In the JournalsPerspective

Aspirin increases risk for major bleeding, decreases CV risk in those without CVD

Patients without CVD who took aspirin has a decreased risk for CV events and an increased risk for major bleeding, according to a meta-analysis published in JAMA.

“This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding,” wrote Sean L. Zheng, BM, BCh, MA, MRCP, academic clinical fellow in the department of cardiovascular medicine at King’s College Hospital NHS Foundation Trust in London, and Alistair J. Roddick, BSc, medical student at King’s College in London.

Studies on aspirin treatment

Researchers analyzed data from 164,225 participants (median age, 62 years; 47% men; 19% diabetes) without CVD from 13 randomized trials. In these trials, participants were assigned aspirin, placebo or no treatment and were followed up for at least 12 months. Inclusion criteria, baseline participant characteristics, follow-up duration, endpoint data, and study drug and control treatment were also included in this meta-analysis.

The primary CV outcome of interest was a composite of nonfatal MI, CV mortality and nonfatal stroke. Secondary CV outcomes of interest were CV-related mortality, all-cause mortality, total stroke, MI and ischemic stroke.

The primary bleeding outcome of interest was major bleeding, which was individually defined by studies. Secondary bleeding outcomes of interest were major gastrointestinal bleeding and intracranial bleeding.

At baseline, the median risk for the primary CV outcome was 9.2%,

During 1,050,511 participant-years of follow-up, patients assigned aspirin had significant reductions in the composite CV outcome compared with those who were assigned placebo or no treatment (57.1 per 10,000 participant-years vs. 61.4 per 10,000 participant-years; HR = 0.89; 95% credible interval, 0.84-0.95). This contributed to an absolute risk reduction of 0.38% and a number needed to treat of 265.

Increased bleeding risk

Compared with participants not assigned aspirin, those who were assigned the treatment had an increased risk for major bleeding (23.1 per 10,000 participant-years vs. 16.4 per 10,000 participant-years; HR = 1.43; 95% credible interval, 1.3-1.56). The absolute risk increase was 0.47% with a number needed to harm of 210.

“Compared with aspirin use in patients with established atherosclerotic cardiovascular disease, aspirin use for primary prevention has been controversial,” Zheng and Roddick wrote. “This uncertainty has been reflected in contradictory guideline recommendations. The current study demonstrates that when considering the totality of evidence, cardiovascular benefits associated with aspirin were modest and equally balanced by major bleeding events.”

In a related editorial, J. Michael Gaziano, MD, MPH, physician at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, wrote: “When applying these results to an individual patient, clinicians must consider other interventions in addition to aspirin such as smoking cessation and control of blood pressure and lipid levels to lower risk. In places of the world in which CVD risk is rising or where other preventive strategies such as statins are less available, aspirin as a low-cost intervention may have a more important role. Aspirin remains an important medication for acute management of vascular events; for use after certain procedures; for secondary prevention; and, after careful selection of the right patients, for primary prevention.” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures. Gaziano reports he served on the executive committee of the ARRIVE trial and served as a consultant and received honoraria from Bayer.

Patients without CVD who took aspirin has a decreased risk for CV events and an increased risk for major bleeding, according to a meta-analysis published in JAMA.

“This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding,” wrote Sean L. Zheng, BM, BCh, MA, MRCP, academic clinical fellow in the department of cardiovascular medicine at King’s College Hospital NHS Foundation Trust in London, and Alistair J. Roddick, BSc, medical student at King’s College in London.

Studies on aspirin treatment

Researchers analyzed data from 164,225 participants (median age, 62 years; 47% men; 19% diabetes) without CVD from 13 randomized trials. In these trials, participants were assigned aspirin, placebo or no treatment and were followed up for at least 12 months. Inclusion criteria, baseline participant characteristics, follow-up duration, endpoint data, and study drug and control treatment were also included in this meta-analysis.

The primary CV outcome of interest was a composite of nonfatal MI, CV mortality and nonfatal stroke. Secondary CV outcomes of interest were CV-related mortality, all-cause mortality, total stroke, MI and ischemic stroke.

The primary bleeding outcome of interest was major bleeding, which was individually defined by studies. Secondary bleeding outcomes of interest were major gastrointestinal bleeding and intracranial bleeding.

At baseline, the median risk for the primary CV outcome was 9.2%,

During 1,050,511 participant-years of follow-up, patients assigned aspirin had significant reductions in the composite CV outcome compared with those who were assigned placebo or no treatment (57.1 per 10,000 participant-years vs. 61.4 per 10,000 participant-years; HR = 0.89; 95% credible interval, 0.84-0.95). This contributed to an absolute risk reduction of 0.38% and a number needed to treat of 265.

Increased bleeding risk

Compared with participants not assigned aspirin, those who were assigned the treatment had an increased risk for major bleeding (23.1 per 10,000 participant-years vs. 16.4 per 10,000 participant-years; HR = 1.43; 95% credible interval, 1.3-1.56). The absolute risk increase was 0.47% with a number needed to harm of 210.

“Compared with aspirin use in patients with established atherosclerotic cardiovascular disease, aspirin use for primary prevention has been controversial,” Zheng and Roddick wrote. “This uncertainty has been reflected in contradictory guideline recommendations. The current study demonstrates that when considering the totality of evidence, cardiovascular benefits associated with aspirin were modest and equally balanced by major bleeding events.”

In a related editorial, J. Michael Gaziano, MD, MPH, physician at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, wrote: “When applying these results to an individual patient, clinicians must consider other interventions in addition to aspirin such as smoking cessation and control of blood pressure and lipid levels to lower risk. In places of the world in which CVD risk is rising or where other preventive strategies such as statins are less available, aspirin as a low-cost intervention may have a more important role. Aspirin remains an important medication for acute management of vascular events; for use after certain procedures; for secondary prevention; and, after careful selection of the right patients, for primary prevention.” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures. Gaziano reports he served on the executive committee of the ARRIVE trial and served as a consultant and received honoraria from Bayer.

    Perspective
    Anthony Bavry

    Anthony Bavry

    The investigators examined the role of aspirin compared with placebo/control in the setting of primary prevention. They concluded that aspirin was associated with a reduction in major adverse CV events; however, this was offset by an increase in major bleeding.

    It is interesting that aspirin was not associated with a reduction in CV mortality or all-cause mortality. The findings from this study have implications for clinical practice. The balance of benefit to harm with aspirin for primary prevention is less certain after this analysis.

    Major bleeding is not benign and needs to carefully be considered when considering the use of this medication for primary prevention. Current risk prediction is crude and unable to precisely identify who will suffer a CV event.

    Better knowledge of risk would help to inform who might benefit from certain CV medications for primary prevention, like aspirin and statins. Individuals who feel this research applies to them should discuss with their provider if aspirin is appropriate for them.

    • Anthony Bavry, MD, MPH
    • Cardiology Todays Intervention Editorial Board Member
      University of Florida

    Disclosures: Bavry reports no relevant financial disclosures.