Is ticagrelor better than clopidogrel?

• Ticagrelor is currently recommended over clopidogrel by current guidelines for people with ACS or following a myocardial infarction (heart attack).
• Trials have found ticagrelor is more effective than clopidogrel at reducing cardiovascular events in people taking low dose aspirin.
• Because clopidogrel is a prodrug and requires conversion in the liver to its active version, clinical response to clopidogrel is variable with 20–40% of patients being classified as non-responders, poor responders or resistant to clopidogrel.
• Ticagrelor is not a prodrug although it does have an active metabolite. Ticagrelor also has a quicker onset of action than clopidogrel and is more potent. Side effects, such as bleeding and bruising are similar although ticagrelor is more likely to cause shortness of breath.
• Ticagrelor is usually taken twice a day whereas clopidogrel is taken once a day

Current guidelines issued by the American Heart Association/American College of Cardiology recommend ticagrelor (or prasugrel) over clopidogrel for dual antiplatelet therapy in conjunction with aspirin in patients with acute coronary syndrome (ACS)/ST‐segment–elevation myocardial infarction (STEMI).

• An exception is that prasugrel is contraindicated for patients with prior stroke or transient ischemic attack. Prasugrel is also not recommended in people aged 75 or older.
• Guidelines issued by the European Society of Cardiology concur with the American guidelines.
• Ticagrelor is recommended for all patients with ACS regardless of age.

Other differences between ticagrelor and clopidogrel include:

• Ticagrelor is not a prodrug whereas clopidogrel is a prodrug.
• This means that clopidogrel needs to be absorbed through the intestine and metabolized by liver enzymes to its active metabolite before it can work.
• Ticagrelor also helps reduce the rate of stent thrombosis (blood clots forming and blocking an area near a stent).
• Clopidogrel is also approved to prevent cardiovascular events in people who either have had a stroke or have peripheral arterial disease (PAD). Ticagrelor can help reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease, the most common type of heart disease.
• Ticagrelor is usually taken twice a day whereas clopidogrel is taken once a day
• Some studies have found that the clinical response to clopidogrel is variable with 20–40% of patients being classified as non-responders, poor responders, or resistant to clopidogrel because of low inhibition of ADP-induced platelet aggregation or activation.
• Apart from genetics (including variations in CYP2C19), other factors that affect the response to clopidogrel include age, diabetes, renal failure, and cardiac failure.
• In the PLATO trial (PLATelet inhibition and patient Outcomes) ticagrelor was shown to be more effective than clopidogrel at reducing cardiovascular events, cardiovascular death, and all-cause death. A subanalysis of this trial found that North American patients were less likely to respond to ticagrelor than clopidogrel, which may be because higher aspirin dosages are used in North America. In patients taking low-dose maintenance aspirin, ticagrelor was more effective than clopidogrel in decreasing cardiovascular events regardless of the geographic region.
• However, an analysis of 10 studies showed similar efficacy and safety profiles for clopidogrel and ticagrelor.
• Shortness of breath (dyspnea) may be more common with ticagrelor. Bleeding and bruising are common to both drugs.
• Ticagrelor was associated with a 21% reduction in major adverse cardiac or cerebrovascular events (MACCE) compared to clopidogrel after STEMI in the elderly and should be preferred in those undergoing emergency PCI when no contraindications are present. It was not associated with a significant elevation in bleeding events for the elderly

How does ticagrelor work?

Ticagrelor works in a different way to other antiplatelet agents, such as aspirin, clopidogrel, and prasugrel. Although it still blocks a substance called ADP (adenosine-5-diphosphate) which plays a crucial role in blood clotting, it does it by reversibly binding to a receptor called P2Y12 on the platelet surface. Reversible binding means platelet activity is restored once concentrations of ticagrelor decrease below a certain level, in contrast to other antiplatelet agents such as clopidogrel and prasugrel which bind irreversibly for the life of the platelet.

Ticagrelor works more quickly than clopidogrel. Within 30 minutes, a 180mg loading dose of ticagrelor inhibited 41% of platelets. It takes almost 8 hours for clopidogrel 600mg to achieve this same effect.

Maximum platelet inhibition (88% inhibition) was reached two hours after a dose of ticagrelor. Crushing tablets and then administering them appears to hasten the time to peak concentrations.

After administration of one dose of ticagrelor, maximum platelet inhibition is achieved at two hours and lasts for another six hours (eight hours total). 24 hours after a dose of ticagrelor, platelet inhibition is still 58%. It takes 56 hours (over 2 days) for platelet inhibition to drop to 56% and 110 hours (over 4 days) for platelet inhibition to drop to 10%.

How does clopidogrel work?

Clopidogrel binds irreversibly to P2Y12 receptors on the platelet surface, which blocks a substance called ADP (adenosine-5-diphosphate) which plays a crucial role in blood clotting. Platelets are blocked from aggregating for the remainder of their lifespan (about seven to 10 days).