Dr. Ashwani Mehta writes on a key drug that created major buzz and controversy in Cardiology this year- aspirin. He reviews the trials that tested the benefit of the use of aspirin for primary prevention of CVD and puts forth his views for Indian Cardiologists.

Aspirin has been the mainstay in the treatment of coronary artery disease and benefits of daily low-dose aspirin therapy to prevent recurrent cardiovascular disease (CVD) events are well established. [1] A large number of people, especially 40 years or older and 28% of adults without known CVD [2] take aspirin to prevent cardiovascular disease. However, results from recent trials evaluating the role of aspirin in primary prevention, have been published and they have now questioned the use of aspirin in prevention of heart disease.

Aspirin’s routine use for primary prevention, however, has been evaluated because of questionable benefits and increased bleeding risk. [3, 4] The drug may reduce the relative risk of a myocardial infarction or stroke, but this benefit could be outweighed by the risk of gastrointestinal bleeding. [5]

In 2014, the U.S. Food and Drug Administration, citing concerns about insufficient evidence, advised the public against using low-dose aspirin therapy for primary prevention of heart attack or stroke. [6] The U.S. Preventive Services Task Force (USPSTF) issued guidelines for aspirin use in primary prevention in 2016 and found insufficient evidence to assess the balance of benefit and harm of starting low-dose aspirin therapy for primary prevention in adults younger than 50 or older than 69 years of age. [7] However, guidelines recommend that adults 50 to 59 years of age start daily low-dose aspirin if they have a 10% or greater 10-year CVD risk, do not have bleeding risk factors, and are willing to take a daily aspirin for at least 10 years. It was also suggested that adults 60 to 69 years of age with similar CVD risk may consider starting low-dose aspirin therapy but may be at higher risk of bleeding and less likely to benefit overall.

The U.S. Preventive Services Task Force recommendation statement (USPSTF) 2016 was based on a systematic review of 11 randomised, controlled trials of aspirin therapy with myocardial infarction and stroke outcomes published between 1988 and 2014, [8] with a review of major gastrointestinal bleeding and haemorrhagic stroke in trial participants. [9]

The goal was to detect adults who were at high enough cardiovascular risk, that their expected benefit from aspirin therapy (including a possible reduction in the risk of developing colorectal cancer) would outweigh the harm of bleeding. [10] However, in this decade or more since most of the trials analysed by the USPSTF took place, fewer adults are smoking in the West and more have been taking statins and anti-hypertensives, which could have reduced the benefits of aspirin.

Looking back at trials from 2019

In the background of emerging equivocal data about the role of aspirin in primary prevention, 3 large randomised trials involving close to 47,000 patients were published recently. These 3 trials tried to address the unresolved issues of aspirin in primary prevention to some extent.

Unsurprisingly, statin use was high in these three studies with maximum use in ASCEND study (75%). Variation in sample size, patient population, drug dosage, compliance, event rates, and study design are other possible explanations. Theoretical addition of other preventive strategies such as statin and angiotensin-converting enzyme inhibitors coupled with better control of CV risk factors has the potential to negate the beneficial effects of aspirin in older trials. [15, 16]

The initial aspirin trials occurred in an era when other risk factors of vascular diseases such as blood pressure and lipid profile were not well controlled. With the development of statins, renin–angiotensin–aldosterone system blockers, and better management of CV risk factors, event rates are already on decline.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.