AstraZeneca has announced results from a post-hoc analysis of a sub-group of the PLATO study. This new analysis evaluated outcomes in 9,946 patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) managed with or without in-hospital revascularisation in relation to measurements at randomisation of high-sensitivity troponin-T (hs-TnT), a biomarker test that may be a more sensitive indicator of ongoing heart muscle damage than previously available troponin tests.
This study was presented at the American Heart Association (AHA) Scientific Sessions (Los Angeles, USA). In the 86.3% (n= 8,587) of NSTE-ACS patients in PLATO with elevated hs-TnT, ticagrelor (Brillinta) tablets reduced the composite of cardiovascular death, myocardial infarction, and stroke, consistent with the results for the overall population of the PLATO study. In the 13.7% (n=1,359) patients with normal hs-TnT, the confidence intervals around the hazard ratios were broad. Because of the limited number of patients without hs-TnT elevation, uncertainties remain regarding the effects of ticagrelor versus clopidogrel on outcomes in hs-TnT normal subgroups.
“Hs-TnT is an important new biomarker that provides a much better ability to identify patients with ongoing myocardial damage. This biomarker allowed identification of NSTE-ACS patients with low levels of myocardial damage that would not have been detected by previous testing,”said James Ferguson, executive director, Medical Affairs and Strategic Development, and vice president for Global Medical Affairs. “This analysis of PLATO shows Brillinta reduced the rate of thrombotic cardiovascular events in those NSTE-ACS patients with elevated hs-TNT, both when managed with revascularisation as well as when managed medically.”
Ticagrelor is indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (unstable angina [UA], non–ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]). In PLATO, ticagrelor has been shown to reduce the rate of a combined end point of cardiovascular death, myocardial infarction, or stroke compared to clopidogrel. In PLATO, the difference between treatments was driven by cardiovascular death and myocardial infarction with no difference in stroke. In patients treated with percutaneous coronary intervention (PCI), ticagrelor reduces the rate of stent thrombosis.
Bleeding rates and adverse events were not assessed in this sub-group analysis. The primary safety end point in the PLATO study was total major bleeding (11.6% for ticagrelor and 11.2% for clopidogrel). In PLATO, non-CABG major + minor bleeding events were more common with ticagrelor vs. clopidogrel (8.7% vs 7% respectively). The rate of non-CABG-related major bleeding was higher for ticagrelor (4.5%) vs clopidogrel (3.8%). Dyspnea was reported in 14% of patients treated with ticagrelor and in 8% of patients treated with clopidogrel.
Specific findings from this post-hoc analysis include:
- Among patients with elevated hs-TnT (>14 ng/L at entry) who were revascularized in-hospital (n=5,011), event rates for the composite of cardiovascular death, myocardial infarction, and stroke were 8.5% for ticagrelor vs. 11.2% for clopidogrel (adjusted hazard ratio [HR], 0.76 [CI 95%, 0.63-0.91]).
- Among patients with elevated hs-TnT managed medically (n=3,576), event rates for the composite of cardiovascular death, myocardial infarction, and stroke were 12.4% for ticagrelor vs. 14.9% for clopidogrel (adjusted HR, 0.81 [CI 95%, 0.68-0.97]).
- Among patients with normal hs-TnT (<14 ng/L at entry) who were revascularised in-hospital, (n=346), event rates for the composite of cardiovascular death, myocardial infarction, and stroke were 12.2% for ticagrelor vs. 11.5% for clopidogrel (adjusted HR, 0.99 [CI 95%, 0.53-1.83]).
- The event rates (composite of cardiovascular death, myocardial infarction, and stroke) were low in the 1,013 medically managed NSTE-ACS patients with normal hs-TnT: 3.1% for ticagrelor vs. 2.4% for clopidogrel (adjusted HR, 1.40 [CI 95%, 0.66-2.97]).
- There was no significant interaction of treatment with hs-TnT status in patients treated with in-hospital revascularisation, but there was an interaction in patients managed medically.
PLATO (Platelet inhibition and patient outcomes) was a large (18,624 patients in 43 countries), head-to-head patient outcomes study of ticagrelor vs. clopidogrel, both given in combination with aspirin and other standard therapy. The study was designed to establish whether copidogrel could achieve a clinically meaningful reduction in cardiovascular events in acute coronary syndrome patients, above and beyond that afforded by clopidogrel. Patients were treated for at least six months and up to 12 months.
PLATO demonstrated that treatment with ticagrelor led to a significantly greater reduction in the primary end point a composite of cardiovascular death, myocardial infarction, or stroke compared to patients who received clopidogrel (9.8% vs 11.7% at 12 months; 1.9% absolute risk reduction [ARR]; 16% relative risk reduction [RRR]; 95% CI, 0.77 to 0.92; P<0.001). The difference in treatments was driven by cardiovascular death and myocardial infarction with no difference in stroke. In PLATO, the absolute difference in treatment benefit versus clopidogrel was seen at 30 days and the Kaplan-Meier survival curves continued to diverge throughout the 12-month treatment period.
The PLATO study also demonstrated that treatment with ticagrelor for 12 months was associated with a 21% RRR in cardiovascular death (4% vs 5.1%; 1.1% ARR; P=0.001) and a 16% RRR in myocardial infarction compared to clopidogrel at 12 months (5.8% vs 6.9%; 1.1% ARR; P<0.005).