ST-Elevation Acute Coronary Syndromes in the Platelet Inhibition and Patient Outcomes (PLATO) Trial Insights From the ECG Substudy

• Published in: Circulation (New York, N.Y.) Vol. 125; no. 3; pp. 514 - 521
• Main Authors: Armstrong, Paul W., Siha, Hany, Fu, Yuling, Westerhout, Cynthia M., Steg, Ph. Gabriel, James, Stefan K., Storey, Robert F., Horrow, Jay, Katus, Hugo, Clemmensen, Peter, Harrington, Robert A., Wallentin, Lars
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 24.01.2012
• Subjects: Acute Coronary Syndrome - diagnosis; Acute Coronary Syndrome - drug therapy; Acute Coronary Syndrome - mortality; Adenosine - administration & dosage; Adenosine - analogs & derivatives; Aged; Angioplasty, Balloon, Coronary; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Electrocardiography - drug effects; Female; Heart; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Myocardial Infarction - diagnosis; Myocardial Infarction - drug therapy; Myocardial Infarction - mortality; Platelet Aggregation Inhibitors - administration & dosage; Purinergic P2Y Receptor Antagonists - administration & dosage; Risk Factors; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Human; Myocardial infarction; Prognosis; Cardiovascular disease; Instrumental dilatation; Coronary heart disease; Myocardial disease; Thrombosis; platelets; Vascular disease; ST elevation; Platelet; Electrocardiography; Acute coronary syndrome; angioplasty
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.111.047530

Ticagrelor, when compared with clopidogrel, reduced the 12-month risk of vascular death/myocardial infarction and stroke in patients with ST-elevation acute coronary syndromes intended to undergo primary percutaneous coronary intervention in the PLATelet inhibition and patient Outcomes (PLATO) trial. This prespecified ECG substudy explored whether ticagrelor's association with vascular death and myocardial infarction within 1 year would be amplified by (1) the extent of baseline ST shift and (2) subsequently associated with fewer residual ST changes at hospital discharge. ECGs were evaluated centrally in a core laboratory in 3122 ticagrelor- and 3084 clopidogrel-assigned patients having at least 1 mm ST-elevation in 2 contiguous leads as identified by site investigators on the qualifying ECG. Patients with greater ST-segment shift at baseline had higher rates of vascular death/myocardial infarction within 1 year. Among those who also had an ECG at hospital discharge (n=4798), patients with ≥50% ΣST-deviation (ΣST-dev) resolution had higher event-free survival than those with incomplete resolution (6.4% versus 8.8%, adjusted hazard ratio 0.69 (0.54-0.88), P=0.003). The extent of ΣST-dev resolution was similar irrespective of treatment assignment. The benefit of ticagrelor versus clopidogrel on clinical events was consistent irrespective of the extent of baseline ΣST-dev (P(interaction)=0.728). When stratified according to conventional times from symptom onset, ie, ≤3 hours, 3 to 6 hours, >6 hours, the extent of baseline ΣST-dev declined progressively over time. As time from symptom onset increased beyond 3 hours, the benefit of ticagrelor appeared to be more pronounced; however, the interaction between time and treatment was not significant (P=0.175). Ticagrelor did not modify ΣST-dev resolution at discharge nor was its benefit affected by the extent of baseline ΣST-dev. These hypothesis-generating observations suggest that the main effects of ticagrelor may not relate to the rapidity or the completeness of acute reperfusion, but rather the prevention of recurrent vascular events by more powerful platelet inhibition or other mechanisms. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.