Tratamiento antiagregante plaquetario oral para el ictus isquémico agudo: una revisión Cochrane / Oral antiplatelet therapy for acute ischaemic stroke: a Cochrane review

Pregunta de la revisión. Queríamos comparar la seguridad y la eficacia del tratamiento antiplaquetario oral frente a placebo o ningún tratamiento en personas con ictus isquémico agudo para ver si los antiplaquetarios orales reducían el número de muertes y mejoraban los resultados a largo plazo en los supervivientes. Fundamento. La mayoría de los ictus están causados por una obstrucción repentina de una arteria del cerebro que suele deberse a un coágulo de sangre (lo que se denomina ictus isquémico). El tratamiento inmediato con antiagregantes plaquetarios, como la aspirina, puede evitar la formación de nuevos coágulos y mejorar así la recuperación tras el ictus. Sin embargo, los antiagregantes plaquetarios también pueden provocar hemorragias cerebrales, lo que podría anular sus efectos beneficiosos. Características del estudio. Se identificaron 11 estudios, hasta agosto de 2020, para su inclusión en la revisión. Estos estudios incluyeron 42.226 participantes. Tres eran nuevos ensayos desde la última actualización. Como en la versión anterior de esta revisión, dos estudios aportaron el 96% de los datos. La mayoría de los participantes en la revisión eran ancianos, con una proporción significativa de más de 70 años. Los hombres y las mujeres estaban representados casi por igual en los ensayos. Parecía haber alguna variación en la gravedad del accidente cerebrovascular entre los ensayos incluidos. La duración programada del tratamiento varió de 5 días a 3 meses y el periodo de seguimiento programado varió de 10 días a 6 meses. Resultados clave. La aspirina, en dosis de 160 mg a 300 mg diarios, iniciada en las 48 horas siguientes a la aparición de los síntomas del ictus, salvó vidas y redujo el riesgo de que se produjera un nuevo ictus en las dos primeras semanas... (AU)

Tratamiento antiagregante plaquetario oral para el ictus isquémico agudo: una revisión Cochrane / Oral antiplatelet therapy for acute ischaemic stroke: a Cochrane review

Pregunta de la revisión. Queríamos comparar la seguridad y la eficacia del tratamiento antiplaquetario oral frente a placebo o ningún tratamiento en personas con ictus isquémico agudo para ver si los antiplaquetarios orales reducían el número de muertes y mejoraban los resultados a largo plazo en los supervivientes. Fundamento. La mayoría de los ictus están causados por una obstrucción repentina de una arteria del cerebro que suele deberse a un coágulo de sangre (lo que se denomina ictus isquémico). El tratamiento inmediato con antiagregantes plaquetarios, como la aspirina, puede evitar la formación de nuevos coágulos y mejorar así la recuperación tras el ictus. Sin embargo, los antiagregantes plaquetarios también pueden provocar hemorragias cerebrales, lo que podría anular sus efectos beneficiosos. Características del estudio. Se identificaron 11 estudios, hasta agosto de 2020, para su inclusión en la revisión. Estos estudios incluyeron 42.226 participantes. Tres eran nuevos ensayos desde la última actualización. Como en la versión anterior de esta revisión, dos estudios aportaron el 96% de los datos. La mayoría de los participantes en la revisión eran ancianos, con una proporción significativa de más de 70 años. Los hombres y las mujeres estaban representados casi por igual en los ensayos. Parecía haber alguna variación en la gravedad del accidente cerebrovascular entre los ensayos incluidos. La duración programada del tratamiento varió de 5 días a 3 meses y el periodo de seguimiento programado varió de 10 días a 6 meses. Resultados clave. La aspirina, en dosis de 160 mg a 300 mg diarios, iniciada en las 48 horas siguientes a la aparición de los síntomas del ictus, salvó vidas y redujo el riesgo de que se produjera un nuevo ictus en las dos primeras semanas... (AU)

The effect of hypercapnia on the directional sensitivity of dynamic cerebral autoregulation and the influence of age and sex.

The cerebral circulation responds differently to increases in mean arterial pressure (MAP), compared to reductions in MAP. We tested the hypothesis that this directional sensitivity is reduced by hypercapnia. Retrospective analysis of 104 healthy subjects (46 male (44%), age range 19-74 years), with five minute recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), non-invasive MAP (Finometer) and end-tidal CO2 (capnography) at rest, during both poikilocapnia and hypercapnia (5% CO2 breathing in air) produced MCAv step responses allowing estimation of the classical Autoregulation Index (ARIORIG), and corresponding values for both positive (ARI+D) and negative (ARI-D) changes in MAP. Hypercapnia led to marked reductions in ARIORIG, ARI+D and ARI-D (p < 0.0001, all cases). Females had a lower value of ARIORIG compared to males (p = 0.030) at poikilocapnia (4.44 ± 1.74 vs 4.74 ± 1.48) and hypercapnia (2.44 ± 1.93 vs 3.33 ± 1.61). The strength of directional sensitivity (ARI+D-ARI-D) was not influenced by hypercapnia (p = 0.46), sex (p = 0.76) or age (p = 0.61). During poikilocapnia, ARI+D decreased with age in females (p = 0.027), but not in males. Directional sensitivity was not affected by hypercapnia, suggesting that its origins are more likely to be inherent to the mechanics of vascular smooth muscle than to myogenic pathways.

Dynamics of the cerebral autoregulatory response to paced hyperventilation assessed using subcomponent and time-varying analyses.

Cerebral blood flow (CBF) can be altered by a change in partial pressure of arterial CO2 (Pco2), being reduced during hyperventilation (HPV). Critical closing pressure (CrCP) and resistance area product (RAP) are parameters that can be studied to understand this change, but their dynamic response has not been investigated during paced HPV (PHPV). Seventy-five participants had recordings at rest and during PHPV. Blood pressure (BP) (Finometer), bilateral CBF velocity (CBFV) (transcranial Doppler), end-tidal CO2 (capnography), and heart rate (HR) were recorded continuously. Subcomponent analysis (SCA) and time-varying CrCP, RAP, and dynamic cerebral autoregulation (autoregulation index, ARI) were estimated by comparing PHPV with poikilocapnia. PHPV caused a change in CBFV (P < 0.01), EtCO2, (P < 0.01), HR (P < 0.001), and RAP (P < 0.01). SCA demonstrated RAP was the main parameter explaining the changes in CBFV due to PHPV. The time-varying step responses for CBFV and RAP during PHPV demonstrated considerable nonstationarity compared with poikilocapnia (P < 0.00001). Although time-varying ARI was temporarily depressed, after 60 s of PHPV it was significantly higher (6.81 ± 1.88) (P < 0.0001) than in poikilocapnia (5.08 ± 1.86). The mean plateau of the RAP step response was -98.3 ± 58.8% 60 s after the onset of PHPV but -71.7 ± 45.0% for poikilocapnia (P = 0.0026), with no corresponding changes in CrCP (P = 0.6). Further work is needed to assess the role of sex and aging in our findings, and the potential for using RAP and CrCP to improve the sensitivity and specificity of CO2 reactivity studies in cerebrovascular conditions.NEW & NOTEWORTHY The dynamic response of critical closing pressure (CrCP) and resistance-area product (RAP) of the cerebral circulation to a step change in mean arterial pressure can shed light on the nonstationary changes induced by paced hyperventilation and the effects of hypocapnia on the autoregulation of cerebral blood flow. Contrary to hypercapnia, where the response is dominated by CrCP, hypocapnia shows an initial depression of cerebral autoregulation, followed by improvements controlled by changes in RAP.

Oral antiplatelet therapy for acute ischaemic stroke.

BACKGROUND: In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the brain. Such damage gives rise to the symptoms of stroke. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and also reduce the risk of early recurrent ischaemic stroke, thereby reducing the risk of early death and improving long-term outcomes in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage. OBJECTIVES: To assess the efficacy and safety of immediate oral antiplatelet therapy (i.e. started as soon as possible and no later than two weeks after stroke onset) in people with acute presumed ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and two trials registers, and performed forward reference/cited reference searching in August 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral antiplatelet therapy (started within 14 days of the stroke) with control in people with definite or presumed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and assessed trial quality. For the included trials, they extracted and cross-checked the data. They assessed risk of bias of each study using the Risk of Bias 1 (RoB1) tool and overall certainty of the evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 11 studies involving 42,226 participants. Three new trials have been added since the last update (743 participants). As per the previous version of this review, two trials testing aspirin 160 mg to 300 mg once daily, started within 48 hours of onset, contributed 96% of the data. The risk of bias was low. The maximum follow-up was six months. With treatment, there was a decrease in death or dependency at the end of follow-up (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91 to 0.99; 7 RCTs, 42,034 participants; moderate-certainty evidence). For every 1000 people treated with aspirin, 13 people would avoid death or dependency (number needed to treat for an additional beneficial outcome 79). AUTHORS' CONCLUSIONS: Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who cannot swallow) and started within 48 hours of onset of presumed ischaemic stroke, significantly decreased death and dependency, and reduced the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications; long-term outcomes were improved.

Vascular and haemodynamic issues of brain ageing.

The population is ageing worldwide, thus increasing the burden of common age-related disorders to the individual, society and economy. Cerebrovascular diseases (stroke, dementia) contribute a significant proportion of this burden and are associated with high morbidity and mortality. Thus, understanding and promoting healthy vascular brain ageing are becoming an increasing priority for healthcare systems. In this review, we consider the effects of normal ageing on two major physiological processes responsible for vascular brain function: Cerebral autoregulation (CA) and neurovascular coupling (NVC). CA is the process by which the brain regulates cerebral blood flow (CBF) and protects against falls and surges in cerebral perfusion pressure, which risk hypoxic brain injury and pressure damage, respectively. In contrast, NVC is the process by which CBF is matched to cerebral metabolic activity, ensuring adequate local oxygenation and nutrient delivery for increased neuronal activity. Healthy ageing is associated with a number of key physiological adaptations in these processes to mitigate age-related functional and structural declines. Through multiple different paradigms assessing CA in healthy younger and older humans, generating conflicting findings, carbon dioxide studies in CA have provided the greatest understanding of intrinsic vascular anatomical factors that may mediate healthy ageing responses. In NVC, studies have found mixed results, with reduced, equivalent and increased activation of vascular responses to cognitive stimulation. In summary, vascular and haemodynamic changes occur in response to ageing and are important in distinguishing "normal" ageing from disease states and may help to develop effective therapeutic strategies to promote healthy brain ageing.