After a heart attack: How do clopidogrel and prasugrel compare?

Treatment with prasugrel and acetylsalicylic acid (ASA) aims to lower the risk of complications for people after a heart attack and associated intervention. Prasugrel and ASA seem to lower especially the risk of having more non-fatal heart attacks better than clopidogrel and ASA. But prasugrel does more often lead to serious bleeding.

Heart attacks (also called myocardial infarctions, or MIs for short) and other cardiovascular diseases are usually the result of the hardening of the blood vessels. Over the course of a lifetime, fats and other substances in the blood build up along the inner walls of the vessels. The arteries then gradually narrow and lose their elasticity. Doctors call this “arteriosclerosis”: the hardening or stiffening of the arteries.

At first, arteriosclerosis does not cause any symptoms. If these deposits increase, however, and the flow of blood through the vessels is considerably constricted, part of the heart muscle may no longer receive enough oxygen. This can result in a number of different acute heart diseases. These include unstable angina and heart attacks.

People with angina (also called “angina pectoris”) most often have pain behind their breastbone and a tightening feeling in their chest. The pain can also radiate into the left or both arms, but also into the lower jaw, the back, or the upper abdomen. Someone who has stable angina has pain repeatedly for a short time during physical exertion. Someone with unstable angina has pain even during mild exertion or while at rest. This means that there is an immediate danger of a heart attack. Unstable angina and heart attacks are also referred to as “acute coronary syndrome”.

A heart attack occurs if a coronary artery is suddenly closed off by a blood clot. You can read about what signs indicate a heart attack here (URL: http://www.informedhealthonline.org/index.230.en.html) . If someone does not receive treatment within a few hours of having a heart attack, a part of the cardiac muscle tissue will die. This can be life-threatening. The probability of surviving a heart attack has risen over the years: in Germany about 3 out of every 4 people survive having a heart attack.

Experts distinguish between two types of heart attacks:

• ST elevation myocardial infarction (STEMI)
• non-ST elevation myocardial infarction (NSTEMI)

In STEMI, the electrocardiogram (ECG or EKG) shows that a certain part, called the ST segment, is elevated. In a NSTEMI the ECG does not show ST segment elevation. These two types of heart attack are treated differently.

Treatment of acute coronary syndrome

A STEMI is often treated with percutaneous coronary intervention (PCI), more commonly known as angioplasty. This involves putting a thin cardiac catheter that has a balloon attached to it into the affected artery. The cardiac catheter is passed into where the vessel is narrowed. There the balloon is inflated with high pressure and presses the deposits into the vessel walls. A thin wire mesh (stent) is frequently also inserted to prevent the vessel from being blocked again.

Both NSTEMI and unstable angina are typically treated with heparin and acetylsalicylic acid (ASA). Heparins are fast-acting anticoagulants that prevent blood clots from forming. ASA is also an anticoagulant (“blood-thinning”) drug, but it works in a different way. For some people who have a NSTEMI or unstable angina, percutaneous coronary intervention is also an option. Whether this intervention is considered for a NSTEMI or unstable angina depends on whether someone has other risk factors. These could include diabetes, a repeated heart attack or certain irregularities in their ECG, for example.

Someone who has percutaneous coronary intervention usually also takes ASA. This drug treatment is started as soon as possible after the heart attack. After the intervention, use of anticoagulant drugs is usually continued permanently to lower the risk of more heart attacks (reinfarctions). ASA can be used on its own or in combination with the drugs clopidogrel or prasugrel. But clopidogrel is not approved for treating people with STEMI who receive percutaneous coronary intervention.

The German Institute for Quality and Efficiency in Health Care (IQWiG) – who publish this website – has now analyzed trials that look at what advantages and disadvantages there are when a combination of ASA and prasugrel is used with percutaneous coronary intervention, and how this combination compares with ASA and clopidogrel. Prasugrel has been on the market in Germany since 2009 under the trade name “Efient”.

Trials comparing clopidogrel and prasugrel

IQWiG did a systematic search for trials on prasugrel that tested the drug in comparison with others in ways that conformed to how they are approved for use in Germany. IQWiG only analyzed trials that are very conclusive – randomized controlled trials. You can read more about these types of trials here (URL: http://www.informedhealthonline.org/index.61.en.html) .

In two trials prasugrel was taken by one group of the participants as the way it is approved for in Germany. In a trial called TRITON these were almost 8,000 people with a NSTEMI or unstable angina who received a percutaneous coronary intervention. In the second trial, called JUMBO, prasugrel was used by fewer than 200 people as it is approved for in Germany. For this reason, the assessments produced by IQWiG are mostly based on the results of the TRITON trial. In each of these trials the drug was compared with the combination of ASA and clopidogrel.

The IQWiG researchers point out that the TRITON trial does have some limitations and that these results cannot be seen as definitive for that reason. One of the particular limitations of the trial was that clopidogrel was used differently than it normally is. Participants used the drug only after it was determined that a percutaneous coronary intervention was to be done. It is usually administered as quickly as possible; that is, as soon as the first symptoms of a heart attack are noticed. Nevertheless, some conclusions can be drawn from the TRITON trial. For STEMI, however, clopidogrel was not used in accordance with its approved use in Germany. So the following information only considers the results of treating unstable angina or NSTEMI.

Prasugrel: Likely has some more benefits, but also more frequently associated with complications

In the TRITON trial there were both advantages as well as disadvantages for prasugrel compared with clopidogrel. The combination of prasugrel and ASA had a slightly higher benefit than clopidogrel and ASA, but it more often led to adverse effects. After one year of observation, the following details became apparent:

• There was no difference between the two drugs as far as mortality was concerned.
• People who took prasugrel and ASA were less likely to have additional non-fatal heart attacks over a time period of one year than people who took clopidogrel and ASA.
• Strokes were also less common – but only for people who had not had previous vascular disease.
• People taking prasugrel and ASA were less likely to have a low blood supply to the heart (ischemia) urgently requiring medical intervention within one year than those taking clopidogrel and ASA. These interventions included percutaneous coronary intervention and bypass surgery.
• The disadvantage of prasugrel and ASA was that it more frequently led to bleeding than did clopidogrel and ASA. This also included serious bleeding, which would require a blood transfusion or treatment in a hospital, for example.
• Also, in the TRITON trial both benign as well as malignant tumors were detected more frequently in the people who took prasugrel and ASA than in those who were taking clopidogrel and ASA. But due to the more common bleeding, the people who were treated with prasugrel were also more frequently given a thorough medical examination. This means that it is possible that during these examinations tumors were identified “by chance”, which would have remained undetected in those taking clopidogrel. The possible risk of these kinds of growths is considered to be very low overall.

How big the difference between the two drugs was

The indication of an additional benefit of prasugrel and ASA compared with clopidogrel and ASA was found regarding the likelihood of another heart attack, among other things:

• 24 out of 1,000 people who took clopidogrel and ASA had another non-fatal heart attack within one year (2.4%).
• 13 out of 1,000 people who took prasugrel and ASA had another non-fatal heart attack within one year (1.3%).

The following observations were made regarding the frequency of serious bleeding:

• 26 out of 1,000 people who took clopidogrel and ASA experienced serious bleeding (2.6%).
• 35 out of 1,000 people who took prasugrel and ASA experienced serious bleeding (3.5%).

Deciding for one of these two treatment options is a question of weighing the advantages and disadvantages. You can find more information about anticoagulant drugs here (URL: http://www.informedhealthonline.org/index.378.56.en.html) .

Author: Institute for Quality and Efficiency in Health Care (IQWiG)


Note

This health information is a summary of a scientific report published by IQWiG. It is not an assessment of the right to have health care services paid for by statutory health insurance funds in Germany. By law, decisions about paying the costs for diagnostic and therapeutic procedures can only be made by the German Federal Joint Committee (G-BA). The Federal Joint Committee takes IQWiG reports into consideration in its decision-making process. You can find information about the decisions of the German Federal Joint Committee on its English-language website, www.english.g-ba.de (URL: http://www.english.g-ba.de/) .