Novel oral anticoagulants: focus on stroke prevention and treatment of venous thrombo-embolism

Anticoagulation for the long-term treatment and prevention of thrombo-embolic diseases as well as for stroke prevention in atrial fibrillation (AF) has been accomplished by vitamin K antagonists for the last half century. Although effective under optimal conditions, the imminent risk of a recurrent event vs. the risk of bleeding due to the narrow therapeutic window, numerous food- and drug interactions, and the need for regular monitoring complicate the long-term use of these drugs and render treatment with these agents complicated. As a result, novel anticoagulants which selectively block key factors in the coagulation cascade are being developed. The efficacy and safety of the direct thrombin inhibitor dabigatran etexilate, as well as of the selective factor Xa inhibitors rivaroxaban and apixaban, have been demonstrated in Phase III trials for stroke prevention in AF and the treatment and secondary prophylaxis of venous thrombo-embolism. This review summarizes the results from recently published pivotal clinical trials and discusses the opportunities as well as uncertainties in the clinical applications of these novel agent

Introduction to the Collection

Includes general information about the scope and content of the original diaries, and a master list of all key words

ST segment resolution as a tool for assessing the efficacy of reperfusion therapy

AbstractRapid, simple and inexpensive measures are needed to assess the efficacy of reperfusion therapy both in clinical practice and in clinical trials testing novel reperfusion regimens. In the last decade, several observations have led to a favorable reappraisal of the utility of ST segment monitoring as a simple means of assessing reperfusion in patients receiving fibrinolytic therapy for acute ST elevation myocardial infarction, and ST resolution is being used increasingly in clinical practice and in clinical research. This review focuses on four interrelated roles for ST segment monitoring: the assessment of epicardial reperfusion and the identification of candidates for rescue percutaneous coronary intervention; the evaluation of microvascular and tissue-level reperfusion; the determination of prognosis early after fibrinolytic therapy; and the use of ST segment resolution to compare different reperfusion regimens

Statin use after acute myocardial infarction by patient complexity: Are the rates right?

Reprinted with permission of the publisher.Background: Guidelines suggest statin use after acute myocardial infarction (AMI) should be close to universal in patients without safety concerns yet rates are much lower than recommended, decline with patient complexity, and display substantial geographic variation. Trial exclusions have resulted in little evidence to guide statin prescribing for complex patients. Objective: Assess the benefits and risks associated with higher rates of statin use after AMI by baseline patient complexity. Research Design: Sample includes Medicare fee-for-service patients with AMIs in 2008-2009. Instrumental variable estimators using variation in local area prescribing patterns by statin-intensity as instruments were used to assess the association of higher statin prescribing rates by statin-intensity on 1-year survival, adverse events, and cost by patient complexity. Results: Providers appear to have individualized statin use across patients based on potential risks. Higher statin rates for non-complex AMI patients were associated with increased survival rates with little added adverse event risk. Higher statin rates for complex AMI patients were associated with tradeoffs between higher survival rates and higher rates of adverse events. Conclusions: Higher rates of statin use for non-complex AMI patients are associated with outcome rate changes similar to existing evidence. For the complex patients in our study, who were least represented in existing trials, higher statin-use rates were associated with survival gains and higher adverse event risks not previously documented. Policy interventions promoting higher statin-use rates for complex patients may need to be re-evaluated taking careful consideration of these tradeoffs.This project was supported by an Agency for Healthcare Research and Quality grant (1R21HS019574-01) under the American Recovery and Reinvestment Act of 2009

Use of Multifactorial Treatments to Address the Challenge of Translating Experimental Myocardial Infarct Reduction Strategies

Myocardial tissue damage that occurs during an ischemic event leads to a spiraling deterioration of cardiac muscle structural and functional integrity. Reperfusion is the only known efficacious strategy and is the most commonly used treatment to reduce injury and prevent remodeling. However, timing is critical, and the procedure is not always feasible for a variety of reasons. The complex molecular basis for cardioprotection has been studied for decades but formulation of a viable therapeutic that can significantly attenuate myocardial injury remains elusive. In this review, we address barriers to the development of a fruitful approach that will substantially improve the prognosis of those suffering from this widespread and largely unmitigated disease. Furthermore, we proffer that ephrinA1, a candidate molecule that satisfies many of the important criteria discussed, possesses robust potential to overcome these hurdles and thus offers protection that surpasses the limitations currently observed

Featuring: Eugene Braunwald

In the Cardiology Masters section of European Cardiology Review, we bring you an insight into the career of a key contributor to the field of cardiology. In this issue, we feature Professor Eugene Braunwald, cardiovascular medicine specialist at Brigham and Women’s Hospital and distinguished Hersey Professor of Medicine at Harvard University, Boston, Massachusetts, US

Feasibility of microbial biodiesel and carotenoid production considering the potential of food processing wastewaters as low cost carbon sources using the example of red yeast Rhodotorula glutinis

Due to the increasing demand for sustainable biofuels, microbial oils as feedstock for the transesterification into biodiesel have gained scientific and commercial interest. Also microbial carotenoids have a considerable market potential as natural colorants. Against this background this thesis assessed the feasibility of biodiesel produced by heterotrophic microorganisms, particularly yeasts, using the example of oleaginous red yeast Rhodotorula glutinis. To improve the economic efficiency of this process, several studies have been conducted in order to test (i) whether wastewaters from the agricultural processing industry can be utilized as low-cost carbon and nutrient source for growth and lipid production by R. glutinis and (ii) if they also facilitate the simultaneous production of beta-carotene and other carotenoids as high-value by-products. It has been shown at a small scale, that agricultural processing wastewaters can be used as feedstock for the microbial production of lipids and carotenoids. The general discussion continues to assess the approach of microbial biodiesel production in a broader context in terms of its economic, environmental and energetic performance. The calculated break-even price of microbial oil, excluding the cost of the carbon source for fermentation, is around double the price of conventional plant oils as competing products. To reduce the costs, cultivation in open raceway ponds was proposed, which led to a cost reduction of around 20 %. In order to assess the potential environmental benefits different life cycle assessments from algae biodiesel production, which share common features with the proposed process, have been analyzed. It was concluded, that microbial biodiesel cannot outperform common 1st generation biodiesel in terms of GHG emissions, whereas factors of eutrophication potential and land competition could be significantly improved. The high climate relevant emissions were mainly driven by the high energy requirements connected to the extraction of microbial oil, which also puts a heavy burden on the energetic efficiency of the process. Considering the potential of continued research and technical development along with the political commitment to promote 2nd and 3rd generation biofuels, it was concluded, that in the long term microbial biodiesel could become a commercial reality above laboratory and pilot scale. Due to the different restrictions this will probably not happen within the next 20-30 years. Contrary to biodiesel, carotenoids are high-value products, with beta-carotene yielding around US$600 per kg. Sustained by this high price and allowing for certain improvements regarding beta-carotene yields and extraction techniques, it can be possible to economically and sustainable produce beta-carotene from R. glutinis in the near future.Aufgrund des steigenden Bedarfs nach nachhaltigen Biokraftstoffen haben mikrobielle Öle als Rohstoff für die Umesterung in Biodiesel an wissenschaftlicher und kommerzieller Bedeutung gewonnen. Auch mikrobiell synthetisierte Carotinoide besitzen ein beachtliches Marktpotenzial im Bereich der natürlichen Farbstoffe. Vor diesem Hintergrund beschäftigt sich die vorliegende Arbeit mit der Möglichkeit der Biodieselproduktion durch heterotrophe Mikroorganismen, insbesondere Hefen, am Beispiel der ölakkumulierenden Rothefe Rhodotorula glutinis. Um die Wirtschaftlichkeit dieses Ansatzes zu verbessern, wurden verschiedene Versuche durchgeführt, um zu überprüfen (i) ob Abwässer der landwirtschaftlichen Verarbeitungsindustrie und des Agribusiness als kostengünstige Kohlenstoff- und Nährstoffquellen für Wachstum und Lipidproduktion von R. glutinis genutzt werden können und (ii) ob sie darüber hinaus die simultane Produktion von Beta-Carotin und weiteren Carotinoiden als hochwertige Nebenprodukte ermöglichen. In kleinem Maßstab konnte gezeigt werden, dass Abwässer aus der landwirtschaftlichen Verarbeitungsindustrie als Ausgangsstoff für die mikrobielle Produktion von Lipiden und Carotinoiden genutzt werden können. Die Gesamtdiskussion führte die Bewertung der mikrobiellen Biodieselproduktion in einem größeren Gesamtzusammenhang fort, der ökonomische, ökologische sowie energetische Parameter mit einschloss. Der errechnete Break-even Preis, exklusive der Kosten für die Kohlenstoffquelle, war etwa doppelt so hoch wie der Preis für herkömmliches Pflanzenöl als relevantem Konkurrenzprodukt. Um Kosten einzusparen, wurde die Kultivierung der Hefen in offenen Teichsystemen (raceway ponds) vorgeschlagen, was zu einer Kostenminderung von ca. 20 Abschließend wurde die Realisierbarkeit der Produktion von Carotinoiden durch R. glutinis bewertet. Im Gegensatz zu Biodiesel stellen Carotinoide hochwertige Produkte dar, wobei Beta-Carotin einen Marktpreis von ca. US$ 600 je kg erzielen kann. Dieser hohe Preis sowie bestimmte Optimierungen bezüglich des Beta-Carotin Ertrags und der angewandten Extraktionsmethoden können in naher Zukunft eine wirtschaftliche und nachhaltige Produktion von Beta-Carotin durch R. glutinis ermöglichen