Controlled trial of aspirin in cerebral ischemia.

Abstract

Adouble-blind trial of aspirin for the treatment of cerebral ischemia was begun in 1972 and continued for 37 months. This was accomplished despite difficulties in controlling a long-term study of a drug which has widespread availability and consumption. The study design, criteria for selection of patients, follow-up surveillance, and methods of data analysis are presented. We report only subjects without carotid surgery before randomization. Patients (178) who had carotid transient ischemic attacks (TIAs) were randomly allocated to aspirin or placebo and followed to determine the incidence of subsequent TIAs,death, cerebral infarction or retinal infarction. Analysis of the first six months of follow-up revealed a statistically significant differential in favar of aspirin when death or cerebral or retinal infarction and the occurrence of TIAs were grouped and considered together as end points. Significance in favor of aspirin treatment was mainly revealed in patients with a history of multiple TIAs and was most evident in those individuals having carotid lesions appropriate to the TIA symptoms. It cannot be inferred from this study that aspirin prevents stroke because when end points were restriced to death or cerebral or retinal infarction, there was no statistically significant differential between the aspirin and placebo treatments.

Análisis de subgrupos: ¿Mejoran la interpretación de los resultados o nos inducen al error?

“…Estas afi rmaciones estaban avaladas por análisis estadísticos que mostraban diferencia signifi cativa entre los subgrupos, pero aún así la información fue errónea e indujo a los clínicos a conductas equivocadas ¿Cuál es la razón?. • La aspirina es inefectiva como prevención secundaria de AVE en mujeres 2,26,27 • La terapia antihipertensiva es inefectiva como prevención cardiovascular primaria en mujeres 30,31 • La terapia antihipertensiva es inefectiva o dañina en ancianos 30 • IECA no reducen la mortalidad y hospitalización en pacientes con ICC que toman AAS 32…”

“…Un estudio publicado a fi nes de la década del '70 mostró en un análisis de subgrupo que la aspirina era efectiva en prevenir infartos al miocardio en mujeres, pero resultaba inefectiva como profi laxis secundaria de accidente vascular isquémico 26 . Este efecto de subgrupo no fue confi rmado por estudios posteriores 27 , pero a priori es poco creíble, ya que la fi siopatología de ambos outcomes es similar. Un efecto de subgrupo tiene mayor credibilidad si el efecto es consistente en outcomes fi siopatológica-mente relacionados.…”

“…Los análisis de subgrupo que muestran efectos que no son consistentes con el conocimiento biológico existente, con frecuencia son irreales. Por ejemplo, hallazgos tales como que la aspirina o la terapia antihipertensiva no son efectivos en mujeres 26,27 y ancianos 28 o que el beta bloqueo no es efectivo en infartos al miocardio de pared inferior 29 , no tienen fundamento biológico y fueron posteriormente refutados por estudios de mejor diseño 2,6,21,22,23 .…”

Cerebrovascular Disease

“…[25][26][27] The benefit of aspirin was demonstrated in reducing the incidence of stroke in patients with prior symptomatic cerebrovascular disease: aspirin has become the mainstay of secondary stroke prevention. Demonstration of some degree of further benefit by other antiplatelet agents was again facilitated by well-designed clinical trials.…”

Modification of angiotensin II-induced relaxation by dipyridamole, phthalazinol and aspirin in isolated dog renal arteries.

“…Results of the efficacy of aspirin in prevention of ischemic cerebral and myocardial diseases are not yet conclusive (3,4). The inhibition by aspirin of PGI2 biosynthesis in the vascular wall may reduce its effectiveness on the diseases (5).…”