Many exciting clinical trial results are being presented at the 2016 European Society of Cardiology (ESC) Congress and published simultaneously this week.
Here’s a sample of some of the more pharmacotherapy-focused research showcased at ESC:
- 1230 patients across 14 sites were randomly assigned to either prasugrel or ticagrelor before percutaneous coronary intervention (PCI).
- Primary endpoint was death, reinfarction, urgent target vessel revascularization, stroke, and serious bleeding requiring transfusion or prolonging hospitalization at 7 days (to reflect primarily the inhospital phase).
- The study was prematurely terminated for futility. The occurrence of the primary endpoint didn’t differ between groups receiving prasugrel and ticagrelor.
This head-to-head comparison of prasugrel and ticagrelor doesn’t support the hypothesis that one is more effective or safer than the other in preventing ischemic and bleeding events in the acute phase of myocardial infarction (MI) treated with primary PCI.
2. PEGASUS-TIMI 542
- Ticagrelor reduced the risk of major adverse cardiovascular events (MACE) when added to low-dose aspirin in stable patients with prior MI, resulting in the approval of ticagrelor 60 mg twice-daily for long-term secondary prevention.
- This study investigated the incidence of stroke, outcomes after stroke, and efficacy of ticagrelor, focusing on the approved dose for reducing stroke in this population.
- Ticagrelor significantly reduced the risk of stroke, driven by a reduction in ischemic stroke.
- Ticagrelor increased TIMI major bleeding but with no statistically significant increase in intracranial hemorrhage or fatal bleeding.
High-risk patients with prior MI are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice-daily significantly reduced this risk without an excess of hemorrhagic stroke, but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered to reduce the risk of not only coronary events, but also stroke.
- Post-acute coronary syndrome (ACS) patients with mean low-density lipoprotein cholesterol (LDL-C) of 93.8 mg/dL at presentation were randomized to simvastatin/ezetimibe or simvastatin/placebo. The primary endpoint was cardiovascular death, major coronary event, or stroke, and the median follow-up was 6 years.
- Among 18,134 patients, 1684 (9.3%) had a prior coronary artery bypass grafting (CABG) (median age 69 years, 82% male).
- During the trial, the median time-weighted LDL-C was 55.0 mg/dL with simvastatin/ezetimibe versus 69.9 mg/dL with simvastatin/placebo in patients with prior CABG. It was 53.6 mg/dL versus 69.5 mg/dL, respectively, in patients without prior CABG.
- Patients with prior CABG receiving simvastatin/ezetimibe had an 8.8% lower absolute risk over simvastatin/placebo in the primary endpoint, whereas patients without prior CABG had a 1.3% lower absolute risk. There were no between-group significant differences in safety endpoints.
The clinical benefit of adding ezetimibe to a statin appears enhanced in patients with prior CABG, supporting the use of intensive lipid-lowering therapy in these high-risk patients following ACS.
4. Dual Antiplatelet Therapy (DAPT) After Complex PCI4
- This study investigated the efficacy and safety of long-term (≥12 months) versus short-term (3 or 6 months) DAPT with aspirin and clopidogrel, according to PCI complexity. It pooled patient-level data from 6 randomized, controlled trials investigating DAPT durations after PCI.
- Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion.
- The primary efficacy endpoint was MACE, defined as the composite of cardiac death, MI, or stent thrombosis. The primary safety endpoint was major bleeding.
- Of 9577 patients included in the pooled dataset for whom procedural variables were available, 1680 (17.5%) underwent complex PCI. Overall, 85% of patients received new-generation drug-eluting stents.
- Compared with short-term DAPT, long-term DAPT yielded significant reductions in MACE in the complex PCI group versus the noncomplex PCI group. The magnitude of the benefit with long-term DAPT was progressively greater per increase in procedural complexity.
- Long-term DAPT was associated with increased risk for major bleeding, which was similar between groups.
Alongside other established clinical risk factors, procedural complexity is an important parameter to take into account in tailoring upfront duration of DAPT.
1. Motovska Z, et al. Prasugrel versus ticagrelor in patients with acute myocardial infarction treated with primary PCI: multicenter randomized PRAGUE-18 study. Circulation. 2016.
2. Bonaca MP, et al. Prevention of stroke with ticagrelor in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54. Circulation. 2016;134(9).
3. Eisen A, et al. The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial, Eur Heart Jour. 2016.
4. Giustino G, et al. Efficacy and safety of dual antiplatelet therapy after complex PCI. JACC. 2016.