Bleeding on Long-Term Antiplatelet Treatment After Vascular Events

Study Questions:

What are the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages?

Methods:

The investigators did a prospective population-based cohort study in patients with a first transient ischemic attack, ischemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine proton-pump inhibitor [PPI] use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. They determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. The authors estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal (GI) bleeding with routine PPI co-prescription on the basis of Kaplan–Meier risk estimates and relative risk reduction estimates from previous trials.

Results:

A total of 3,166 patients (1,582 [50%] aged ≥75 years) had 405 first bleeding events (n = 218 GI, n = 45 intracranial, and n = 142 other) during 13,509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to the hospital, 117 (37%) were missed by administrative coding. Risk of nonmajor bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR], 3.10; 95% confidence interval [CI], 2.27-4.24; p < 0.0001), particularly for fatal bleeds (5.53, 2.65-11.54; p < 0.0001), and was sustained during long-term follow-up. The same was true of major upper GI bleeds (≥75 years HR, 4.13; 2.60-6.57; p < 0.0001), particularly if disabling or fatal (10.26, 4.37-24.13; p < 0.0001). At age ≥75 years, major upper GI bleeds were mostly disabling or fatal (45 [62%] of 73 patients vs. 101 [47%] of 213 patients with recurrent ischemic stroke), and outnumbered disabling or fatal intracerebral hemorrhage (n = 45 vs. n = 18), with an absolute risk of 9.15 (95% CI, 6.67-12.24) per 1,000 patient-years. The estimated NNT for routine PPI use to prevent one disabling or fatal upper GI bleed over 5 years fell from 338 for individuals <65 years, to 25 for individuals aged ≥85 years.

Conclusions:

The authors concluded that among patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding was higher and more sustained in older patients than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper GI bleeding.

Perspective:

This population-based study reports that the long-term risks and severity of bleeding in patients receiving predominantly aspirin-based secondary prevention increased steeply with age. Furthermore, the risks of major bleeding in patients at older ages were higher and more sustained than at younger ages, and the functional outcome was much worse, with a substantial risk of disabling or fatal upper GI bleeding. Since one half of the major bleeds in older patients were upper GI, and the estimated NNT for PPI use to prevent major upper GI bleed appears low, its use may be considered, but serious side effects of PPI including renal dysfunction, fractures, dementia, and possible increased risk of death needs to be factored in before routine use in all elderly patients on aspirin. Ultimately, a randomized trial is needed to assess true risk versus benefits of PPI in this patient population.

Clinical Topics: Geriatric Cardiology, Prevention

Keywords: Aspirin, Cerebral Hemorrhage, Gastrointestinal Hemorrhage, Geriatrics, Ischemic Attack, Transient, Myocardial Infarction, Platelet Aggregation Inhibitors, Proton Pump Inhibitors, Primary Prevention, Risk, Secondary Prevention, Stroke, Vascular Diseases


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