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aspirina y riesgo.pptx
- 1. ASPIRINA PREVENCION PRIMARIA Wikler Bernal Torres Universidad Libre, Cali
- 3. N Engl J Med 2018; 379:1529-1539 . P: Pacientes 40 años con DM sin evidencia de enfermedad cardiovascular 7.4 años de seguimiento I: ASA 100 mg vs - aleatorizacion 2x2 con ácidos grasos n-3, 1 gr diario C: Placebo O: Primer evento vascular serio (IAM no fatal - ACV no fatal - AIT o Muerte cardiovascular (excluyendo hemorragia IC) Primer evento sangrado mayor ( hemorragia intracraneal, TGI o cualquier sangrado serio (hospitalización, transfusión o muerte) 14 400
- 4. 12%
- 5. N Engl J Med 2018; 379:1529-1539 En pacientes con diabetes sin enfermedad CV, Aspirina reduce eventos CV en un 12% pero aumenta el riesgo de sangrado 29%
- 6. P: Hombres > 55 AÑOS + 2 factores riesgo Mujer > 60 años + > 3 factores de riesgo I= ASA 100 mg dia C= placebo O =Compuesto tiempo a primer evento CV: IAM, ACV, muerte cardiovascular, angina inestable o TIA. Eventos sangrado severidad por GUSTO Lancet 2018; 392: 1036–46 12.546 Riesgo de enfermedad coronaria a 10 años entre 10-20%
- 7. Lancet 2018; 392: 1036–46 Se excluyeron pacientes con alto riesgo de sangrado (úlceras, ACO, AINES) o Multicentrico, doble ciego, prevención primaria o 7 países (Alemania, Italia, Irlanda, Polonia, España, UK y USA • Colesterol total > 200 mg/dL – H / > 240 - M • LDL > 130 mg/dL - H / > 160 – M • Tabaquismo (cualquier cigarrillo en el ultimo año) • HDL < 40 mg/dL • TAS > 140 mmHg • Historia familiar de enfermedad cardiovascular
- 8. Lancet 2018; 392: 1036–46 LA TASA DE EVENTOS FUE MUCHO MÁS BAJA DE LO ESPERADO HACE QUE EL ESTUDIO SEA MÁS REPRESENTATIVO DE UNA POBLACIÓN DE BAJO RIESGO AUMENTO DE EVENTOS DE SANGRADO
- 9. N Engl J Med 2018; 379:1509-1518 P: > 70 años (negros e hispanos > 65 a), Sin enfermedad CV establecida, demencia o discapacidad I: ASA 100 mg dia C: Placebo O: Compuesto de muerte, demencia o discapacidad física persistente Securidad: hemorragia mayor y enfermedad cardiovascular 19.114
- 13. El uso de dosis bajas de aspirina como estrategia de prevención primaria en adultos mayores resultó en un riesgo significativamente mayor Hemorragia mayor Sin menor tasa de enfermedad cardiovascular CONCLUSION
- 17. CONCLUSIONES Journal of the American College of Cardiology. Jun 2019, 73 (23) 2915-2929 ASA previente eventos isquémicos no fatales pero aumenta eventos de sangrado Mayor Beneficio cuando el riesgo estimado de ASCVD fue ≥7.5% a 10 años Uso de ASA en prevencion primario depende del riesgo de ASCVD y el riesgo de sangrado Preferencias del paciente Dosis de prevencion baja (≤ 100 mg / día)
- 18. Lancet 2009; 373: 1849–60 P: 95.000 PACIENTES EN PREVENCION PRIMARIA(6 ETUDIOS) 17.000 EN PREVENCION SECUNDARIA (16 ESTUDIOS) I: ASPIRINA C: PLACEBO O: EVENTOS VASCULARES SERIOS (INFARTO, ACCIDENTE CEREBROVASCULAR, MUERTE CV) ,SANGRADO MAYOR METANALISIS DE EVENTOS VASCULARES SERIOS Y SANGRADO MAYOR (EXTRACRANEAL, TGI NECESIDAD DE TRANSFUSIÓN O MUERTE) - ASA VS NO ASA
- 19. Lancet 2009; 373: 1849–60
- 20. Lancet 2009; 373: 1849–60
- 21. Lancet 2009; 373: 1849–60
- 22. RESULTADOS • 1671 eventos (0.51% por año) vs 1883 evento (0,57% por año)- Reducción del 12% RR 0.88 p < 0.0001 - Poca heterogeneidad. • El predictor de riesgo mas importante fue la edad EVENTOS CORONARIOS • P 1º • Reducción 18% en eventos coronarios mayores, reducción absoluta pequeña 0,28% vs 0,34% RR 0,82 p =<0.001 • Reducción 23% IAM no fatal • Poco impacto en mortalidad • La reducción de los eventos es similar en P1º - P2º ( RR 0,82 - RR 0,80) pero la magnitud del beneficio absoluto difiere (0.06% por año vs 1% por año) • P2º • Sin heterogeneidad para los eventos coronarios mayores entre hombres y mujeres. Lancet 2009; 373: 1849–60 20% 22% 19%
- 23. CONCLUSIÓN EN PREVENCIÓN PRIMARIA, LA REDUCCIÓN PROPORCIONAL DE EVENTOS VASCULARES SERIOS NO DEPENDE DE LA EDAD O EL SEXO, LA MORTALIDAD VASCULAR NO SE REDUJO SIGNIFICATIVAMENTE (NO USO DE ASPIRINA) EN PREVENCIÓN SECUNDARIA HAY UN BENEFICIO SUSTANCIAL EN LA REDUCCIÓN DE LOS EVENTOS VASCULARES NO FATALES, A PESAR DE LA HEMORRAGIA CEREBRAL Lancet 2009; 373: 1849–60
- 25. European Heart Journal (2016) 37, 2315–2381
- 26. ASPIRINA COR LOE Recomendación IIb A La aspirina en dosis bajas (75-100 mg/día VO) se puede considerar para la prevención primaria de la ASCVD en adultos seleccionados de 40 a 70 años de edad que tienen un mayor riesgo de ASCVD pero no un mayor riesgo de sangrado. III B-R La aspirina en dosis bajas no debe administrarse de forma rutinaria para la prevención primaria de la ASCVD en adultos mayores de 70 años. III C-LD No se debe administrar aspirina en dosis bajas para la prevención primaria de la ASCVD en adultos de cualquier edad que tengan un riesgo mayor de sangrado. Arnett et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease
- 27. Journal of the American College of Cardiology. Jun 2019, 73 (23) 2915-2929
- 28. GRACIAS
Notas del editor
- Aspirin has been reported to modulate several metabolic pathways, at least in part through acetylation of proteins involved in inflammation, haemostasis, thrombosis and cell proliferation18. The best- characterized target of aspirin is the enzyme prostaglandin G/H synthase, which has two isoforms, PGHS1 and PGHS2, endowed with both cyclooxygenase (COX) and hydroperoxidase activities. PGHS1 and PGHS2 catalyse the conversion of arachidonic acid to the cyclic endoperoxides prostaglandin G2 (PGG2) and PGH2, which are biosynthetic intermediates in the formation of biologically active prostanoids, including thromboxane A2 (TXA2), the major arachidonic acid derivative in human platelets (Fig. 1). Covalent acetylation of critical serine residues in PGHS1 and PGHS2 by aspirin permanently inactivates the COX activity of these enzymes (which are referred to colloquially as COX1 and COX2) and blocks to a variable extent this pathway of arachidonic acid metabolism, thereby reducing prostanoid production. In contrast to the acetylation of other proteins by aspirin, which has been described on the basis of in vitro experiments often using millimolar concentrations of aspirin, acetylation of COX isozymes has the following distinctive characteristics that make it the most plausible mechanism of action explaining the multifaceted, pharmacological effects of aspirin18 (Fig. 2). First, the COX1 enzyme and aspirin have been co- crystallized and the 3D model shows that the acetylation site within the COX channel, just below the COX catalytic site, can explain the irreversible inactivation of COX activity19 (Fig. 2a). Second, acetylation of platelet COX1 by aspirin is a saturable process that has been characterized in vitro and ex vivo20 (Fig. 2b). Third, this effect is necessary and sufficient to account for saturable suppression of the platelet production of TXB2, an inactive metabolite of TXA2, at low (micromolar) drug concentrations in vitro and following oral administration of low- dose aspirin (50–100 mg daily), as assessed both ex vivo and in vivo2,21 (Fig. 2c). In turn, virtually complete suppression by low- dose aspirin of the platelet biosynthesis of TXA2, a potent inducer of platelet aggregation, can account for the saturability of the clinical effects of aspirin in preventing atherothrombosis in the same dose range1. The same mechanism of action can also explain the increase in gastrointestinal bleeding complications associated with the use of low- dose aspirin because of the role of TXA2-dependent platelet function in primary haemostasis1. Moreover, it has been suggested that platelet COX1 inhibition at sites of colorectal mucosal injury contributes to the chemopreventive effect of low- dose aspirin therapy against sporadic adenoma recurrence and its neoplastic transformation in humans.
- Estudio realizado en Oxford. 7,4 años de seguimiento. 2rio: Ca del TGI y combinación de evento vascular serio y revascularización arterial
- Poblacion de australia y USA.
- Aspirin use for primary prevention decreased nonfatal ischemic events and increased nonfatal bleeding events (Central Illustration). The benefits were more pronounced when estimated ASCVD risk was ˃7.5% over 10 years. These findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patient based on estimated ASCVD risk and perceived bleeding risk, as well as patient preferences regarding types of events prevented versus potential bleeding caused. When aspirin is used for primary prevention, a low dose (≤100 mg/day) should be recommended. Los resultados de eficacia incluyeron muerte por todas las causas, muerte cardiovascular (CV), infarto de miocardio (IM), accidente cerebrovascular, ataque isquémico transitorio (AIT) y eventos cardiovasculares adversos importantes. Los resultados de seguridad incluyeron sangrado mayor, sangrado intracraneal, sangrado fatal y sangrado gastrointestinal (GI) mayor. Se realizó una búsqueda sistemática
- Serious vascular events in primary prevention trials—proportional effects of aspirin allocation Actual numbers for aspirin-allocated trial participants, and adjusted numbers for control-allocated trial participants, are presented, together with the corresponding mean yearly event rate (in parentheses). Participants can contribute only once to the total of serious vascular events. Rate ratios (RRs) for all trials are indicated by squares and their 99% CIs by horizontal lines. Subtotals and their 95% CIs are represented by diamonds. Squares or diamonds to the left of the solid line indicate benefi t. MI=myocardial infarction. CHD=coronary heart disease. *Myocardial infarction, stroke, or vascular death. Vascular death is coronary heart disease death, stroke death, or other vascular death (which includes sudden death, death from pulmonary embolism, and death from any haemorrhage, but in the primary prevention trials excludes death from an unknown cause).
- Selected outcomes in primary and secondary prevention trials of aspirin, by sex Actual numbers for aspirin-allocated trial participants, and adjusted numbers for control-allocated trial participants, are presented together with the corresponding mean yearly event rate (in parentheses). Rate ratios (RRs) for all trials are indicated by squares and their 99% CIs by horizontal lines. Subtotals and their 95% CIs are represented by diamonds. Squares or diamonds to the left of the solid line indicate benefi t. *Myocardial infarction, stroke (haemorrhagic or other), or vascular death
- Box and whisker plot showing the proportion of people at given levels of predicted risk of major extracranial bleeding (MEB) and predicted risk of major coronary events (MCE), indicating that those individuals at the highest absolute risk of MCE are also at the highest risk of bleeding. Data are from the 2009 ATT Collaboration meta- analysis of 95,000 individuals in six trials of primary prevention of cardiovascular disease41. The estimated risk of MCE (nonfatal myocardial infarction or death related to coronary heart disease) and of MEB are plotted for each individual (methods described in reF.41) before being organized into four categories of annual risk of MCE (<0.5%, ≥0.5 and <1.0%, ≥1.0 and <1.5%, and ≥1.5%). The box corresponds to the interquartile range and the whisker to the ninety- fifth percentile of predicted risk of MEB. **The criteria for determining a ‘margin of safety’ for an excess of benefit over hazard that minimizes the risk of harm for healthy people are, of course, subjective, but the statistical problem of identifying eligible patients might be inherent irrespective of where this margin is set.