Annual Risk of Major Bleeding Among Persons Without Cardiovascular Disease Not Receiving Antiplatelet Therapy

Abstract

A decision to initiate aspirin therapy for primary prevention of cardiovascular disease (CVD) requires consideration of both treatment benefits and harms. The most significant harm associated with aspirin is major bleeding, yet there is a paucity of data on bleeding risk in suitable community populations. OBJECTIVE To determine the risk of major bleeding among people without CVD who are not receiving antiplatelet therapy. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 359 166 individuals aged 30 to 79 years receiving primary care in New Zealand who had CVD risk assessment between 2002 and 2015. Participants were censored at the earliest date on which they had a first major bleeding event, died, or met any baseline cohort exclusion criteria or the study end date of December 31, 2015. Analyses were repeated after excluding people with medical conditions associated with increased bleeding risk (non-high-risk cohort; n=305 057) and after further excluding people receiving other medications associated with increased bleeding risk (nonmedication cohort; n=240 254). EXPOSURES Sex and age group in 10-year bands from 30 to 79 years. MAIN OUTCOMES AND MEASURES Risk of a major bleeding event (hospitalization or death associated with bleeding); nonfatal gastrointestinal tract bleeding; and gastrointestinal tract bleeding-related case fatality. RESULTS Mean participant age was 54 years (SD, 10 years), 44% were women, and 57% were European. Among the 359 166 individuals in the baseline cohort, 3976 had a major bleeding event during 1 281 896 person-years of follow-up. Most had gastrointestinal (GI) bleeding (n=2910 [73%]). There were 274 fatal bleeding events (7%), of which 153 were intracerebral. The risk of a nonfatal GI bleeding event per 1000 person-years was 2.19 (95% CI, 2.11-2.27), 1.77 (95% CI, 1.69-1.85) and 1.61 (95% CI, 1.52-1.69), in the baseline, non-high-risk, and nonmedication cohorts, respectively. Case fatality associated with GI bleeding was 3.4% (95% CI, 2.2%-4.1%), 4.0% (95% CI, 3.2%-5.1%), and 4.6% (95% CI, 3.6%-6.0%) in the baseline, non-high-risk, and nonmedication cohorts, respectively. CONCLUSIONS AND RELEVANCE In a population not receiving antiplatelet therapy, the annual risk of major bleeding events and nonfatal major bleeding was estimated. These findings could inform population-level guidelines for primary prevention of CVD.

Thirty-Year Incidence and Mortality Trends in Upper and Lower Gastrointestinal Bleeding in Finland

“…person-years, which was similar to findings in the present study. 24 A review of studies from Europe on acute upper GIB that used data from the 1990s reported that the incidence rate of acute upper GIB ranged from 0.36 to 1.72 per 1000 person-years, 13 which was within or higher than the range shown in the present study. Compared with the present study, the incidence rates of upper GIB in the United States (from 1998 to 2006) were higher at between 1.46 and 1.70 per 1000 person-years and were comparable to those of Spain (from 1996 to 2005), which ranged from 0.47 to 0.87 per 1000 person-years.…”

Adverse drug reactions in older adults: a retrospective comparative analysis of spontaneous reports to the German Federal Institute for Drugs and Medical Devices

“…atrial fibrillation) in older adults may account for this finding. A cohort study has shown that the risk for bleeding, especially gastrointestinal bleeding, inherently increases with rising age [60], it may then be potentiated by antithrombotics. In this respect, higher numbers of ADR reports with regard to gastrointestinal and nervous system haemorrhages associated with direct oral anticoagulants have been seen in patients aged 60 years or older compared to younger patients in a study performed in two large ADR databases from USA and Japan [61].…”

The relationship between DOAC levels and clinical outcomes: The measures tell the tale–Response from original authors Lijfering et al

“…First, Brunetti and Bo argue that "major bleeding incidences observed in DOAC experimental and observational studies are quite reassuring", thereby referring to major bleeding rates (1.6%-2.3% per year) among elderly individuals not receiving antithrombotic therapies. 3 We agree that major bleeding is a multicausal disease and that DOACs are not the only factor that can induce bleeding. Still DOACs have, like all anticoagulants, the side effect of bleeding, as for instance has been shown in placebo-controlled trials in which the risk of major or clinically relevant bleeding is elevated for DOAC use.…”