journal article
Download Only Collection
Home
Joseph, Philip; Pare, Guillaume; Wallentin, Lars; Connolly, Stuart; Yusuf, Salim; Wang, Jia; Ezekowitz, Michael; Eikelboom, John; Siegbahn, Agneta; Reilly, Paul; Themeles, Ellison; Oldgren, Jonas
doi: 10.1136/heartjnl-2015-307586pmid: 26552755
ObjectiveCarboxylesterases, which convert dabigatran etexilate to its active form, dabigatran, have also been shown to influence lipoprotein metabolism, although any pleotropic effects of the drug based on this possible mechanism has not been evaluated. We examined the effects of dabigatran etexilate on serum lipoprotein markers in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study.Methods2513 participants from the RE-LY randomised control trial with baseline and 3-month apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) measurements were included. We prospectively compared the effects of dabigatran 110 mg twice daily, dabigatran 150 mg twice daily and warfarin on changes in ApoB and ApoA1 concentrations using a mixed model analysis.ResultsFrom baseline to 3 months, a significant reduction in ApoB concentration was observed with low-dose dabigatran (−0.057 (95% CI −0.069 to −0.044) g/L, p<0.001) and high-dose dabigatran (−0.065 (95% CI −0.078 to −0.053) g/L, p<0.001) but not warfarin (−0.006 g/L (95% CI −0.018 to 0.007) g/L, p=0.40). Compared with warfarin, ApoB reduction was significantly greater with both doses of dabigatran (p<0.001 for both groups). Reductions in ApoA1 concentrations did not statistically differ with either dose of dabigatran when compared with warfarin.ConclusionsDabigatran is associated with a significant (∼7%) reduction in ApoB concentration, suggesting a novel effect of this drug on lipoprotein metabolism. Further studies are needed to determine the mechanism of this observed effect, and its impact on clinical outcomes.
Mohamed Omer, Safraz; Krishna, Smriti Murali; Li, Jiaze; Moxon, Joseph Vaughan; Nsengiyumva, Vianne; Golledge, Jonathan
doi: 10.1136/heartjnl-2015-308322pmid: 26573094
BackgroundStem cell (SC) administration is a potential therapeutic strategy to improve blood supply in patients with peripheral artery disease (PAD). The aim of this systematic review and meta-analysis was to investigate the efficacy of extraembryonic tissue-derived SC (ETSC) in improving blood flow within animal models of hindlimb ischaemia (HLI).MethodsPubMed, ScienceDirect and Web of Science were searched to identify studies which investigated ETSCs within animal HLI models. A meta-analysis was performed focusing on the effect of ETSCs on limb blood flow assessed by laser Doppler imaging using a random effects model. Methodological quality was assessed using a newly devised quality assessment tool.ResultsFive studies investigating umbilical cord-derived SCs (three studies), placental SCs (one study), amnion and chorionic SCs (one study) were included. A meta-analysis suggested that administration of ETSCs improved the restoration of blood flow within the HLI models used. The methodological quality of the included studies was assessed as poor. Problems identified included lack of randomised design and blinding of outcome assessors; that the animal models did not incorporate recognised risk factors for human PAD or atherosclerosis; the models used did not have established chronic ischaemia as is the cases in most patients presenting with PAD; and the studies lacked a clear rationale for the dosage and frequency of SCs administered.ConclusionsThe identified studies suggest that ETSCs improve recovery of limb blood supply within current animal HLI models. Improved study quality is, however, needed to provide support for the likelihood of translating these findings to patients with PAD.
Showing 1 to 4 of 4 Articles