compared with abciximab infusion and uncoated-stent implantation in patients with STEMI undergoing percutaneous coronary intervention. DESIGN, SETTING, AND PATIENTS: An open-label, 2 x 2 factorial trial of 745 patients presenting with STEMI or new left bundle-branch block at 16 referral centers in Italy, Spain, and Argentina between October 2004 and April 2007. INTERVENTIONS: High-dose bolus tirofiban vs abciximab infusion and sirolimus-eluting stent vs uncoated stent implantation. MAIN OUTCOME MEASURES: For drug comparison, at least 50% ST-segment elevation resolution at 90 minutes postintervention with a prespecified noninferiority margin of 9% difference (relative risk, 0.89); for stent comparison, the rate of major adverse cardiac events, defined as the composite of death from any cause, reinfarction, and clinically driven target-vessel revascularization within 8 months. RESULTS: ST-segment resolution occurred in 302 of 361 patients (83.6%) who had received abciximab infusion and 308 of 361 (85.3%) who had received tirofiban infusion (relative risk, 1.020; 97.5% confidence interval, 0.958-1.086; P < .001 for noninferiority). Ischemic and hemorrhagic outcomes were similar in the tirofiban and abciximab groups. At 8 months, major adverse cardiac events occurred in 54 patients (14.5%) with uncoated stents and 29 (7.8%) with sirolimus stents (P = .004), predominantly reflecting a reduction of revascularization rates (10.2% vs 3.2%). The incidence of stent thrombosis was similar in the 2 stent groups. CONCLUSIONS: In patients with STEMI undergoing percutaneous coronary intervention, compared with abciximab, tirofiban therapy was associated with noninferior resolution of ST-segment elevation at 90 minutes following coronary intervention, whereas sirolimus-eluting stent implantation was associated with a significantly lower risk of major adverse cardiac events than uncoated stents within 8 months after intervention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00229515.

Two-by-two factorial comparison of high-bolus-dose tirofiban followed by standard infusion versus abciximab and sirolimus-eluting versus bare-metal stent implantation in patients with acute myocardial infarction: design and rationale for the MULTI-STRATEGY trial.

BACKGROUND: Current treatment standards for patients undergoing primary percutaneous coronary intervention support early infusion of abciximab, followed by bare-metal stent (BMS) implantation. Whether the use of sirolimus-eluting stent (SES) would result in a further improvement of clinical outcomes remains to be proven. Similarly, whether tirofiban administered at high-bolus dose (HBD) followed by standard infusion is a valuable alternative to abciximab in the setting of ST-segment elevation myocardial infarction remains uncertain. STUDY DESIGN: Multicentre evaluation of single high-bolus dose tirofiban versus abciximab and sirolimus-eluting versus bare metal stent in acute myocardial infarction (MULTI-STRATEGY) is a phase III, open-label, multinational investigator-driven clinical trial evaluating, with a 2-by-2 factorial design, the safety/efficacy profile of 4 interventional strategies of reperfusion: tirofiban given at HBD (bolus of 25 microg/kg over 3 minutes), followed by an infusion of 0.15 microg/kg per minute for 18 to 24 hours versus abciximab and SES, as compared to BMS implantation in primary percutaneous coronary intervention. The coprimary objectives are (i) the evaluation of the effect of SES versus BMS on the incidence of major adverse cardiac events within 8 months of the index procedure and (ii) the degree of ST-segment resolution obtained after the mechanical intervention for the comparison of HBD tirofiban versus abciximab. The protocol mandates clinical follow-up for 5 years. CONCLUSIONS: MULTI-STRATEGY will evaluate the role of SES and HBD tirofiban versus BMS and abciximab in the acute management of patients presenting with ST-segment elevation myocardial infarction.

Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events.

OBJECTIVE: We investigated in patients with ongoing myocardial infarction (MI) whether coagulation factor VII (FVII) and tissue factor (TF) levels are affected at admission by genetic components and whether they may predict subsequent cardiovascular events. METHODS AND RESULTS: 256 patients admitted for MI were evaluated for FVII and TF antigen levels before any treatment at entry, and were genotyped for FVII and TF polymorphisms. FVII gene insertions at -323, 11293 and the -402G/A change predicted FVII levels and explained 14% of variance. The -603 TF gene polymorphism failed to affect significantly TF levels (P=0.07). These variables were correlated with the incidence of death (36 patients) and reinfarction (9 patients) after a median follow-up of 397 days. Events were independently predicted by FVII (HR 2.1, 95% CI 1.2 to 5.7) and TF (HR 4.1, 95% CI 2 to 11) levels. Composite end point was significantly worse when both parameters were above the receiver-operating characteristics (ROC) values (HR 8.3, 95% CI 5 to 18, compared with FVII and TF below), and above the ROC value of TF (>630 pg/mL) it differed among FVII genotype groups. CONCLUSIONS: Admission FVII and TF antigen levels, partially predicted by polymorphisms, are independent predictors of mortality and reinfarction in patients with acute MI.

Stent and Dual Antiplatelet Therapy Duration Comparisons in the Setting of a Multicenter Randomized Controlled Trial: Can the Operator Experience Affect the Study Results?

BACKGROUND: Operator experience influences outcomes after percutaneous coronary intervention, but this association in the controlled setting of a randomized, clinical trial is unclear. METHODS AND RESULTS: We investigated operator-related outcomes (30-day and 2-year efficacy and safety end points) among patients undergoing percutaneous coronary intervention and randomized to different dual antiplatelet therapy durations and stent types. A total of 2003 patients were analyzed, and 7 operator groups were compared. The majority of preprocedural and postprocedural characteristics were imbalanced. The primary end point of the study, the composite of death, myocardial infarction, or cerebrovascular accidents, did not differ among operators at 30 days or 2 years. There were no significant differences also for all other individual and composite end points analyzed at 30 days and 2 years, except for 2-year stent thrombosis (P=0.048) and bleeding events (P=0.022 for Bleeding Academic Research Consortium type 2, 3, or 5). Adjusted comparisons for the main end points showed slight differences among operators at 30 days, but not at 2 years. There was no interaction of operator with dual antiplatelet therapy duration (P=0.112) or stent type (P=0.300). Results remained entirely consistent when operators were stratified by their experience. CONCLUSIONS: There was a weak signal of heterogeneity across study operators for the 30-day, but not the 2-year, main study outcomes. No clear effect of operator or operator experience was observed for the comparative efficacy and safety profile of the randomized stent types or dual antiplatelet therapy duration regimens. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00611286.

Tumor necrosis factor-alpha receptor 1 is a major predictor of mortality and new-onset heart failure in patients with acute myocardial infarction: the Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) study.

BACKGROUND: Tumor necrosis factor alpha-alpha (TNF-alpha) activation is an independent prognostic indicator of mortality in patients with heart failure (HF). Despite the recognition that several TNF family cytokines are elevated during myocardial infarction, their role in predicting subsequent prognosis in these setting remains poorly understood. METHODS AND RESULTS: We performed a systematic evaluation of TNF-alpha and its type 1 and 2 soluble receptors, together with interleukin (IL)-6, IL-1 receptor antagonist, and IL-10, in 184 patients (132 men; mean age, 64+/-12) consecutively admitted for myocardial infarction. We correlated their values to short- and long-term incidence of death and HF (primary outcome). In 10 patients, we also studied the presence of transcardiac gradients for TNF-alpha and its soluble receptors. The control group comprised 45 healthy subjects who were sex and age matched (33 men; mean age, 65+/-6 years) to the patients. All tested cytokines were increased in patients, and no transcardiac or systemic AV difference was found. After a median follow-up of 406 days (range, 346 to 696 days), 24 patients died and 32 developed HF. Univariate analysis showed that all cytokines were related to outcome, whereas after adjustment for baseline and clinical characteristics, sTNFR-1 remained the only independent predictor of death and HF (hazard ratio, 2.9; 95% CI, 1.9 to 3.8, tertile 1 versus 3), together with left ventricular ejection fraction, Killip class, and creatine kinase-MB at peak. CONCLUSIONS: sTNFR-1 is a major short- and long-term predictor of mortality and HF in patients with acute myocardial infarction.

The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial.

OBJECTIVES: We sought to determine the safety and efficacy of high-dose bolus (HDB) tirofiban in high-risk patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: The use of HDB tirofiban in the catheterization laboratory is controversial. In particular, in patients with acute coronary syndromes undergoing PCI, there is no evidence that tirofiban administered in the catheterization laboratory is superior to heparin alone. This finding probably reflects the suboptimal platelet inhibition when tirofiban is employed at RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) regimen. METHODS: A total of 202 patients (mean age 69 +/- 8 years; 137 males [68%]) undergoing high-risk PCI, pretreated with thienopyridines, were consecutively randomized to HDB tirofiban (25 microg/kg/3 min, and infusion of 0.15 microg/kg/min for 24 to 48 h) or placebo immediately before the procedure and then followed for a median time of 185 days (range 45 to 324 days) for the occurrence of the primary composite end point of death, myocardial infarction, target vessel revascularization (TVR), and bailout use of glycoprotein (GP) IIb/IIIa inhibitors. RESULTS: The cumulative incidence of the primary end point was 35% and 20% in placebo and HDB tirofiban groups, respectively (hazard ratio 0.51, 95% confidence interval 0.29 to 0.88; p = 0.01). This difference was mainly due to the reduction of myocardial infarction and bailout use of GP IIb/IIIa inhibitors, with no significant effect on TVR or death. The safety profile did not differ between tirofiban and placebo. CONCLUSIONS: The use of tirofiban, when administered at HDB, is safe and significantly reduces the incidence of ischemic/thrombotic complications during high-risk PCI.

Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial.

CONTEXT: Bare-metal stenting with abciximab pretreatment is currently considered a reasonable reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus-eluting stents significantly reduce the need for target-vessel revascularization (TVR) vs bare-metal stents but substantially increase procedural costs. At current European list prices, the use of tirofiban instead of abciximab would absorb the difference in cost between stenting with sirolimus-eluting vs bare-metal stents. OBJECTIVE: To evaluate the clinical and angiographic impact of single high-dose bolus tirofiban plus sirolimus-eluting stenting vs abciximab plus bare-metal stenting in patients with STEMI. DESIGN, SETTING, AND PATIENTS: Prospective, single-blind, randomized controlled study (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction [STRATEGY]) of 175 patients (median age, 63 [interquartile range, 55-72] years) presenting to a single referral center in Italy with STEMI or presumed new left bundle-branch block and randomized between March 6, 2003, and April 23, 2004. INTERVENTION: Single high-dose bolus tirofiban regimen plus sirolimus-eluting stenting (n = 87) vs standard-dose abciximab plus bare-metal stenting (n = 88). MAIN OUTCOME MEASURES: The primary end point was a composite of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months. Secondary outcomes included freedom, at day 30 and month 8, from major cardiac or cerebrovascular adverse events (composite of death, reinfarction, stroke, and repeat TVR). RESULTS: Cumulatively, 14 of 74 patients (19%; 95% confidence interval [CI], 10%-28%) in the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50%; 95% CI, 44%-56%) in the abciximab plus bare-metal stent group reached the primary end point (hazard ratio, 0.33; 95% CI, 0.18-0.60; P<.001 [P<.001 by Fischer exact test]). The cumulative incidence of death, reinfarction, stroke, or TVR was significantly lower in the tirofiban plus sirolimus-eluting stent group (18%) vs the abciximab plus bare-metal stent group (32%) (hazard ratio, 0.53; 95% CI, 0.28-0.92; P = .04), predominantly reflecting a reduction in the need for TVR. Binary restenosis was present in 6 of 67 (9%; 95% CI, 2%-16%) and 24 of 66 (36%; 95% CI, 26%-46%) patients in the tirofiban plus sirolimus-eluting stent and abciximab plus bare-metal stent groups, respectively (P = .002). CONCLUSION: Tirofiban-supported sirolimus-eluting stenting of infarcted arteries holds promise for improving outcomes while limiting health care expenditure in patients with myocardial infarction undergoing primary intervention.

Long-term clinical outcomes after drug eluting stent implantation in women with de novo coronary lesions. Results from the REAL (REgistro Regionale AngiopLastiche Emilia-Romagna) multicenter registry.

BACKGROUND: The long-term effectiveness of drug eluting stents (DESs) in a real-world setting of female patients is currently unclear. METHODS AND RESULTS: We analyzed long-term follow-up (up to 3 years) data from all female patients with de novo lesions enrolled in a prospective web-based multicenter registry (REAL Registry; study period, July 2002-June 2006) including all 15 hospitals performing PCI in the Emilia-Romagna region of Italy. Among the 3549 women without ST elevation myocardial infarction, 2434 were treated with BMSs alone and 1115 with DESs alone. At 3 years, use of DESs was associated with a lower propensity score adjusted incidence of MACE [cardiac mortality, non-fatal myocardial infarction and target vessel revascularization (TVR); 19.5% vs. 24.4%; HR 0.75, p=0.006)] and TVR (11.6% vs. 15.6%; HR 0.68, p=0.004) compared with BMSs. No difference was apparent in terms of adjusted 3-year cardiac mortality or myocardial infarction. Nevertheless, after the first 6 months of follow-up, a non significantly increased risk of myocardial infarction and stent thrombosis was found in the DES group. CONCLUSIONS: In this real-world female registry, the use of DESs was associated with a 3-year reduction of TVR and MACE in comparison with the use of BMSs. However, the observed (non-significant) increment of late AMI makes performing larger studies to clarify the long-term safety of DESs mandatory.

Long-term outcome after drug eluting stenting in patients with ST-segment elevation myocardial infarction: data from the REAL registry.

BACKGROUND: The long-term safety and efficacy of drug eluting stents (DES) implanted during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is unclear. The purpose of this study was to compare the long-term outcome of STEMI patients undergoing primary PCI with DES vs. bare metal stent (BMS) implantation. METHODS: In the present analysis 4764 patients were enrolled (706, 15%, received DES). We assessed the cumulative incidence of major adverse cardiac events (MACE) and stent thrombosis (ST). RESULTS: Overall, no significant difference emerged for the rates of death and reinfarction. DES implantation was associated to a reduction of target vessel revascularization (TVR) (HR 0.65, 95%CI 0.47-0.91; p=0.01), leading to a MACE reduction (HR 0.7, 95%CI 0.56-0.86; p<0.01). In particular, during the first 2 years we observed less adverse events in the DES group, mainly because of a lower TVR rate (TVR: HR 0.56, 95%CI 0.37-0.83, p<0.01; MACE: HR 0.71, 95%CI 0.54-0.94, p=0.01). On the contrary, during the third year, adverse events tended to be higher in the DES group. ST did not differ between DES and BMS groups (p=0.6). No differences were observed between sirolimus eluting stents and paclitaxel eluting stents. CONCLUSIONS: DES implantation during primary PCI is safe and associated with a significant TVR and MACE reduction in the first two years, whereas a trend to have more adverse events in the third year is observed. More data about long-term follow-up are needed to better evaluate both safety and efficacy of DES in the setting of STEMI.

Efficacy and safety of drug-eluting stents in ST-segment elevation myocardial infarction: a meta-analysis of randomized trials.

BACKGROUND: Recent concerns have emerged on the potential higher risk of stent thrombosis after DES implantation, that might be even more pronounced among STEMI patients. Thus, the aim of the current study was to perform a meta-analysis to evaluate the benefits and safety of DES as compared to BMS in patients undergoing primary angioplasty for STEMI. METHODS: The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. RESULTS: A total of 11 trials were included in the meta-analysis, involving 3605 patients (1888 or 52.3% randomized to DES and 1719 or 47.7% randomized to BMS). At 12 months follow-up, no significant difference was observed in mortality (4.1% vs 4.4%, OR [95% CI]=0.91 [0.66-1.27], p=0.59, reinfarction (3.1% vs 3.4%, OR [95% CI]=0.85 [0.58, 1.23], p=0.38 or stent thrombosis (1.6% vs 2.2%, OR [95% CI]=0.76 [0.47, 1.23], p=0.22), whereas DES were associated with a significant reduction in TVR (5.0% vs 12.6%, OR [95% CI]=0.36 [0.28, 0.47], p<0.0001). Safety and efficacy of DES were confirmed at 18 to 24 months follow-up (data available from 4 trials including 1178 patients). CONCLUSIONS: This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, SES and PES, as compared to BMS, are safe and associated with a significant reduction in TVR at 1 and 2 years follow-up.

Abciximab: a reappraisal of its use in coronary care.

Platelet reactivity plays a pivotal role in the pathogenesis of ischemic adverse events during and after acute coronary syndromes (ACS), and percutaneous coronary intervention (PCI). Glycoprotein (GP) IIb/IIIa inhibitors are the strongest antiplatelet agents currently available on the market and three different compounds, namely abciximab, tirofiban, and eptifibatide, have been approved for clinical use. Abciximab has been investigated in the clinical field far more extensively than the other GPIIb/IIIa inhibitors. Abciximab is an anti-integrin Fab fragment of a human - mouse chimeric monoclonal antibody with high affinity and a slow dissociation rate from the GP IIb/IIIa platelet receptor. Abciximab, given shortly before the coronary intervention, is superior to placebo in reducing the acute risk of ischemic complications (EPIC, EPISTENT, EPILOG trials); moreover, in the ISAR-REACT 2 study abciximab has been shown to reduce the risk of adverse events in patients with non ST-segment elevation ACS who are undergoing PCI even after optimal pre-treatment with 600 mg of clopidogrel. Finally, abciximab has been also used in abciximab-coated stent, with only bolus administration regimen and for direct intracoronary use with promising results that may extend and/or modify its current use in clinical practice in future.