Zusammenfassung
Anhand von selektierten Publikationen aus den vergangenen 12 Monaten werden aktuelle
Entwicklungen und Neuheiten in der Prävention und Behandlung des Schlaganfalls dargestellt.
In der Primärprävention ist die Kombination eines ACE-Hemmers und eines Kalziumantagonisten
wirksamer als die Kombination eines ACE-Hemmers mit einem Diuretikum. Bei Patienten
mit Diabetes mellitus ist niedrig dosiertes ASS in der Primärprävention makrovaskulärer
Ereignisse nicht wirksam. Eine aggressive Behandlung des Diabetes mellitus Typ II
reduziert mikrovaskuläre Ereignisse, führt aber nicht zu einer Reduktion von Herzinfarkt,
Schlaganfall oder vaskulärem Tod. Die Sicherheit und Effektivität der systemische
Thrombolyse mit rt-PA konnte auch in dem erweiterten Zeitfenster zwischen 3–4,5 h
nach ischämischem Schlaganfall nachgewiesen werden. Es gibt Hinweise, dass eine Komedikation
mit Omeprazol zu einer Abschwächung der Clopidogrelwirkung führt. Bei Patienten mit
Vorhofflimmern, die Kontraindikationen gegen die orale Antikoagulation haben oder
diese ablehnen, ist eine Kombinationstherapie aus Clopidogrel und ASS der ASS-Monotherapie
überlegen. Die Kombinationstherapie ASS und Clopidogrel ist jedoch mit einem eindeutig
erhöhten Blutungsrisiko in der Schlaganfallsekundärprophylaxe verbunden. Aufgrund
der Langzeitergebnisse bleibt die Karotisendarteriektomie bei > 70 %igen symptomatischen
Karotisstenosen die Therapie der 1. Wahl und kann sowohl in Lokalanästhesie als auch
in Allgemeinnarkose durchgeführt werden.
Abstract
On the basis of selected publications from the past 12 months, current developments
and innovations in the prevention and treatment of stroke are presented. For primary
prevention, the combination of an ACE inhibitor and a calcium antagonist has proved
to be more effective than the combination of an ACE inhibitor with a diuretic. For
patients with diabetes mellitus low-dose ASA is not effective for the primary prevention
of macrovascular events. Aggressive treatment of diabetes mellitus type II reduces
microvascular events but does not lead to a reduction in heart attack, stroke or vascular
mortality. The safety and efficacy of systemic thrombolysis with rt-PA has also been
demonstrated in the expanded time window of 3 to 4.5 hours after ischaemic stroke.
There are indications that a comedication with omeprazol can lead to a reduction of
the effects of clopidogrel. In patients with atrial fibrillation, those with contraindications
against an oral anticoagulation, or those who reject the latter therapy, the combination
of clopidogrel with ASA is superior to an ASA monotherapy. However, the combination
therapy of ASA with clopidogrel is associated with a markedly higher bleeding risk
in the secondary prophylaxis of stroke. On the basis of long-term results, carotid
endarterectomy is the treatment of first choice in cases of symptomatic > 70 % carotid
stenosis and can be performed either under local anaesthesia or under general anaesthesia.
Schlüsselwörter
Schlaganfall - Prävention - klinische Studien
Keywords
stroke - prevention - clinical trials
Literatur
- 1
Lopez-Garcia E, Rodriguez-Artalejo F, Rexrode K M. et al .
Coffee consumption and risk of stroke in women.
Circulation.
2009;
119
1116-1123
- 2
Douglas I J, Smeeth L.
Exposure to antipsychotics and risk of stroke: self controlled case series study.
BMJ.
2008;
337
a1227
- 3
Jamerson K, Weber M A, Bakris G L. et al .
Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients.
N Engl J Med.
2008;
359
2417-2428
- 4
Toole J F, Malinow M R, Chambless L E. et al .
Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke,
myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP)
randomized controlled trial.
JAMA.
2004;
291
565-575
- 5
The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators .
Homocysteine lowering with folic acid and B vitamins in vascular disease.
N Engl J Med.
2006;
354
1567-1577
- 6
Spence J D.
Homocysteine-lowering therapy: a role in stroke prevention?.
Lancet Neurol.
2007;
6
830-838
- 7
Ridker P M, Manson J E, Buring J E. et al .
Homocysteine and risk of cardiovascular disease among postmenopausal women.
JAMA.
1999;
281
1817-1821
- 8
Albert C M, Cook N R, Gaziano J M. et al .
Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality
among women at high risk for cardiovascular disease: a randomized trial.
JAMA.
2008;
299
2027-2036
- 9
Hodis H N, Mack W J, Dustin L. et al .
High-dose B vitamin supplementation and progression of subclinical atherosclerosis:
a randomized controlled trial.
Stroke.
2009;
40
730-736
- 10
Briel M, Ferreira-Gonzalez I, You J J. et al .
Association between change in high density lipoprotein cholesterol and cardiovascular
disease morbidity and mortality: systematic review and meta-regression analysis.
BMJ.
2009;
338
b92
- 11
Ridker P M, Danielson E, Fonseca F A. et al .
Rosuvastatin to prevent vascular events in men and women with elevated C-reactive
protein.
N Engl J Med.
2008;
359
2195-2207
- 12
Sesso H D, Buring J E, Christen W G. et al .
Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians'
Health Study II randomized controlled trial.
JAMA.
2008;
300
2123-2133
- 13
Bjelakovic G, Nikolova D, Gluud L L. et al .
Mortality in randomized trials of antioxidant supplements for primary and secondary
prevention: systematic review and meta-analysis.
JAMA.
2007;
297
842-857
- 14
Chiuve S E, Rexrode K M, Spiegelman D. et al .
Primary prevention of stroke by healthy lifestyle.
Circulation.
2008;
118
947-954
- 15
Ogawa H, Nakayama M, Morimoto T. et al .
Low-dose aspirin for primary prevention of atherosclerotic events in patients with
type 2 diabetes: a randomized controlled trial.
JAMA.
2008;
300
2134-2141
- 16
Skyler J S, Bergenstal R, Bonow R O. et al .
Intensive glycemic control and the prevention of cardiovascular events: implications
of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American
Diabetes Association and a scientific statement of the American College of Cardiology
Foundation and the American Heart Association.
Circulation.
2009;
119
351-357
- 17
Gerstein H C, Miller M E, Byington R P. et al .
Effects of intensive glucose lowering in type 2 diabetes.
N Engl J Med.
2008;
358
2545-2559
- 18
Patel A, MacMahon S, Chalmers J. et al .
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
N Engl J Med.
2008;
358
2560-2572
- 19
Duckworth W, Abraira C, Moritz T. et al .
Glucose control and vascular complications in veterans with type 2 diabetes.
N Engl J Med.
2009;
360
129-139
- 20
Hacke W, Kaste M, Bluhmki E. et al .
Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.
N Engl J Med.
2008;
359
1317-1329
- 21
Hacke W, Donnan G, Fieschi C. et al .
Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS,
and NINDS rt-PA stroke trials.
Lancet.
2004;
363
768-774
- 22
Barreto A D, Martin-Schild S, Hallevi H. et al .
Thrombolytic therapy for patients who wake-up with stroke.
Stroke.
2009;
40
827-832
- 23
Martin-Schild S, Hallevi H, Albright K C. et al .
Aggressive blood pressure-lowering treatment before intravenous tissue plasminogen
activator therapy in acute ischemic stroke.
Arch Neurol.
2008;
65
1174-1178
- 24
Hacke W, Furlan A J, Al-Rawi Y. et al .
Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion
weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind,
placebo-controlled study.
Lancet Neurol.
2009;
8
141-150
- 25
Hacke W, Albers G, Al-Rawi Y. et al .
The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour
window acute stroke thrombolysis trial with intravenous desmoteplase.
Stroke.
2005;
36
66-73
- 26
Furlan A J, Eyding D, Albers G W. et al .
Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety
and efficacy 3 to 9 hours after stroke onset.
Stroke.
2006;
37
1227-1231
- 27
Leonardi-Bee J, Bath P, Phillips S. IST Collaborative Group .
Blood pressure and clinical outcomes in the International Stroke Trial.
Stroke.
2002;
33
1315-1320
- 28
Potter J F, Robinson T G, Ford G A. et al .
Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised,
placebo-controlled, double-blind pilot trial.
Lancet Neurol.
2009;
8
48-56
- 29
den Hertog H M, van der Worp H B, van Gemert H M. et al .
The Paracetamol (Acetaminophen) In: Stroke (PAIS) trial: a multicentre, randomised,
placebo-controlled, phase III trial.
Lancet Neurol.
2009;
8
434-440
- 30
Mathew J P, Mackensen G B, Phillips-Bute B. et al .
Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine
in cardiac surgery.
Stroke.
2009;
40
880-887
- 31
Diener H C, Ringleb P A, Savi P.
Clopidogrel for secondary prevention of stroke.
Expert Opin Pharmacother.
2005;
6
755-764
- 32
Weimar C, Goertler M, Rother J. et al .
Systemic Risk Score Evaluation in Ischemic Stroke Patients (SCALA): A prospective
cross sectional study in 85 German stroke units.
J Neurol.
2007;
254
1562-1568
- 33
Weimar C, Goertler M, Rother J. et al .
Predictive value of the Essen Stroke Risk Score and Ankle Brachial Index in acute
ischaemic stroke patients from 85 German stroke units.
J Neurol Neurosurg Psychiatry.
2008;
79
1339-1343
- 34
Weimar C, Diener H C, Alberts M J. et al .
The Essen stroke risk score predicts recurrent cardiovascular events: a validation
within the REduction of Atherothrombosis for Continued Health (REACH) registry.
Stroke.
2009;
40
350-354
- 35
Joubert J, Reid C, Barton D. et al .
Integrated care improves risk-factor modification after stroke: initial results of
the Integrated Care for the Reduction of Secondary Stroke model.
J Neurol Neurosurg Psychiatry.
2009;
80
279-284
- 36
Berrouschot J, Schwetlick B, von Twickel G. et al .
Aspirin resistance in secondary stroke prevention.
Acta Neurol Scand.
2006;
113
31-35
- 37
Hankey G J, Eikelboom J W.
Aspirin resistance.
Lancet.
2006;
367
606-617
- 38
Krasopoulos G, Brister S J, Beattie W S. et al .
Aspirin „resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis.
BMJ.
2008;
336
195-198
- 39
Ho P M, Maddox T M, Wang L. et al .
Risk of adverse outcomes associated with concomitant use of clopidogrel and proton
pump inhibitors following acute coronary syndrome.
JAMA.
2009;
301
937-944
- 40
Simon T, Verstuyft C, Mary-Krause M. et al .
Genetic determinants of response to clopidogrel and cardiovascular events.
N Engl J Med.
2009;
360
363-375
- 41
Mega J L, Close S L, Wiviott S D. et al .
Cytochrome p-450 polymorphisms and response to clopidogrel.
N Engl J Med.
2009;
360
354-362
- 42
Weimar C, Benemann J, Katsarava Z. et al .
Adherence and quality of oral anticoagulation in cerebrovascular disease patients
with atrial fibrillation.
Eur Neurol.
2008;
60
142-148
- 43
Healey J S, Hart R G, Pogue J. et al .
Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin
in patients with atrial fibrillation according to stroke risk: the atrial fibrillation
clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE-W).
Stroke.
2008;
39
1482-1486
- 44
The ACTIVE Investigators .
Effect of clopidogrel added to aspirin in patients with atrial fibrillation.
N Engl J Med.
2009;
360
2066-2078
- 45
Connolly S J, Pogue J, Eikelboom J. et al .
Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends
on the quality of international normalized ratio control achieved by centers and countries
as measured by time in therapeutic range.
Circulation.
2008;
118
2029-2037
- 46
Massie B M, Collins J F, Ammon S E. et al .
Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart
failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial.
Circulation.
2009;
119
1616-1624
- 47
Usman M H, Notaro L A, Nagarakanti R. et al .
Combination antiplatelet therapy for secondary stroke prevention: enhanced efficacy
or double trouble?.
Am J Cardiol.
2009;
103
1107-1112
- 48
Diener H, Bogousslavsky J, Brass L. et al .
Acetylsalicylic acid on a background of clopidogrel in high-risk patients randomised
after recent ischaemic stroke or transient ischaemic attack: The MATCH trial results.
Lancet.
2004;
364
331-334
- 49
Bhatt D L, Fox K A, Hacke W. et al .
Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic
events.
N Engl J Med.
2006;
354
1706-1717
- 50
Sacco R, Diener H, Yusuf S. et al .
Randomized comparison of aspirin and extended-release dipyridamole to copidogrel for
prevention of recurrent strokes.
N Engl J Med.
2008;
239
1238-1251
- 51
Ringleb P A, Allenberg J, Bruckmann H. et al .
30 day results from the SPACE trial of stent-protected angioplasty versus carotid
endarterectomy in symptomatic patients: a randomised non-inferiority trial.
Lancet.
2006;
368 (9543)
1239-1247
- 52
Eckstein H H, Ringleb P, Allenberg J R. et al .
Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study
to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised
trial.
Lancet Neurol.
2008;
7
893-902
- 53
Mas J L. for the EVA-3S Investigators .
Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis.
N Engl J Med.
2006;
355
1660-1671
- 54
Mas J L, Trinquart L, Leys D. et al .
Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis
(EVA-3S) trial: results up to 4 years from a randomised, multicentre trial.
Lancet Neurol.
2008;
7
885-892
- 55
Stingele R, Berger J, Alfke K. et al .
Clinical and angiographic risk factors for stroke and death within 30 days after carotid
endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.
Lancet Neurol.
2008;
7
216-222
- 56
Jansen O, Fiehler J, Hartmann M. et al .
Protection or nonprotection in carotid stent angioplasty: the influence of interventional
techniques on outcome data from the SPACE Trial.
Stroke.
2009;
40
841-846
- 57
Lewis S C, Warlow C P, Bodenham A R. et al .
General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre,
randomised controlled trial.
Lancet.
2008;
372
2132-2142
- 58
Siddiq F, Vazquez G, Memon M Z. et al .
Comparison of primary angioplasty with stent placement for treating symptomatic intracranial
atherosclerotic diseases: a multicenter study.
Stroke.
2008;
39
2505-2510
- 59
Chimowitz M I, Lynn M J, Howlett-Smith H. et al .
Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis.
N Engl J Med.
2005;
352
1305-1316
- 60
Turan T N, Maidan L, Cotsonis G. et al .
Failure of antithrombotic therapy and risk of stroke in patients with symptomatic
intracranial stenosis.
Stroke.
2009;
40
505-509
- 61
Ozdemir A O, Tamayo A, Munoz C. et al .
Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism.
J Neurol Sci.
2008;
275
121-127
- 62
Serena J, Marti-Fabregas J, Santamarina E. et al .
Recurrent stroke and massive right-to-left shunt: results from the prospective Spanish
multicenter (CODICIA) study.
Stroke.
2008;
39
3131-3136
- 63
Menon R, Kerry S, Norris J W. et al .
Treatment of cervical artery dissection: a systematic review and meta-analysis.
J Neurol Neurosurg Psychiatry.
2008;
79
1122-1127
- 64
The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators
.
High-dose atorvastatin after stroke or transient ischemic attack.
N Engl J Med.
2006;
355
549-559
- 65
Chaturvedi S, Zivin J, Breazna A. et al .
Effect of atorvastatin in elderly patients with a recent stroke or transient ischemic
attack.
Neurology.
2009;
72
688-694
- 66
Sillesen H, Amarenco P, Hennerici M G. et al .
Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis:
a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol
Levels (SPARCL) trial.
Stroke.
2008;
39
3297-3302
- 67
Molyneux A J, Kerr R S, Yu L M. et al .
International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus
endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised
comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and
aneurysm occlusion.
Lancet.
2005;
366
809-817
- 68
Molyneux A J, Kerr R S, Birks J. et al .
Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised
mortality ratios after clipping or coiling of an intracranial aneurysm in the International
Subarachnoid Aneurysm Trial (ISAT): long-term follow-up.
Lancet Neurol.
2009;
8
427-433
Prof. Dr. H. C. Diener
Direktor der Neurologischen Klinik und Poliklinik, Universität Duisburg-Essen
Hufelandstr. 55
45147 Essen
Email: hans.diener@uni-due.de
