Discrepancy between short-term and long-term effects of bone marrow-derived cell therapy in acute myocardial infarction: a systematic review and meta-analysis

Abstract Background Bone marrow-derived cell therapy has been used to treat acute myocardial infarction. However, the therapeutic efficacy of this approach remains controversial. Here, we performed a systematic review and meta-analysis to evaluate short-term and long-term effectiveness of bone marrow-derived therapy. Methods We searched eight databases (Ovid-Medline, Ovid-EMBASE, Cochrane Library, KoreaMed, KMBASE, KISS, RISS, and KisTi) up to December 2014. Demographic characteristics, clinical outcomes, and adverse events were analyzed. We identified 5534 potentially relevant studies; 405 were subjected to a full-text review. Forty-three studies with 2635 patients were included in this review. Results No safety issues related to cell injection were reported during follow-up. At 6 months, cell-injected patients showed modest improvements in left ventricular ejection fraction (LVEF) compared with the control group. However, there were no differences between groups at other time points. In the cardiac MRI analysis, there were no significant differences in infarct size reduction between groups. Interestingly, mortality tended to be reduced at the 3-year follow-up, and at the 5-year follow-up, cell injection significantly decreased all-cause mortality. Conclusions This meta-analysis demonstrated discrepancies between short-term LV functional improvement and long-term all-cause mortality. Future clinical trials should include long-term follow-up outcomes to validate the therapeutic efficacy of cell therapy

Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis

BACKGROUND: Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents. METHODS: We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. FINDINGS: Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021). INTERPRETATION: The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents