Aspirin has been one of the most widely used medicines around the world for more than a century, most recently in low-dose form as a treatment for cardiovascular problems such as a heart attack or a stroke. However, its reign has been challenged by more recent drugs, and new research published in The Lancet could see it lose its crown to a younger pretender.

Researchers analysing clinical trials involving nearly 30,000 people with coronary artery disease — which can include those who’ve had a heart attack or suffer from angina — found that a low dose of aspirin doesn’t offer as much protection as the newer antiplatelet (blood-thinning) drug clopidogrel. A finding that could change UK guidelines which, at least for most people with coronary artery disease, advocate taking a daily aspirin for the rest of their lives.

Clopidogrel may be the newer of the two drugs but it has been in use since the late Nineties and is the medicine of choice for preventing recurrent problems in most people who have had a stroke, or who have “furred-up” arteries in their legs. However, aspirin remains the standard long-term preventive for people with coronary artery disease. For now.

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Both medicines work by reducing the stickiness of platelets, the smallest components of blood that clump together after injury to help to form clots and stem bleeding. A potentially life-saving physiological response if you are involved in a road traffic accident or undergoing surgery, but a potentially fatal one if the platelets happen to be activated in a narrow blood vessel supplying your heart or brain.

The use of antiplatelet medicines took off in the UK after the publication in 1988 of the landmark ISIS-2 trial, which found that daily low-dose aspirin was a life-saver for people who had a heart attack. It indicated that one month of taking the drug prevented 25 deaths, and another 10-15 non-fatal heart attacks or strokes, for every 1,000 people. And the longer they took the aspirin the greater the benefit. It was game-changing.

Clopidogrel was licensed about a decade after the ISIS-2 trial and was initially mainly used as a substitute for people who couldn’t take aspirin. It has a different mechanism of action (see below) but the net effect — reduced platelet “stickiness” — is much the same. Indeed, these days the drugs are often used together, at least in the short to medium term, after a heart attack, coronary artery bypass surgery, stenting and heart valve surgery.

However, as well as preventing unwanted clots in arterial bottlenecks the drugs can prevent useful clots and lead to troublesome bleeding: anything from bruising after a trivial knock or shaving nicks that won’t stop oozing to life-threatening haemorrhage in some cases. Reassuringly the Lancet paper shows that while clopidogrel is better than aspirin at preventing heart attacks (and strokes) in most people with coronary artery disease, it carries no extra risk of these types of dangerous bleeding. It is often the preferred option.

• Switching aspirin for alternative drug ‘reduces risk of heart attack’

If, as expected, guidance is changed to favour clopidogrel, millions more will end up on the drug (more than a third of people over 65 in the UK take a daily low-dose aspirin at present), but there are a couple of flies in the ointment.

First, a person’s response to clopidogrel can be affected by their genetic make up, with about 30 per cent of those with European ancestry (and 50 per cent of those with east Asian ancestry) having genes that render the drug less effective. However, the researchers behind the Lancet study concluded that while it may reduce efficacy in acute treatment, such as in the days or weeks after developing heart problems, there is less evidence that it significantly impairs longer-term prevention for most.

Second, the commonly prescribed anti-stomach acid medication omeprazole, and its sister drug esomeprazole, can reduce clopidogrel’s efficacy. The latest evidence suggests this may not be as worrying as initially thought, but the combination is still best avoided. Lansoprazole, another popular member of the same family of acid-suppressing drugs, is deemed a safer choice.

Unlike aspirin, clopidogrel is prescription-only, so people will not be able to self-medicate. Fewer people self-treat with daily low-dose aspirin than used to, but I still come across healthy middle-aged people who buy it over the counter to ward off an early heart attack or stroke. However, the evidence is clear: if you are not at higher than normal risk of stroke or heart attack, the risks of aspirin (mainly bleeding) are likely to outweigh the benefits. Take an antiplatelet medicine only if advised to do so by your doctor.

Oh, and it is clo-pid-o-grill. At least that’s how I pronounce it…
Visit cks.nice.org.uk for more information on how people who have already had one can prevent further heart attacks

How aspirin and clopidogrel work

Aspirin irreversibly blocks an enzyme in platelets that encourages them to clump and stick together (a natural part of the clotting process). This effect lasts for the whole seven to ten-day life of the platelets and wanes only when they are replaced by new ones.

Clopidogrel binds to a receptor on the surface of platelets (called P2Y12 adenosine diphosphate) but the result is much the same. And, like aspirin, the inhibition is irreversible and lasts the life of the platelet.

Other antiplatelet drugs include ticagrelor, prasugrel and dipyridamole. For more information visit bhf.org.uk.