impacto del control de los distintos factores de riesgo en la fase aguda del avc: objetivos

Impacto del control de los distintos Factores de Riesgo en la fase aguda del AVC: Objetivos.

Vicente Giner Galvañ.

Unidad de HTA y Riesgo Cardiometabólico.Servicio de Medicina Interna. Hospital Verge dels Lliris. Alcoi. Alacant.

Valencia, 8 y 9 de Junio de 2012

IsquémicoIsquémico

HemorrágicoHemorrágico

IdiopáticoIdiopático

LacunarLacunar

CardioembólicoCardioembólico

Arterio-arterialArterio-arterial

TrombóticoTrombótico

Pequeño vasoPequeño vaso

Gran vasoGran vaso

IsquémicoIsquémico

HemorrágicoHemorrágico

IdiopáticoIdiopático

LacunarLacunar

CardioembólicoCardioembólico

Arterio-arterialArterio-arterial

TrombóticoTrombótico

Pequeño vasoPequeño vaso

Gran vasoGran vaso

HTAHTA

DisglucemiaDisglucemia

DislipidemiaDislipidemia

Arritmias (FA)Arritmias (FA)

SAHSSAHS

IntroducciónIctus: entidad vascular altamente heterogénea

Hospital Verge dels Lliris. Alcoy.http//alcoi.san.gva.es

Al contrario de lo que ocurre en otras enfermedades vasculares, el ictus es una entidad heterogénea tanto en sus diferentes formas de presentación clínica como en su etiopatogenia diversa.

Sus factores de riesgo y su pronóstico a corto y largo plazo también varían según el subtipo de ictus.

IntroducciónIctus: entidad vascular altamente heterogénea


La mortalidad intrahospitalaria fue del 12,9%, dentro de los márgenes de la mayoría de las series publicadas.

La hipertensión arterial (HTA) se presentóen el 55,5%, seguida por la fibrilación auricular (FA) (29,8%) y la diabetes mellitus (DM) (23,4%).

Arboix A. Rev Esp Cardiol. 2008;61:1020-9.

Arboix A. Rev Esp Cardiol. 2008;61:1020-9.

IntroducciónIctus: entidad potencialmente curable


El tratamiento agudo del ictus se puede subclasificar en 2 partes:

1.- Medidas generales y de control de complicaciones (Control PA, glucemia, infecciones/temperatura, arritmias…).

2.- Tratamiento recanalizador.


En el paciente no subsidiario de trombolisis

En el paciente subsidiario de trombolisis

IntroducciónIctus: entidad potencialmente curable

Presión arterial

Factores de riesgo en el AVC agudo Presión arterial / HTA


Por cada 10 mmHg de incremento de PAS por encima de 180 mmHg el riesgo de deterioro neurológico se incrementa un 40% y de mal pronóstico global un 23%.

Robinson T. Cerebrovasc Dis. 1997;7:264 -72.



Es común la detección de elevación de la PA en las primeras horas de evolución del ictus, de tal forma que valores de PAS>160 mmHg son detectables en el 60% y atribuibles a estrés, dolor, retención urinaria… (HTA reactiva).

Robinson T. Cerebrovasc Dis. 1997;7:264 -72.

Toyoda K et al. Stroke 2006;37:2637-2639



Toyoda K. Stroke 2006;37:2637-9.





Acute SBP values between 12 and 36 hours

postadmission, but not those on admission or at 6 hours,

were predictive of neurological deterioration within the initial 3 weeks of

ischemic stroke, particularly for cardioembolic stroke

patients.





Acute Acute SBP values between SBP values between 12 and 36 hours12 and 36 hours

postadmission, postadmission, but not those on admission or at 6 hours, ,

were predictivewere predictive of of neurological deterioration neurological deterioration

within the initial 3 weeks of within the initial 3 weeks of ischemic stroke, particularly ischemic stroke, particularly

for cardioembolic stroke for cardioembolic stroke patients. patients.




Vemmos KN. J Hum Hypertens. 2004;18:253-9.




Dawson S. Stroke 2000;31:463-8.

Registro FINAPRES





Registro FINAPRES




Tomii Y. Strroke. 2011; 42: 3511-17.

Registro MAPA




Registro MAPA

Tomii Y. Strroke. 2011; 42: 3511-17.

Mean ambulatory BP monitoring values changed from 150.5±19.5/85.7±11.3 mmHg on Day 1 to 139.6±19.3/80.0±11.7 mmHg on Day 7.




Registro MAPA

Tomii Y. Strroke. 2011; 42: 3511-17.

After multivariate adjustment, mean values of systolic BP (OR, 0.63; 95% CI, 0.45–0.85), diastolic BP (0.61; 0.37–0.98), pulse pressure (0.55; 0.33–0.85), and HR (0.61; 0.37–0.98) recorded on Day 1 as well as mean HR on Day 7 (0.47; 0.23–0.87) were inversely associated with independence.




Tomii Y. Strroke. 2011; 42: 3511-17.

Factores de riesgo en el AVC agudo Presión arterial / HTA: Manejo en fase aguda del ictus


There are several questions about the management of arterialhypertension in the setting of acute stroke.

Should patients previously taking antihypertensive medications continue taking them during the first hours after stroke?

Are some of these medications contraindicated or indicated? Should new antihypertensive agents be started?

What level of blood pressure would mandate initiation of new antihypertensive treatment?

Which medication should be administered in this situation?

AHA/ASA Guideline. Stroke 2007; 38: 1655-711.

Factores de riesgo en el AVC agudo Presión arterial / HTA: Manejo en fase aguda del ictus


There are several questions about the management of arterialhypertension in the setting of acute stroke.

Should patients previously taking antihypertensive medications continue taking them during the first hours after stroke?

Are some of these medications contraindicated or indicated? Should new antihypertensive agents be started?

What level of blood pressure would mandate initiation of new antihypertensive treatment?

Which medication should be administered in this situation?

Unfortunately, definite answers to these questions are not available.


PA en la fase aguda del ictus Estudios disponibles


AcrónimoAcrónimoReferenciaReferencia

MuestraMuestra IntervenciónIntervención Resultado finalResultado final

ACCESACCESStroke. 2003;34:1699.Stroke. 2003;34:1699.

500

Estudio de seguridad

Candesartán vs. Placebo

a 24h del ictus para ↓ PAS 15-20%.

Menor morbimortalidad en candesartán al año (RR 0,475).

Rodríguez-García JLRodríguez-García JLAm J Hypertens.2005;18:379.Am J Hypertens.2005;18:379.

Captopril vs. Amlodipino

a las 24h del ictus

Pequeñas reducciones de PA produjeron beneficio a corto plazo.

Eames PJEames PJCerebrovasc Dis. 2005;19:253.Cerebrovasc Dis. 2005;19:253. 37 ictus isquémicos

Bendrofluazida vs. Placebo

en 24h del AVC durante 7 días

No efectiva en reducción de PA clínica ni latido a latido (FINAPRES).

Eveson DJEveson DJAm J Hypertens.2007;20:270-7Am J Hypertens.2007;20:270-7..

40

hipertensos con ictus isquémico

Lisinopril vs. Placebo

en las primeras 24 hSin diferencias funcionales a los 90

días.

PA en la fase aguda del ictus Estudios disponibles


AcrónimoAcrónimoReferenciaReferencia

MuestraMuestra IntervenciónIntervención Resultado finalResultado final

CHHIPS pilotoCHHIPS pilotoLancet Neurol. 2009; 8:48.Lancet Neurol. 2009; 8:48.

179 hipertensos con AVC isquémico o

hemorrágico

Labetalolo vs. Lisinopril

vs. Placebo

en las 36 h iniciales

Reducción de mortalidad a tres meses (RR 0,40)

COSSACSCOSSACSLancet Neurol. 2010;9:767-75. Lancet Neurol. 2010;9:767-75.

763 pacientes con antiHTA y AVC

isquémico

“mantener antiHTA habituales” vs. “suspenderlos”

en las 48 h

Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events.

SCASTSCASTStroke. 2011;42:2995-8.Stroke. 2011;42:2995-8.

2029

Pacientes con AVC isquémico o hemorrágico

Candesartán vs. Placebo

a las 24h del ictus.

Sin diferencias a 6 meses

(Tendencia a efecto negativo funcional y morbimortalidad con

candesartán a corto plazo)

PIL-FASTPIL-FASTTrials 2011; 12:152Trials 2011; 12:152

60 hipertensos con ictus isquémico en fase pre-hospital

(piloto)

Lisinopril vs. Placebo

en las primeras 3 h si PAS >160 mmHg

En marcha

PA en la fase aguda del ictus Momento de inicio de tto antiHTA


Scandinavian Candesartan Acute Scandinavian Candesartan Acute Stroke Trial (SCAST).Stroke Trial (SCAST). Sandset EC. Stroke 2012 May 24. [Epub ahead of print]

Effect of change in blood pressure during the first 2 days of stroke on the risk of early adverse events and poor outcome.

2029 patients presenting within 30 hours of acute stroke and with systolic blood pressure (SBP) ≥140 mm Hg. Treatment was given for 7 days.

Change in blood pressure was defined as the difference in SBP between baseline and Day 2.




OUTCOMES:

Early adverse events (recurrent stroke, stroke progression, and symptomatic hypotension) during the first 7 days.

Secondary effect parameters were neurological status at 7 days and functional outcome at 6 months




Patients with a large decrease or increase/no change in SBP had a significantly increased risk of early adverse events relative to patients with a small decrease (OR, 2.08; 95% CI, 1.19-3.65 and OR, 1.96; 95% CI, 1.13-3.38, respectively).

PA en la fase aguda del ictus PA y fibrinolisis


Patients who have elevated blood pressure and are otherwise eligible for treatment of rtPA may have their blood pressure lowered so that their systolic blood pressure is <185 mmHg and their diastolic blood pressure is <110 mmHg (Class I, Level of Evidence B) before lytic therapy is started.




If medications are given to lower blood pressure, the clinician should be sure that the blood pressure is stabilized at the lower level before treating with rtPA and maintained below 180/105 mmHg for at least the first 24 hours after intravenous rtPA treatment.




Butcher K. Stroke 2010;41:72-7.

PA en la fase aguda del ictus PA y Fibrinolisis


HI: petechial hemorrhagic infarction.PH: parenchymal hematoma.HT: Hemorragic transformation

Butcher K. Stroke 2010;41:72-7.



Because the maximum interval from stroke onset until treatment with rtPA is short, many patients with sustained hypertension above recommended levels cannot be treated with intravenous rtPA.


PA en la fase aguda del ictus PA en la fase aguda del ictus


Glucemia

Factores de riesgo en el AVC agudo Glucemia


Hyperglycaemia occurs in 30-40% of patients with acute ischaemic stroke, also in individuals without a known history of diabetes.

Luitse MJ. Lancet Neurol. 2012;11:261-71.

Factores de riesgo en el AVC agudo Glucemia: Hiperglucemia inducida por el ictus agudo


Nyika D. Nature Reviews Neurology. 2010; 6,145-55.




Admission hyperglycaemia is associated with poor functional outcome, possibly through aggravation of ischaemic damage by disturbing recanalisation and increasing reperfusion injury.





Admission hyperglycaemia is associated with poor functional outcome, possibly through aggravation of ischaemic damage by disturbing recanalisation and increasing reperfusion injury.

Uncertainty surrounds the question of whether glucose-lowering treatment for early stroke can improve clinical outcome.

Achievement of normoglycaemia in the early stage of stroke can be difficult, and the possibility of hypoglycaemia remains a concern.


Factores de riesgo en el AVC agudo Glucemia: Ensayos clínicos de control de la glucemia


Kruyt ND. et al. Nat. Rev. Neurol. 2010. doi:10.1038/nrneurol.2009.231


Insulin for glycaemic control in acute ischaemic stroke. Squizzato A, Romualdi E, Dentali F, Ageno W.Cochrane Database Syst Rev. 2011 Sep 7;(9):CD005346.


We included seven trials involving 1296 participants (639 participants in the intervention group and 657 in the control group).

Outcomes: death, disability and dependence, hypoglicemia.


Squizzato A. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD005346.


We found that there was no difference between treatment and control groups in the outcome of death or disability and dependence (OR 1.00, 95% CI 0.78 to 1.28) or final neurological deficit (SMD -0.12, 95% CI -0.23 to 0.00).

The rate of symptomatic hypoglycaemia was higher in the intervention group (OR 25.9, 95% CI 9.2 to 72.7).

In the subgroup analyses of diabetes mellitus (DM) versus non-DM, we found no difference for the outcom

PA en la fase aguda del ictus Glucemia en la fase aguda del ictus



Persistent hyperglycemia (>140 mg/dL) during the first 24 hours after stroke is associated with poor outcomes, and thus it is generally agreed that hyperglycemia should be treated in patients with acute ischemic stroke.




The minimum threshold described in previous statements likely was too high, and lower serum glucose concentrations (possibly >140 to 185 mg/dL) probably should trigger administration of insulin, similar to the procedure in other acute situations accompanied by hyperglycemia Class IIa, Level of Evidence C




Close monitoring of glucose concentrations with adjustment of insulin doses to avoid hypoglycemia isrecommended.

Simultaneous administration of glucoseand potassium also may be appropriate.

Lípidos

Factores de riesgo en el AVC agudo Lípidos


Choi KH. J Neurol Sci. 2012. [Epub ahead of print]



Functional Neurology 2011; 26:133-9.



Statin treatment for 4 days may increase circulating EPC (Endothelial progenitor cells) levels, probably by NO-related mechanisms. Sobrino T. Eur J Neurol 2012 May 28. doi: 10.1111/j.1468-1331.2012.03770.x. [Epub ahead of print]



The purpose of the present review is to systematically evaluate the effectiveness of statin pretreatment on functional outcome of acute ischemic stroke and to assess potential adverse events associated with statin use.

Lakhan SE. Int Arch Med. 2010; 3::22.

Recurrence of stroke in patients who had suffered from a previous stroke was analyzed with and without statin therapy.

Incidence and severity of adverse reactions was reviewed.




Pretreatment with statins was associated with a favorable outcome in acute ischemic stroke, with few incidences of adverse reactions.




The beneficial effects of prior statin therapy in acute ischemic stroke were shown to be especially profound in whites, diabetics, elderly patients with hypertension and other vascular diseases, and in patients with ideal low density lipoprotein (LDL) levels.



Statins for acute ischemic stroke.Squizzato A, Romualdi E, Dentali F, Ageno W.Cochrane Database Syst Rev 2011 Aug 10;(8):CD007551.

SELECTION CRITERIA: We included all randomized controlled trials (RCTs) comparing statins (any type and dosage) versus placebo or no treatment, administered within two weeks of the onset of acute ischemic stroke or TIA.

The primary outcomes were mortality from ischemic stroke and mortality from adverse drug effects, bleedings and infections.



Statins for acute ischemic stroke.Squizzato A, Romualdi E, Dentali F, Ageno W.Cochrane Database Syst Rev 2011 Aug 10;(8):CD007551.

MAIN RESULTS: We included eight RCTs involving 625 participants. Only one study was judged as 'low risk' of bias.

AUTHORS' CONCLUSIONS: Insufficient data were available from randomized trials to establish if statins are safe and effective in cases of acute ischemic stroke and TIA.

Arch Bronconeumol 2004;40:196-202.

Factores de riesgo en el AVC agudo SAHS e ictus



RC: Roncopatía crónica.HS: Hipersomnia diurna.




Antes del ictus, el 64,7% de los pacientes eran roncadores, el 21,6% presentaba apneas nocturnas repetidas y el 35,6%, somnolencia diurna.



Stroke of respiratory centers can lead to apnea.

Dyken ME. Chest. 2009;136:1668-77.

Factores de riesgo en el AVC agudo SAHS post-AVC


Dyken ME. Chest. 2009;136:1668-77.



Dyken ME. Chest. 2009;136:1668-77.


Snoring preceding stroke, documentation of apneas immediately prior to transient ischemic attacks, the results of autonomic studies, and the circadian pattern of stroke, suggest that untreated OSA can contribute to stroke.





Dyken ME. Chest. 2009;136:1668-77.

Factores de riesgo en el AVC agudo SAHS e ictus: Mecanismos patofisiológicos


OSA has variably been reported to increase the odds of having the metabolic syndrome anywhere from fivefold to ninefold.

OSA elevates sympathetic nerve activity (SNA) as a result of the reflex effects of hypoxia, hypercapnia, and decreased input from thoracic stretch receptors.

Autonomic effects may also explain the high prevalence of cardiac arrhythmias reported in up to 48% of apneic individuals.

In patients with atrial fibrillation, the risk of OSA has been estimated to be 49%, and noncompliance with CPAP has been associated with a greater recurrence rate of atrial fibrillation after cardioversion.

The elevation of catecholamines and platelet activation associated with OSA may further increase thrombus and embolus formation, and stroke risk

Dyken ME. Chest. 2009;136:1668-77.

Factores de riesgo en el AVC agudo SAHS e ictus: Mecanismos patofisológicos


Netzer N. Stroke 1998;29:87-93.





Although cohort studies indicate that OSA is a stroke risk factor, controversy surrounds the cost-effectiveness of the screening for and treatment of OSA once stroke has occurred.

Dyken ME. Chest. 2009;136:1668-77.



Positional sleep apnea (OSA that is worse in the supine position secondary to gravitational effects on the oropharynx) appears to be a prominent feature in acute stroke.

In a study of 43 subjects with acute stroke or TIA, the mean AHI determined with patients in the supine position of 17.7±20 was significantly higher than the

mean AHI of 8.4±14.6 determined with patients in other than the supine position (p<0.001). Wierzbicka A. J Physiol Pharmacol. 2006; 57:385-90.

55 subjects were assessed within 72 h of stroke, and after 6 months, by using cardiorespiratory polygraphy. Initially, 78% of patients had OSA (AHI ≥10), with 65% demonstrating positional apnea. After 6 months, the prevalence of OSA was only 49% (33% with positional apnea).

Dziewas R. Neurol Res. 2008;30:645-8.

Dyken ME. Chest. 2009;136:1668-77.


Stroke. 2012;43:295-6.

Hypercapnia due to sleep apnea is assumed to contribute to early neurological deterioration by causing cerebral vasodilatation in arteries unaffected by ischemia with a subsequent steal of blood from ischemic and peri-ischemic areas of the brain.

CPAP therapy improves neurological outcome and may reduce the mortality of patients with stroke with obstructive sleep apnea.

CPAP therapy, however, might be beneficial as “acute prophylactic” treatment in the first night after stroke because hemodynamic disturbances due to sleep apnea have markedly detrimental effects at this stage.

Factores de riesgo en el AVC agudo SAHS en la fase aguda del ictus: recomendaciones


En todo ictus valorar posibilidad de SAHS previamente no conocido (cuatro peguntas a familiares).

En todo ictus evitar decúbito supino (cabeza incorporada).

En SAHS ya conocido mantener CAPP* previa. En sospecha de SAHS no conocida valorar CPAP*.*Valoración individual según estado neurológico del paciente.

Conclusiones

Factores de riesgo en el AVC agudo Conclusiones


Muy escasa evidencia.

La moderación y la vigilancia parece ser la clave (Unidad de ictus).

Es absolutamente necesaria la individualización de las actitudes (Unidad de ictus).

Valorar nuevos abordajes aunque no probados poco invasivos (SAHS).

Estricta necesidad de cambio conceptual (Código Ictus).

impacto del control de los distintos factores de riesgo en la fase aguda del avc: objetivos

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