Prasugrel

Is prasugrel safe?

For the people it is meant for, mostly adults under 75 who weigh at least 60 kg and have just had a heart attack or unstable angina (an acute coronary syndrome) treated with a stent, prasugrel prevents more heart attacks and stent clots than clopidogrel. It also causes more serious bleeding, including more fatal bleeding. That trade-off is the whole story of this drug, and the US label puts it in a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary.

We score prasugrel 67, level with ticagrelor (67) and below clopidogrel (72). Prasugrel has the highest fatal-bleeding figure of the three and the strictest list of people who must not take it. It has the simplest interaction profile. A low score is not a reason to stop: the label warns that stopping early after a heart attack or stent raises the risk of stent clots, heart attack and death.

How it compares with clopidogrel

Both drugs are prodrugs that the liver turns into a compound that blocks the P2Y12 receptor on platelets for the rest of each platelet's 7 to 10 day life. Prasugrel's conversion is quicker and more reliable. The label reports no relevant effect of the CYP2C19CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary gene, which is the weak point of clopidogrel.

The TRITON-TIMI 38 trial compared the two in 13,608 people with acute coronary syndromes who were having a stent, all also on aspirin:

The benefit came mainly from fewer non-fatal heart attacks, and deaths from any cause did not differ. Put simply, prasugrel traded a few fatal bleeds for a larger number of prevented heart attacks and stent clots. Bleeding was most frequent in the first days of treatment, according to the label.

Who must not take it

The trial found three groups in whom the balance tipped the wrong way, and the labels act on all three.

A past stroke or TIA. People with this history had more strokes on prasugrel (6.5%, including 2.3% with bleeding into the brain) than on clopidogrel (1.2%). The US and EU labels rule it out for them.

Age 75 or over. Fatal bleeding was 1.0% against 0.1% on clopidogrel, and the benefit was uncertain. Both labels say it is generally not recommended. The US label allows it in high-risk cases such as diabetes or a previous heart attack. In those cases the EU label sets a 5 mg maintenance dose.

Weight under 60 kg. Lighter people get more of the active drug. Major or minor bleeding was 10.1% against 6.5% on clopidogrel. The US label says to consider 5 mg a day. The EU label requires it.

Bypass surgery is the other big risk. Among patients who needed a bypass operation during the trial, surgery-related bleeding was 14.1% on prasugrel against 4.5% on clopidogrel. The label says not to start prasugrel in anyone likely to need urgent bypass surgery, and to stop it at least 7 days before any operation when possible. The EU label also rules it out in severe liver disease.

Prasugrel or ticagrelor?

Doctors who want something stronger than clopidogrel usually choose between these two. In ISAR-REACT 5, an open-label trial of 4,018 people with acute coronary syndromes, death, heart attack or stroke at one year was 6.9% on prasugrel against 9.3% on ticagrelor. Major bleeding was 4.8% against 5.4%, not a significant difference. On the strength of that trial, European (ESC) guidelines since 2020 say prasugrel should be considered in preference to ticagrelor for people going on to a stent procedure, and the 2023 guideline on acute coronary syndromes kept that advice. Critics, including the Dutch working group on acute coronary syndromes in 2024, point out that it rests on a single open-label study.

Prasugrel is taken once a day, does not cause the breathlessness that about one in seven people get on ticagrelor, and has fewer interactions. Its effect lasts longer once stopped, which matters before surgery.

Interactions

Prasugrel has a short interaction list. The US label says it can be taken with medicines that block or speed up liver enzymes, statins, digoxin and stomach protectors such as omeprazole. The ones that matter:

• Warfarin, apixaban and other anticoagulants add to bleeding risk.
• NSAIDs such as ibuprofen and naproxen, taken regularly, raise the risk of gut bleeding.
• Opioids such as morphine delay and reduce its absorption, which matters during an emergency heart attack.
• Aspirin is taken with it on purpose. The US label gives 75 to 325 mg a day.

Practical points

The US dose is a single 60 mg loading dose, then 10 mg once a day with aspirin. The tablet should be swallowed whole. Thrombotic thrombocytopenic purpura (TTP), a rare blood disorder that can be fatal, has been reported, sometimes within two weeks of starting. Fever, confusion, purple skin spots or yellow skin need urgent care. So do black stools, vomiting blood, or a sudden severe headache.

Tell every doctor and dentist that you take prasugrel. Talk to your cardiologist before stopping it for any procedure. In an overdose, call Poison Control on 1-800-222-1222 in the US or NHS 111 in the UK.

How we scored it

Dependence (98) and track record (85) are strong. Interactions (68) score better than for clopidogrel or ticagrelor because prasugrel avoids their liver-enzyme problems. Serious side effects (50) reflect four times the fatal bleeding of clopidogrel in its main trial. Regulatory warnings (40) are held down by a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary that excludes whole groups of patients.