Latest developments in stroke treatment

Lisbon (ptp003/17.06.2018/09:00) Stroke has reached epidemic proportions: there are 600,000 newly reported cases in Europe each year. "Death rates have been declining for two decades, thanks to major advances in prevention, treatment and rehabilitation. But there is still room for improvement when it comes to avoiding permanent injury following a stroke, and preventing strokes from happening in the first place. The latest research results will make a significant contribution to this," said Prof Franz Fazekas (Graz) at the 4th Congress of the European Academy of Neurology (EAN) in Lisbon.

A recent study (Amarenco et al) highlighted the importance of secondary prevention in reducing the risk of recurrent stroke. It showed how high the risk is of suffering an additional stroke after a small stroke or a transitory ischaemic attack (TIA). The study analysed data from around 3,800 patients at a five-year follow-up. Almost 13 percent of patients - 469 people - either had a stroke or developed an acute coronary syndrome, or had died within five years of the original stroke event. "345 patients had strokes during the observation period, 196 in the first year alone and 149 in the remaining four years," EAN President elect Prof Fazekas said.

Dual antiplatelet therapy with clopidogrel and aspirin

Researchers are working hard to identify ways of protecting high-risk groups from recurrent stroke. One recent study (Johnston et al) was able to demonstrate the suitability of a combined dose of the thrombocyte aggregation inhibitor clopidogrel and aspirin as a preventive measure. "The combination therapy was more successful than aspirin alone, but also carried a heightened risk of major bleeding. Nevertheless, in individual cases, use of this dual therapy, which prevents the aggregation of blood platelets, is justified and certainly worthwhile," Prof Fazekas confirmed. In the study a cohort of almost 4,900 patients was accompanied for 90 days following a minor cerebral infarction or a transitory ischaemic attack, and given either clopidogrel and aspirin, or just aspirin and a placebo. Only 5 percent of patients in the first group suffered a cerebral infarction, heart attack or died as a result of an ischeamic problem in the monitoring period, i.e. 121 out of 2,432 patients. In the control group (aspirin and placebo) 6.5 percent, or 160 of 2,499 patients, went on to experience major ischaemic events. Major haemorrhage occurred in 23 patients in the clopidogrel-aspirin group, compared with just 10 in the aspirin-placebo group.

Embolic stroke: rivaroxaban increases haemorrhage risk

The results of a study investigating prevention of embolic strokes of unknown cause (Hart et al) revealed scant evidence of benefits: contrary to hopes, the orally administered factor Xa inhibitor rivaroxaban, a blood thinning agent, proved no better than aspirin. In fact, it was shown to increase the risk of haemorrhage. "That is regrettable, as we urgently need to find ways to prevent these kinds of strokes," commented Prof. Fazekas. Around a fifth of all strokes are caused by embolisms, and survivors have an elevated risk of suffering another stroke due to the formation of a blood clot. "Before initiating any anticoagulation therapy we still need to determine if there really exists a cardioembolic source," the expert explained. More than 7,000 stroke patients were enrolled in the study and treated with rivaroxaban (at a dose of 15mg per day) or aspirin (100mg per day) for an average of 11 months. The number of recurrent ischaemic events was virtually the same in both groups (158 in the rivaroxaban group, 156 in the aspirin group). However, major bleeding occurred in 62 patients in the rivaroxaban group, which was almost three times as many as in the aspirin group, where 23 patients suffered from haemorrhage.

Thrombolysis still helps after more than 4.5 hours

A number of breakthroughs in the field of acute treatment were discussed at the 4th EAN Congress: The latest WAKE UP study (Thomalla et al) presented evidence how intravenous thrombolysis can still be effectively used even when the time of stroke onset is not exactly known. "According to European treatment guidelines, intravenous thrombolysis is only a viable option if the treatment is initiated within 4.5 hours of the attack. This means that we have to know when the stroke occurred which is unfortunately not the case in 14 to 27 percent of strokes, most often because stroke symptoms are just noted when people awake from sleep. We now have clues how MRI may identify those patients in whom thrombolysis is beneficial even if we do not know the exact time of stroke onset," explained Prof Fazekas, who worked on the study. The trial compared the results of around 500 patients who suffered a stroke with an unknown time of onset. All the patients had ischaemic lesions which were visible only on diffusion-weighted MRI while fluid-attenuated inversion recovery (FLAIR) imaging was negative, suggesting that the stroke must have occurred just recently and probably not more than 4.5 hours earlier. Half of those enrolled in the trial received intravenous alteplase, with the remainder given a placebo. After 90 days 53.3 percent of the alteplase group showed a favourable treatment outcome, as opposed to just 41.8 percent of patients in the placebo group. Individuals that received the thrombolytic drug also presented significantly better functional outcome than participants given the placebo. On a scale of 0 (no symptoms) to 6 (death) the thrombolytic group averaged 1, and the placebo group 2. Mortality rates were higher in the non-placebo group (10 deaths compared with 2) and there was some increased incidence of intracranial bleeding (2 vs. 0.4 percent) but this did not outweigh the positive effects of thrombolysis.

Sources: 4th EAN Congress Lisbon 2018: Workshop "Imaging selection of stroke patients for specific treatment interventions". P. Amarenco et al, Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke, New England Journal of Medicine , DOI: 10.1056/NEJMoa1800410; R.G. Hart et al, Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source, New England Journal of Medicine, May 16, 2018, DOI: 10.1056/NEJMoa1802686; S. C. Johnston et al, Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA, New England Journal of Medicine, May 16, 2018, DOI: 10.1056/NEJMoa1800410; G. Thomalla et al, MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset, New England Journal of Medicine, May 16, 2018, DOI: 10.1056/NEJMoa1804355

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