High-dose Bolus Tirofiban Research Articles

Primary Percutaneous Coronary Intervention with High-Bolus Dose Tirofiban: The FASTER (Favorite Approach to Safe and Effective Treatment for Early Reperfusion) Multicenter Registry.

Objectives To investigate the safety and clinical efficacy of tirofiban during primary percutaneous coronary interventions (pPCI). Background Gp IIb/IIIa inhibitors (GPI) use during pPCI has declined over years, mainly for the increased hemorrhagic risk associated to their use and for the availability of potent, fast-acting oral antiplatelet drugs. However, several pharmacodynamic studies showed suboptimal platelet inhibition with P2Y12-blockers, such as prasugrel or ticagrelor. Methods Patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI were prospectively enrolled in a multicenter registry conducted in high-volume centers in Italy. All patients received intraprocedural tirofiban. The primary safety endpoint was the occurrence of in-hospital bleedings according to the Bleeding Academic Research Consortium definition. In-hospital major adverse coronary events (MACE, defined as death, reinfarction, stent thrombosis, and target vessel revascularization), final TIMI flow, myocardial blush grade, and ST-segment resolution were also evaluated. Results A total of 472 patients (mean age 61 ± 11 years, 83% males) were enrolled in 16 Italian centers from October 2015 to June 2018. Mean basal thrombus grade score was 3.47 ± 1.25. PCI was performed by transradial approach in 88% of patients. We observed a very low rate of 30 days BARC bleedings (2.1%) and MACE (0.8%). Complete (>70%) ST-segment resolution was observed in 67% of patients. Conclusions In the FASTER registry, the use of tirofiban during primary PCI, performed with a transradial approach in most cases, in patients with high thrombus burden was associated with high rates of complete ST-segment resolution and low rates of in-hospital bleeding and MACE.

Efficacy and safety of single high-dose versus double high-dose intracoronary bolus tirofiban in patients with ST-segment elevation myocardial infarction

Objectives: We evaluated the efficacy and safety of single high-dose versus double high-dose intracoronary bolus tirofiban in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: A total of 80 patients, who were admitted to our clinic and underwent primary PCI, were included in this observational cohort study. The patients were divided into the single high-dose group (n = 40) and the double high-dose group (n = 40) according to the intracoronary bolus tirofiban regime. The primary endpoint was assumed as the incidence of major adverse cardiac event (s) (MACE) defined as all-cause mortality and repeat coronary revascularization (target vessel revascularization [TVR]) at 30 days. MACE and bleeding events were evaluated at 7 and 30 days. Results: The primary endpoint was not significantly different between the single and the double high-dose groups (40.0% vs. 17.5%, p = 0.994). However, a significantly lower 30-day TVR rate was observed in the double high-dose group (27.5% vs. 7.5%, p = 0.019). No significant difference was observed in terms of 30-day all-cause mortality between the two groups (12.5% vs. 10.0%, p = 0.712). Major bleeding events were not observed in any group. Multivariate logistic regression analysis demonstrated that CRUSADE score (Hazard ratio [HR]: 5.721; 95% CI: 2.036 to 16.073, p = 0.001) and platelet count (HR: 1.009; 95% CI: 1.000 to 1.018, p = 0.048) were the independent predictors of bleeding at 7 days. Conclusions: Double high-dose intracoronary bolus tirofiban in STEMI patients undergoing primary PCI was associated with significantly lower 30-day TVR rates without an increase in bleeding events. However, it did not significantly affect MACE and all-cause mortality rates.

Effect of Upstream High Bolus Dose of Tirofiban in Primary PCI for the Patients With STEMI on Short Term Outcome

Effect of Upstream High Bolus Dose of Tirofiban in Primary PCI for the Patients With STEMI on Short Term Outcome

Comparison of In-Hospital Bleeding and Cardiovascular Events with High-Dose Bolus Tirofiban and Shortened Infusion to Short-Duration Eptifibatide as Adjunctive Therapy for Percutaneous Coronary Intervention

Potent platelet inhibition is one of the most important medical interventions to prevent ischemic complications during and after percutaneous coronary intervention (PCI). Practice has evolved with the introduction of potent oral P2Y12 inhibitors that provide quick, effective platelet inhibition, and the need for routine glycoprotein IIb/IIIa inhibitors (GPIs) has decreased. Additionally, a shorter duration of GPI infusion has been shown to be safe with adequate oral antiplatelet loading, but clinical outcome data are limited to eptifibatide. This single-center, retrospective cohort study analyzed in-hospital outcomes for patients who received adjunctive GPI therapy for PCI before and after an institution-wide switch to high-dose bolus tirofiban with shortened infusion from short-duration eptifibatide. The primary end point was a composite in-hospital outcome of major and minor bleeding and cardiovascular events (death, myocardial infarction, coronary artery bypass grafting, ischemic stroke, and target vessel revascularization). Secondary end points included bleeding and cardiovascular event types. A total of 357 and 446 patients received eptifibatide and tirofiban, respectively, from February 1, 2014 through September 30, 2017. Thirty five eptifibatide and 46 tirofiban patients experienced an in-hospital composite event (9.8% vs 10.3%, p = 0.81). There was no difference found between in-hospital bleeding (6.4% vs 5.4%, p = 0.52) or cardiovascular events (5.6% vs 6.5%, p = 0.60) with the use of eptifibatide or tirofiban, respectively. Multivariable analysis showed that patients with transradial access or an indication of unstable angina were less likely to experience an in-hospital composite event (OR 0.30 and 0.19, respectively, p <0.001 for both). In conclusion, the use of high-dose bolus tirofiban with shortened infusion versus short-duration eptifibatide was not associated with an increase of in-hospital bleeding or cardiovascular events.

Intracoronary high-dose bolus tirofiban administration during complex coronary interventions: A United States-based case series

The GP IIb/IIIa inhibitors (GPIs) rapidly provide therapeutic levels of platelet aggregation inhibition and serve as adjunct pharmacotherapy to oral P2Y12 inhibitors that exhibit a significant delay in onset of action for patients with Acute Coronary Syndrome (ACS). Intracoronary (IC) administration of the high dose bolus (HDB) tirofiban has not been extensively studied. Compared to intravenous delivery, IC administration can lead to higher local drug concentration and, therefore, provide instantaneous disruption of platelet aggregation in the culprit vessel. This report describes the successful resolution of thrombus using IC HDB tirofiban in 7 high-risk coronary interventions with complications such as recurrent thrombosis and cardiogenic shock in ACS patients. This report represents the first case series of IC HDB tirofiban performed in North America and suggests that IC HDB tirofiban may represent an effective and safe strategy to achieve rapid thrombus resolution in ACS patients.

High-dose bolus tirofiban versus low-dose bolus in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Aim of the present study was to determine effects of high-dose versus low-dose intravenous (IV) bolus tirofiban on angiographic measures, ST resolution, enzymatic infarct size, and clinical outcomes in patients with acute coronary syndrome (ACS) who were undergoing percutaneous coronary intervention (PCI) and received current pharmacoinvasive therapy. Acute coronary syndrome patients (n=271, 85.6% male; mean age: 57.9±12.6 years) from between 2009 and 2015 who received IV tirofiban therapy following PCI were retrospectively analyzed. All patients had received maintenance tirofiban infusion (0.15 µg/kg/min) after bolus dose and 600 mg clopidogrel. Percentage of patients undergoing drug eluting stent implantation procedure was 33.5%. Tirofiban was administered to all patients in bailout situation or for thrombotic complication after PCI. High-dose IV bolus group (25 µg/kg; n=140) was associated with greater ST segment resolution (66% vs. 50%, p=0.013) and reduced peak troponin release [12.4 ng/dL (range: 6.5-21.5 ng/dL) vs. 16.4 ng/dL (range: 10.1-27.4 ng/dL), p=0.001] compared with low-dose bolus group (10 µg/kg, n=131). Cardiovascular event rates were similar between groups at in-hospital, 1-month, and 6-month follow-up (p=1.000, 1.000, and 0.287, respectively). Percentage of patients with post-procedural Thrombolysis in Myocardial Infarction (TIMI) grade III flow, major, and minor bleeding were similar (p=0.085, 1.000, and 0.965, respectively). Use of high-dose IV bolus tirofiban in addition to aspirin and high-dose clopidogrel improves ST segment resolution, reduces infarct size, and does not increase bleeding events in patients with ACS undergoing PCI compared with low-dose bolus. Angiographic measures and clinical endpoints were similar between groups.

Comparison of heparin, bivalirudin, and different glycoprotein IIb/IIIa inhibitor regimens for anticoagulation during percutaneous coronary intervention: A network meta-analysis.

Numerous GPIs are available for PCI. Although they were tested in randomized controlled trials, a comparison between the different GPI strategies is lacking. Thus, we performed a Bayesian network meta-analysis to compare different glycoprotein IIb/IIIa inhibitor (GPI) strategies with heparin and bivalirudin for percutaneous coronary intervention (PCI). MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched by two independent reviewers for randomized controlled trials comparing high-dose bolus tirofiban, abciximab, eptifibatide, heparin with provisional glycoprotein IIb/IIIa inhibitors, and bivalirudin with provisional GPI that reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare between different anticoagulation strategies for all-cause mortality, myocardial infarction, major adverse cardiovascular events, major bleeding, minor bleeding, need for transfusion, and thrombocytopenia. A total of 41 randomized controlled trials with 38,645 patients were included in the analysis, among which 2654 were randomized to high-dose bolus tirofiban, 6752 to abciximab, 1669 to eptifibatide, 16,500 to heparin, and 11,070 to bivalirudin. Mean age was 64±11years, 75% were male, 91% were treated with stenting, 71% with clopidogrel, and 74% for acute coronary syndrome. High-dose bolus tirofiban was associated with a significant reduction in all-cause mortality compared with heparin (OR 0.57 [credible intervals 0.37, 0.9]) and eptifibatide (OR 0.44 [credible intervals 0.19, 1.0]). GPI regimens had less myocardial infarction and major adverse cardiovascular events but greater bleeding compared with heparin and bivalirudin. There was no difference among the GPI therapies for other outcomes, including myocardial infarction, major adverse cardiovascular events, and major bleeding. Our network meta-analysis of 38,645 patients demonstrated that GPI regimens were associated with a reduction in recurrent myocardial infarction or major adverse cardiovascular events for PCI, while bivalirudin was associated with the lowest risk of bleeding.

CRT-200.83 Comparison of High-Dose Bolus Tirofiban With Other Anticoagulation Strategies for Percutaneous Coronary Intervention: A Network Meta-Analysis of Randomized Controlled Trials

Numerous randomized controlled trials (RCTs) have been conducted comparing different anticoagulation strategies for percutaneous coronary intervention (PCI) but comparison between different glycoprotein IIb/IIIa inhibitors (GPI) is limited. Thus, we performed a Bayesian network meta-analysis to

Impact of upstream high bolus dose tirofiban on left ventricular systolic function in patients with acute anterior myocardial infarction treated by primary coronary intervention

Background: Glycoprotein IIb/IIIa inhibitor therapy during primary percutaneous coronary intervention (PCI) decreases the incidence of major adverse cardiac events. Aim: To study the impact of high bolus dose tirofiban on left ventricular ejection fraction in patients with acute anterior ST segment elevation MI treated with primary PCI. Patients and methods: Forty patients presenting to Ain Shams University, and specialized hospitals with the diagnosis of acute anterior STEMI were treated with primary PCI. Twenty patients were given conventional intravenous bolus dose tirofiban (10 lg/kg) upstream prior to primary angio- plasty and twenty patients were given intravenous high bolus dose tirofiban (25 lg/kg) upstream prior to PCI. In-hospital follow up was done including echocardiography, and serial cardiac enzymes in addition to clinical follow up for MACE and bleeding complications. Results: Successful primary angioplasty was attained in all patients. The LV systolic function was significantly better in the high bolus dose group in comparison to the conventional bolus dose groups (48% vs 41%, P 0.05). Both regimens were safe and the bleeding complications were minimal and did not differ between the study groups. Conclusion: In patients presenting with acute anterior STEMI and treated with primary PCI, the high bolus dose tirofiban given intravenously upstream prior to PCI seems to be a safe and effective regimen to achieve a better left ventricular ejection fraction in comparison to the conventional bolus dose regimen, without increasing the risk of bleeding. a 2014 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology.

Short‐term Effect of Upstream Administration in Comparison to Deferred Injection of Tirofiban on Patients with Acute ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

High bolus dose tirofiban has been demonstrated to provide greater inhibition of platelet aggregation, but the most appropriate timing of its administration remains unknown. To evaluate the efficacy of upstream vs. deferred administration of tirofiban in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) on clinical outcomes. The 660 patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were divided into upstream (n=330, administration of tirofiban to all patients in emergency room) and deferred groups (n=330, treatment of patients with large thrombus burden or no-reflow phenomenon in cardiac catheterization laboratory during PCI). The primary end-points were death, nonfatal myocardial infarction (MI), stent thrombosis (ST), revascularization of targeted vessels (TVR) or major adverse cardiac events (MACE) at 1 month and 6 months following PCI, with safety end-point at 7 days. Compared with that of the deferred group, there was a significant increase of left ventricular ejection fraction (LVEF) in the upstream group within 7 days (55.5 ± 6.6% vs. 54.6 ± 7.9%, P=0.011). The rates of 7-day and 1-month MACE in the upstream group were lower than those in the deferred group (1.5% vs. 4.2%, 3.3% vs. 7.0%, P=0.037 and 0.034, respectively). However, there were higher tendencies for major and minor bleedings in the upstream group (1.8% vs. 0.9%, 2.7% vs. 1.5%, P=0.315 and 0.280, respectively). To the Chinese patients with acute myocardial infarction undergoing primary PCI, upstream administration of tirofiban was slightly superior to deferred injection for short-term clinical outcomes.

CRT-33 Peri-procedural CK-MB Levels In Percutaneous Coronary Intervention With High-dose Bolus Tirofiban Vs. Abciximab Plus Either Unfractionated Heparin Or Bivalirudin: An Analysis From TENACITY

TENACITY was a randomized 2 × 2 factorial trial comparing high-dose bolus (HDB) tirofiban vs. abciximab, and unfractionated heparin (UFH) vs. bivalirudin, in patients undergoing percutaneous coronary intervention (PCI). The primary endpoint of 30-day death, myocardial infarction, or urgent target

The effect of pre‐hospital glycoprotein IIb–IIIa inhibitors on angiographic outcome in STEMI patients who are candidates for primary PCI

Aim of this study was to assess the effect of early initiation of high bolus dose tirofiban on top of dual antiplatelet therapy on angiographic outcome before and after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infraction patients. Glycoprotein IIb/IIIa inhibitors are effective inhibitors of platelet aggregation, and have shown to reduce thrombotic complications in patients undergoing PCI. This is a pre-specified angiographic analysis of the On-TIME 2 trial (N = 984) and its open label run-in phase (N = 414). All angiographic parameters, including quantitative coronary angiography (QCA) were performed in an independent angiographic core lab. Of the 1,398 patients, 709 patients (50.7%) were randomized to pre-hospital tirofiban. An open infarct related vessel (TIMI 2 or 3 flow) at initial angiography was more often present in the tirofiban group as compared to the no tirofiban group (58.3% vs. 49.7%, P = 0.002). Tirofiban also reduced initial thrombus burden (P for trend = 0.035) as well as thrombus grade 5 (46.9% vs. 54.3%, P = 0.016) and showed a trend toward a reduction in large thrombus burden (LTB) (69.4% vs. 74.5%, P = 0.055). After PCI, a trend towards a lower corrected TIMI frame count (cTFC) in the tirofiban group was found. A significant interaction was found with time of initiation of study drug, with highest efficacy of tirofiban when given within 76 min after symptom onset, with a significantly lower cTFC after PCI (21.9 ± 17.6 vs. 23.9 ± 18.5, P = 0.008, P for interaction P = 0.006). In patients undergoing primary PCI, pre-hospital administration of tirofiban reduces initial thrombus burden and improves initial patency of the infarct related vessel before PCI. Initiation of tirofiban seems to be most effective when given very early after the onset of symptoms; however, this finding needs confirmation in other studies. The On-TIME 2 trial is registered, at http://isrctn.org, number ISRCTN06195297.

Sex-specific benefits of sirolimus-eluting stent on long-term outcomes in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: Insights from the Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study trial

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.

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)

BackgroundThe 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 resultsComplete 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. ConclusionsThe 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.

The Impact of Age on Effects of Pre-hospital Initiation of High Bolus Dose of Tirofiban Before Primary Angioplasty for ST-Elevation Myocardial Infarction

Glycoprotein IIb/IIIa inhibitors are favourable in ST-elevation myocardial infarction (STEMI) patients, and the additional value of early pre-hospital high bolus dose tirofiban has recently been established. The aim of this study was to determine the impact of age on myocardial reperfusion and clinical outcomes of pre-hospital administration of high bolus dose tirofiban. This is a pre-specified sub-analysis of the multicentre, double-blind, placebo-controlled, randomised On-TIME 2 trial and it's open label phase. The primary endpoint was mean residual ST segment deviation 1h after primary PCI and was evaluated in three age groups. Of the 466 patients in the highest tertile (≥68years), median age was 74.4years (IQR 71.3-78.6years) and 231 (50%) were randomised to tirofiban. Mean residual ST segment deviation 1 h after PCI was significantly lower in elderly patients pre-treated with tirofiban compared to elderly patients without tirofiban pre-treatment (4.2 ± 5.2mm vs 6.4 ± 7.5mm, p = 0.001). Furthermore, elderly patients pre-treated with tirofiban had a non-significantly higher rate of 30-day major or minor bleeding compared to elderly patients without tirofiban pre-treatment (14.2% vs 9.0%, p = 0.088). 30-day net adverse clinical events in elderly patients with- or without tirofiban was not significantly different (11.9% vs 15.2%, p = 0.300). The effect of pre-hospital initiation of high bolus dose tirofiban on myocardial reperfusion, as determined by ST-segment resolution is highest in the elderly patients. However, this was associated with a trend towards more bleeding complications, resulting in a balanced clinical effect after 30-day follow-up. Future studies should evaluate whether the elderly STEMI patient may benefit from highly effective and safer antiplatelet therapy.

A randomized two‐by‐two comparison of high‐dose bolus tirofiban versus abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary revascularization and stent placement: The tirofiban evaluation of novel dosing versus abciximab with clopidogrel and inhibition of thrombin (TENACITY) study trial

In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain. Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 μg/kg) plus 12-hr infusion (0.15 μg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%. With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations.

Persistent Coronary No Flow After Wire Insertion Is an Early and Readily Available Mortality Risk Factor Despite Successful Mechanical Intervention in Acute Myocardial Infarction: A Pooled Analysis From the 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

These studies sought to investigate the impact on mortality of coronary flow after passage of the wire through the culprit vessel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical reperfusion. Reduced spontaneous coronary flow before percutaneous coronary intervention influences mortality in patients with STEMI. Response to vessel wiring in patients with an occluded coronary artery before intervention might further discriminate outcomes irrespective of pre- and post-intervention coronary flow. Data from the 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) trials were pooled: of 919 index procedures, 902 films (98%) were technically adequate for core laboratory TIMI (Thrombolysis In Myocardial Infarction) flow determination. TIMI flow grade 0 was present before percutaneous coronary intervention in 59% of infarct vessels, TIMI flow grade 1 to 2 was found in 21%, whereas the remainder of infarct arteries presented with TIMI flow grade 3. In 49% of patients who showed persistent TIMI flow grade 0 after wire insertion (AWI), mortality was higher at 30 days (5.3%) and 1 year (9.4%) compared with patients in whom TIMI flow grade before percutaneous coronary intervention was either >0 (0.8%; p < 0.003 and 3.6%, p < 0.008) or improved from 0 AWI (1.5%, p < 0.04 and 3.6%, p < 0.02). After correcting for multiple imbalances, including baseline and final flow, persistent TIMI flow grade 0 AWI remained associated at 30 days to 2-fold (risk ratio [RR]: 2.1, 95% confidence interval [CI]: 1.08 to 5.00; p = 0.038) and at 1 year to almost 3-fold increases of mortality (RR: 2.7, 95% CI: 1.3 to 5.6; p = 0.008). STEMI patients displaying persistent no-flow AWI have a lower survival rate despite an apparently successful mechanical intervention. As an early marker for high residual mortality risk, persistent no-flow AWI may qualify STEMI patients for dedicated pharmacomechanical treatment strategies.

Prediction of 1-Year Clinical Outcomes Using the SYNTAX Score in Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Substudy of the 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

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: SXLOW ≤9 (n = 311), 9 < SXMID ≤16 (n = 234), SXHIGH >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)

Prehospital triple antiplatelet therapy in patients with acute ST elevation myocardial infarction leads to better platelet aggregation inhibition and clinical outcome than dual antiplatelet therapy

ObjectiveTo assess whether prehospital initiation of high-dose tirofiban in addition to high-dose clopidogrel results in more adequate inhibition of platelet aggregation (IPA) and better clinical outcome after primary percutaneous coronary...

Effect of Early, Pre-Hospital Initiation of High Bolus Dose Tirofiban in Patients With ST-Segment Elevation Myocardial Infarction on Short- and Long-Term Clinical Outcome

The purpose of this trial was to study the effect of a high bolus dose (HBD) of tirofiban on clinical outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) placebo-controlled, double-blind, randomized trial showed that early administration of HBD tirofiban in the ambulance improves ST-segment resolution in patients with STEMI undergoing primary percutaneous coronary intervention. The effect of early tirofiban treatment on clinical outcome is unclear. The On-TIME 2 trial consisted of 2 phases: an open-label phase, followed by a double-blind, placebo-controlled phase. STEMI patients were randomized to either HBD tirofiban or no tirofiban (phase 1) or placebo (phase 2) in addition to aspirin, heparin, and high-dose clopidogrel. The protocol pre-specified a pooled analysis of the 2 study phases to assess the incidence of major adverse cardiac events at the 30-day follow-up and on total mortality at the 1-year follow-up. During a 3-year period, 1,398 patients were randomized, 414 in phase 1 and 984 in phase 2. Major adverse cardiac events at 30 days were significantly reduced (5.8% vs. 8.6%, p = 0.043). There was a strong trend toward a decrease in mortality (2.2% vs. 4.1%, p = 0.051) in patients who were randomized to tirofiban pre-treatment, which was maintained during the 1-year follow-up (3.7% vs. 5.8%, p = 0.08). No clinically relevant difference in bleeding was observed. Early, pre-hospital initiation of HBD tirofiban, in addition to high-dose clopidogrel, improves the clinical outcome after primary percutaneous coronary intervention in patients with STEMI. (Ongoing 2b/3a inhibition In Myocardial infarction Evaluation; ISRCTN06195297).