BACKGROUND
Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy — heart-rate control or rhythm control — remains controversial.
METHODS
Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test.
RESULTS
Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P = 0.76). There were no significant between-group differences in the rates of death (P = 0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P = 0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P = 0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P = 0.41).
CONCLUSIONS
Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.)
Background
The late durability of endovascular aneurysm repair (EVAR) has been limited by progressive aortic degeneration believed to be mediated by matrix metalloproteases (MMP). The goal of this study was to evaluate the effect of a MMP inhibitor, doxycycline, on EVAR.
Methods and Results
Patients undergoing EVAR were randomized to doxycycline (100mg twice daily) or placebo for 6 months following the procedure. Clinical data, blood samples and CT scans were obtained pre-operatively, post-operatively (blood only), and at 1 and 6 month follow-up. Forty-four subjects were analyzed based on intention-to-treat. Plasma MMP-9 decreased significantly below baseline in the doxycycline (N=20) treated patients at 6 months (−16.4±20.7%, P<0.05) while there was a non-significant increase in the placebo (N=24) group (128.1±73.5%). This was primarily related to changes between one and six months. In patients with endoleaks at 6 months, plasma MMP-9 increased in 83% of the placebo treated patients, but in only 14% of the doxycycline treated group (P<.03). Among endoleak-free patients with AneuRx or Excluder endografts, doxycycline treatment resulted in greater decreases in maximum aortic diameter than placebo treatment (−13.3±3.3% vs. −3.8±3.0%, P<.05). Furthermore, doxycycline treatment significantly reduced the aortic neck dilatation at six months in Excluder treated patients.
Conclusion
There is evidence of persistent MMP release representing ongoing aortic degradation after endografting which can be inhibited by doxycycline therapy. In analyses based on the endograft used, treatment with doxycycline also demonstrated evidence of increased aortic dimensional stability, a surrogate marker for long-term success of EVAR. Although encouraging, these results require confirmation in larger patient populations. Doxycycline should undergo more thorough evaluation as a potential adjuvant treatment to improve the results of EVAR, particularly in certain subgroups.
Aneurysm development in the elastase model is dependent on the quantity of active elastase infused. Exposure of animals to tobacco smoke after a relatively minor aortic elastase injury produces increases in elastin degradation and aneurysm size without affecting MMP-9 or MMP-12 expression. To our knowledge, this is the first demonstration in an animal model that smoking can act as a synergistic factor in AAA development. Further understanding of the relationship between smoking and AAA in this model may help unveil the pathophysiologic pathways involved between cigarette smoke and AAAs.
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