Long-term Tolerability of Ticagrelor for the Secondary Prevention of Major Adverse Cardiovascular Events

Christian Deaton, Mercer University College of Pharmacy

Ticagrelor (Brilinta®) is a P2Y12 antagonist that reversibly binds to the adenosine diphosphate (ADP) P2Y12 receptor on the platelet surface, ultimately reducing platelet aggregation.  Due to the reversible antagonism of the P2Y12 receptor, recovery of platelet function is likely to depend on serum concentrations of ticagrelor. [1]

The use of ticagrelor has been recommended to reduce the rate of cardiovascular death, stroke, or MI. [2]

Current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommend aspirin 81-325 mg and clopidogrel 75 mg after a myocardial infarction.

Ticagrelor has been approved as an alternative to clopidogrel for the use of reducing the rate of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or history of MI.  Ticagrelor also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS. [3]

Long-term Tolerability of Ticagrelor for the Secondary Prevention of Major Adverse Cardiovascular Events  [4]
Design Randomized, blinded, placebo; N= 15,214
Objective To investigate the reasons and timing of discontinuation of treatment with ticagrelor among stable patients prior myocardial infarction
Study Groups Ticagrelor 90 mg; N= 4,755

Ticagrelor 60 mg; N= 4,959

Placebo; N= 5,500

Methods Patients randomly assigned to 90 mg of ticagrelor twice daily, 60 mg of ticagrelor twice daily, or placebo, with all of the patients receiving a low dose of aspirin.
Duration October 2010 to December 2014
Primary Outcome Measure Composite of cardiovascular death, myocardial infarction, or stroke leading to drug discontinuation
Baseline Characteristics
  Placebo 60 mg 90 mg
Age, avg 65 64 64
Female, n 1,285 1,089 1,033
Hypertension, n 4,242 3,793 3,638
Current smoker, n 874 857 810
Diabetes mellitus, n 1,711 1,621 1,481
ST-segment elevation myocardial infarction (STEMI), n 2.994 2,699 2,610
Non ST-segment elevation myocardial infarction (NSTEMI), n 2,189 1,963 1,896
Results Discontinuation due to an adverse event was 32% for the 90 mg of ticagrelor group, 29%for the 60 mg of ticagrelor, and 21% for the placebo group
Adverse Events Common Adverse Events: dyspnea (10%)
Serious Adverse Events: bleeding (12%)
Percentage that Discontinued due to Adverse Events: (21%)
Study Author Conclusions Among patients who completed 1 year of treatment, the subsequent rates of discontinuation were low. Moreover, for patients receiving the study drug, there was a substantial benefit to ticagrelor.

 

Ticagrelor has been approved as alternative therapy for patients with prior history of MI to reduce the rate of cardiovascular death, myocardial infarction (MI), and stroke. The study revealed that discontinuation rates due to adverse events were higher in those who were receiving the drug therapy versus the placebo group.  Patients in a randomized, placebo-controlled trial may have been more likely to discontinue treatment for mild adverse events versus patients receiving open-label therapy who could anticipate a benefit from the treatment. Therefore, the rates of drug discontinuation due to dyspnea or minor bleeding may be overestimated in the analysis due to their lack of information on what adverse events to possibly expect.

 

References

  1. Brilinta (ticagrelor) [prescribing information]. Wilmington, DE: AstraZeneca; September 2015
  2. Bonaca, Marc, et al. Long term use of ticagrelor in patients with prior myocardial infarction. New England Journal of Medicine.  March 14, 2015
  3. ACCF/AHA Task Force on Practice Guidelines. Manual for ACCF/AHA Guideline Writing Committees: Methodologies and Policies from the ACCF/AHA Task Force on Practice Guidelines. American College of Cardiology and American Heart Association. 2006
  4. Bonaca MP, Bhatt DL, Oude Ophuis T, et al. Long-term Tolerability of Ticagrelor for the Secondary Prevention of Major Adverse Cardiovascular Events: A Secondary Analysis of the PEGASUS-TIMI 54 Trial.JAMA Cardiol. 2016
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