Marco Stefano Nazzaro

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial

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 stratified 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, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined 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 difference 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. FUNDING The Medicines Company and Terumo.

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.

Major improvement of percutaneous cardiovascular procedure outcomes with radial artery catheterisation: results from the PREVAIL study

Objective: To obtain a “snapshot” view of access-specific percutaneous cardiovascular procedures outcomes in the real world. Design: Multicentre, prospective study performed over a 30-day period. Setting: Nine hospitals with invasive cardiology facilities, reflecting the contemporary state of healthcare. Patients: Unselected consecutive sample of patients undergoing any percutaneous cardiovascular procedure requiring an arterial access. Interventions: Percutaneous cardiovascular procedures by radial or femoral access Main outcome measures: The primary outcome was the combined incidence of in-hospital (a) major and minor haemorrhages; (b) peri-procedural stroke; and (c) entry-site vascular complications. The secondary outcome was the combined incidence of in-hospital death and myocardial infarction/reinfarction. For analysis purposes, outcomes were allocated to arterial access-determined study arms on an intention-to treat basis. Multivariable analysis adjusted using propensity score was performed to correct for selection bias related to arterial site. Results: A total of 1052 patients were enrolled: 509 underwent radial access and 543 femoral access. In both groups, 40% underwent a coronary angioplasty. Relative to femoral access, radial access was associated with a lower incidence both of primary (4.2% vs 1.96%, p = 0.03, respectively) and secondary endpoints (3.1% vs 0.6%, p = 0.005, respectively). Multivariate analysis, adjusted for procedural and clinical confounders, confirmed that intention-to-access via the radial route was significantly and independently associated with a decreased risk both of primary (OR 0.37, 95% CI 0.16 to 0.84) and secondary endpoints (OR 0.14, 95% CI 0.03 to 0.62). Conclusions: Our study indicates strikingly better outcomes of percutaneous cardiovascular procedures with radial access versus femoral access in contemporary, real-world clinical settings.

Maintenance of Long-Term Clinical Benefit With Sirolimus-Eluting Stents in Patients With ST-Segment Elevation Myocardial Infarction: 3-Year Results of the SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent In Acute Myocardial Infarction) Trial

OBJECTIVES The aim of this study was to investigate whether the reported favorable 1-year outcome of the sirolimus-eluting stent (SES) versus the bare-metal stent (BMS) in the SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent In Acute Myocardial Infarction) trial, in the setting of ST-segment elevation myocardial infarction (STEMI), is maintained at 3-year follow-up. BACKGROUND At present, only long-term registry data, but not randomized trials, on the safety and effectiveness of SES in STEMI patients are available. METHODS Overall, 320 STEMI patients were randomized to receive SES or BMS. The primary end point was the incidence of major adverse cardiovascular events (MACE), at 3-year follow-up. The secondary end points were the rate of target lesion revascularization (TLR) and target vessel revascularization (TVR) and target vessel failure (TVF). The incidence of late events, starting from clopidogrel withdrawal, was also investigated. RESULTS The 3-year incidence of MACE was lower in the SES group compared with the BMS group (12.7% vs. 21%, p = 0.034), as were TLR (7% vs. 13.5%, p = 0.048), TVR (8% vs. 16%, p = 0.027), and TVF (11.5% vs. 20.5%, p = 0.028) rates. The 3-year survival rate free from MACE, TLR, and TVF was significantly higher in the SES group than in the BMS group (87%, 93%, and 89.5% vs. 79%, 86.5%, and 79.5%, respectively, p < 0.05). The lower incidence of adverse events in the SES group was driven by TLR reduction and achieved in the first year of follow-up. The cumulative incidence of death and recurrent myocardial infarction, starting from clopidogrel discontinuation, was comparable in the 2 groups. CONCLUSIONS The clinical benefits of SES have been shown to be greater than those of BMS at 3-year follow-up.

3-year clinical outcome of patients with chronic total occlusion treated with drug-eluting stents.

OBJECTIVES The aim of this study was to evaluate whether percutaneous coronary intervention (PCI) with drug-eluting stent (DES) reduces major adverse cardiac events (MACE) in patients with chronic coronary total occlusions (CTO) compared with bare-metal stent (BMS) during 3-year follow-up. BACKGROUND The long-term prognosis of patients with CTO treated with PCI and DES implantation is poorly investigated. METHODS We compared the 3-year clinical outcome of 124 patients with CTO after successful PCI with DES implantation with that of 159 patients with CTO previously treated with BMS. MACE were defined as death, myocardial infarction, and target lesion revascularization (repeat PCI or coronary artery bypass surgery) and were considered as combined primary end point. RESULTS After 3 years, the composite end point was significantly lower in the DES than in the BMS group: 18% versus 28%, respectively, (p < 0.05). The difference was due to the reduction of target lesion revascularization with DES compared with BMS-8% versus 21%, respectively, (p < 0.004). The Cox proportional hazards model identified: DES versus BMS (adjusted hazard ratio [HR]: 0.338, 95% confidence interval [CI]: 0.19 to 0.60, p = 0.0001), lesion length (HR: 1.033, 95% CI: 1.008 to 1.058, p = 0.012), and final minimal lumen diameter (HR: 0.456, 95% CI: 0.232 to 0.898, p = 0.023) as independent predictors of MACE at 3-year follow-up. CONCLUSIONS After 3 years, DES were superior to BMS in reducing MACE in patients with CTO and should be considered the preferred treatment strategy.

Three-year follow-up of 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)

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 3 years 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.

Clinical outcome of patients with chronic total occlusion treated with drug-eluting stents

BACKGROUND There is limited evidence on the medium-term prognosis of patients with chronic total occlusion successfully treated with drug-eluting stent (DES) implantation. METHODS We compared the medium-term outcome of 111 patients with chronic total occlusion (CTO) successfully treated with implantation of sirolimus-or paclitaxel-eluting stents versus 112 patients treated with bare metal stents. RESULTS During an overall follow-up period of 18 months, the composite endpoint of death, myocardial infarction or target lesion revascularization was significantly lower in the drug-eluting stent than in the bare metal stent group: 8.1% vs. 21.6%, respectively (p=0.005). The difference was due to the reduction of target lesion revascularization with DES compared to bare metal stents: 3.6% vs. 18.9%, respectively (p<0.001). The Cox proportional hazards model identified DES as an independent predictor of adverse cardiac events (adjusted hazard ratio, 0.16; 95% confidence interval 0.05 to 0.52, p=0.002). CONCLUSIONS During medium-term follow-up use of DES is associated with improved outcome compared to use of bare metal stents in patients with CTO.

Comparison of the feasibility and effectiveness of transradial coronary angiography via right versus left radial artery approaches (from the PREVAIL Study)

It remains undefined if transradial coronary angiography from a right or left radial arterial approach differs in real-world practice. To address this issue, we performed a subanalysis of the PREVAIL study. The PREVAIL study was a prospective, multicenter, observational survey of unselected consecutive patients undergoing invasive cardiovascular procedures over a 1-month observation period, specifically aimed at assessing the outcomes of radial approach in the contemporary real world. The choice of arterial approach was left to the discretion of the operator. Prespecified end points of this subanalysis were procedural characteristics. Of 1,052 patients consecutively enrolled, 509 patients underwent transradial catheterization, 304 with a right radial and 205 with a left radial approach. Procedural success rates were similar between the 2 groups. Compared to the left radial group, the right radial group had longer procedure duration (46 ± 29 vs 33 ± 24 minutes, p <0.0001) and fluoroscopy time (765 ± 787 vs 533 ± 502, p <0.0001). At multivariate analysis, including a parsimonious propensity score for the choice of left radial approach, duration of procedure (beta coefficient 11.38, p <0.001) and total dose-area product (beta coefficient 11.38, p <0.001) were independently associated with the choice of the left radial artery approach. The operators proficiency in right/left radial approach did not influence study results. In conclusion, right and left radial approaches are feasible and effective to perform percutaneous procedures. In the contemporary real world, however, the left radial route is associated with shorter procedures and lower radiologic exposure than the right radial approach, independently of an operators proficiency.

Long-term outcome of sirolimus-eluting vs bare-metal stent in the setting of acute myocardial infarction: 5-year results of the SESAMI trial

BACKGROUND few long-term randomized data on safety and effectiveness of sirolimus-eluting stent (SES) in the ST-segment elevation myocardial infarction (STEMI) setting are available. The aim of the present investigation was to evaluate the 5-year clinical outcome of SES vs bare-metal stent (BMS) implantation in patients with STEMI. METHODS 320 STEMI patients were randomized to receive SES or BMS. The primary end-point was the incidence of target vessel failure (TVF) at 5-year follow-up. The secondary end-points were the rate of target lesion revascularization (TLR), major adverse cardiovascular events (MACE), death or non-fatal MI and stent thrombosis (ST). Event rates from 1 to 5 years in patients undergoing TLR and those TLR free at 1 year were also investigated. RESULTS The 5-year survival rate free from TVF and TLR was significantly higher in the SES than in the BMS group (85% vs 76% p=0.038; 92% vs 85% p=0.045, respectively). The lower incidence of adverse events was achieved in the first year of follow-up. The cumulative incidence of MACE, death or non-fatal MI and ST was comparable in the 2 groups at 5-year follow-up. Moreover death or MI incidence was 5% in the patients who did not experience TLR within 1-year and 16% in those who experience TLR in the same period (p=0.033). Predictors of death or MI during 5-year follow-up were TLR within 1 year (OR 3.4, 95% CI 1.1-10.1; p=0.04) and small vessels treatment (OR 4.8 95% CI 1.7-13.0; p=0.002). CONCLUSIONS The clinical benefits of SES are maintained up to 5years without safety concerns.

Does the site of bleeding matter? A stratified analysis on location of TIMI-graded bleedings and their impact on 12-month outcome in patients with ST-segment elevation myocardial infarction

AIMS 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. METHODS AND RESULTS 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). CONCLUSIONS 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.