Updated evidence on intracoronary abciximab in ST-elevation myocardial infarction: A systematic review and meta-analysis of randomized clinical trials

Abstract Background: Intracoronary (IC) abciximab administration remains a promising approach aimed to increase a drug concentration in the target area and possibly improve clinical outcomes in the setting of ST-segment elevation myocardial infarction (STEMI). The goal of this literature review and meta-analysis is to update available knowledge comparing IC and intravenous (IV) abciximab administration in STEMI patients. Methods: A total of 7 randomized clinical trials (RCTs) with a median follow-up of 3 months were included in the meta-analysis (n = 3311). All-cause mortality was selected as the primary end point while recurrent myocardial infarction (re-MI), target vessel revascularization (TVR) and major bleeding complications were the secondary end points. Results: IC abciximab did not provide any benefits in terms of all-cause mortality as compared with IV abciximab (odds ratio [OR] 0.67; 95% confidence interval [CI] 0.34 1.34). However, this neutral effect was driven by the AIDA STEMI trial. The IC route was associated with a reduced rate of re-MI when compared with IV administration (OR 0.61; 95% CI 0.40 0.92) but the difference disappeared after one of the RCTs was excluded from the analysis. Both strategies were equal regarding TVR (OR 0.66; 95% CI 0.40 1.09) and major bleeding complications (OR 1.18; 95% CI 0.76 1.83). Conclusions: Our updated meta-analysis shows that the clinical superiority of IC over IV abciximab administration in STEMI patients is no longer clear after the release of the AIDA STEMI trial results. Further research in high-risk STEMI patients is warranted to finally determine clinical advantages of IC vs IV abciximab administration. (Cardiol J 2012; 19, 3:230 242

Low-molecular-weight heparins vs. unfractionated heparin in the setting of percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis

Summary. Background: The aim of the current study was to perform two separate meta-analyses of available studies comparing low-molecular-weight heparins (LMWHs) vs. unfractionated heparin (UFH) in ST-elevation myocardial infarction (STEMI) patients treated (i) with primary percutaneous coronary intervention (pPCI) or (ii) with PCI after thrombolysis. Methods: All-cause mortality was the prespecified primary endpoint and major bleeding complications were recorded as the secondary endpoints. Relative risk (RR) with a 95%confidence interval (CI) and absolute risk reduction (ARR) were chosen as the effect measure. Results: Ten studies comprising 16 286 patients were included. The median followup was 2 months for the primary endpoint. Among LMWHs, enoxaparin was the compound most frequently used. In the pPCI group, LMWHs were associated with a reduction in mortality [RR (95% CI) = 0.51 (0.41–0.64), P < 0.001, ARR = 3%] and major bleeding [RR (95% CI) = 0.68 (0.49–0.94), P = 0.02, ARR = 2.0%] as compared with UFH. Conversely, no clear evidence of benefits with LWMHs was observed in the PCI group after thrombolysis. Metaregression showed that patients with a higher baseline risk had greater benefits from LMWHs (r = 0.72, P = 0.02). Conclusions: LMWHs were associated with greater efficacy and safety than UFH in STEMI patients treated with pPCI, with a significant relationship between risk profile and clinical benefits. Based on this meta-analysis, LMWHs may be considered as a preferred anticoagulant among STEMI patients undergoing pPCI

Drug-coated balloons in treatment of in-stent restenosis: a meta-analysis of randomised controlled trials

Background Drug-coated balloons (DCBs) have been developed for the percutaneous treatment of coronary artery disease. An initial focus has been the management of in-stent restenosis (ISR) but randomised controlled trials (RCTs) have been small and powered only for angiographic endpoints. Objective The aim of the work was to assess the clinical and angiographic outcomes of patients treated for ISR with DCB versus control (balloon angioplasty or drug-eluting stents) by a meta-analysis of RCTs. Methods A comprehensive search was performed of RCTs where patients with ISR were randomly assigned to either DCB or alternative coronary intervention. Outcome measurements were death, myocardial infarction (MI), target lesion revascularisation (TLR), binary definition of restenosis and in-lesion late luminal loss (LLL). Results Four studies were identified that fulfilled the inclusion criteria. Pooled odds ratios (ORs) were calculated for patients treated for ISR (n = 399). Mean follow-up duration was 14.5 months. DCBs were associated with lower rates of TLR [8.8 vs. 29.7 % OR (95 % confidence interval, CI) 0.20 (0.11–0.36), p\0.0001], binary restenosis [10.3 vs. 41.3 % OR (95 % CI) 0.13 (0.07–0.24), p\0.00001] and MI [0.5 vs. 3.8 %, OR (95 % CI) 0.21 (0.04–1.00), p = 0.05]. No significant heterogeneity was identified. Conclusion Drug-coated balloons appear to be effective versus control in reducing TLR and possibly MI versus balloon angioplasty or drug-eluting stents in the management of ISR

Optimal Timing of Coronary Invasive Strategy in Non–ST-Segment Elevation Acute Coronary Syndromes

Background: The optimal timing of coronary intervention in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACSs) is a matter of debate. Conflicting results among published studies partly relate to different risk profiles of the studied populations. Purpose: To do the most comprehensive meta-analysis of current evidence on early versus delayed invasive treatment in NSTE-ACS. Data Sources: MEDLINE, PubMed Central, and Google Scholar databases; conference proceedings; ClinicalTrials.gov registry; and Current Controlled Trials registry through May 2012. Study Selection: Available randomized, controlled trials (RCTs) and observational studies comparing early versus delayed intervention in the NSTE-ACS population. Data Extraction: Data were extracted for populations, interventions, outcomes, and risk of bias. All-cause mortality was the prespecified primary end point. The longest follow-up available in each study was chosen. The odds ratio with 95% CI was the effect measure. Data Synthesis: Seven RCTs (5370 patients) and 4 observational studies (77 499 patients) were included. Early intervention was less than 20 hours after hospitalization or randomization for RCTs and 24 hours or less for observational studies. Meta-analysis of the RCTs was inconclusive for a survival benefit associated with the early invasive strategy (odds ratio, 0.83 [95% CI, 0.64 to 1.09]; P 0.180); a similar result emerged from the observational studies. With early versus late intervention, the odds ratios in the RCTs were 1.15 (CI, 0.65 to 2.01; P 0.63) and 0.76 (CI, 0.56 to 1.04; P 0.090) for myocardial infarction and major bleeding during follow-up, respectively. Limitation: Current evidence from RCTs is limited by the small overall sample size, low numbers of events in some trials, and heterogeneity in the timing of intervention and in patient risk profiles. Conclusion: At present, there is insufficient evidence either in favor of or against an early invasive approach in the NSTE-ACS population. A more definitive RCT is warranted to guide clinical practice. Primary Funding Source: None

Low-dose of oral factor Xa inhibitors in patients with a recent acute coronary syndrome: A systematic review and meta-analysis of randomized trials

BACKGROUND: Recently, randomized controlled trials (RCTs) have shown that therapy with new oral activated factor X (Xa) inhibitors in acute coronary syndrome (ACS) yielded a reduction of ischemic events. However, this therapy was associated with a dose-related increase in major bleeding complications. We aimed to perform a systematic review and meta-analysis to appraise the clinical efficacy and safety of the lowest doses of oral factor Xa inhibitors compared with placebo in patients after a recent ACS. METHODS: The primary endpoint was cardiovascular mortality. The rate of new myocardial infarction (MI) was the secondary efficacy endpoint, whereas major bleeding complications were recorded as a safety endpoint. Five RCTs were included in the meta-analysis enrolling a total of 25,643 patients. RESULTS: There was no significant difference in mortality between patients treated with new antithrombotics compared with those receiving the standard therapy: odds ratio (OR), [95% confidence interval (CI)] = 0.97 [0.72-1.31], p = 0.86. Recurrent MI rates were decreased in the anti-Xa group: OR [95%CI] = 0.86 [0.76-0.98], p = 0.02, number needed to treat (NNT) = 189. The administration of new oral anticoagulants was associated with a strongly increased risk of major bleedings compared with the standard treatment: OR [95%CI] = 3.24 [2.29-4.59], p < 0.001, number needed to harm (NNH) = 104; similarly, intracranial bleeding rates were significantly higher in the anti-Xa arm. CONCLUSIONS: The addition of the new oral anticoagulants on top of standard therapy in the setting of ACS results in an excessive risk of major bleedings without any clear evidence of outweighing clinical benefits