Life Extension Magazine®

Spilled low-dose aspirin that maybe too regularly

Is Aspirin Needed Today

Recent studies show low-dose aspirin may not be needed to reduce heart attack and stroke risk in healthier Americans.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in October 2024. Written by: William Faloon.

Starting in the 1970s, a number of published studies found that people who regularly took aspirin had reduced risk of heart attack and other vascular disorders.^1-4

As evidence mounted, the FDA approved low-dose aspirin in 1998 to treat high-risk patients, including those who had already suffered a heart attack or ischemic stroke.

Tacit approval to take low-dose aspirin daily was also given for healthy adults concerned about occlusive vascular disorders.

One of aspirin’s beneficial effects is to prevent blood platelets from clumping and blocking blood flow,^5,6 including inside a coronary or cerebral artery.

Back in the early years when aspirin demonstrated efficacy, the typical Americans’ behavior patterns put them at high risk for abnormal platelet clumping, which in turn caused soaring numbers of heart attacks and strokes.⁷

In the period of 1980 to 2014, however, death rates from cardiovascular disease incrementally plummeted by 50%.⁸

This improvement coincides with better control of blood pressure and lipids, and a decrease in smoking tobacco,^5,6 along with changing dietary practices and improved cardiovascular procedures and interventions.

Overlooked by the mainstream is an almost 20-fold increase in the use of dietary supplements, many of which have many similar effects as aspirin in protecting the cardiovascular system.⁹

Recent studies are finding that aspirin is not reducing heart attack/stroke risk in today’s healthier American population compared to earlier decades.^5,6 Aspirin is still proving effective in certain high-risk groups, as will be described in this editorial.^5,10

So the debate swirling in medical settings is whether otherwise healthy Americans should continue taking low-dose aspirin.

Our analysis reveals that adults at low risk of cardiovascular disease who control their risk factors, including protecting against abnormal platelet clumping, may not need daily low-dose aspirin. This editorial describes our rationale.

If we travel back to the 1950s-1970s era, a typical American man or woman might, after waking up, eat a breakfast consisting of bacon, eggs, and buttered toast, with sugar and/or cream-laden coffee. Many would also light up a cigarette.

The morning hours are when blood platelets are most “sticky.”

Mornings are also when most sudden heart attacks were occurring in those decades.¹¹

Consumption of polyphenol-rich fruits, vegetables, and dietary supplements in this 1950s-1970s period was low.

Systolic blood pressure over 150mmHg was quite normal, and many people had high cholesterol levels,^12,13 sometimes exceeding 300 mg/dL.

Add together the above five paragraphs and you may see why sudden-death heart attacks surged to epidemic levels during the 1950s-1970s period.

Typical breakfast foods consumed in that time period increased abnormal platelet aggregation (clumping), smoking caused more platelet clumping, and few anti-platelet-clumping foods or nutrients were consumed.

So, when studies published in the prior decades identified regular aspirin users as having reduced heart attack rates, there was a biological explanation for this, since aspirin markedly lowered the platelet clumping that was encouraged by typical lifestyles during this era.

“In 1965, 45% of Americans smoked, today it’s only 15%… That’s the lowest percentage ever recorded.”*

*Smithsonian.com based on Centers for Disease Control and Prevention 2015 report.19

American Heart Association Update March 18, 2019

Earlier this year, the American Heart Association published an article that corresponds to much of what we state as it relates to changing American health behavior patterns. Here is an excerpt from the news report:

“Heart attack rates have gone down in more modern society with lower smoking rates and better treatment of blood pressure, better treatment of cholesterol… There probably was more of a role for aspirin back in the older trials, even though the bleeding issue has always been seen there.”³⁶

The reasons cited by the American Heart Association, and many more provided in this editorial, indicate why otherwise healthy American adults may no longer need low-dose aspirin for primary heart attack prevention.

What Has Changed Today?

Even a cursory look at health behavior patterns in the 1950s-1970s compared to recent years reveals startling changes.

There have been huge reductions in average blood pressure readings and lipid numbers.^12,14,15 These two factors alone dramatically reduce platelet clumping (thrombotic) risks.^16,17

Dietary practices among health conscious individuals reduce or eliminate breakfast foods like bacon, ham, and fried eggs that contribute to platelet aggregation.

Specifically, health-conscious individuals have become aware that ingestion of saturated fats (and certain other fats like trans-fats) is a culprit behind platelet aggregation and subsequent coronary heart attacks and ischemic strokes.

Tobacco usage has plummeted¹⁸ while intake of nutrients that protect against platelet aggregation has soared.

Stated succinctly, there is no comparison between the vascular health status of the typical American in the 1950s-1970s and the same indices in more recent decades.

Plummeting incidences of heart attacks and strokes caused by abnormal platelet aggregation attest to this.

So, while aspirin saved many lives in the past, it may not have this same effect today. That’s because there is far less abnormal platelet clumping and thus less coronary or cerebral artery blockage (occlusion) happening.^5,6

Current Conventional “Primary Prevention” Guidelines for Daily Low-Dose Aspirin

Primary prevention in cardiovascular disease is defined as reducing the risk of having an initial cardiovascular event, like a heart attack (myocardial infarct) or stroke (cerebrovascular accident).

In comparison, secondary prevention is defined as reducing the risk of having a second, or subsequent, cardiovascular event.

Low-dose (75-100 mg daily) aspirin use for secondary prevention is well established.³⁵

However, based upon several new, high-quality clinical studies (randomized, placebo-controlled, direct intervention trials), the use of aspirin for generalized primary prevention has been revised.^28-32

These revisions reflect the differences between patient populations today in comparison with the past^5,6 – for example, patients today achieve better blood pressure control, have better cholesterol profiles, and use less tobacco than “comparable” patients in the past, especially 30-plus years ago.

According to the 2019 Guidelines for Primary Prevention of Cardiovascular Disease from the American College of Cardiology (ACC) and the American Heart Association (AHA), current recommendations on the use of aspirin for primary prevention stipulate:⁵

Low-dose aspirin (75-100 mg orally daily) may be considered for primary prevention of cardiovascular disease in high-risk adults (e.g., patients at high risk of a cardiovascular event, like type II diabetes patients as well as those patients with multiple cardiovascular risk factors such as poor blood pressure control, active tobacco use, and elevated LDL cholesterol) aged 40-70 years, not at increased bleeding risk;
Low-dose aspirin should not be administered on a routine, generalized basis for primary prevention of cardiovascular disease among otherwise healthy adults >70 years, not at high cardiovascular risk;
Low-dose aspirin should not be administered for primary prevention among adults at any age who are at increased bleeding risk.

Nutrients That Impede Platelet Aggregation

Thrombosis is the leading cause of death in persons over age 50.²⁰

The major cause of thrombosis is abnormal platelet aggregation (clumping) inside arteries and veins.

It is critical that aging persons follow anti-thrombotic practices that include ingesting nutrients that help prevent blood platelets from sticking together.

I believe every reader of Life Extension Magazine® is already taking many of these anti-platelet nutrients. They include plant polyphenols like curcumin, green tea, pine bark, and pomegranate, optimized forms of folate, vitamins B6 and B12, along with omega-3 fatty acids.^21-27

These nutrients have differing anti-platelet properties. This is important because there are several mechanisms that cause abnormal platelet aggregation.

Compare what health-conscious Americans have done in recent decades to reduce their thrombotic heart attack and stroke risks to the 1950s-1970s period. The difference is night and day.

It helps explain why recent studies seeking to demonstrate the effect of aspirin on heart attack prevention in healthy people have largely failed to do so.^28-32

Today’s radically altered health behavior patterns drastically reduce platelet stickiness. Further reducing platelet aggregation with aspirin may not add additional benefit to healthy people, as recent studies indicate.^5,6

Reduced Secondhand Smoke Exposure Slashes Thrombotic Cardiovascular Risks

Most of you may recall being chronically exposed to other people’s cigarette smoke in the workplace, around recreation areas, while traveling, and at home.

Here is what the Surgeon General and the Institute of Medicine write about the cardiovascular dangers of secondhand smoke:^37-42

Exposure to secondhand smoke has immediate adverse effects on the cardiovascular system and can cause coronary heart disease and stroke.
Secondhand smoke causes nearly 34,000 premature deaths from heart disease each year in the United States among nonsmokers.
Nonsmokers who are exposed to secondhand smoke at home or at work increase their risk of developing heart disease by 25%–30%.
Secondhand smoke increases the risk for stroke by 20%− 30%.
Secondhand smoke exposure causes more than 8,000 deaths from stroke annually.
Breathing secondhand smoke can have immediate adverse effects on your blood and blood vessels, increasing the risk of having a heart attack.
Breathing secondhand smoke interferes with the normal functioning of the heart, blood, and vascular systems in ways that increase the risk of having a heart attack.
Even brief exposure to secondhand smoke can damage the lining of blood vessels and cause your blood platelets to become stickier. These changes can cause a deadly heart attack.

Over the past 25 years, public health initiatives have resulted in huge reductions in secondhand smoke exposure, which further lowers thrombotic heart attack and ischemic stroke risk.

These data help further explain why studies in early years showed reduced heart attack risk in aspirin users.

In today’s relatively secondhand-smoke-free world, the potent anti-thrombotic effects of daily aspirin are not always going to show reduced heart attack risk because this major environmental threat has been largely eliminated.

Blood Pressure and Platelet Aggregation

With each heartbeat, blood is pushed through your arteries into microscopic capillaries and then out through veins for return to your heart.

Elevated systolic blood pressure increases mechanical stress that compromises the integrity of the inner arterial wall called the endothelium. This can lead to a pro-inflammatory and pro-thrombotic state that is an underlying cause of heart attack or ischemic stroke.

Blood pressure guidelines in earlier years allowed levels that were too high. Back in those days medications to treat hypertension were not particularly effective compared to more recent decades.³³

When aspirin was showing significant efficacy in reducing heart attack risk, people with high blood pressure, including prehypertension, were not adequately controlling it with diet, lifestyle, and medication.

This same problem persists today among people who are not proactive in protecting against vascular disease.

Average blood pressure readings have been dropping in recent decades in most population groups, though the growing number of overweight/obese individuals is counteracting this favorable trend.

Those who achieve better blood pressure control enjoy reduced platelet aggregation.³⁴

These individuals are therefore less likely to benefit from daily aspirin use compared to past generations that lived with elevated blood pressure.

Lipids and Blood Pressure

Foods and nutrients with anti-platelet properties

In the early 1980s, the standard reference ranges for LDL cholesterol and triglycerides were too high. These antiquated reference ranges put many people at risk for coronary artery occlusion and subsequent heart attack (myocardial infarction) in earlier decades.

Elevated lipids accelerate atherosclerotic processes. This increases the risk of platelets aggregating around unstable arterial plaque and causing coronary and cerebral artery blockages.

Huge declines in average lipid levels beginning in the late 1980s provide further rationale for why aspirin is not demonstrating similar beneficial effects in more recent studies.^5,6,12,15

Back in the previous period (1950s-1970s) little was done in the conventional setting to prevent atherosclerosis, be it diet, exercise, supplements or drugs.

These facts cannot be overstated. When Americans were suffering epidemic levels of heart attacks, laboratory reference ranges for blood lipids were frighteningly high.

This predisposed a large swath of Americans to abnormal platelet aggregation that aspirin helped protect against.

Many of today’s health-conscious people may no longer need this additional anti-platelet protection, as their blood pressure and blood lipids are markedly lower.

Who Should Take Aspirin?

The term “primary prevention” applies to the use of low-dose aspirin in seemingly healthy individuals who have elevated risk factors for coronary heart attack and ischemic stroke.

The box on the next page describes patient groups who should be taking low-dose aspirin for primary prevention, i.e. before they suffer a thrombotic heart attack or stroke.

The term “secondary prevention” applies to people who already suffer angina and/or severe coronary blockage, or are survivors of a heart attack, transient ischemia attack, ischemic stroke or other occlusive arterial disease.

For this group of individuals with preexisting vascular disease, aspirin is clearly established for secondary prevention, i.e. preventing another cardiovascular event.^10,35

The debate going on now is what to recommend to normal, aging people with borderline vascular risks.

Alternative practitioners have long claimed the anti-platelet effects of healthy diets, exercise, and nutrient extracts that exhibit aspirin-like properties are more than sufficient.

The bottom line is that there are no clear-cut answers for otherwise healthy, aging people.

What Should You Do?

For many readers of this magazine, daily low-dose aspirin may be a reasonable option, but there is no real “typical” reader of this magazine.

I’m sometimes surprised that those who support our healthy longevity projects do not always optimize their own cardiovascular health.

What’s important to understand is that there are several mechanisms by which an abnormal clot can form inside a blood vessel.

By consuming a healthy diet, taking a spectrum of anti-platelet nutrients, and avoiding other platelet clumping factors, thrombotic risks are likely to be significantly reduced, and the published medical literature supports this.

References

Elwood PC, Cochrane AL, Burr ML, et al. A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. Br Med J. 1974 Mar 9;1(5905):436-40.
Aspirin in coronary heart disease. The Coronary Drug Project Research Group. J Chronic Dis. 1976 Oct;29(10):625-42.
Linos A, Worthington JW, O’Fallon W, et al. Effect of aspirin on prevention of coronary and cerebrovascular disease in patients with rheumatoid arthritis. A long-term follow-up study. Mayo Clin Proc. 1978 Sep;53(9):581-6.
Breddin K, Loew D, Lechner K, et al. Secondary prevention of myocardial infarction. Comparison of acetylsalicylic acid, phenprocoumon and placebo. A multicenter two-year prospective study. Thromb Haemost. 1979 Feb 28;41(1):225-36.
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Circulation. 2019 Mar 17:CIR0000000000000678.
Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005 Mar 31;352(13):1293-304.
Haft JI. Role of blood platelets in coronary artery disease. Am J Cardiol. 1979 Jun;43(6):1197-206.
Roth GA, Dwyer-Lindgren L, Bertozzi-Villa A, et al. Trends and Patterns of Geographic Variation in Cardiovascular Mortality Among US Counties, 1980-2014. JAMA. 2017 May 16;317(19):1976-92.
Available at: https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-new-efforts-strengthen-regulation-dietary. Accessed May 31, 2019.
Smith SC, Jr., Benjamin EJ, Bonow RO, et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011 Nov 29;124(22):2458-73.
Schwartz BG, Mayeda GS, Burstein S, et al. When and why do heart attacks occur? Cardiovascular triggers and their potential role. Hosp Pract (1995). 2010;38(3):144-52.
Carroll MD, Lacher DA, Sorlie PD, et al. Trends in serum lipids and lipoproteins of adults, 1960-2002. JAMA. 2005 Oct 12;294(14):1773-81.
Moser M. Historical perspectives on the management of hypertension. J Clin Hypertens (Greenwich). 2006 Aug;8(8 Suppl 2):15-20; quiz 39.
Collaboration NCDRF. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. Lancet. 2017 Jan 7;389(10064):37-55.
Hopstock LA, Bonaa KH, Eggen AE, et al. Longitudinal and secular trends in total cholesterol levels and impact of lipid-lowering drug use among Norwegian women and men born in 1905-1977 in the population-based Tromso Study 1979-2016. BMJ Open. 2017 Aug 21;7(8):e015001.
Blann AD, Nadar S, Lip GY. Pharmacological modulation of platelet function in hypertension. Hypertension. 2003 Jul;42(1):1-7.
Sikora J, Kostka B, Marczyk I, et al. Effect of statins on platelet function in patients with hyperlipidemia. Arch Med Sci. 2013 Aug 30;9(4):622-8.
CDC. Centers for Disease Control and Prevention. Achievements in Public Health, 1900-1999: Tobacco Use — United States, 1900-1999. MMWR. 1999;48(43):986-93.
Available at: https://www.smithsonianmag.com/smart-news/only-15-percent-americans-smoke-180956504/. Accessed June 10, 2019.
Becker Richard C. MD. Textbook of Coronary Thrombosis and Thrombolysis. Boston: Kluwer Academic; 1997.
Araghi-Niknam M, Hosseini S, Larson D, et al. Pine bark extract reduces platelet aggregation. Integr Med. 2000 Mar 21;2(2):73-7.
Hirsch GE, Viecili PRN, de Almeida AS, et al. Natural Products with Antiplatelet Action. Curr Pharm Des. 2017;23(8):1228-46.
Malpass K. B vitamins show benefit in absense of antiplatelet therapy. Nature Reviews Neurology. 2012;8:298.
Mattiello T, Trifiro E, Jotti GS, et al. Effects of pomegranate juice and extract polyphenols on platelet function. J Med Food. 2009 Apr;12(2):334-9.
Mohd Nor NH, Othman F, Mohd Tohit ER, et al. Medicinal Herbals with Antiplatelet Properties Benefit in Coronary Atherothrombotic Diseases. Thrombosis. 2016;2016:5952910.
Phang M, Garg ML, Sinclair AJ. Inhibition of platelet aggregation by omega-3 polyunsaturated fatty acids is gender specific-Redefining platelet response to fish oils. Prostaglandins Leukot Essent Fatty Acids. 2009 Jul;81(1):35-40.
Vognild E, Elvevoll EO, Brox J, et al. Effects of dietary marine oils and olive oil on fatty acid composition, platelet membrane fluidity, platelet responses, and serum lipids in healthy humans. Lipids. 1998 Apr;33(4):427-36.
Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018 Sep 22;392(10152):1036-46.
Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014 Dec 17;312(23):2510-20.
McNeil JJ, Nelson MR, Woods RL, et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. N Engl J Med. 2018 Oct 18;379(16):1519-28.
McNeil JJ, Wolfe R, Woods RL, et al. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. N Engl J Med. 2018 Oct 18;379(16):1509-18.
McNeil JJ, Woods RL, Nelson MR, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N Engl J Med. 2018 Oct 18;379(16):1499-508.
Saklayen MG, Deshpande NV. Timeline of History of Hypertension Treatment. Front Cardiovasc Med. 2016;3:3.
Gupta S, Gupta VK, Dhamija RK, et al. Platelet aggregation patterns in normotensive and hypertensive subjects. Indian J Physiol Pharmacol. 2002 Jul;46(3):379-82.
Godley RW, Hernandez-Vila E. Aspirin for Primary and Secondary Prevention of Cardiovascular Disease. Tex Heart Inst J. 2016 Aug;43(4):318-9.
Available at: https://www.heart.org/en/news/2019/03/18/avoid-daily-aspirin-unless-your-doctor-prescribes-it-new-guidelines-advise. Accessed June 7, 2019.
Available at: https://www.cdc.gov/tobacco/data_statistics/fact_sheets/secondhand_smoke/health_effects/index.htm. Accessed June 7, 2019.
Available at: https://www.hhs.gov/sites/default/files/consequences-smoking-consumer-guide.pdf. Accessed June 7, 2019.
Available at: https://www.ncbi.nlm.nih.gov/books/NBK44324/. Accessed June 7, 2019.
Available at: https://www.cdc.gov/tobacco/data_statistics/sgr/50th-anniversary/index.htm. Accessed June 7, 2019.
Available at: https://www.ncbi.nlm.nih.gov/books/NBK219565/. Accessed June 7, 2019.
Available at: https://www.cdc.gov/tobacco/data_statistics/sgr/2010/index.htm. Accessed June 7, 2019.
Bogani P, Galli C, Villa M, et al. Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis. 2007 Jan;190(1):181-6.
Visioli F, Caruso D, Grande S, et al. Virgin Olive Oil Study (VOLOS): vasoprotective potential of extra virgin olive oil in mildly dyslipidemic patients. Eur J Nutr. 2005 Mar;44(2):121-7.
Agrawal K, Melliou E, Li X, et al. Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial. J Funct Foods. 2017 Sep;36:84-93.
Kang WS, Lim IH, Yuk DY, et al. Antithrombotic activities of green tea catechins and (-)-epigallocatechin gallate. Thromb Res. 1999 Nov 1;96(3):229-37.
Hubbard GP, Wolffram S, Lovegrove JA, et al. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost. 2004 Dec;2(12):2138-45.
McEwen B, Morel-Kopp MC, Tofler G, et al. Effect of omega-3 fish oil on cardiovascular risk in diabetes. Diabetes Educ. 2010 Jul-Aug;36(4):565-84.
Nomura S, Kanazawa S, Fukuhara S. Effects of eicosapentaenoic acid on platelet activation markers and cell adhesion molecules in hyperlipidemic patients with Type 2 diabetes mellitus. J Diabetes Complications. 2003 May-Jun;17(3):153-9.
Mori TA, Beilin LJ, Burke V, et al. Interactions Between Dietary Fat, Fish, and Fish Oils and Their Effects on Platelet Function in Men at Risk of Cardiovascular Disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 1997 1997/02/01;17(2):279-86.
Hartweg J, Farmer AJ, Holman RR, et al. Potential impact of omega-3 treatment on cardiovascular disease in type 2 diabetes. Curr Opin Lipidol. 2009 Feb;20(1):30-8.
Ramirez-Boscá A, Soler A, Carrión Gutierrez MA, et al. Antioxidant Curcuma extracts decrease the blood lipid peroxide levels of human subjects. Age. 1995 October 01;18(4):167-9.
Ramirez Bosca A, Carrion Gutierrez MA, Soler A, et al. Effects of the antioxidant turmeric on lipoprotein peroxides: Implications for the prevention of atherosclerosis. Age (Omaha). 1997 Jul;20(3):165-8.
Ramirez Bosca A, Soler A, Carrion-Gutierrez MA, et al. An hydroalcoholic extract of Curcuma longa lowers the abnormally high values of human-plasma fibrinogen. Mech Ageing Dev. 2000 Apr 14;114(3):207-10.
Wongcharoen W, Phrommintikul A. The protective role of curcumin in cardiovascular diseases. Int J Cardiol. 2009 Apr 3;133(2):145-51.
Vachharajani V, Wang SW, Mishra N, et al. Curcumin modulates leukocyte and platelet adhesion in murine sepsis. Microcirculation. 2010 Aug;17(6):407-16.
Gulati OP. Pycnogenol(R) in chronic venous insufficiency and related venous disorders. Phytother Res. 2014 Mar;28(3):348-62.
Kim DS, Kim MS, Kang SW, et al. Pine bark extract enzogenol attenuated tumor necrosis factor-alpha-induced endothelial cell adhesion and monocyte transmigration. J Agric Food Chem. 2010 Jun 9;58(11):7088-95.
Aviram M, Dornfeld L, Rosenblat M, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr. 2000 May;71(5):1062-76.
Polagruto JA, Schramm DD, Wang-Polagruto JF, et al. Effects of flavonoid-rich beverages on prostacyclin synthesis in humans and human aortic endothelial cells: association with ex vivo platelet function. J Med Food. 2003 Winter;6(4):301-8.