New Estimates of Bleeding Risks May Help CVD Prevention

Providing information that could be used to help inform the decision to initiate primary prevention therapies like aspirin, researchers from New Zealand have calculated risks of major bleeding among people without cardiovascular disease who are not taking antiplatelet therapy.

“Population-level guidelines need to undertake modeling to determine the most suitable recommendations for the populations that they’re designed for,” lead author Vanessa Selak, PhD (University of Auckland, New Zealand), told TCTMD. “What we’re hoping is that [this paper] will provide customized data that is specifically designed to address the question of the bleeding risk” in people for whom consideration is being given to initiating aspirin therapy for primary prevention and that “will help support modeling that’s being undertaken in the development of population-level guidelines.”

The paper, published in the June 26, 2018, issue of JAMA, also could be used to give patients and physicians a more accurate estimate of baseline bleeding risk when they’re considering aspirin therapy, Selak said, adding that the next step will be to develop a risk calculator for clinical use.

Filling a Gap

There remain some questions about use of aspirin for primary prevention in certain groups because of concerns about how the bleeding risks balance out with the clinical benefits.

In April 2016, the US Preventive Services Task Force (USPSTF) released recommendations on the use of aspirin to prevent cardiovascular disease and colorectal cancer. In those recommendations, the task force supports use of low-dose aspirin for primary prevention of CVD and cancer among adults in their 50s who have 10-year CVD risk of at least 10% and says the decision to initiate low-dose aspirin in people in their 60s should be individualized. Evidence was deemed insufficient to make recommendations for people younger than 50 or older than 69.

Selak and colleagues point out, however, that the task force “was unable to find a suitable published study that directly measured bleeding risk in an untreated cohort for use in the simulation models” used to estimate major bleeding risks.

“I felt that we could provide a more appropriate estimate specifically for the purposes of informing population guidelines on the use of aspirin in primary prevention,” Selak said.

To that end, the investigators turned to a prospective study of 359,166 people ages 30 to 79 (mean age 54 years; 44% women) who received primary care in New Zealand, were free from CVD, were not taking antiplatelet therapy, and had a CVD risk assessment performed between 2002 and 2015.

Over a median follow-up of 2.8 years, 1.1% of individuals had a major bleeding event, defined as hospitalization or death associated with bleeding. Most bleeds (73%) involved the GI tract, with the rest classified as intracerebral (13%) or “other” (14%).

Overall, only 7% of bleeds resulted in death. The majority of fatal bleeds (56%) were intracerebral.

The rate of nonfatal major bleeding per 1,000 person-years increased from the youngest (ages 30 to 39) to the oldest (ages 70 to 79) age groups for both men (from 1.8 to 6.4) and women (from 1.5 to 5.0). Similar patterns were seen for nonfatal GI, intracerebral, and “other” bleeds.

In terms of fatal GI bleeds, rates per 1,000 person-years ranged from 0.01 in the youngest men to 0.40 in the oldest and from 0.04 in the youngest women to 0.23 in the oldest. Case fatality tied to GI bleeding was 3.4% overall, ranging from 0.7% in the youngest men to 7.3% in the oldest and from 3.7% in the youngest women to 6.1% in the oldest.

Case fatality for all bleeding events was 6.9%, but that figure was much higher for intracerebral bleeding (29.5%) than for GI or “other” bleeding (3.4% and 4.2%, respectively).

Informing Prevention Guidelines

The authors note that the risk of nonfatal GI bleeds and case fatality associated with GI bleeding observed in the study were higher than estimates used by the USPSTF to make its recommendations, with a consistent disparity across age groups and in both women and men.

For example, the rate of nonfatal GI bleeding per 1,000 person-years was 5.1 in the oldest men and 3.5 in the oldest women in this study, with corresponding rates of 3.9 and 2.3, respectively, in USPSTF modeling.

“If data from this study were used, the net benefit of aspirin for primary prevention would be lower than that estimated by the USPSTF,” Selak and colleagues write.

They add, however, that “the magnitude of the reduction in net benefit of aspirin, and hence the likely effect on current USPSTF recommendations, is difficult to predict without updating the simulation modeling using these inputs for both GI bleeding risk and case fatality. As noted by the USPSTF, there is a paucity of data on absolute bleeding risk from community cohorts, and this is the first large-scale study that, to our knowledge, has directly measured the risk of major bleeding by sex and age group in a contemporary community cohort of people without CVD and not receiving antiplatelet therapy.”

Though it is likely, if the models are updated using these new data on major bleeding risks, “that there is still a net benefit (albeit smaller) of aspirin for people aged 50 to 59 years,” the investigators conclude, “this is less certain for people aged 60 to 69 years, particularly men. Hence, these findings do not necessarily invalidate the USPSTF recommendations.”

Selak added that for people in their 60s, these new data “can help to support increased understanding for patients in that age group,” who—in discussion with their physicians—can think about whether “it would be suitable for them to consider aspirin or remain on aspirin for primary prevention.”