Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction

Kevin Shores, PharmD Candidate 2015, Mercer University College of Pharmacy

About 720,000 people suffer heart attacks each year, coming to about one every 34 seconds.1 When a patient suffers a myocardial infarction, it is very common for dual antiplatelet therapy to be initiated for a short time. Guidelines differ on which antiplatelet medications are recommended and the duration of care, but the evidence is clear that dual antiplatelet therapy reduces the risk of clot development.2

A recently published study addressed this lack of long term evidence for the use of dual antiplatelet therapy in patients with a myocardial infarction.3

Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction
Design Randomized, double-blind, placebo-controlled clinical trial; 21,162 participants
Objective To investigate the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome
Study Groups Group 1: Participants given ticagrelor 90 mg twice daily

Group 2: Participants given ticagrelor 60 mg twice daily

Group 3: Participants given a placebo twice daily

Methods Participants (n=21,162) who had had a myocardial infarction 1-3 years earlier were randomized to ticagrelor 90 mg, ticagrelor 60 mg, or placebo. All patients received low-dose aspirin and were followed for a median of 33 months.
Duration Randomization occurred from October 2010 to May 2013, and participants were followed for a median of 33 months.
Primary outcome measure The composite of cardiovascular death, myocardial infarction, or stroke
Baseline Characteristics Age: Ticagrelor 90 mg (65.4), ticagrelor 60 mg (65.2), placebo (65.4)

Female: Ticagrelor 90 mg (23.9%), ticagrelor 60 mg (23.6%), placebo (24.3%)

Median years since myocardial infarction: Ticagrelor 90 mg (1.7), ticagrelor 60 mg (1.7), placebo (1.7)

Medication at enrollment

Aspirin at any dose: Ticagrelor 90 mg (99.8%), ticagrelor 60 mg (99.9%), placebo (99.9%)

Statin: Ticagrelor 90 mg (92.6%), ticagrelor 60 mg (92.2%), placebo (93.2%)

Beta-blocker: Ticagrelor 90 mg (82.4%), ticagrelor 60 mg (82.3%), placebo (83.2%)

ACE inhibitor or ARB: Ticagrelor 90 mg (80.9%), ticagrelor 60 mg (79.9%), placebo (80.6%)

Results Composite of cardiovascular death, myocardial infarction, or stroke

Ticagrelor 90 mg (7.85%), ticagrelor 60 mg (7.77%), placebo (9.04%)

Hazard ratio of ticagrelor 90 mg vs. placebo – 0.85 (p=0.008)

Hazard ratio of ticagrelor 60 mg vs. placebo – 0.84 (p=0.004)

Adverse Events Adverse events reported:

Minor bleeding: Ticagrelor 90 mg (1.31%), ticagrelor 60 mg (1.18%), placebo (0.36%) (p<0.001)

Dyspnea: Ticagrelor 90 mg (18.93%), ticagrelor 60 mg (15.84%), placebo (6.38%) (p<0.001)

Renal event: Ticagrelor 90 mg (3.30%), ticagrelor 60 mg (3.43%), placebo (2.89%)

Bradyarrhythmia: Ticagrelor 90 mg (2.04%), ticagrelor 60 mg (2.32%), placebo (1.98%)

Gout: Ticagrelor 90 mg (2.28%), ticagrelor 60 mg (1.97%), placebo (1.51%) (p=0.01)

Serious adverse events:

Major bleeding: Ticagrelor 90 mg (2.60%), ticagrelor 60 mg (2.30%), placebo (1.06%) (p<0.001)

Fatal bleeding or nonfatal intracranial hemorrhage: Ticagrelor 90 mg (0.63%), ticagrelor 60 mg (0.71%), placebo (0.60%)

Adverse events that led to trial discontinuation:

Bleeding: Ticagrelor 90 mg (7.81%), ticagrelor 60 mg (6.15%), placebo (1.50%) (p<0.001)

Dypsnea: Ticagrelor 90 mg (6.50%), ticagrelor 60 mg (4.55%), placebo (0.79%) (p<0.001)

Study Author Conclusions In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding.

This study was very comprehensive and well powered, and the results should be strongly weighted when considering patient care. The lack of evidence for long term dual antiplatelet therapy has definitely been a void in management guidelines, and with a few more strongly powered studies it is possible that this void could soon be filled. It will be important for physicians to monitor for bleeding and dyspnea, as they were significantly increased with ticagrelor, but overall this clinical trial should give healthcare professionals more tools to provide the best patient care possible.

References

  1. “Heart Disease Facts.”The Heart Foundation. 1 Jan. 2015. http://www.theheartfoundation.org/heart-disease-facts/heart-disease-statistics/. Accessed March 15, 2015
  2. Carreras, E. “Dual Antiplatelet Therapy for Heart Disease.”Dual Antiplatelet Therapy for Heart Disease.  http://circ.ahajournals.org/content/129/21/e506.full. Accessed March 15, 2015
  3. Bonaca, M., Deepaak, B., Cohen, M., Steg, P., et al.” Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction.”The New England Journal of Medicine. DOI: 10.1056/NEJMoa1500857. Accessed March 15, 2015
Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s