[Show abstract][Hide abstract] ABSTRACT: Background. It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management.
Methods. We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated,
blocked, and stratifi ed by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defi ned as death, myocardial infarction, or stroke, and net adverse clinical events, defi ned as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627.
Findings. We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74–0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73–0·96; p=0·0092). The diff erence was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49–0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53–0·99; p=0·045).
Interpretation. In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality.
The Lancet 06/2015; 385(9986):2465-76. DOI:10.1016/S0140-6736(15)60292-6 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of drug-eluting stent (DES) instead of bare-metal stent (BMS) in patients at high stent thrombosis or bleeding risk as well as in those at low restenosis risk (ie, uncertain DES candidates) remains a matter of debate. Zotarolimus-Eluting Endeavor Sprint stent (E-ZES) (Santa Rosa, CA) is a hydrophilic polymer-based second-generation device with unique drug fast-release profile, which may allow for a shorter dual antiplatelet therapy (DAPT) duration without safety concerns.
The primary objective is to assess whether E-ZES implantation followed by a shorter than currently recommended course of DAPT will decrease the incidence of 12-month major adverse cardiovascular events as compared with BMS in undefined DES recipients. Actual duration of DAPT regimen will be dictated by patients' characteristics and not by stent type and, as such, can be as short as 30 days after intervention in both stent groups.
The ZEUS study is an open-label randomized clinical trial conducted at 20 clinical sites in Italy, Switzerland, Portugal, and Hungary. With 1,600 individuals, this study will have 85% power to detect a 33% difference in the primary end point consisting of the composite of death, nonfatal myocardial infarction, or target vessel revascularization.
The ZEUS trial aims to assess whether the use of E-ZES, followed by a DAPT duration regimen based on patients' characteristics and not by stent type, is superior to conventional BMS implantation in undefined DES recipients who qualify for the presence of high thrombosis, bleeding, or low restenosis risk criteria.
American heart journal 11/2013; 166(5):831-8. DOI:10.1016/j.ahj.2013.07.033 · 4.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While bleeding in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI) is known to be associated with poor outcomes, the differential prognostic impact of access-site related versus non access-site related bleedings is unknown. We aimed to assess the relative impact of access-site related bleeding, as compared to non access-site related, on 12-month clinical outcome in patients undergoing intervention for STEMI.
Thirty-day bleeding endpoints, stratified into access-site versus non access-site, were examined according to the TIMI scale in 744 patients with STEMI enrolled in the MULTISTRATEGY trial. TIMI major or minor bleeding complications occurred in 56 (7.5%) patients within 30 days, 46% had an access-site related bleed and 34% required blood transfusion. Bleeding severity and the need for transfusion were equally distributed between site access- versus non-site access-related bleeds. After adjustment, patients with any TIMI rated bleed were more likely to die or develop recurrent MI within 12 months (HR 2.1 [95% CI: 1.13-3.8]; p=0.02). This ratio was entirely driven by non-site access-related bleeds (adjusted HR: 2.66 [95% CI: 1.21-5.8]; p=0.007), whereas site-access bleeds were not associated with worse outcomes (HR: 0.74 [95% CI: 0.16-3.4]; p=0.70).
While bleeds of any TIMI severity within 30 days were independently associated with worse cardiovascular outcomes at 12 months, thus confirming previous analyses, this relationship was entirely driven in our study by non access-site related haemorrhagic events. Investigation on whether the site of bleeding complications may preferentially impact cardiovascular outcomes is warranted.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 02/2012; 8(1):71-8. DOI:10.4244/EIJV8I1A12 · 3.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the relation between female sex and sirolimus-eluting stent (SES) use on long-term outcomes in acute myocardial infarction.
There are no data on sex-specific differences in long-term benefit of SES use compared with bare-metal stent (BMS) use among patients undergoing primary percutaneous coronary interventions.
We performed a post hoc analysis of the MULTISTRATEGY trial. Hazard ratios (HRs) of events with 95% CI for sex and stent type were computed using Cox proportional regression with adjustment for confounders.
A total of 744 patients, 64 years old (55-73 years old), 179 (24.1%) women, were enrolled. After a follow-up of 1,080 days, SES use was associated with a significant reduction of major adverse cardiovascular events, that is, the composite of all-cause death, reinfarction, or clinically driven target vessel revascularization (TVR) (13.9% vs 23.6%, adjusted HR 0.62, 95% CI 0.41-0.94, P = .026) and of TVR (6.1% vs 15.1%, adjusted HR 0.35, 95% CI 0.19-0.63, P < .001) in men. Conversely, SES use was not associated to a better outcome among women (major adverse cardiovascular events 21.9% in SES vs 18.2% in the BMS group, adjusted HR 1.27, 95% CI 0.53-3.02, P = .59; TVR 6.6% vs 9.1%, adjusted HR 0.62, 95% CI 0.17-2.21, P = .46).
In this analysis, the clinical benefit of SES use, over BMS, at 3-year follow-up was restricted to men and was not observed among women.
American heart journal 01/2012; 163(1):104-11. DOI:10.1016/j.ahj.2011.09.026 · 4.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The Multicentre Evaluation of Single high-dose Bolus TiRofiban versus Abciximab with Sirolimus-eluting Stent or Bare Metal Stent in Acute Myocardial Infarction Study [MULTISTRATEGY]) randomised 745 patients with ST-elevation myocardial infarction to receive high-dose bolus (HDB) tirofiban or abciximab infusion and sirolimus-eluting (SES) or uncoated-stent (BMS) implantation. Tirofiban was non-inferior to abciximab in terms of ST-segment resolution after intervention, whereas 8 month-major adverse cardiac events occurred in 14.5% in the BMS and 7.8% in the SES groups (P=0.0039), reflecting a reduction of reintervention rates (10.2% vs. 3.2%). A three-year follow-up was performed to extend previous short- to mid-term findings. METHODS AND RESULTS: Complete data at 3years was available for 736 patients (99%). All-cause mortality was 6.7% in the tirofiban and 7.8% in the abciximab (P=0.56) and 7.5% in the BMS vs 7.0 in the SES groups, P=0.79. The composite of all-cause death or MI was identical at 12.9% in tirofiban and abciximab groups, P=0.99 and it occurred in 13.2% in the BMS vs. 12.6% in the SES groups (P=0.83). The need for reintervention remained more than twice as common with BMS (13.7%; versus 6.2%, P=0.0006). The cumulative rate of stent thrombosis (ST) did not differ. This is inspite of a higher very late definite, probable or possible ST thrombosis rate in the SES group. CONCLUSIONS: The 3-year follow-up of MULTISTRATEGY demonstrated comparable outcomes with HDB Tirofiban or abciximab and a sustained efficacy of SES to reduce reintervention with no difference in death, repeat MI or ST.
International journal of cardiology 08/2011; 165(1). DOI:10.1016/j.ijcard.2011.07.106 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study sought to evaluate the impact of SYNTAX score (SXscore), and compare its performance in isolation and combination with the PAMI (The Primary Angioplasty in Myocardial Infarction Study) score, for the prediction of 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention.
Patients with STEMI were excluded from the original SYNTAX score (SXscore) algorithm. Therefore, the utility of using the SXscore in this patient group remains undefined.
SXscore was calculated retrospectively in 807 patients with STEMI enrolled in the randomized STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) clinical trials. Clinical outcomes of all-cause death, reinfarction, and clinically driven target vessel revascularization were subsequently stratified according to SXscore tertiles: SX(LOW) ≤ 9 (n = 311), 9 < SX(MID) ≤ 16 (n = 234), SX(HIGH) >16 (n = 262).
At 1-year follow-up, all clinical outcomes including mortality, mortality/reinfarction, major adverse cardiac events (MACE) (a composite of all-cause death, reinfarction and target vessel revascularization), and definite, definite/probable, and any stent thrombosis were all significantly higher in patients in the highest SXscore tertile. SXscore was identified as an independent predictor of mortality, MACE, and stent thrombosis out to 1-year follow-up. The combination SYNTAX-PAMI score led to a net reclassification improvement of 15.7% and 4.6% for mortality and MACE, respectively. The C-statistics for the SXscore, PAMI score, and the combined SYNTAX-PAMI score were 0.65, 0.81, and 0.73 for 1-year mortality, and 0.68, 0.64, and 0.69 for 1-year MACE, respectively.
SXscore does have a role in the risk stratification of patients with STEMI having primary percutaneous coronary intervention; however, this ability can be improved through a combination with clinical variables. (Multicentre 2×2 Factorial Randomised Study Comparing Tirofiban Versus Abciximab and SES Versus BMS in AMI; NCT00229515).
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate the long-term outcome after elective percutaneous coronary intervention in low-risk patients screened for aspirin and/or clopidogrel responsiveness in the 3T/2R (Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel) trial.
The impact of aspirin and/or clopidogrel poor response on long-term outcome is debated.
Aspirin and clopidogrel response was measured with the VerifyNow system aspirin and P2Y12 assays. After percutaneous coronary intervention (PCI), death, stroke, and myocardial infarction were assessed up to 1 year.
Overall, 1,277 patients were screened, and 826 (65%) were treated with PCI. In all, 124 patients were found to be aspirin poor responders, and there were 179 clopidogrel poor responders (totally, 278 poor responders). The 1-year end point was significantly higher in poor responders as compared to full responders (15.8% vs. 8.6%, p=0.002), which is principally due to more myocardial infarction occurrence. At multivariable analysis, clopidogrel poor response emerged as an independent predictor (hazard ratio: 1.15, 95% confidence interval: 1.03 to 1.28). Receiver-operator characteristic analysis identifies≤23 of percentage of platelet inhibition and ≥208 of P2Y12 reactivity units as optimal cut offs to predict 1-year end point. Excluding periprocedural events, also peri-PCI myocardial infarction, which is strongly related to aspirin/clopidogrel poor response, was an independent predictor (hazard ratio: 1.25, 95% confidence interval: 1.14 to 1.37). Glycoprotein IIb/IIIa inhibitor administration reduces this risk in poor responders (21.2% vs. 34.7%, p=0.02), but not in full responders (6.3% vs. 6.5%, p=0.8).
Poor response to clopidogrel is an independent predictor of periprocedural myocardial infarction and worse 1-year outcome in low-risk patients undergoing PCI, whereas poor response to aspirin failed to predict a worse outcome. Contrary to what was observed in poor responders, glycoprotein IIb/IIa inhibitor therapy failed to provide a benefit in aspirin and/or clopidogrel full responders.
Journal of the American College of Cardiology 10/2010; 56(18):1447-55. DOI:10.1016/j.jacc.2010.03.103 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Myocardial revascularization with drug-eluting stents (DESs) is emerging as an alternative to conventional coronary artery bypass surgery in patients with multivessel coronary artery disease (MV-CAD). First-generation DESs have yielded equivalent safety results at mid-term compared with surgery, but inferior efficacy in preventing the recurrence of ischemic symptoms. The outcome of percutaneous coronary intervention with a second-generation everolimus DES as compared with a paclitaxel DES in patients with MV-CAD has not been established.
The aim of the study is the assessment of the efficacy and performance of the XIENCE V everolimus-eluting stent in the treatment of de-novo coronary artery lesions in patients with MV-CAD.
The study is composed of two parts: a prospective, double arm, randomized multicenter trial to assess the angiographic efficacy of the XIENCE V everolimus-eluting coronary stent system (EECSS) compared with the Taxus Liberté Paclitaxel Eluting Coronary Stent System (Taxus Liberté Stent) and a prospective, open-label, single arm, controlled registry to analyze the clinical efficacy and safety of XIENCE V EECSS at mid-term and long-term follow-up in patients treated for MV-CAD.
For the EXECUTIVE randomized trial, the primary endpoint is in-stent late lumen loss at 9 months. For the EXECUTIVE registry, the primary endpoint is a composite of all death, myocardial infarction (Q-wave and non-Q-wave), and ischemia-driven target vessel revascularization at 12 months. The study will be conducted at 30 study centers in Italy and 600 patients will be enrolled in total: 200 patients will be enrolled (1: 1) in the randomized trial and 400 patients will enter the registry.
It was calculated that, assuming a mean in-stent late lumen loss of 0.20 +/- 0.41 mm in the XIENCE V EECSS arm and 0.30 +/- 0.53 mm in the Taxus Liberté stent arm, and a noninferiority margin delta of 0.12 (according to the SPIRIT III results), the analysis of 81 lesions per arm would provide over 90% power. Therefore, 200 patients will be enrolled to account for dropouts.
The present study is expected to provide as yet unavailable information about the performance of second-generation stents in the specific setting of patients with MV-CAD.
Journal of Cardiovascular Medicine 04/2010; 11(4):299-309. DOI:10.2459/JCM.0b013e3283331e69 · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: A protective role of the presence of collateral arteries, generating smaller infarcts, improved ventricular function, fewer future cardiovascular events, and improved survival following a myocardial ischemia has been described in numerous reports. However little is known about atherosclerotic disease of the collateral vessels, and the possibility to treat critical stenosis of these vessels has never been described. Therefore this report describes a unique case of percutaneous coronary intervention on a well developed yet atherosclerotic coronary collateral vessel triggering an acute coronary syndrome with hemodynamic instability. In the present case balloon angioplasty and stenting of the collateral vessel was safe and effective. Nonetheless, further studies are warranted.
[Show abstract][Hide abstract] ABSTRACT: To assess whether glycoprotein IIb/IIIa inhibition using tirofiban in low risk patients undergoing percutaneous coronary intervention (PCI) may reduce the risk of periprocedural myocardial infarction compared to standard care in poor responders to aspirin and/or clopidogrel.
We will enroll patients at ten European sites or more to participate in the Tailoring Treatment with Tirofiban in patients showing Resistance to aspirin and/or Resistance to clopidogrel (3T/2R) study with a pre-specified sample size of 240 patients out of 1,100 or more who will undergo screening. The primary outcome measure is troponin I or T elevation ratio at least three times the upper limit of normal within 48 h after completion of the PCI.
The results of 3T/2R study will evaluate whether tailored intensification of anti-platelet treatment based on poor individual response to oral anti-platelet agents may modulate the risk of periprocedural myocardial infarction during PCI. Our findings attempt at unraveling a new era of individualized anti-platelet treatment through the use of point-of-care assessment.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
High-dose bolus tirofiban vs abciximab infusion and sirolimus-eluting stent vs uncoated stent implantation.
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.
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.
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.
clinicaltrials.gov Identifier: NCT00229515.
JAMA The Journal of the American Medical Association 05/2008; 299(15):1788-99. DOI:10.1001/jama.299.15.joc80026 · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
American heart journal 08/2007; 154(1):39-45. DOI:10.1016/j.ahj.2007.03.023 · 4.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Percutaneous treatment of acquired coronary fistula with covered stent
Acquired aorto-coronary fistulae (ACF) is a rare complication of coronary artery bypass graft (CABG) surgery. Surgical repair has been generally recommended, but percutaneous techniques have also been described; coils were used primarily in smaller fistula while double umbrella or vascular occlusion devices were used in larger ones. To the best of our knowledge the use of coronary covered stent has never been reported. A 73-year-old man underwent CABG in November 2004 for unstable angina and left internal mammary artery (LIMA) was anastomosed to left anterior descending (LAD) coronary artery. Three months later he underwent a control angiogram to check for the reappearance of effort angina, which demonstrated an inadvertent LIMA-great cardiac vein (GCV) anastomosis. After discussions, an attempt to close the ACF with implantation of a covered stent was performed.
Using a percutaneous right internal jugular vein approach, coronary sinus was selectively cannulated and a 0.014-in. coronary guide wire was advanced selectively to the GCV, then a covered stent was deployed across the anastomotic site, obtaining the immediate occlusion of the ACF.
No contrast medium flowed into the distal part of the GCV at the reinjection of the coronary sinus and a selective injection into LIMA showed the absence of flow through LIMA, confirming the occlusion of the anastomotic site.
We have demonstrated successful occlusion of an iatrogenic ACF by using percutaneous stenting of GCV with covered stent via coronary sinus approach, which seems to be technically less demanding, safer, and time sparing.