–But many experts think the evidence base is slim at best.
The U.S. Preventive Services Task Force (USPSTF) finalized the update to its guidelines regarding the use of aspirin for the primary prevention of cardiovascular disease and colorectal cancer. The USPSTF is now recommending that people between the ages of 50 and 59 who are at increased risk for cardiovascular disease (10% or greater 10-year risk) and do not have an elevated risk of bleeding should consider aspirin for the primary prevention of both cardiovascular disease and colorectal cancer.
The USPSTF gave a more neutral “C” recommendation for adults 60-69 years of age. The full recommendations, evidence review, and a decision analysis are contained in five papers published in Annals of Internal Medicine.
Low-dose daily aspirin can help prevent heart attacks, ischemic stroke, and colorectal cancer, according to the USPSTF. But aspirin can also cause gastrointestinal bleeding and hemorrhagic strokes, so the benefits must be weighed against the risks.
But, several different experts cautioned, the evidence behind the recommendations is still quite weak.
“What is important to know is that this recommendation is based on only two high quality studies that were not performed recently,” said Harlan Krumholz, MD, of Yale. “The benefit is considered to be modest. And the main point is that this is not a slam-dunk decision; it is highly personal, should be based on each person’s preferences and goals, and it is an ideal setting for shared decision-making.”
Aspirin has been a topic of heated discussion for more than a generation now. Aspirin is still broadly accepted for secondary prevention in patients with known cardiovascular disease. But its role in primary prevention has been debated and is far less accepted than in the past, when many thought it should be a component of a broadly useful polypill.
In 2009, the USPSTF gave a top grade A recommendation for prevention of myocardial infarction (MI) in men aged 45 to 79 and for prevention of stroke in women aged 45 to 79. In the new recommendations, the USPSTF was less supportive (grade B and C) and shrank the age range (50 to 70), noted Sanjay Kaul, MD, of Cedars-Sinai Medical Center in Los Angeles. Earlier USPSTF guidelines discouraged the use of aspirin and nonsteroidal anti-inflamatory drugs (NSAIDs) for the prevention of colorectal cancer. The cancer recommendation is new in the 2015/2016 recommendations.
“The new recommendations appear reasonable,” said Kaul. “The evidentiary support is stronger for both men and women between the ages of 50 and 60 who are at high risk for cardiovascular disease (>10% risk for atherosclerotic CVD over 10 years) and at low bleeding risk, and less strong for men and women between the ages of 60 and 70. Recommendations no longer focus on gender differences (MI benefit seen in men versus stroke benefit seen in women) which was previously driven by a post-hoc analysis of endpoints in the Women’s Health Study, which failed to win on the primary composite endpoint.”
Early supporter of aspirin and the polypill Salim Yusuf, MD, DPhil, of McMaster University in Hamilton, Ontario, said he now believes that there is insufficient evidence to support a primary prevention recommendation:
“The current data with aspirin in primary prevention of CVD are inconclusive as a significant part of the data comes from trials of low-risk people (e.g. physicians and other health professionals). There are several well designed trials in higher-risk people without CVD (e.g. the elderly or those with diabetes or other risk factors) underway and these will help us as their results are expected within the next 5 years.”
Yusuf said the possibility that aspirin might prevent cancer, especially colorectal cancer, “is intriguing and is also being prospectively studied.”
“Let’s wait for all these trials before we develop the final word regarding aspirin in primary prevention,” said Yusuf. “In the meantime, statins may be a better bet in primary prevention based on the totality of the evidence— along with avoidance of tobacco, blood pressure control in hypertension, and regular exercise and perhaps a prudent diet, such as the Mediterranean diet.”
Kaul pointed out that the FDA has not approved a primary prevention indication for aspirin:
“It is important to understand why the FDA does not consider aspirin treatment to yield a favorable benefit-risk balance for primary prevention of CVD. None of the nearly dozen individual studies, including those conducted in patients with diabetes, have yielded a positive outcome benefit with respect to MI, stroke or mortality. Not many recall that the most famous study, the Physician’s health Study, was stopped prematurely because of futility! It is only when one pools the data that a modest treatment benefit becomes apparent.
The FDA does not view meta-analysis as sufficiently robust approach to approve drugs or biologics. It views meta-analysis as observational with all its limitations; hence it has limited utility for regulatory decisions. Moreover, the meta-analytic results are not adjusted for multiple comparisons, thereby inflating the potential of false-positive or Type 1 errors. Furthermore, the positive predictive value of meta-analytic results of small, inconclusive trials is very low, i.e., it has low replicability. The FDA will only consider meta-analysis for sparse safety data as they have done for assessing CV risk associated with diabetes drugs.”