Why has advice on aspirin for heart protection changed?

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For many decades, aspirin has been advised to prevent heart attacks, both for those with pre-existing cardiovascular disease (CVD) and to prevent coronary heart disease (CHD). Baby aspirin (low dose aspirin – usually a 75-81 mg tablet) has become an article of faith for cardiac protection in American adults. So, for many Americans, it came as a surprise that recent guidelines released by the American Heart Association and the American College of Cardiology changed their recommendation on prescribing aspirin for the primary prevention of cardiovascular and coronary heart disease. Although the UK and Europe have previously changed their positions on the use of aspirin for heart attack prevention, US guidelines are influencing medical practice in many other parts of the world. Thus, the reasons for a change of position in these guidelines must be understood even in India.

How does aspirin reduce the risk?

Coronary artery disease occurs through two main pathological processes affecting the arteries that supply blood to the heart. Atherosclerosis involves fatty deposition in parts of the arterial wall as well as fibrosis. Sometimes these “plaques” calcify. If the plaques reduce the luminal diameter of the coronary artery, reaching 70% or more of the width of this passage (50% in the case of the left main coronary artery), blood flow is considerably impeded. Especially during times of intense physical activity or stress, where high blood pressure and high heart rate increase the oxygen needs of the heart muscle. This mismatch between supply and demand causes angina pectoris or chest discomfort. He settles on the rest.

However, soft plaques tend to rupture even if they are small and are usually not obstructive. When they rupture, their exposed fatty core comes into contact with the blood flowing through the artery. This activates the “platelets” which are part of the blood cells. The aggregation of platelets forms a clot. If large, the clot can completely block (occlude) the passage of blood. While the “obstruction” causes angina pectoris, the “occlusion” triggers a heart attack. Sometimes a ruptured plaque can produce angina even at rest or with minimal exertion (unstable angina) before causing a heart attack or myocardial infarction (MI). These acute conditions are often grouped together as “acute coronary syndromes” (ACS).

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Aspirin is an antiplatelet drug that irreversibly inactivates the platelet cyclooxygenase enzyme and suppresses the production of a Thromboxane A2 coagulation promoter. This makes the platelets unable to clump together. Since the action of each dose is limited to only the platelets which are then in circulation and a new generation of platelets continues to be produced to replace those which die naturally within a few days, a daily dose of aspirin is prescribed. to prevent young and sticky diseases. platelets from clumping together.

Aspirin moves from secondary prevention to primary prevention

The first clinical trials aimed to evaluate the protective effect of aspirin in those who had already had a heart attack. Several trials, in different parts of the world, have unequivocally shown significant benefit in reducing death and recurrent heart attacks in people who have survived a heart attack or myocardial infarction. Thus, aspirin became an indispensable part of secondary post-MI prophylaxis for all people who could tolerate the drug without gastrointestinal side effects. It has also been used after the insertion of coronary stents.

In light of this success, attention has turned to primary prevention. “Why not prevent the heart attack in the first place, by preventing clots from forming on any plaque?”, was the question posed. In 2003, Wald and Law from the UK even proposed a six-drug ‘polypill’ combination to prevent heart attacks, for use in all people over the age of 55. Besides aspirin, the others chosen were a beta-blocker, a diuretic, an angiotensin converting enzyme (ACE-I) inhibitor, a statin and folic acid.

The editor of the British Medical Journal (BMJ) has gone too far, calling this untested hypothesis the BMJ’s most important scientific publication for 50 years. Several polypill trials and separate trials of aspirin followed, for the primary prevention of coronary artery disease. The folic acid quickly disappeared because it was ineffective. Of the three antihypertensive drugs, beta-blockers and ACE-I remained initially for coronary artery disease, while diuretics proved effective in preventing stroke. As the adverse metabolic effects of prolonged beta-blocker therapy on blood sugar, triglycerides, and HDL cholesterol became known, this class of drugs gave way to calcium channel blockers like amlodipine for the blood pressure control in primary prevention. Statins remained constant. ACE-I and related angiotensin receptor blockers (ARBs) have gained a reputation for blood pressure control and vascular protection.

Change position on aspirin

Aspirin has gone through the phases of universal acceptance, doubt, debate and revised recommendations in the field of primary prevention. Although it remains undisputed for secondary prevention, the question has been asked whether the benefits of using aspirin in the primary prevention of coronary artery disease unequivocally outweigh the risks of serious bleeding in the brain or stomach. Over time, the evidence has accumulated, through clinical trials, meta-analyses and post-marketing surveillance. As the evidence grew, the recommendations changed.

In May 2009, the Anti-Thrombotic Trialists’ Collaboration (ATT) published a study in The Lancet, saying, “In primary prevention without prior disease, aspirin has uncertain net worth because reduction of occlusive events must be put outweigh any increase in major bleeds”. British clinical practice has become more cautious against the routine use of aspirin for the primary prevention of coronary heart disease. Clinical trials continued to assess the role of aspirin alone or in combination. While statins were effective in lowering harmful blood lipids like LDL cholesterol, antihypertensive drugs brought this risk factor under control, smoking rates declined in Western populations, healthier eating habits were adopted, and physical activity increased. encouraged, questions were raised about the additional 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 antiplatelet drugs in the primary prevention of atherothrombosis “remains controversial due to the uncertain balance of benefits and potential risks”. when combined with other prevention strategies. The risk of coronary artery disease increases with age. The risk of severe bleeding from aspirin also increases with age. It is therefore particularly necessary to weigh the benefits against the risks in this age group and to ask whether these benefits cannot be obtained by other means, including non-drug measures.

The remarkable benefits of a Mediterranean diet and other conservative diets on the primary prevention of coronary heart disease have been well demonstrated in clinical trials and long-term cohort studies. Antihypertensive and cholesterol-lowering drugs have also shown great benefits for primary prevention. So why risk aspirin in primary prevention, even if it can continue in secondary prevention? This line of thinking has emerged in recent years.

Additionally, there has been criticism that most risk calculators overestimate the risk of a cardiovascular event over 10 years because they do not take into account other benefits of treatment that may reduce this risk over this long period.

Recent US guidelines

The US Preventive Services Task Force (USPSTF) published its most recent guidelines in the April 26, 2022 issue of the Journal of the American Association (JAMA). It advises against the use of low-dose aspirin for the prevention of cardiovascular disease in people 60 years of age or older. He left the decision on the use of aspirin, in people aged 40 to 59 who have a predicted risk of 10% or more of a cardiovascular event in the next 10 years, to the treating physician. He concluded that the net benefit of aspirin use in this group is small. The decision must be individualized, depending on the nature of the risk factors and associated conditions such as diabetes.

It doesn’t make sense, for example, to put a heavy smoker on aspirin because of a high 10-year risk, without getting them to quit. Especially since smoking increases the risk of subarachnoid hemorrhage where the use of aspirin can aggravate the danger.

One of the arguments used to promote the routine use of aspirin for the primary prevention of coronary artery disease was that the drug also protected against colorectal cancer. This was initially based on tenuous evidence. The USPSTF, in a detailed review of available evidence, found it insufficient to support a protective effect. Therefore, the overall benefits do not outweigh the risks across the 40-59 age group as a whole. It further concluded “with moderate certainty that initiation of aspirin use for the primary prevention of cardiovascular events in adults 60 years of age or older has no clear benefit”.

Guidelines for the primary prevention of coronary artery disease and cardiovascular disease are periodically revised, based on an objective assessment of the best evidence available to date. The recent modification of the guidelines, aimed at disfavoring the routine use of aspirin for this purpose, takes into account the reduction in the expected benefit of aspirin due to the increased protection offered by other drugs and non-drug measures while that the risk of serious bleeding complications associated with the use of aspirin remain unchanged. There will be subgroups of individuals for whom the drug may be used with caution, if the expected benefits are high due to associated risk factors and the drug is well tolerated. It can still be used selectively, although the cloak of “magic medicine” has slipped away and routine use is best avoided.

K. Srinath Reddy is the President of Public Health Foundation of India and previously headed the Department of Cardiology at AIIMS Delhi. He was the first Indian President of the World Heart Federation.

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