Key result
Ticagrelor substantially reduces MACE in patients with prior MI and multivessel disease.
Why the study?
Patients with prior MI and multivessel coronary disease are at high risk for recurrent coronary events, motivating evaluation of the efficacy and safety of ticagrelor in this population.
RCT (n=12,558)
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“We know that atherosclerosis is a systemic disease, and one important observation from this paper is that patients with multivessel disease, even if they've been stented, are still at very high risk. Most clinicians know that [but] just simply knowing when a patient has their MI if they've had multivessel disease can be an important in terms of determining the optimal intensity and duration of [dual antiplatelet therapy (DAPT)].”
“All they tell you is that this patient had at some point multivessel disease, but we don't know if over the period of 3 years they had undergone revascularization or not, [or if] they were reduced to single-vessel disease or no-vessel disease,... so I think that's a limitation.”
“Taken together, the PEGASUS-TIMI 54 subset analyses give validation to existing data supporting improved outcomes with higher intensity and longer duration of antiplatelet therapy with ticagrelor in certain high-risk patient cohorts. Specifically, the data support that the presence of [multivessel disease] may be an indication to pursue extended DAPT with ticagrelor for up to 3 years in the absence of limiting adverse effects.”
Ticagrelor may reduce events in multivessel disease; leaves open confirmation in definitive trials.
BACKGROUND: Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events. OBJECTIVES: The authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) trial. METHODS: Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months. RESULTS: A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HR CONCLUSIONS: Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).
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Bansilal et al. (2018) conducted an RCT in prior myocardial infarction (MI) and multivessel coronary disease (MVD) (n=12,558). Ticagrelor vs. placebo was evaluated on composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]). Patients with prior MI and multivessel disease had a higher MACE risk than those without (9.37% vs. 8.57%), and ticagrelor provided substantial risk reductions in this high-risk group.
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