IMPORTANCE: Low-dose aspirin is used for primary cardiovascular disease prevention and may have benefits for colorectal cancer prevention.
OBJECTIVE: To review the benefits and harms of aspirin in primary cardiovascular disease prevention and colorectal cancer prevention to inform the US Preventive Services Task Force.
DATA SOURCES: MEDLINE, PubMed, Embase, and the Cochrane Central Register of Controlled Trials through January 2021; literature surveillance through January 21, 2022.
STUDY SELECTION: English-language randomized clinical trials (RCTs) of low-dose aspirin (≤100 mg/d) compared with placebo or no intervention in primary prevention populations.
DATA EXTRACTION AND SYNTHESIS: Single extraction, verified by a second reviewer. Quantitative synthesis using Peto fixed-effects meta-analysis.
MAIN OUTCOMES AND MEASURES: Cardiovascular disease events and mortality, all-cause mortality, colorectal cancer incidence and mortality, major bleeding, and hemorrhagic stroke.
RESULTS: Eleven RCTs (N = 134 470) and 1 pilot trial (N = 400) of low-dose aspirin for primary cardiovascular disease prevention were included. Low-dose aspirin was associated with a significant decrease in major cardiovascular disease events (odds ratio [OR], 0.90 [95% CI, 0.85-0.95]; 11 RCTs [n = 134 470]; I2 = 0%; range in absolute effects, -2.5% to 0.1%). Results for individual cardiovascular disease outcomes were significant, with similar magnitude of benefit. Aspirin was not significantly associated with reductions in cardiovascular disease mortality or all-cause mortality. There was limited trial evidence on benefits for colorectal cancer, with the findings highly variable by length of follow-up and statistically significant only when considering long-term observational follow-up beyond randomized trial periods. Low-dose aspirin was associated with significant increases in total major bleeding (OR, 1.44 [95% CI, 1.32-1.57]; 10 RCTs [n = 133 194]; I2 = 4.7%; range in absolute effects, 0.1% to 1.0%) and in site-specific bleeding, with similar magnitude.
CONCLUSIONS AND RELEVANCE: Low-dose aspirin was associated with small absolute risk reductions in major cardiovascular disease events and small absolute increases in major bleeding. Colorectal cancer results were less robust and highly variable.
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death and colorectal cancer (CRC) is the third leading cause of death in the United States.
PURPOSE: To systematically review evidence for the effectiveness of aspirin to prevent myocardial infarction (MI), stroke, cardiovascular death, and all-cause mortality in those without a history of CVD. In addition, to review evidence for CRC incidence and mortality associated with aspirin use in primary and secondary CVD populations. To further review harms associated with aspirin use.
DATA SOURCES: We searched MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials to identify literature that was published between January 2014 and January 14, 2021. We supplemented our searches with reference lists from the previous review, relevant existing systematic reviews, suggestions from experts, and Clinicaltrials.gov to identify ongoing trials. We conducted ongoing surveillance for relevant literature through January 21, 2022.
STUDY SELECTION: Two investigators independently reviewed identified abstracts and full text articles against a set of a priori inclusion and quality criteria.
DATA ANALYSIS: One investigator abstracted data into an evidence table and a second investigator checked these data. We conducted Peto fixed effects meta-analyses to estimate the effect size of aspirin in preventing MI, stroke, CVD-related death and all-cause mortality, CRC incidence and mortality, major bleeding, major gastrointestinal (GI) bleeding, intracranial bleeding, hemorrhagic stroke, and extracranial bleeding. Additionally, we conducted sensitivity analyses using Mantel-Haenszel fixed effects and Restricted Maximum Likelihood random effects.
RESULTS: We included 13 fair- to good-quality randomized, controlled trials (RCTs) (N=161,680) examining the effectiveness of aspirin for the primary prevention of CVD. Based on pooled analysis of 11 primary CVD prevention trials using aspirin ≤100 mg/day, low-dose aspirin reduces the risk of major CVD events (total MI, total stroke, CVD mortality) by 10 percent (k=11, N=134,470; Peto odds ratio [OR], 0.90 [95% confidence interval (CI), 0.85 to 0.95]), MI by 11 percent (k=11, N=134,470; Peto OR, 0.89 [95% CI, 0.82 to 0.96]), and ischemic stroke by 18 percent (k=5, N=79,334; Peto OR, 0.82 [95% CI, 0.72 to 0.92]) with no differences in CVD mortality (k=11, N=134,470; Peto OR, 0.95 [95% CI, 0.86 to 1.05]) or all-cause mortality (k=11, N=134,470; Peto OR 0.98 [95% CI, 0.93 to 1.03]). Absolute risk reductions in major CVD events in the trials ranged from 0.08 to 2.5 percent. Aspirin’s benefits were similar when trials of all doses were pooled. Sensitivity analyses restricted to more recent trials where usual care includes aggressive risk factor modification including statin therapy show diminished effects of aspirin for major CVD events and total MI but larger effects for total ischemic stroke compared to older trials. A small subset of the trials reporting CVD outcomes also reported CRC outcomes. Based on 4 low-dose aspirin trials (N=86,137) recruiting primary CVD prevention populations, there was no statistically significant association between aspirin and CRC incidence when analyzing randomized trial periods (Peto OR 1.07 [95% CI, 0.92 to 1.24]; trial period 5-10 years). Analysis including post-trial observation periods up to 20 years and including trials with high-dose aspirin up to 500 mg/day (k=2; N=45,015) in primary prevention populations show statistically significant reductions in CRC incidence (0.70 [95% CI, 0.50 to 0.98] and 0.82 [95% CI, 0.69 to 0.98]). Two low-dose aspirin RCTs (N=59,020) in primary CVD prevention populations report CRC mortality during the trial period (5-10 years) showing results concerning for possible harm with one trial demonstrating a statistically significant increase in CRC mortality in older adults. At 18 years of followup, including post-trial observational periods, three primary CVD prevention trials with mean daily aspirin doses ranging from 75 to 500 mg showed aspirin was associated with a decreased risk of CRC mortality (Peto OR 0.76 [95% CI, 0.62 to 0.94]). Low-dose aspirin is associated with a 31 percent increase in intracranial bleeding events (k=11; N=134,470; Peto OR, 1.31 [95% CI, 1.11 to 1.54]), and 53 percent increase in extracranial bleeding events (k=10; N=133,194; Peto OR 1.53 [95% CI, 1.39 to 1.70]). The absolute increases ranged from −0.2 to 0.4 percent for intracranial bleeding events and 0.2 to 0.9 percent for extracranial bleeding events. There is no compelling evidence to suggest that aspirin has a different relative CVD benefit or bleeding risk in specific populations defined by age, sex, race and ethnicity, diabetes status, or baseline 10-year CVD risk. Aspirin’s CVD benefits appear to begin within the first 1-2 years of administration and the bleeding harms begin soon after aspirin initiation; there are limited data for more precise time increments or longer durations.
LIMITATIONS: Primary CVD prevention trials used different aspirin doses in heterogeneous populations with relatively short study followup, with duration mostly ranging from 4-6 years. Trials reporting CRC incidence and mortality outcomes are limited by short trial duration and multiple comparisons; observational followup of trials are limited by heterogeneity of aspirin doses, duration, indications, and populations with risk of biases and confounding. Estimates of rare bleeding harms are imprecise.
CONCLUSIONS: In primary prevention populations, low-dose aspirin reduces major CVD events, MI and ischemic stroke, but also increases major GI bleeding, extracranial bleeding, and intracranial bleeding. Our evidence suggests aspirin is associated with a possible long-term reduction in CRC incidence and mortality based on post-trial period observation, but the results are limited for low-dose aspirin among primary CVD prevention populations. More precise real-world U.S.-based estimates for bleeding events in the general population and specific populations with elevated CVD risk are necessary to accurately estimate the net benefit. Depending on CVD risk, this absolute CVD benefit in specific populations could potentially outweigh the bleeding risks. Models to identify these populations are needed.
Hemorragia digestiva baja es una causa frecuente de hospitalización, particularmente en los ancianos, y su incidencia parece ir en aumento. Sangrado diverticular colónica es la forma más común de hemorragia digestiva baja y es responsable de un 30-40% de los episodios de sangrado. Los factores de riesgo asociados con la hemorragia diverticular son la obesidad, la hipertensión, anticoagulantes, la diabetes mellitus y la enfermedad isquémica del corazón. Estudios recientes han sugerido una relación entre el uso de medicamentos no esteroides antiinflamatorios (AINE) y sangrado diverticular del colon; Sin embargo, la mayoría de los estudios fueron pequeños con amplios intervalos de confianza. Se identificaron los estudios mediante la búsqueda en las bases de datos PubMed y Scopus (desde el inicio hasta el 31 de diciembre de 2012) y mediante la búsqueda en las bibliografías de los artículos pertinentes. Los riesgos relativos (RR) Resumen con un 95% intervalos de confianza (IC) se calcularon con efectos fijos y modelos de efectos aleatorios. Un total de seis estudios (estudios de casos y controles de cinco y un estudio de cohortes) cumplieron los criterios de inclusión para el análisis. AINE sin aspirina (NANSAIDs) y aspirina se asoció con un mayor riesgo de sangrado diverticular del colon (RR = 2,48; IC del 95%: 1,86 a 3,31), con heterogeneidad moderada entre estos estudios (P = 0,11 heterogeneidad, I (2) = 44,4%). Estratificación de evaluar la heterogeneidad encontró que ambos NANSAIDs (RR = 2,24; IC del 95%: 1,63 a 3,09; 5 estudios) y aspirina (RR = 1,73; IC del 95% 1.31 a 2.30; 3 estudios) se asociaron con el riesgo de diverticular sangrado. El uso de aspirina / NANSAIDs se asoció fuertemente y consistentemente con un mayor riesgo de sangrado diverticular del colon. Se necesitan más estudios para estratificar a los individuos en riesgo de sangrado diverticular asociada con el uso de estos agentes.
OBJETIVOS: Debido al uso generalizado de la aspirina para la prevención de las enfermedades cardiovasculares, los efectos secundarios asociados a dosis tromboprofilaxis son de interés. Este estudio resume el riesgo relativo (RR) para los graves complicaciones gastrointestinales superiores (UGIC) asociados con la exposición de aspirina en general y con dosis de aspirina específicos y formulaciones en particular.
MÉTODOS: Después de una revisión sistemática, 17 originales de los estudios epidemiológicos publicados entre 1990 y 2001 fueron seleccionados de acuerdo a criterios predefinidos. La heterogeneidad de los efectos fue explorado. Las estimaciones agrupadas se calcularon de acuerdo a las características del estudio y patrones de uso de la aspirina.
RESULTADOS: El riesgo relativo global de UGIC asociado con el uso de aspirina fue de 2,2 (95% intervalo de confianza (IC): 2,1, 2,4) para los estudios de cohortes y anidados estudios caso-control y de 3.1 (IC 95%: 2.8, 3.3) para los no- anidados estudios caso-control. Los estudios originales se encontró una relación dosis-respuesta entre UGIC y la aspirina, aunque el riesgo se eleva aún a dosis bajas o de hasta 300 mg día (-1). El RR fue de 2,6 (IC 95%: 2.3, 2.9) para la normal, 5,3 (IC 95%: 3.0, 9.2) para el buffer, y 2,4 (IC 95%: 1.9, 2.9) para las formulaciones de aspirina con cubierta entérica.
CONCLUSIONES: La aspirina se asoció con UGIC incluso cuando se utiliza en dosis bajas o en formulaciones tamponadas o con cubierta entérica. Los últimos hallazgos pueden explicarse en parte por la canalización de los pacientes susceptibles a estas formulaciones.
Low-dose aspirin is used for primary cardiovascular disease prevention and may have benefits for colorectal cancer prevention.
OBJECTIVE:
To review the benefits and harms of aspirin in primary cardiovascular disease prevention and colorectal cancer prevention to inform the US Preventive Services Task Force.
DATA SOURCES:
MEDLINE, PubMed, Embase, and the Cochrane Central Register of Controlled Trials through January 2021; literature surveillance through January 21, 2022.
STUDY SELECTION:
English-language randomized clinical trials (RCTs) of low-dose aspirin (≤100 mg/d) compared with placebo or no intervention in primary prevention populations.
DATA EXTRACTION AND SYNTHESIS:
Single extraction, verified by a second reviewer. Quantitative synthesis using Peto fixed-effects meta-analysis.
MAIN OUTCOMES AND MEASURES:
Cardiovascular disease events and mortality, all-cause mortality, colorectal cancer incidence and mortality, major bleeding, and hemorrhagic stroke.
RESULTS:
Eleven RCTs (N = 134 470) and 1 pilot trial (N = 400) of low-dose aspirin for primary cardiovascular disease prevention were included. Low-dose aspirin was associated with a significant decrease in major cardiovascular disease events (odds ratio [OR], 0.90 [95% CI, 0.85-0.95]; 11 RCTs [n = 134 470]; I2 = 0%; range in absolute effects, -2.5% to 0.1%). Results for individual cardiovascular disease outcomes were significant, with similar magnitude of benefit. Aspirin was not significantly associated with reductions in cardiovascular disease mortality or all-cause mortality. There was limited trial evidence on benefits for colorectal cancer, with the findings highly variable by length of follow-up and statistically significant only when considering long-term observational follow-up beyond randomized trial periods. Low-dose aspirin was associated with significant increases in total major bleeding (OR, 1.44 [95% CI, 1.32-1.57]; 10 RCTs [n = 133 194]; I2 = 4.7%; range in absolute effects, 0.1% to 1.0%) and in site-specific bleeding, with similar magnitude.
CONCLUSIONS AND RELEVANCE:
Low-dose aspirin was associated with small absolute risk reductions in major cardiovascular disease events and small absolute increases in major bleeding. Colorectal cancer results were less robust and highly variable.
