For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts Haemostasis is crucial for the maintenance of the integrity of the cardiovascular system. Too little of it leads to bleeding, as extensively described in the case of the Tsarevich Alexei Nikolajewitsch Romanow, who was a bleeder due to a mutation in factor VII or IX. Too much haemostasis on the other hand leads to intravascular thrombus formation in either the venous or the arterial system, with often detrimental clinical consequences such as pulmonary embolisms, stroke, and death. For the prevention of the latter scenarios, anticoagulation has been introduced, initially with warfarin, a vitamin K antagonist, and more recently with novel oral anticoagulants or NOACs1 such as abixaban, edoxaban,2,3 or rivaroxaban4 interfering with factor X, and dabigatran, a thrombin antagonist.5 The dosage of these agents is crucial to be effective and avoid bleeding, as outlined in the most recent ESC Guidelines.6 With NOACs, renal function and body mass have to be considered,7 an issue addressed in the Current Opinion ‘Antithrombotic therapy and body mass’ authored by Bianca Rocca on behalf of the ESC Working Group on Thrombosis.8 The authors note that extremely low and high body weights have become common due to frailty with ageing and the epidemic of obesity, respectively. These extreme body weights affect cardiovascular risk, including mortality, as well as the pharmacokinetics and safety profiles of antithrombotic drugs. Further research is warranted to optimize antithrombotic therapy in underweight as well as in different classes of obese patients, to guide dosing, dose adjustment, and/or reference intervals, and to establish whether the balance of benefits and risks of antithrombotic drugs can be improved. Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. In a second Current Opinion entitled ‘Proposed standardized neurological endpoints for cardiovascular clinical trials’, Alexandra Jane Lansky and colleagues from the Yale School of Medicine in New Haven, Connecticut, USA9 remind us that current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit–risk assessment of such procedures should be based on well-defined neurological outcomes. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies. A traumatic injury requires proper haemostasis to avoid excessive blood loss or damage to vital organs. In their article entitled ‘Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study’ Laila Staerk and colleagues from the Gentofte University Hospital in Copenhagen, Denmark examined the risks of mortality, stroke, major bleeding, and recurrent traumatic injury associated with resumption of vitamin K antagonists or NOACs following traumatic injury in 4541 elderly patients with atrial fibrillation.10 Within 90 days after traumatic injury, 60.6% resumed vitamin K antagonists, 16.7% NOACs, and 22.7% did not resume anticoagulation, while 9.5% were switched from vitamin K antagonists to NOACs. Compared with non-resumption, vitamin K antagonists and NOAC resumption were associated with lower all-cause mortality with a hazard ratio of 0.48 and 0.55, respectively and ischaemic stroke with a hazard ratio of 0.56 and 0.54, respectively (Figure 1). On the other hand, major bleeding hazard increased, with hazard ratios of 1.30 and 1.15, respectively. Thus, atrial fibrillation patients resuming vitamin K antagonists or NOACs following traumatic injury have a lower hazard of all-cause mortality and ischaemic stroke, but an increased hazard of major bleeding, but without additional hazards of recurrent traumatic injury. Whether anticoagulation following traumatic injury should generally not be withheld in atrial fibrillation is discussed in an Editorial by Christopher B. Granger from the Duke University Medical Center in Durham, North Carolina (USA).11 Figure 1 View largeDownload slide Standardized absolute risks of outcomes associated with non-resumption vs. resumption of VKA and NOAC following traumatic injury. For each treatment option separately, the standardized absolute risks are based on the outcome-specific multiple Cox regression models and obtained as averages of the predicted risks had all patients received this treatment. NOAC, non-vitamin K antagonist oral anticoagulant; VKA, vitamin K antagonist (from Staerk L, Fosbøl EL, Lamberts M, Bonde AN, Gadsbøll K, Sindet-Pedersen C, Holm EA, Gerds TA, Ozenne B, Lip GYH, Torp-Pedersen C, Gislason GH, Olesen JB. Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study. See pages 1698–1705). Figure 1 View largeDownload slide Standardized absolute risks of outcomes associated with non-resumption vs. resumption of VKA and NOAC following traumatic injury. For each treatment option separately, the standardized absolute risks are based on the outcome-specific multiple Cox regression models and obtained as averages of the predicted risks had all patients received this treatment. NOAC, non-vitamin K antagonist oral anticoagulant; VKA, vitamin K antagonist (from Staerk L, Fosbøl EL, Lamberts M, Bonde AN, Gadsbøll K, Sindet-Pedersen C, Holm EA, Gerds TA, Ozenne B, Lip GYH, Torp-Pedersen C, Gislason GH, Olesen JB. Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study. See pages 1698–1705). Patients with valvular heart disease requiring surgical valve replacement in the aortic position do better with mechanical valves than bioprosthesis.12 However, mechanical valves require anticoagulation with vitamin K antagonists and hence are prone to bleeding.13 A particularly difficult clinical scenario is anticoagulation in patients with mechanical heart valves after intracerebral haemorrhage. In their article entitled ‘Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves’, Hagen B. Huttner and colleagues from Universitatsklinikum Erlangen in Germany investigated anticoagulation reversal and resumption strategies and their complications to define an optimal time window for restarting anticoagulation in 137 such patients.14 In half of these patients, anticoagulation was restarted and was associated with a 26% increase in haemorrhagic complications and only a trend to decreased thrombo-embolic complications. Adjusting for crossovers provided an incidence rate ratio of 10.31 in disadvantage of anticoagulation for haemorrhages. A timing analysis showed harm until day 13 after intracerebral haemorrhage with a hazard ratio of 7.06. The hazard for both complications was increased for restarted anticoagulation until day 6 with, a hazard ratio of 2.51. Restarting anticoagulation within <2 weeks after intracerebral haemorrhage in patients with mechanical heart valves was associated with increased haemorrhagic complications. Optimal weighing between least risks for thrombo-embolic and haemorrhagic complications provided an earliest starting point of anticoagulation at day 6, but only for patients at high thrombo-embolic risk. The clinical applicability of these findings is highlighted in an Editorial by Freek W.A. Verheugt from the Onze Lieve Vrouwe Gasthuis in Amsterdam, the Netherlands.15 A further difficult clinical scenario are patients with atrial fibrillation undergoing percutaneous coronary intervention or PCI, as outlined in a recent ESC Focused Update on Dual Antiplatelet Therapy.16 In a meta-analysis entitled ‘Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention’ Deepak L. Bhatt and colleagues from the Harvard Medical School in Boston, Massachusetts (USA) studied the safety and efficacy of dual vs. triple antithrombotic therapy in 5317 patients of whom 57% received dual antiplatelet therapy.17 Compared with triple anticoagulation, TIMI bleeding was reduced by 47%, while major adverse cardiac events did not differ. Thus. compared with triple anticoagulation, dual antiplatelet therapy reduced TIMI major or minor bleeding by half with comparable outcomes. Whether dual antiplatelet therapy may be a better option than triple anticoagulation in atrial fibrillation following PCI is critically discussed in an Editorial by Gilles Montalescot from the Pitié-Salpêtrière University Hospital in Paris, France.18 Observational studies indicate that statins reduce the risk of recurrent venous thrombosis.19 However, the mechanism is unknown. In their article ‘Rosuvastatin use improves measures of coagulation in patients with venous thrombosis’, Willem Lijfering and colleagues from the Leids Universitair Medisch Centrum in Leiden, the Netherlands determined whether statin therapy improves the coagulation profile.20 A total of 247 patients who had unprovoked venous thrombosis were randomized to rosuvastatin 20 mg/day for 4 weeks or no intervention. For all tested coagulation factors, mean levels were decreased by rosuvastatin, whereas they hardly differed in controls (Figure 2). Subgroup analyses revealed that the decrease in coagulation factors by rosuvastatin was more pronounced in participants with unprovoked venous thrombosis and cardiovascular risk factors. These results suggest that statin therapy might be beneficial in patients at risk of recurrent venous thrombosis. Figure 2 View largeDownload slide Effects of rosuvastatin on measures of coagulation (from Biedermann JS, Kruip MJHA, van der Meer FJ, Rosendaal FR, Leebeek FWG, Cannegieter SC, Lijfering WM. Rosuvastatin use improves measures of coagulation in patients with venous thrombosis. See pages 1740–1747). Figure 2 View largeDownload slide Effects of rosuvastatin on measures of coagulation (from Biedermann JS, Kruip MJHA, van der Meer FJ, Rosendaal FR, Leebeek FWG, Cannegieter SC, Lijfering WM. Rosuvastatin use improves measures of coagulation in patients with venous thrombosis. See pages 1740–1747). The editors hope that this issue of the European Heart Journal will be of interest to its readers. References 1 Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2017; 38: 2137– 2149. Google Scholar PubMed 2 O’Donoghue ML, Ruff CT, Giugliano RP, Murphy SA, Grip LT, Mercuri MF, Rutman H, Shi M, Kania G, Cermak O, Braunwald E, Antman EM. Edoxaban vs. warfarin in vitamin K antagonist experienced and naive patients with atrial fibrillation. Eur Heart J 2015; 36: 1470– 1477. Google Scholar CrossRef Search ADS PubMed 3 Steffel J, Giugliano RP, Braunwald E, Murphy SA, Atar D, Heidbuchel H, Camm AJ, Antman EM, Ruff CT. Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial. Eur Heart J 2015; 36: 2239– 2245. Google Scholar CrossRef Search ADS PubMed 4 Camm AJ, Amarenco P, Haas S, Hess S, Kirchhof P, Kuhls S, van Eickels M, Turpie AG. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2016; 37: 1145– 1153. Google Scholar CrossRef Search ADS PubMed 5 Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139– 1151. Google Scholar CrossRef Search ADS PubMed 6 Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbüchel H; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39: 1330– 1393. Google Scholar CrossRef Search ADS PubMed 7 Sandhu RK, Ezekowitz J, Andersson U, Alexander JH, Granger CB, Halvorsen S, Hanna M, Hijazi Z, Jansky P, Lopes RD, Wallentin L. The ‘obesity paradox’ in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Eur Heart J 2016; 37: 2869– 2878. Google Scholar CrossRef Search ADS PubMed 8 Rocca B, Fox KAA, Ajjan RA, Andreotti F, Baigent C, Collet J-P, Grove EL, Halvorsen S, Huber K, Morais J, Patrono C, Rubboli A, Seljeflot I, Sibbing D, Siegbahn A, Ten Berg J, Vilahur G, Verheugt FWA, Wallentin L, Weiss TW, Wojta J, Storey RF. Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis. Eur Heart J 2018; 39: 1672– 1686. 9 Lansky AJ, Messe SR, Brickman AM, Dwyer M, Bart van der Worp H, Lazar RM, Pietras CG, Abrams KJ, McFadden E, Petersen NH, Browndyke J, Prendergast B, Ng VG, Cutlip DE, Kapadia S, Krucoff MW, Linke A, Scala Moy C, Schofer J, van Es G-A, Virmani R, Popma J, Parides MK, Kodali S, Bilello M, Zivadinov R, Akar J, Furie KL, Gress D, Voros S, Moses J, Greer D, Forrest JK, Holmes D, Kappetein AP, Mack M, Baumbach A. Proposed standardized neurological endpoints for cardiovascular clinical trials: An academic research consortium initiative. Eur Heart J 2018; 39: 1687– 1697. 10 Staerk L, Fosbøl EL, Lamberts M, Bonde AN, Gadsbøll K, Sindet-Pedersen C, Holm EA, Gerds TA, Ozenne B, Lip GYH, Torp-Pedersen C, Gislason GH, Olesen JB. Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study. Eur Heart J 2018; 39: 1698– 1705. 11 Pokorney SD, Granger CB. Traumatic injury: another unjustified reason to stop oral anticoagulation for atrial fibrillation. Eur Heart J 2018; 39: 1706– 1708. Google Scholar CrossRef Search ADS 12 Glaser N, Jackson V, Holzmann MJ, Franco-Cereceda A, Sartipy U. Aortic valve replacement with mechanical vs. biological prostheses in patients aged 50–69 years. Eur Heart J 2016; 37: 2658– 2667. Google Scholar CrossRef Search ADS PubMed 13 Korteland NM, Etnel JRG, Arabkhani B, Mokhles MM, Mohamad A, Roos-Hesselink JW, Bogers A, Takkenberg JJM. Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation. Eur Heart J 2017; 38: 3370– 3377. Google Scholar CrossRef Search ADS PubMed 14 Kuramatsu JB, Sembill JA, Gerner ST, Sprugel MI, Hagen M, Roeder SS, Endres M, Haeusler KG, Sobesky J, Schurig J, Zweynert S, Bauer M, Vajkoczy P, Ringleb PA, Purrucker J, Rizos T, Volkmann J, Mullges W, Kraft P, Schubert A-L, Erbguth F, Nueckel M, Schellinger PD, Glahn J, Knappe UJ, Fink GR, Dohmen C, Stetefeld H, Fisse AL, Minnerup J, Hagemann G, Rakers F, Reichmann H, Schneider H, Wöpking S, Ludolph AC, Stösser S, Neugebauer H, Röther J, Michels P, Schwarz M, Reimann G, Bäzner H, Schwert H, Claßen J, Michalski D, Grau A, Palm F, Urbanek C, Wöhrle JC, Alshammari F, Horn M, Bahner D, Witte OW, Günther A, Hamann GF, Lücking H, Dörfler A, Achenbach S, Schwab S, Huttner HB. Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves. Eur Heart J 2018; 39: 1709– 1723. 15 Verheugt FWA. Anticoagulation resumption after intracranial haemorrhage with mechanical valves: a data-free zone. Eur Heart J 2018; 39: 1724– 1725. Google Scholar CrossRef Search ADS 16 Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2018; 39: 213– 260. Google Scholar CrossRef Search ADS PubMed 17 Golwala HB, Cannon CP, Steg PG, Doros G, Qamar A, Ellis SG, Oldgren J, Ten Berg JM, Kimura T, Hohnloser SH, Lip GYH, Bhatt DL. Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials. Eur Heart J 2018; 39: 1726– 1735. 18 Hammoudi N, Montalescot G. The times they are a changin. Eur Heart J 2018; 39: 1736– 1739. 19 Kunutsor SK, Seidu S, Khunti K. Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies. Eur Heart J 2017; 38: 1608– 1612. Google Scholar CrossRef Search ADS PubMed 20 Biedermann JS, Kruip MJHA, van der Meer FJ, Rosendaal FR, Leebeek FWG, Cannegieter SC, Lijfering WM. Rosuvastatin use improves measures of coagulation in patients with venous thrombosis. Eur Heart J 2018; 39: 1740– 1747. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions please email: email@example.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
European Heart Journal – Oxford University Press
Published: May 11, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera