Stroke: Better prevention in cases of atrial fibrillation, minimally invasive surgery for blood clots in the brain.
Better drugs for stroke prevention for patients with atrial fibrillation, good results in the removal of blood clots in the brain using keyhole surgery: researchers reported progress in the fight against strokes, the second-largest cause of death at the Meeting of the European Neurological Society (ENS) in Prague. There is highly promising new research into the problem of stroke-related brain damage sometimes continuing to spread despite treatment.
“Strokes are the second most important cause of death, and one of the most relevant public health problems altogether, with 16 million new cases worldwide every year, and 5.5 million deaths,” Prof. Guido Stoll (Department of Neurology at the University Hospital of Würzburg) said on Monday at the 22nd Meeting of the European Neurological Society (ENS). “It is all the more pleasing to be able to report significant progress both in preventive medication and in treatment of acute cases.” The ENS Meeting has brought together more than 3,000 experts in Prague.
Among the most important recent developments is the emergence of new, more convenient drugs to prevent thromboses developing in cases of atrial fibrillation, which can lead to embolisation by blocking cerebral blood vessels (ischemic stroke). There are also improved therapeutic options to report: the possibility of minimally invasive removal of blood clots in acute infarction. There are also new insights into the mechanisms involved in “reperfusion injury”: the continued progress of brain damage despite the removal or dissolution of the blood clot.
Atrial fibrillation: more convenient thromboprophylaxis, equally effective with reduced risk of complications
Atrial fibrillation, which affects well over 4.5 million people across the EU, is a factor in about 10% of all ischemic strokes. As a result of irregular heartbeats blood clots (thrombi) form in the left atrium of the heart. If these dissolve and flow towards the brain the result can be a stroke. “Prophylaxis against this risk factor has now become easier and safer, and works just as effectively,” said Prof Stoll. The current standard therapy for the prevention of thrombosis, the blood-thinning agent MarcumarR, had great disadvantages, he said. One was of a serious risk of bleeding and great variations in absorption, sometimes dependent on nutrition, both compromising the drug’s effectiveness in preventing strokes. This meant regular monitoring of blood coagulation and frequent dose adjustments were required.
“Two recently approved drugs for this condition have set new standards,” said Prof Stoll. These were the thrombosis inhibitor Dabigatran and the coagulation factor Xa inhibitor Rivaroxaban. “These are just as effective in preventing cerebral embolism, but carry a much lower risk of cerebral haemorrhage, which is particularly feared. We can also be confident of reliable levels of affect at fixed doses, so that patients are spared the arduous coagulation monitoring checks. A third drug, Apixaban also inhibits coagulation factor Xa and is already being used as prophylactic against thromboses in hip and knee surgery. Given excellent results from studies, this drug too may be poised to be approved as a prophylaxis against embolism in patients with atrial fibrillation.”
New alternatives: minimally-invasive removal of thrombosis
It has long been known that thrombolysis medication to treat larger thromboses, especially in the area of the carotid artery or in a main branch of the middle cerebral artery, is insufficiently effective in dissolving them, and can result in severe strokes. But there is new hope: mechanical removal of thromboses (thrombectomy) using micro-catheters and minimally invasive high-tech medicine. The ENS Congress discussed the latest data on thrombectomy, which guides a tiny “basket” via a catheter up to the occluded brain vessel. There, the thrombosis is “captured” and withdrawn. There had been very promising experiences, inter alia with 200 patients in Bern, reported Prof Stoll. “It makes special sense to combine the highly innovative thrombectomy procedure with blood-thinning medication within the first few hours after a stroke.”
In suitably equipped centres it could become standard in the future for patients with occlusion of large vessels supplying the brain. Another advantage of thrombectomy lay in the fact that this method could be safely applied in the case of patients suffering strokes immediately after surgery or other intervention where thrombolysis was out of the question due too high risk of bleeding.
Reperfusion injury: first promising research
However, in a numerically significant number of cases, infarction-related brain damage continues despite successful lysis and/or removal of the thrombosis; the reason is a mysterious process known as reperfusion injury. “Our many years of effort to discover the reasons for this paradox are at last bearing fruit,” said Prof Stoll. “The endothelium, the inner lining of the cerebral vessels, can be so altered by a temporary interruption of the blood supply that platelets suddenly stick to the vessel wall, are activated, and reduce, or actually stop, the blood-flow, even in smaller connected cerebral vessels.
We have found that in addition to platelets other inflammatory processes are responsible, in particular the complement system. In animal experiments we have now been able to show that a drug that inhibits the so-called complement factor C1 (C1-Esterase) and has already been approved for other indications, reduced the size of the infarct by half if administered early enough after a stroke. There is still a long road ahead before this discovery can be used clinically, but it is a very promising road which will, one day, result in us mastering reperfusion injury”.
Strokes – medicine’s problem child. Rising death toll despite successes
Every six seconds someone dies of a stroke. It is the second-most common cause of death in the world, the third-most in developed countries, and the most common cause of acquired disability in adults and for the need for care in old age. “Although in recent years it has been possible to cut the relative frequency (prevalence) of strokes in western industrialized countries, thanks to rising life expectancy the number of cases continues to rise here too, more than offsetting these advances,” said Prof Stoll.
“The annual number of new cases is rising dramatically in economically emerging countries in Asia like China, but also in Eastern Europe, where living standards are catching up. As early as 2030, world-wide there will be 23 million new strokes every year, with maximum growth in low-income countries; the absolute number of stroke patients will rise to 62 million. An interesting new finding is that the causes are the same everywhere, with no evidence of cultural specifics.”
Large-scale epidemiological studies identified 10 factors which together account for 90 per cent of individual stroke risks. These are: excessively high blood pressure, followed by smoking (passive smoking too!), diabetes, obesity, poor diet, lack of exercise, atrial fibrillation, excessive alcohol consumption, unfavourable blood fat values, and psycho-social factors such stress and depression. This list shows that we can significantly influence our risk of strokes by changing our lifestyles, regular check-ups, and regular medication,” said Prof Stoll.
ENS Abstract O 294: C1-inhibitor protects from ischemic stroke in rodents by combined anti-inflammatory and anti-thrombotic mechanisms