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Long-term DAPT offers ongoing post-MI benefit

Publish date: March 15, 2015

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Post-MI patients need long-term secondary prevention

The results from PEGASUS-TIMI 54 provide a powerful message for secondary prevention: Patients who have had a prior myocardial infarction remain at an increased risk for subsequent ischemic events, even when maintained on what is currently standard therapy and even when they are several years out from their event.

Dr. Richard C. Becker

We have no perfect antiplatelet drugs. Treating patients like those enrolled in the trial with an agent like ticagrelor further reduced their risk for ischemic events, but at the price of increasing their risk for major bleeds. The good news was that the rates of fatal bleeds and intracranial hemorrhages did not increase with ticagrelor treatment. Selecting the right patients to treat with prolonged dual antiplatelet therapy (DAPT) requires good judgment as well as understanding the patient’s values and preferences. From the clinician’s perspective it is the fatal bleeds or intracranial hemorrhages that are most comparable to cardiovascular deaths, myocardial infarctions or strokes. Although I do not want to minimize the impact of other major or minor bleeds that might require transfusions, these are not considered as important for patient well being as the ischemic events that ticagrelor treatment reduced.

I believe that the findings from PEGASUS-TIMI 54 will work their way into everyday practice with clinicians increasingly keeping patients on prolonged DAPT following percutaneous coronary interventions or a myocardial infarction. Problems with bleeding or dyspnea usually appear relatively early for patients on DAPT. The new findings give us increased confidence that once these patients get to a year out from the onset of treatment they can safely continue treatment and derive ongoing benefit from it, especially higher-risk patients, even though the 60-mg formulation of ticagrelor is not currently available. The new results complement those reported last year from the DAPT trial, which also addressed the safety and incremental value of more prolonged DAPT for higher-risk MI and acute coronary syndrome patients.

Richard C. Becker, M.D. is professor and director of the University of Cincinnati Heart, Lung and Vascular Institute. He has been a consultant to and received research grants from AstraZeneca, the company that sponsored PEGASUS-TIMI 54 and that markets ticagrelor (Brilinta). He made these comments in an interview.

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When placed in the context of prior reports the new findings also raise the possibility that the generic, and hence much cheaper, thienopyridine clopidogrel might provide roughly the same long-term benefit as more expensive ticagrelor, especially for patients without a genetic profile that makes them poor clopidogrel metabolizers. This may be an attractive option for patients who have a problem paying for ticagrelor long term.

“I’d rather prescribe a patient a cheaper medication that might be a bit less effective than create an economic hardship,” Dr. Harrington said in an interview. The results from the DAPT trial, which included some post-PCI patients who received long-term DAPT with clopidogrel plus aspirin “give you a certain comfort” with the idea of substituting clopidogrel for ticagrelor when affordability is a major concern, Dr. Harrington noted.

PEGASUS-TIMI 54 enrolled 21, 162 patients who were 1-3 years out from a prior myocardial infarction at 1,161 sites in 31 countries. Enrolled patients also had to be at least 50 years old, and have at least one additional risk factor for ischemic events such as age 65 years or older, diabetes, multivessel coronary artery disease, or chronic renal dysfunction. The enrolled patients averaged 1.7 years out from their index MI. Randomization assigned patients to treatment with 90 mg ticagrelor b.i.d., 60 mg ticagrelor b.i.d., or placebo, and all patients also received daily treatment with 75-150 mg aspirin.

After a median follow-up of 33 months on treatment, the combined rate of cardiovascular death, myocardial infarction, or stroke – the study’s primary endpoint – occurred in 7.85% of patients on the 90-mg ticagrelor dosage, 7.77% of those on the 60-mg dosage, and in 9.04% of patients on placebo receiving aspirin only, statistically significant differences for the study’s primary endpoint for each of the two ticagrelor dosages. Concurrent with the report at the meeting the results also appeared online (N. Engl. J. Med. 2015; [doi:10.1056/nejmoa1500857]). This translated into hazard ratios of 0.85 for the 90 mg dosage and 0.84 for the 60 mg dosage compared with placebo.

The study’s primary safety outcome was the incidence of TIMI major bleeding events, which occurred in 2.60% of patients on the higher ticagrelor dosage, 2.30% of those on the 60 mg dosage, and in 1.06% of those on placebo, which converted into hazard ratios of 2.69 for the 90-mg dosage and 2.32 for the lower dosage for TIMI major bleeds compared with aspirin alone.

mzoler@frontlinemedcom.com

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