A comparison of contemporary versus older studies of aspirin for primary prevention

Abstract

Background: Recent aspirin trials have not shown similar benefits for primary prevention as older studies.

Objective: To compare benefits and harms of aspirin for primary prevention before and after widespread use of statins and colorectal cancer screening.

Methods: We compared studies of aspirin for primary prevention that recruited patients from 2005 onward with previous individual patient data (IPD) meta-analyses that recruited patients from 1978 to 2002. Data for contemporary studies were synthesized using random-effects models. We report vascular [major adverse cardiovascular events (MACE), myocardial infarction (MI) and stroke], bleeding, cancer and mortality outcomes.

Results: The IPD analyses of older studies included 95 456 patients for CV prevention and 25 270 for cancer mortality, while the four newer studies had 61 604 patients. Relative risks for vascular outcomes for older versus newer studies follow: MACE: 0.89 [95% confidence interval (CI) 0.83-0.95] versus 0.93 (0.86-0.99); fatal haemorrhagic stroke: 1.73 (1.11-2.72) versus 1.06 (0.66-1.70); any ischaemic stroke: 0.86 (0.74-1.00) versus 0.86 (0.75-0.98); any MI: 0.84 (0.77-0.92) versus 0.88 (0.77-1.00); and non-fatal MI: 0.79 (0.71-0.88) versus 0.94 (0.83-1.08). Cancer death was not significantly decreased in newer studies (1.11, 0.92-1.34). Major haemorrhage was significantly increased (older studies RR 1.48, 95% CI 1.25-1.76 versus newer studies RR 1.37, 1.24-1.53). There was no effect on all-cause mortality, cardiovascular mortality, fatal stroke or fatal MI.

Conclusions: Per 1200 persons taking aspirin for primary prevention for 5 years, there will be 4 fewer MACEs, 3 fewer ischaemic strokes, 3 more intracranial haemorrhages and 8 more major bleeding events. Aspirin should no longer be recommended for primary prevention

This article was featured on the December 7, 2021, Lunch and Learn discussion

In this segment of the recording, Dr. Mark Ebell, MD, Professor at the University of Georgia College of Public Health, and Dr. Frank Moriarty, Senior Lecturer at the Royal College of Surgeons in Ireland presented the paper.

Summary of Discussion Highlights:

• Harms of aspirin use were consistent between old and new studies

• There is no longer any reduction in cancer incidence or mortality

• There was a consistent decrease in ischemic stroke, although small

• There is no longer any reduction in non-fatal myocardial infarction (heart attack)

• For every 1200 people who are taking aspirin for primary prevention for five years, you'll see four fewer major adverse cardiovascular events (MACEs), three fewer ischemic strokes, but three more intracranial hemorrhages and eight more major bleeding events. On balance, aspirin should no longer be recommended for primary prevention of cancer or cardiovascular disease.
• 2021 Draft Recommendation Statement of US Preventive Services Task Force
  1. For adults aged 60 years or older, The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults age 60 years or older.
  2. For adults between the age of 40 to 59 years with a 10% or greater 10-year cardiovascular disease (CVD) risk the USPSTF recommends the decision to initiate low-dose aspirin use for the primary prevention of CVD in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk should be an individual one. Evidence indicates that the net benefit of aspirin use in this group is small. Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit.