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25–26 January 2019
More than 200 neurologists, cardiologists and various other specialists braved the wintery Berlin weather to attend European Society of Cardiology (ESC) Heart and Stroke, the annual conference of the ESC Council for Stroke. Since its inception at ESC 2016, the Council for Stroke has grown to more than 1200 members, and this was reflected in the increased participation at this event compared with the first meeting in 2018.
Conference director and chairperson of the ESC Council for Stroke Professor Wolfram Döhner (Berlin, Germany) explained that the conference aims to look at stroke from a wide angle, with a particular emphasis on the interaction of stroke and cardiology. Reflecting the broad range of attendees, the programme featured a mix of symposia, debates and workshops on topics related to stroke prevention and treatment.
The Bayer-sponsored symposium on ‘Practical Management of Patients at Risk of Stroke’ covered the latest data from the non-vitamin K antagonist oral anticoagulants (NOACs) in the prevention of a broad range of stroke aetiologies. In his introduction to the symposium, Professor Döhner highlighted the importance of understanding the role of antithrombotic therapies across all ischaemic stroke, and the need for even more data to support physician decision-making. With the increasing push towards individualized medicine, he reminded the audience of factors that may impact appropriate anticoagulant therapy, such as co-morbidities, concomitant medications, compliance and patient preference.
Figure 1. Ischaemic strokes may be separated into five categories.1 Understanding the most appropriate antithrombotic therapy is essential for the management of each of these stroke types.
In his symposium presentation, Professor Darius Nabavi (Berlin, Germany) discussed the COMPASS trial, which compared rivaroxaban 2.5 mg twice daily plus aspirin with aspirin alone in patients with stable coronary or peripheral artery disease.2 The trial was stopped early due to overwhelming efficacy of the dual pathway regimen for the prevention of major adverse cardiovascular events (the composite of cardiovascular death, myocardial infarction or stroke) – an effect that was driven largely by a 42% reduction in the risk of stroke. This protective effect was also seen in patients with a history of prior stroke (~350 patients per arm), with a recent subanalysis reporting a 58% relative risk reduction with rivaroxaban plus aspirin compared with aspirin alone.3
The COMPASS results were also discussed in the morning plenary session, with Dr Wael Sumaya (Sheffield, UK) asking the question ‘Is antiplatelet therapy enough?’ in patients at high risk of stroke. Presenting on behalf of Professor Rob Storey, Dr Sumaya reviewed data from both the PEGASUS TIMI 54 and COMPASS trials, before addressing the question of how to treat patients with atrial fibrillation (AF) who experience an acute coronary syndrome.
A patient with AF and co-morbidities may pose a challenge to the prescribing cardiologist, warranting careful consideration of the most appropriate therapy and dose for the patient. Professor Jan Beyer-Westendorf (London, UK and Dresden, Germany) opened his symposium presentation by describing a case familiar to many cardiologists – a 73-year-old woman with newly diagnosed paroxysmal AF and a creatinine clearance of 40 ml/min. This combination of AF and renal impairment is common, with one-third of patients with AF having an estimated glomerular filtration rate (eGFR) between 15 and 59 ml/min.4 However, as Professor Beyer-Westendorf explained, several factors should be taken into account when considering the optimal treatment strategy.
“The good news is that cardiologists are very experienced in treating AF with renal impairment because the combination is so common – we see it every day. But the devil is in the detail, and it is important to highlight what to do and what to avoid to further improve patient care.”
Renal impairment is associated with both an increase in stroke risk and an increase in bleeding risk – a paradox that leads some physicians to shy away from NOACs in favour of traditional vitamin K antagonists in these patients. However, subanalyses of the phase III trials for all four NOACs have demonstrated consistently lower stroke and bleeding risk compared with warfarin in patients with renal impairment, with a benefit–risk profile as strong or stronger than in patients with normal renal function.5-8
Figure 2. Retrospective claims database analysis showing the risk of renal outcomes in patients treated with rivaroxaban versus warfarin.9
Furthermore, recent evidence suggests that NOACs may have additional benefits over warfarin in terms of preservation of renal function: although kidney function was found to decline over time with both NOACs and warfarin in the pivotal phase III trials, both rivaroxaban and dabigatran were associated with a significantly better preservation of renal function compared with warfarin.10,11 The same was not observed for apixaban.12 These data are supported by a retrospective claims database analysis showing that rivaroxaban was associated with a significantly lower risk of major renal events such as ≥30% decline in eGFR, a doubling in creatinine levels, acute kidney injury or kidney failure.9
One of the leading causes of kidney disease is diabetes – in itself, a risk factor for both ischaemic stroke and bleeding in patients with AF. Registry data have shown that the combination is especially dangerous, with a 10-year mortality of 31% in patients with both diabetes and kidney disease compared with only 8% in patients with neither.13 Highlighting the impact these co-morbidities have on the overall risk, Professor Beyer-Westendorf stressed the importance of considering all the evidence when selecting the most appropriate therapy for each patient.
A recent update to the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guidelines on the management of atrial fibrillation14 recognizes that “over time, NOACs (particularly dabigatran and rivaroxaban) may be associated with lower risks of adverse renal outcomes than warfarin in patients with AF”.
Management of patients with AF presents a daily challenge to the prescribing physician – while anticoagulation mitigates the increased risk of ischaemic stroke, it may increase the risk of bleeding events. Professor Nabavi highlighted this delicate balance with two cases of patients with AF receiving inadequate anticoagulant therapy, leading to an ischaemic stroke in one patient and a haemorrhagic stroke in the other.
“Many physicians fear haemorrhagic complications of oral anticoagulation most, resulting in a tendency to undertreatment. But as stroke physicians we must remember the high risk of ischaemic stroke in patients with atrial fibrillation and protect them with anticoagulation appropriate to their risk factors.”
A wealth of data from randomized clinical trials supports the use of NOACs for both primary and secondary stroke prevention in patients with AF. A meta-analysis of clinical trials reported an 8% relative reduction in the risk of ischaemic stroke and a 51% relative risk reduction for haemorrhagic stroke compared with warfarin.15 In secondary prevention, a 2014 meta-analysis demonstrated a 14% relative risk reduction and a 0.8% absolute risk reduction in the risk of ischaemic stroke with NOACs versus warfarin – comparable to the risk reduction observed with aspirin, statins or reducing blood pressure in secondary stroke prevention.16 The safety benefit of NOACs is also preserved in patients with a previous stroke, with reductions in the rates of both intracranial and fatal bleeding.
Figure 3. Rates of intracranial and fatal bleeding in patients with a prior stroke receiving either warfarin or rivaroxaban in the ROCKET AF study.17
Professor Christian Nolte (Berlin, Germany) addressed the question of how and when to initiate or resume anticoagulation following an acute ischaemic stroke in patients with AF. Although randomized clinical trials of all four NOACs excluded patients with a stroke in the 7–30 days prior to randomization, recent registry data has suggested that initiation of anticoagulation is optimal between days 5 and 14 after a stroke.18 Current clinical guidelines recommend adjusting the timing of initiation depending on the size and severity of the infarct, with later initiation recommended for larger lesions due to the greater risk of parenchymal haemorrhage.19
MA recurring theme at the conference was the importance of accurately detecting AF, particularly paroxysmal AF. Although several studies have shown increased AF detection with longer ECG monitoring, limited resources may restrict the availability of prolonged monitoring. Dr Constanze Schmidt (Heidelberg, Germany) presented a score to predict the presence of paroxysmal AF,20 offering the possibility to focus resources on those at greatest risk. Professor Isabelle van Gelder (Groningen, the Netherlands) additionally presented data showing that the burden of subclinical paroxysmal AF is a predictor of stroke,21 making the identification and accurate measurement of AF even more important. To this end, there was excitement around the ongoing Apple Heart study, which uses data from the Apple watch to detect abnormal heart rhythms, and the CATCH ME study, which aims to identify the causes of AF in the elderly and develop clinical tools to personalize the prevention and management of AF.