For decades, aspirin has been advised to prevent heart attacks, both to prevent pre-existing cardiovascular disease (CVD) and coronary heart disease (CHD). Baby aspirin (low-dose aspirin – usually 75-81 mg tablets) became the article of confidence for heart protection in American adults. Therefore, for many Americans, it came as a surprise that recent guidelines issued by the American Heart Association and the American College of Cardiology changed their recommendation to prescribe aspirin for primary prevention of CVD and CHD. Although the UK and Europe have previously changed their position on the use of aspirin for heart attack prevention, US guidelines affect medical practice in many other parts of the world. Therefore, it is necessary to understand the reasons for the change of stance in those guidelines in India as well.
How does aspirin reduce the risk?
CHD occurs through two main pathological processes affecting the arteries that supply blood to the heart. In atherosclerosis, along with fibrosis, fat accumulates in parts of the arterial wall. Sometimes, these ‘plaques’ become calcified. If the plaques reduce the luminal diameter of the coronary artery, it increases the width of the artery by 70% or more (50% in the case of the left main coronary artery), significantly interfering with blood flow. Especially during periods of high physical activity or stress, where high blood pressure and high heart rate increase the need for oxygen to the heart muscle. That demand-supply mismatch causes angina or chest discomfort. It sits comfortably.
However, soft plates, although small, are prone to rupture and are generally not obstructive. When they rupture, their exposed fatty core comes in contact with blood flowing from the artery. It activates the platelets, which are part of the blood cells. The accumulation of platelets forms clots. If large, the clot can completely block the blood vessels. ‘Obstruction’ causes angina and ‘obstruction’ causes heart attack. Occasionally, even at rest or minimal exertion (unstable angina) before a heart attack or myocardial infection (MI) develops, plaque rupture can cause angina. These acute conditions are often linked together as ‘Acute Coronary Syndrome’ (ACS).
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Aspirin is an anti-platelet drug that invariably inactivates the cyclooxygenase enzyme of platelets and inhibits the production of a clotting promoter of thromboxane A2. This makes it impossible for platelets to accumulate together. The function of each dose is limited to the platelets that are then circulating, and a new generation of platelets continues to be produced to replace those that die naturally within a few days. Platelets from accumulating together.
Track aspirin secondary to primary prevention
Preliminary clinical trials were conducted to evaluate the protective effect of aspirin in heart attack patients. Numerous trials, in different parts of the world, have shown significant benefits in reducing death and recurrent heart attacks in people who have survived a heart attack or myocardial infarction. As such, aspirin became an indispensable component of post-MI secondary prophylaxis for all individuals who could tolerate the drug without gastro-intestinal side effects. It is also used after coronary stent insertion.
With that success in mind, the focus shifted to primary prevention. “First of all, why not prevent a heart attack by preventing clots from forming on a panel?”, The question arose. In 2003, Wald and Law from the UK also proposed a six-drug combination ‘Polypil’ to prevent heart attack, for use in all people over the age of 55. In addition to aspirin, beta-blockers, diuretics, angiotensin converting enzyme inhibitors (ACE-I), statins and folic acid were selected.
The editor of the British Medical Journal (BMJ) went overboard, calling that unfamiliar hypothesis the most important scientific publication in BMJ for 50 years. Several polypropylene trials and isolated aspirin trials were followed for primary prevention of CHD. Folic acid quickly disappeared because it was ineffective. Of the three blood pressure-lowering drugs, beta-blockers and ACE-I were initially used for CHD, while diuretics proved their effectiveness in stroke prevention. Long-term beta-blocker therapeutic metabolic effects on blood sugar, triglycerides, and HDL cholesterol became known, with drugs of that class paving the way for calcium channel blockers such as amlodipine to control blood pressure in primary prevention. Statins remained stable. ACE-I and related angiotensin receptor blockers (ARBs) have a reputation for controlling blood pressure and vascular protection.
Changing stance on aspirin
Aspirin has gone through stages of global acceptance, skepticism, debate and revised recommendations in the field of primary prevention. While this remains undisputed for secondary prevention, a question has been raised as to whether the benefits of aspirin use in primary prevention of CHD clearly outweigh the risk of severe bleeding in the brain or abdomen. Over time, evidence has been built through clinical trials, meta-analyzes, and post-marketing monitoring. As the evidence grew, the recommendations changed.
In May 2009, the Anti-Thrombotic Trialist Collaboration (ATT) published a study in The Lancet, stating, “Aspirin is of uncertain net value in primary prevention without prior disease because the reduction in occlusive events needs to be weighed against any increase. . ” British clinical practice has become more secure against the regular use of aspirin for primary prevention of CHD. Clinical trials continued to evaluate the role of aspirin, alone or in combination. Statins have effectively lowered harmful blood lipids such as LDL cholesterol, lowered blood pressure medications to control risk factors, reduced smoking rates in the Western population, adopted healthy eating habits and promoted physical activity, raising questions about the added benefits of aspirin.
In 2017, a review by Paltrano and colleagues in the Journal of the American College of Cardiology (JACC) stated that the role of anti-platelet drugs in the primary prevention of atherothrombosis remains “controversial due to the uncertain balance of potential benefits and risks when combined with other prevention strategies.” CHD risk increases with age. The risk of severe bleeding due to aspirin also increases with age. Therefore, it is necessary to weigh the benefits versus the risks, especially in that age group and ask the question whether those benefits cannot be achieved through other means including non-drug measures.
Significant benefits of the Mediterranean diet and other rational diets in the primary prevention of CHD have been well demonstrated in clinical trials and long-term cohort studies. Medications that lower blood pressure and cholesterol have also been shown to be of great benefit for primary prevention. So why is aspirin at risk for primary prevention, even though it may continue for secondary prevention? That line of thinking has appeared in recent years.
Furthermore, there has been criticism that most risk calculators promote a 10-year risk of heart disease because they do not take into account other treatment benefits that may reduce that long-term risk.
Recent US guidelines
The US Preventive Services Task Force (USPSTF) published the latest guidelines in the April 26, 2022 issue of the American Federation Journal (JAMA). It recommends not using aspirin in small doses to prevent heart disease in people 60 years of age or older. The decision to use aspirin in people aged 40-59 has predicted a 10% or higher risk of heart attack in the next 10 years, leaving the treating physician. It concludes that the net benefit of aspirin use in this group is small. Decisions should be personalized based on the nature of the risk factors and related conditions such as diabetes.
For example, because of the high 10-year risk, it makes no sense for a heavy smoker to quit smoking. Especially when smoking increases the risk of subarachnoid hemorrhage where aspirin use may increase the risk.
One of the arguments used to promote regular use of aspirin for primary prevention of CHD was that the drug was also protective against colorectal cancer. This was initially based on weak evidence. The USPSTF, in a detailed review of the available evidence, found it insufficient to support the protective effect. Therefore, the overall benefits do not outweigh the risks of the overall 40-59 age group. It further concludes that “with moderate certainty that there is no net benefit in starting aspirin use for the primary prevention of CVD events in adults 60 years or older.”
The guidelines for the primary prevention of CHD and CVD undergo periodic revisions, based on an objective evaluation of the best evidence available to date. Recent changes in the guidelines for denying regular use of aspirin for this purpose take into account the reduction in the expected benefits from aspirin due to the increased protection provided by other drugs and non-drug measures at risk of severe bleeding. Complications remain low with aspirin use. There will be subgroups of individuals where the drug can be used with caution, if the expected benefits due to the associated risk factors are high and the drug is well tolerated. It can still be used as a choice, even if the cover of the ‘magic potion’ is gone and regular use is ignored.
K. Srinath Reddy is the chairman of the Public Health Foundation of India and was earlier the head of the cardiology department at the AIIMS in Delhi. He was the first Indian president of the World Heart Federation.