The results of a sub-analysis of the PEGASUS-TIMI 54 study, which evaluated reasons and rates for discontinuation of Ticagrelor ( Brilinta, Brilique ) in patients with a history of myocardial infarction ( one to three years prior to study randomization ) and the efficacy in those patients who stayed on therapy, were announced.
The data were presented at the 2015 American Heart Association ( AHA ) Scientific Sessions.
The pooled analysis of the results showed that in patients who stayed on therapy, Ticagrelor reduced the rate of the composite efficacy endpoint of cardiovascular death, myocardial infarction, or stroke at three years ( hazard ratio, HR=0.79, 95% CI 0.70-0.88 ), consistent with the results of the overall population of the PEGASUS study.
Discontinuation resulting from an adverse event was 8.9% in the placebo arm, 19% and 16.4% in the Ticagrelor 90 mg and 60 mg arms, respectively, and was most frequently due to bleeding and dyspnea.
Rates of adverse reactions leading to discontinuation were highest in the first year at 16% in the 90 mg arm, 13% in the 60 mg arm, and 6% in the placebo arm.
In those patients who stayed on therapy, discontinuation rates over the subsequent two years were 6.5% in the 90 mg arm, 6.0% in the 60 mg arm, 4.6% in the placebo arm.
On September 3, 2015, the US Food and Drug Administration ( FDA ) approved a new 60-mg tablet dosage strength for Brilinta to be used in patients with a history of heart attack beyond the first year. With this expanded indication, Brilinta is now indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome ( ACS ) or a history of myocardial infarction. For at least the first 12 months following acute coronary syndrome, Ticagrelor is superior to Clopidogrel.
Brilinta also reduces the rate of stent thrombosis in patients who have been stented for treatment of acute coronary syndrome.
PEGASUS-TIMI 54 ( PrEvention with TicaGrelor of SecondAry Thrombotic Events in High-RiSk Patients with Prior AcUte Coronary Syndrome – Thrombolysis In Myocardial Infarction Study Group ) is a trial with more than 21,000 patients from over 1,100 sites in 31 countries.
The study assessed Ticagrelor tablets at either 60 mg twice daily or 90 mg twice daily plus once daily low-dose Aspirin [ Acetylsalicylic acid ] compared to placebo plus once daily low-dose Aspirin for the secondary prevention of atherothrombotic events in patients greater-than or equal to 50 years of age who had experienced a myocardial infarction one to three years prior to study start and had at least 1 risk factor for thrombotic cardiovascular events ( age greater-than or equal to 65 years, diabetes mellitus requiring medication, at least one other prior myocardial infarction, evidence of multivessel coronary artery disease or a creatinine clearance less than 60 ml/min ).
The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction or stroke at 36 months.
Patients were treated for at least 12 months and up to 48 months with a median follow-up time of 33 months.
Ticagrelor 60 mg plus Aspirin significantly reduced the primary composite end point of cardiovascular death, myocardial infarction, or stroke by 16% relative risk reduction [ RRR ] ( absolute risk reduction, ARR=1.27% ) vs placebo plus Aspirin at 3 years ( 7.8% vs 9.0%; HR=0.84; P=0.0043 ).
In PEGASUS, TIMI Major Bleeding rates were 1.7% for Ticagrelor 60 mg plus Aspirin vs 0.8% for placebo plus Aspirin. TIMI Major or Minor Bleeding rates were 2.4% for Ticagrelor 60 mg plus Aspirin vs 1.0% for placebo plus Aspirin.
Only the 60 mg dose is approved for use in patients with a history of myocardial infarction beyond 12 months. ( Xagena )
Source: AstraZeneca, 2015