Understanding the Long Term Use of Ticagrelor

October 8, 2025 •

4 min read

Clinical trials like PEGASUS-TIMI 54 have demonstrated that the long term use of ticagrelor can significantly reduce the rate of major adverse cardiovascular events in high-risk patients with a prior heart attack. This approach is an extension of the initial standard dual antiplatelet therapy (DAPT) protocol, which typically lasts for a certain period following an acute coronary syndrome (ACS).

Quick Summary

Extending ticagrelor therapy beyond the initial treatment period can significantly reduce the risk of future cardiovascular events in high-risk patients who have previously had a heart attack. This benefit comes with an increased risk of bleeding, and its appropriateness is determined by a careful assessment of the patient's individual ischemic and bleeding risks.

Key Points

Significant Benefit: Long-term ticagrelor therapy can significantly reduce the risk of major adverse cardiovascular events (MACE), including heart attack, stroke, and cardiovascular death, in high-risk patients with prior myocardial infarction.
Extended Duration: For patients at high ischemic risk who have tolerated the initial dual antiplatelet therapy, ticagrelor may be extended beyond 12 months, often with a lower strength, for several years or more.
Increased Bleeding Risk: The primary risk of long-term ticagrelor is an increased risk of bleeding, which can range from minor issues like bruising and nosebleeds to major, non-fatal bleeding events.
Common Side Effects: Besides bleeding, a common side effect is shortness of breath (dyspnea), which is often mild and tends to resolve over time. Other potential side effects include dizziness and bradyarrhythmia.
Individualized Decision: The decision to use long-term ticagrelor must be personalized, weighing the ongoing risk of cardiovascular events against the risk of bleeding, and should always be made in consultation with a cardiologist.
Adherence is Critical: Abruptly stopping ticagrelor without a doctor's guidance can dramatically increase the risk of a heart attack or stroke.

The Rationale for Extending Ticagrelor Therapy

For patients who have experienced a heart attack, the risk of having a subsequent cardiovascular event, such as another heart attack or stroke, remains elevated for years. Dual antiplatelet therapy (DAPT), consisting of aspirin plus a P2Y12 inhibitor like ticagrelor, is the standard of care for at least the first year after an acute coronary syndrome (ACS), especially following procedures like percutaneous coronary intervention (PCI) with stent placement. However, long-term clinical trials have shown that extending potent antiplatelet therapy further can provide additional protection against these future ischemic events.

Evidence from the PEGASUS-TIMI 54 Trial

The landmark PEGASUS-TIMI 54 trial provided the strongest evidence supporting the long-term use of ticagrelor. This study enrolled over 21,000 patients who had experienced a myocardial infarction one to three years prior and still had at least one additional risk factor for cardiovascular events. Patients were randomized to receive ticagrelor or a placebo, in addition to low-dose aspirin.

The results were compelling, showing that long-term ticagrelor significantly reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke compared to placebo. The benefits were consistent and persisted over the median 33-month follow-up period, demonstrating the sustained protective effect of extended therapy.

Extended Therapy Dosage and Duration

Based on trial data, the approach to long-term ticagrelor use differs from the acute phase treatment.

Extended Treatment:

For extended treatment beyond the initial period, a lower strength may be used. The goal of a lower dose is to maintain a protective effect while mitigating the increased risk of bleeding.

Duration:

The duration of extended therapy is individualized based on a patient's risk profile. Guidelines suggest considering extended ticagrelor therapy for several years in high-risk patients who have a history of heart attack and no heightened bleeding risk.

Assessing the Benefits and Risks

Extended ticagrelor therapy offers significant benefits but requires a careful balancing act with the increased risk of bleeding. The decision to continue therapy long-term must be a shared one between the patient and their cardiologist, based on a comprehensive risk assessment.

Comparison of Benefits vs. Risks for Long-Term Ticagrelor


Feature	Benefits	Risks
Cardiovascular Events	Significantly reduced risk of MACE (CV death, MI, stroke)	Increased risk of major and minor bleeding events
Myocardial Infarction (MI)	Lower incidence of subsequent MI	Increased risk of non-fatal major bleeding
Bleeding	Manageable risk profile for many, especially with appropriate dosing	Dyspnea (shortness of breath) is common but often mild
Overall	Persistent protection from thrombotic events in high-risk patients	Potential for less frequent but bothersome side effects like bleeding and dyspnea

Long-Term Side Effects and Management

Patients on extended ticagrelor therapy need to be aware of and monitor for potential side effects, particularly bleeding.

Bleeding: Increased bleeding is a significant consideration. While minor bleeding like nosebleeds and bruising is frequent, the risk of major bleeding is also elevated. Patients should be vigilant and report any unusual bleeding to their doctor. In some cases, a strategy of ticagrelor monotherapy after a short course of DAPT has shown a lower bleeding rate than continued DAPT.
Dyspnea (Shortness of Breath): Mild to moderate shortness of breath can occur, especially in the initial weeks of treatment. For most patients, this is transient and resolves over time. If persistent or severe, it warrants medical evaluation.
Bradyarrhythmia: Ticagrelor can cause a slowed heart rate, which is typically asymptomatic but should be monitored in patients with pre-existing heart rhythm issues.
Other Side Effects: Other long-term effects can include headache, dizziness, and an increase in uric acid levels, which can precipitate gout in some individuals.

Ticagrelor vs. Clopidogrel in the Long Term

When comparing long-term P2Y12 inhibitor options, the choice between ticagrelor and clopidogrel is influenced by several factors, including patient risk, tolerability, and individual response to therapy. Numerous studies have compared these two drugs, with findings often highlighting ticagrelor's more potent and consistent antiplatelet effect. For instance, the PLATO trial demonstrated ticagrelor's superiority over clopidogrel in reducing MACE in ACS patients, albeit with a higher rate of non-procedure-related bleeding. However, real-world data and studies in specific populations, such as the elderly or certain Asian groups, have shown varying benefit-risk profiles. Clopidogrel's effectiveness is also dependent on genetic factors affecting its metabolism, which is not an issue with ticagrelor.

The Importance of Adherence and Discontinuation

Adherence to the prescribed regimen is crucial for the success of long-term ticagrelor therapy. Abruptly stopping ticagrelor significantly increases the risk of a heart attack or stroke, often within a few days. Patients should never stop this medication on their own, even if they experience minor bleeding. In cases where surgery is required, a doctor will provide specific instructions on temporarily discontinuing and restarting the medication to manage bleeding risk.

Long-Term Ticagrelor Monotherapy

An evolving approach in some guidelines involves transitioning to ticagrelor monotherapy after an initial period (e.g., 1-3 months) of DAPT in select patients. This strategy, primarily studied in patients undergoing PCI, has been shown to potentially reduce bleeding risk without increasing ischemic events compared to continuing DAPT for a longer duration. This provides another option for individualizing long-term antiplatelet therapy.

Conclusion: Weighing the Long-Term Strategy

Long-term ticagrelor use represents a potent and effective strategy for mitigating recurrent cardiovascular events in high-risk patients who have survived a heart attack. Clinical evidence from trials like PEGASUS-TIMI 54 firmly supports its benefits in reducing heart attacks, strokes, and cardiovascular death, even years after the initial event. However, this strategy is not without risks, most notably an increased propensity for bleeding. A personalized approach, carefully balancing the patient's individual ischemic risk against their bleeding risk, is essential for determining the appropriate duration and treatment approach. Patients should maintain open communication with their healthcare providers regarding side effects and never stop treatment without medical supervision.

For more information on the outcomes and tolerability of long-term ticagrelor, consult studies such as the one published in the Journal of the American Heart Association examining patients with prior coronary stenting.

Frequently Asked Questions

After a heart attack, the standard of care is to take dual antiplatelet therapy (DAPT) with ticagrelor and aspirin for at least 12 months. For certain high-risk patients, therapy may be extended beyond this period.

For extended treatment beyond 12 months, a lower strength may be considered. This reduced approach helps maintain antiplatelet effects while aiming to decrease bleeding risk.

The most common long-term side effects include an increased tendency to bleed (manifesting as nosebleeds, bruising, etc.) and shortness of breath (dyspnea). The risk of major bleeding is also elevated.

No, you should never stop taking ticagrelor without first consulting your doctor. Abrupt discontinuation can significantly increase your risk of a heart attack or stroke within a few days.

Compared to clopidogrel, ticagrelor has shown superior efficacy in reducing cardiovascular events in ACS patients, particularly within the first year. For long-term use, the benefit-risk profile depends on individual patient factors, as ticagrelor typically carries a higher bleeding risk.

Yes. While much focus is on patients with prior stenting, long-term ticagrelor has also demonstrated benefits in high-risk patients with a history of MI who did not undergo stenting, by preventing spontaneous atherothrombotic events.

The decision is individualized and based on a careful assessment of the patient's ischemic risk (risk of future clots) versus their bleeding risk. Guidelines suggest it for high-risk patients with prior MI who have tolerated initial therapy without major bleeding.