Behandeling van bloeddruk in de acute fase van het herseninfarct Erik Hoff / 07-04-2005 CAT Neurologie

Bloeddruk en herseninfarct Observationele studies: Zowel hoge als lage bloeddruk is geassocieerd met slechte prognose (op korte termijn) Zowel hoge als lage bloeddruk is geassocieerd met toename mortaliteit (op lange termijn) Interventie studies: Secundair preventie van recidief CVA en cardiovasculaire events door antihypertensiva (hypertensieve/normotensieve patienten)

Hypertensie Bij opname heeft 80% van de patiënten een verhoogde bloeddruk Afwegingen bij eventuele behandeling: Tegen: Natuurlijk beloop is spontane afname in eerste week (dag 4-10) Hypotensie bedreigt ischemische penumbra (CBF wordt afhankelijk van systemische bloeddruk door verstoring van cerebrovasculaire reactiviteit en dynamische autoregulatie) Veranderde fysiologische responsen op bloeddruk veranderingen door stoornis autonome zenuwstelsel (baroreceptorreflex <=> orthostase) Voor: Systolische RR > 150 mmHg geassocieerd met vroeg recidief infarct (4.2% toename per 10 mmHg stijging) Cerebraal oedeem en hemorragische transformatie

Protocol Herseninfarct hoge bloeddruk in acute stadium niet behandelen tenzij RR > 220/120 mmHg of complicaties optreden (zoals nierbeschadiging, hypertensieve encephalopathie)

Probleemstelling 40% van de patienten met een herseninfarct gebruikt antihypertensiva bij opname 20% van de patienten heeft een normale of lage bloedruk Moeten we antihypertensiva stoppen bij normotensieve patienten? P: normotensieve patient met herseninfarct en antihypertensiva I: stoppen van antihypertensiva C: continueren van antihypertensiva O: functionele outcome

COSSACS (Continue Or Stop post-Stroke Antihypertensives Collaborative Study) Most stroke patients will develop elevated blood pressure levels as an acute complication of the stroke However, up to 40% of acute stroke patients on hospital admission are already taking antihypertensive therapy What to do: continue or discontinue antihypertensive therapy following acute stroke? www.le.ac.uk/cv/research/COSSACS/COSSACShome.html

COSSACS (II) COSSACS is a multi-centre, prospective, randomised, open, blinded-endpoint study (UK only) It assesses whether existing antihypertensive therapy should be continued or discontinued within 24 hours of stroke onset and subsequent two weeks The trial will assess the short- (2 weeks) and long-term (6 months) rates of death and disability in the continued versus discontinued groups Will provide information to support the future evidence-based management of acute post-stroke hypertension

ENOS (Efficacy of Nitric Oxide in Stroke) collaborative, international, multicentre, prospective, randomised, single-blind, blinded endpoint, parallel-group, controlled trial designed to test the safety and efficacy of: (i) transdermal glyceryl trinitrate (a nitric oxide donor) or control; and (ii) continuing or temporarily stopping prior anti-hypertensive medication 5000 patients with acute ischaemic or haemorrhagic stroke will be enrolled within 48 hours of the onset of stroke and treatment will be given for 7 days. The primary outcome is death or dependency (modified Rankin Scale >2) and will be determined at 3 months by observers blinded to treatment Status (as of 2 April 2005): Enrolled patients: 331 (see logon page for the very latest figure) Participating centres: 21 Participating countries: 6 (Australia, Canada, Philippines, Poland, Singapore, UK) http://www.nottingham.ac.uk/stroke-medicine/enos/

Zoekstrategie PubMed Zoekterm: acute stroke blood pressure antihypertensive treatment NOT hypertension 103 abstracts (19 reviews) 1 humane studie, rest preventie en/of toch hypertensie

Nazir FS, Overell JR, Bolster A, Hilditch TE, Lees KR Nazir FS, Overell JR, Bolster A, Hilditch TE, Lees KR. Effect of perindopril on cerebral and renal perfusion on normotensives in mild early ischaemic stroke: a randomized controlled trial. Cerebrovasc Dis. (2005) Effect of the angiotensin-converting enzyme inhibitor perindopril on blood pressure, global and focal cerebral blood flow (CBF) and glomerular filtration rate (GFR) in a normotensive acute stroke population Twenty-five patients within 4-8 days of mild ischaemic stroke/transient ischaemic attack and with diastolic blood pressure 70-90 mm Hg were randomized to receive perindopril 2 or 4 mg daily versus placebo Antihypertensive therapy with perindopril may be introduced in the first week after mild ischaemic stroke in normotensive patients without affecting global or regional CBF or affecting GFR

Conclusie Twee lopende studies naar wel of niet stoppen van antihypertensiva in acute fase herseninfarct (waarvan één met primair doel) Geen onderzoeksdata betreffende stoppen van antihypertensiva bij normotensieve of hypotensieve patienten Voorstel: bij hypotensieve patienten stop antihypertensiva Bij normotensieve patienten en/of twijfel kortwerkende antihypertensiva stoppen (maar meestal ‘slow release’) of overleg voorschrijvend arts / hypertensioloog / cardioloog

REFERENTIES: Lawes CM et al. Blood pressure and stroke: an overview of published reviews. Stroke (2004) Adams HP Jr et al. Guidelines for the early management of patients with ischemic stroke: A scientific statement from the Stroke Council of the American Stroke Association. Stroke (2003) Robinson TG and Potter JF. Blood pressure in acute stroke. Age and Ageing (2004) Chalmers J. The management of blood pressure in acute stroke. Lancet Neurol (2003)