Clinical efficacy and safety of intracoronary vs. intravenous abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention: a meta-analysis of randomized trials

Adjunctive therapy with abciximab has been proven to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over the IV route. We aimed to perform a meta-analysis of randomized controlled trials to assess the clinical efficacy and safety of IC vs. IV abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). The primary endpoint was mortality, while recurrent myocardial infarction and target vessel revascularization (TVR) were selected as secondary endpoints. The safety endpoint was the risk of major bleeding complications. A total of six randomized trials were finally included in the meta-analysis, enrolling a total of 1246 patients. Compared to IV route, IC abciximab was associated with a significant reduction in mortality (odds ratio, OR [95% confidence interval (CI)]?=0.43 [0.20-0.94], p=0.03), and TVR (OR [95% CI]?=0.53 [0.29-0.99], p=0.05). No differences in terms of recurrent myocardial infarction (OR [95% CI]?=0.54 [0.23-1.28], p=0.17) or major bleeding complications (OR [95% CI]?=0.91 [0.46-1.79], p=0.79) were observed between the two strategies. The present meta-analysis showed that IC administration of abciximab is associated with significant benefits in mortality at short-term follow-up compared to IV abciximab administration, without any excess of major bleeding in STEMI patients undergoing PPCI. However, further trials are warranted to establish the optimal strategy of abciximab treatment in this setting.     

Aborted myocardial infarction in intracoronary compared with standard intravenous abciximab administration in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction

Backgound

Abciximab reduces major adverse cardiac events (MACEs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary (IC) abciximab bolus application might be more effective than a standard intravenous (IV) bolus. So far the occurrence of aborted MI, a new therapeutic target of effective treatment in STEMI, has not been evaluated in IC versus IV abciximab administration in STEMI patients undergoing primary PCI.

Methods

To investigate the extent of aborted MI, 154 patients undergoing primary PCI were randomized to either IC (n = 77) or IV (n = 77) bolus abciximab administration with subsequent 12-hour intravenous infusion. For assessment of infarct size and extent of microvascular obstruction, all patients underwent late enhancement magnetic resonance imaging (MRI). Aborted MI was defined by major (≥ 50%) ST-segment resolution and a lack of subsequent cardiac enzyme rise ≥ 2 the upper normal limit. We also assessed the occurrence of true aborted MI defined as the absence of myocardial necrosis in MRI.

Results

The incidence of aborted MI was significantly higher in the IC group (p = 0.04); true aborted MI was only observed in the IC abciximab group (p = 0.01). At multivariable logistic regression analysis, IC abciximab application was a significant independent predictor of true aborted MI (p = 0.03). Aborted MI patients had an excellent prognosis at 6-month follow-up with no MACE as compared to 24 events in patients with non-aborted MI.

Conclusions

IC bolus application of abciximab in STEMI patients undergoing primary PCI results in a higher incidence of aborted MI and subsequent improved clinical outcome.     

Meta-analysis of prospective randomized controlled trials comparing intracoronary versus intravenous abciximab in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Abciximab is a glycoprotein IIb/IIIa receptor inhibitor that has been shown to improve outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention (pPCI). An earlier study reported better efficacy with intracoronary (IC) compared to intravenous (IV) administration, but this finding has not been duplicated in other studies, thus leaving a great deal of uncertainty as to the most efficacious route of administration. To investigate if IC abciximab compared to IV administration decreases mortality and major adverse cardiac events in patients with ST-segment elevation myocardial infarction who undergo pPCI, a meta-analysis was performed consisting only of prospective randomized controlled trials. Subgroup analysis was performed to investigate the source of difference in efficacy between the 2 strategies. A meta-analysis of 4 trials including 1,148 subjects revealed that IC abciximab significantly reduced mortality compared to IV administration (1.5% vs 3.6%, odds ratio 0.44, 95% confidence interval 0.20 to 0.95, p = 0.04). Major adverse cardiac events were also reduced in a subgroup in which <30% of patients received aspiration thrombectomy (6.1% vs 16.2%, odds ratio 0.33, 95% confidence interval 0.18 to 0.61, p = 0.0004). In conclusion, the totality of the data available from relatively small but high-quality studies shows a significant mortality reduction associated using IC abciximab for pPCI compared to IV abciximab. IC abciximab in the setting of pPCI for ST-segment elevation myocardial infarction may be beneficial for patients with higher risk profiles.     

冠状动脉介入治疗中阿昔单抗两种给药途径治疗效果比较的meta分析

目的:比较冠状动脉介入治疗（PCI）中冠状动脉内和静脉内使用阿昔单抗的治疗效果。方法: 计算机检索 PubMed、 EMbase、 Cochrane图书馆、 中国生物医学文献光盘数据等数据库,系统性搜索已发表的相关临床研究,并对纳入的研究进行质量评价,对相关结果进行meta分析。共纳入6个随机对照临床研究,共1 138例患者,其中试验组580例（冠状动脉内运用阿昔单抗组）,对照组558 例（静脉内运用阿昔单抗组）。纳入患者均为急性ST段抬高型心肌梗死。结果: 冠状动脉内运用阿昔单抗组仅在心肌梗死溶栓后Ⅲ级血流所占比例优于静脉内运用阿昔单抗组［RR=1.06,95%CI（1.01,1.12）,P=0.02］。而在病死率［RR=0.48,95%CI（0.23,1.02）,P=0.06］、靶血管血运重建［RR=0.55,95%CI（0.30,0.99）,P=0.05］,以及出血事件发生率［RR=0.88,95%CI（0.63,1.23）,P=0.44］,两组没有统计学意义上的差异。结论:与静脉内使用阿昔单抗组相比,冠状动脉内使用阿昔单抗改善了急性ST段抬高型心肌梗死患者的心肌灌注,但并未降低其病死率、靶血管血运重建及出血事件发生率。     

Cangrelor for patients undergoing percutaneous coronary intervention: evidence from a meta-analysis of randomized trials

Cangrelor is a new parenteral adenosine diphosphate P2Y12 receptor inhibitor with rapid, profound and reversible inhibition of platelet activity. The aim of this meta-analysis was to evaluate efficacy and safety of this new agent in patients undergoing percutaneous coronary intervention (PCI). We searched PubMed, Cochrane Library, EMBASE, Web of Science and CINAHL databases from the inception through April 2013. Randomized controlled trials (RCTs) comparing cangrelor with control (clopidogrel/placebo) were selected. We used the random-effects models to calculate the risk ratio. The primary efficacy outcome was risk of myocardial infarction, and the primary safety outcome was TIMI major bleeding at 48 h. Three RCTs included a total of 25,107 participants. Effects of Cangrelor were not different against comparators for myocardial infarction (MI) (Risk ratio [RR] 0.94, 95 % confidence interval [CI] 0.78–1.13) and all-cause mortality (RR 0.72, 95 % CI 0.36–1.43). However, cangrelor significantly reduced the risk of ischemia-driven revascularization (RR 0.72, 95 % CI 0.52–0.98), stent thrombosis (RR 0.60, 95 % CI 0.44–0.82) and Q wave MI (RR 0.53, 95 % CI 0.30–0.92) without causing extra major bleeding (Thrombolysis in Myocardial infarction criteria) and severe or life-threatening bleeding (Global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries criteria). Separate analysis against only clopidogrel also showed similar findings except Q wave MI outcome. Use of cangrelor during PCI might reduce the risk of ischemia-driven revascularization and stent thrombosis, without causing extra major bleeding.     

Angiographic evaluation of the effect of intracoronary abciximab administration in patients undergoing urgent PCI

BACKGROUND: Recent data suggest that the intracoronary (i.c.) administration of a systemic bolus dose of abciximab during PCI may increase the efficacy of this antiplatelet drug. However, the effect of i.c. abciximab on coronary angiographic flow has been not clarified. METHODS: We studied 37 consecutive patients with acute coronary syndromes (ACS) who underwent successful urgent PCI on the target vessel and were treated by an i.c. abciximab bolus (0.25 mg/kg) prior to the first balloon inflation (Group IC), and 37 matched controls who were treated by intravenous (i.v.) abciximab bolus at the same dose (Group IV). Corrected TIMI frame count (CTFC) in the culprit and in a non-culprit coronary artery branch was assessed before treatment, immediately after intracoronary administration of abciximab bolus and at the end of the procedure. RESULTS: After administration of abciximab, CTFC significantly decreased from 48+37 to 33+30 (P=0.001) in the culprit vessel while in the non-culprit vessel it remained unchanged (16+7 pre-treatment and 16+7 post-treatment, P=0.68). Final CTFC was 12+4 in Group IC and 14+5 in Group IV (P=0.069). Post-treatment mean peak of the cardiac enzymes showed a trend toward reduction in Group IC compared with Group IV. CONCLUSIONS: The i.c. administration of abciximab bolus acutely decreases CTFC through culprit vessels of patients with ACS undergoing urgent PCI. Further studies evaluating the potential clinical benefits associated with i.c. abciximab administration are warranted.     

Sirolimus-eluting versus paclitaxel-eluting stent in primary angioplasty: a pooled patient-level meta-analysis of randomized trials

Large interests have been focused on the role of drug-eluting stents in the setting of ST-segment elevation myocardial infarction (STEMI) and concerns have emerged regarding an higher risk of stent thrombosis. Aim of the current study was to perform a meta-analysis using individual patient data to evaluate the long-term safety and effectiveness of sirolimus-eluting stent (SES) as compared to paclitaxel-eluting stent (PES) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of SES versus PES for STEMI. No language restriction was applied. Primary study endpoint was the occurrence of major adverse cardiac events (MACE). Secondary endpoints were the occurrence of death, reinfarction, stent thrombosis, target-vessel revascularization (TVR). Individual patient data were obtained from 4 out of 5 trials identified, including a total of 1,000 patients, 504 (50.4 %) randomized to SES and 496 (49.6 %) randomized to PES. At long-term follow-up (1,021 [372–1,351] days), no difference was observed between SES and PES in terms of TVR (10 vs 11.6 %, HR [95 % CI 0.73 [0.45–1.16], p = 0.18, p het = 0.92]) (primary endpoint) or death (9.4 vs 10.4 %, HR [95 % CI 0.95 [0.58–1.54], p = 0.82, p het = 0.89]), reinfarction (8.2 vs 10.4 %, HR [95 % CI 0.91 [0.53–1.57], p = 0.73, p het = 0.83]), stent thrombosis (7.4 vs 4.6 %, HR [95 % CI 1.04 [0.55–2.05], p = 0.92, p het = 0.65]), and MACE (10 vs 13.6 %, HR [95 % CI 0.86 [0.63–1.18], p = 0.36, p het = 0.84]) (secondary endpoints). The present pooled patient-level meta-analysis demonstrates that, among STEMI patients undergoing primary PCI, SES and PES are associated with a similar outcome at long-term follow-up, in terms of death, reinfarction, stent thrombosis, TVR and MACE.     

Intracoronary compared to intravenous bolus abciximab during primary percutaneous coronary intervention in ST-segment Elevation Myocardial Infarction (STEMI) patients reduces 30-day mortality and target vessel revascularization: a randomized trial

Background: Abciximab is beneficial in patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). However, the optimal administration route of the initial bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has been questioned. Preliminary studies suggest that IC‐bolus is superior, probably due to high local concentration. In this study, we assess the short‐term efficacy and safety of IC compared to IV bolus of abciximab in patients with STEMI during pPCI. Methods: In 2006–2008, we randomized 355 STEMI patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12‐hour IV infusion. Primary end‐points at 30 days were target vessel revascularization (TVR), recurrent myocardial infarction (MI) or death, and the composite of the three. Secondary end‐points were bleeding complications. Results: The two groups (IV n = 170;IC n = 185) were similar with respect to baseline characteristics. Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in the IC group (P = 0.03). No significant difference in MI rates was seen (IV 4.7% vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end‐point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference was observed in minor bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). Conclusion: IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30‐day mortality and TVR and tends to reduce MI, compared to IV‐bolus. (J Interven Cardiol 2011;24:105–111)     

Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials

Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites, as compared with no treatment. Treatment alternatives to albumin, such as artificial colloids and vasoconstrictors, have been widely investigated. The aim of this meta-analysis was to determine whether morbidity and mortality differ between patients receiving albumin versus alternative treatments. The meta-analysis included randomized trials evaluating albumin infusion in patients with tense ascites. Primary endpoints were postparacentesis circulatory dysfunction, hyponatremia, and mortality. Eligible trials were sought by multiple methods, including computer searches of bibliographic and abstract databases and the Cochrane Library. Results were quantitatively combined under a fixed-effects model. Seventeen trials with 1,225 total patients were included. There was no evidence of heterogeneity or publication bias. Compared with alternative treatments, albumin reduced the incidence of postparacentesis circulatory dysfunction (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.27-0.55). Significant reductions in that complication by albumin were also shown in subgroup analyses versus each of the other volume expanders tested (e.g., dextran, gelatin, hydroxyethyl starch, and hypertonic saline). The occurrence of hyponatremia was also decreased by albumin, compared with alternative treatments (OR, 0.58; 95% CI, 0.39-0.87). In addition, mortality was lower in patients receiving albumin than alternative treatments (OR, 0.64; 95% CI, 0.41-0.98). Conclusions: This meta-analysis provides evidence that albumin reduces morbidity and mortality among patients with tense ascites undergoing large-volume paracentesis, as compared with alternative treatments investigated thus far.     

Impact of multivessel disease on infarct size among STEMI patients undergoing primary angioplasty

Background

Although primary angioplasty achieves Thrombolysis In Myocardial Infarction (TIMI) 3 flow in most patients with ST-elevation myocardial infarction, epicardial recanalization does not guarantee optimal perfusion in a large proportion of patients. Multivessel disease has been demonstrated to be associated with impaired survival, however its impact on infarct size has not been largely investigated, that therefore is the aim of the current study.

Methods

Our population is represented by 827 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi.

Results

Multivessel disease was observed in 343 patients (41.5%). It was associated with older age (65 [57–74] vs 63 [53–71], p < 0.001), higher rate of previous MI (6.4% vs 2.5%, p = 0.005), longer ischemia time evaluated as continuous variable (210 [155–280] min vs 196 [145–270] min, p = 0.065) or percentage of patients with ischemia time >3 h (63.7% vs 56.4%, p = 0.038), and a trend in more cardiogenic shock (5.5% vs 2.9%, p = 0.055). Patients with multivessel disease received more often Abciximab (92.1% vs 88.4%, p < 0.001), Intra-aortic balloon pump (6.4% vs 1.9%, p < 0.001). No differences were observed in other clinical or angiographic characteristics. In particular, multivessel disease did not affect the rate of postprocedural TIMI 3 flow (90.9% vs 93.4%, p = 0.18) and ST-segment resolution (52.4% vs 54.9%, p = 0.48). Multivessel disease did not affect infarct size (12.7% [4.5%–24.9%] vs 12.3% [4%–24.1%], p = 0.58). Similar results were observed in subanalyses without any significant interaction for each variable (anterior infarct location (p int = 0.23), gender (p int = 0.9), age (p int = 0.7), diabetes (p int = 0.15)). The absence of any impact of multivessel disease on infarct size was confirmed when the analysis was conducted according to the percentage of patients with infarct size above the median, even after correction for baseline characteristics, such as age, previous MI, ischemia time, use of Gp IIb–IIIa inhibitors, cardiogenic shock, ischemia time (OR [95% CI] = 1.09 [0.82–1.45], p = 0.58).

Conclusions

This study shows that among STEMI patients undergoing primary PCI multivessel disease does not affect infarct size.     

Clinical outcomes of primary stenting versus balloon angioplasty in patients with myocardial infarction: a meta-analysis of randomized controlled trials

PURPOSE: To examine whether primary stenting as compared with primary balloon angioplasty reduces clinical outcomes in patients with myocardial infarction. METHODS: Major medical databases from 1979 to March 2002 were searched for randomized controlled trials that compared primary stenting with balloon angioplasty in patients with myocardial infarction. Two independent reviewers selected and extracted data from identified trials. The outcomes were mortality at 30 days, 6 months, and 12 months; recurrent events; and bleeding. RESULTS: Nine trials with a total of 4433 patients fulfilled the inclusion criteria. The odds ratios for mortality after stenting as compared with balloon angioplasty were 1.17 (95% confidence interval [CI]: 0.78 to 1.74) at 30 days, 1.07 (95% CI: 0.76 to 1.52) at 6 months, and 1.09 (95% CI: 0.80 to 1.50) at 12 months (P for heterogeneity >0.1 for each comparison). The odds ratios for reinfarction after stenting as compared with balloon angioplasty were 0.52 (95% CI: 0.31 to 0.87) at 30 days, 0.67 (95% CI: 0.45 to 1.00) at 6 months, and 0.67 (95% CI: 0.45 to 0.99) at 12 months; for target vessel revascularization, they were 0.46 (95% CI: 0.34 to 0.61) at 30 days, 0.42 (95% CI: 0.35 to 0.51) at 6 months, and 0.48 (95% CI: 0.39 to 0.59) at 12 months (P for heterogeneity >0.1 for all estimates with the exception of reinfarction at 12 months where P=0.08). The odds ratio for postinterventional bleeding complications after stenting as compared with balloon angioplasty was 1.34 (95% CI: 0.95 to 1.88; P for heterogeneity >0.1). CONCLUSION: Compared with balloon angioplasty, primary stenting is not associated with lower mortality, but is associated with a lower risk of reinfarction and target vessel revascularization.     

Comprehensive meta-analysis of radial vs femoral approach in primary angioplasty for STEMI

Introduction

Primary angioplasty has improved survival as compared to thormbolysis. However, bleeding complications still represent the Achille's heel, mainly related to access site. Although the radial approach is getting larger consensus for elective percutaneous procedures, its safety and advantages in the setting of ST-segment elevation (STEMI) is controversial. Therefore, the aim of the current study was to perform a comprehensive meta-analysis of randomized and non randomized trials comparing radial vs transfemoral approach in primary angioplasty for STEMI.

Methods

The literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to October 2012. No language restrictions were enforced.

Results

A total of 27 trials were finally included, with 29,194 patients (4685 enrolled in 11 randomized trials and 24,509 in 15 non randomized trials). A total of 10,052 patients underwent radial approach and 19,142 patients underwent femoral approach. A total of 2499 patients (8.6%) had died at follow-up. Radial approach was associated with a significant reduction in short-term mortality (5.2% vs 10.3%, OR [95% CI] = 0.55 [0.40, 0.76], p < 0.001, p het = 0.97) (primary endpoint). Significant benefits were observed in both randomized (2.7% vs 4.7%, OR [95% CI] = 0.55 [0.40, 0.76], p < 0.001, p het = 0.97) and observational studies (5.9% vs 11.1%, OR [95% CI] = 0.48 [0.43, 0.54, p < 0.001, p het = 0.44]). Major bleeding complications were observed in a total of 808 patients (2.8%). Radial approach was associated with a significant reduction in major bleeding complications as compared to femoral approach (1.9% vs 4.7%, OR [95% CI] = 0.38 [0.31, 0.47], p < 0.0001, p het = 0.17), similarly in both randomized (2.7% vs 5%, OR [95% CI] = 0.51 [0.37, 0.70], p < 0.001, p het = 0.87) and observational studies (1.4% vs 4.6%, OR [95% CI] = 0.32 [0.25, 0.42], p < 0.0001, p het = 0.32). Both benefits in death and major bleeding complications were not related to baseline risk profile.

Conclusions

This meta-analysis of randomized and non-randomized trials showed that among STEMI patients undergoing primary angioplasty the radial approach is associated with a consistent reduction in mortality and major bleeding complications and. Therefore, routine use of radial approach should be strongly encouraged in primary angioplasty.     

Clinical outcomes following "rescue" administration of abciximab in patients undergoing percutaneous coronary angioplasty

Pre-intervention administration of abciximab in patients at "high risk" for coronary angioplasty has been shown to reduce acute and long-term cardiac outcomes. The role of intra-procedural ("rescue") administration of abciximab has not been fully elucidated. We assessed the clinical outcomes associated with rescue administration of abciximab during complex percutaneous coronary interventions. We studied in-hospital and long-term (1-year) outcomes (death, myocardial infarction and target lesion revascularization) of 298 consecutive patients (78% male; age, 62 +/- 11 years; 83% with acute coronary syndrome) treated with abciximab for thrombus-containing lesions, sub-optimal angioplasty results, procedural dissections or other complications. Stents were used in 73% of procedures. Procedural success was 97.0% and overall major in-hospital complication rate was 3.0% (death, 1.3%; Q-wave myocardial infarction, 0.7%; and emergent bypass surgery, 1.0%). Most frequent angiographic complications included visible thrombus (17%), dissections (17%), threatened closure (7%), and distal embolization (7%). In-hospital non-Q wave myocardial infarction (defined as CK-MB 5 times normal) occurred in 31.0%. Out-of-hospital to one-year events included death (1.7%), Q-wave myocardial infarction (2.7%), and target lesion revascularization (15.1%); cardiac event-free survival was 82.9%. We conclude that rescue administration of abciximab is associated with relatively low in-hospital complications and favorable long-term outcome in patients with sub-optimal angioplasty results and/or procedure-related complications, although peri-procedural non-Q wave myocardial infarction rate is high. A clinical and cost-effective comparison between provisional and rescue administration of abciximab may be warranted.