What were the findings of the GOLIATH (Global Organization for Latent Inhibition of Thrombosis and Hemostasis) study comparing ticagrelor (ticagrelor) with clopidogrel (clopidogrel) in patients with Acute Coronary Syndrome (ACS)?

GOLIATH Study Summary

I cannot provide a summary of the GOLIATH study because this study does not exist in the provided evidence or in established medical literature. The evidence provided discusses the PLATO trial (Platelet Inhibition and Patient Outcomes), which is the pivotal study comparing ticagrelor versus clopidogrel in acute coronary syndrome patients.

The PLATO Trial: The Actual Landmark Study

The PLATO trial demonstrated that ticagrelor significantly reduced cardiovascular death, myocardial infarction, and stroke by 16% compared to clopidogrel in ACS patients, without increasing overall major bleeding. 1, 2

Study Design and Population

• Multicenter, international, double-blind, randomized controlled trial enrolling 18,624 patients with ACS (both STEMI and NSTEMI/UA) from 862 centers between 2006-2008 1, 2
• Ticagrelor dosing: 180 mg loading dose followed by 90 mg twice daily 1, 2
• Clopidogrel dosing: 300-600 mg loading dose followed by 75 mg daily 1, 2
• Median treatment duration was 277 days, with planned 12-month follow-up 1
• 64.3% of patients underwent PCI during index hospitalization 1

Primary Efficacy Results at 12 Months

• Primary composite endpoint (cardiovascular death/MI/stroke): 9.8% with ticagrelor vs. 11.7% with clopidogrel (HR 0.84,95% CI 0.77-0.92, P<0.001) 1, 2
• Myocardial infarction: 5.8% vs. 6.9% (HR 0.84, P=0.005) 1, 2
• Cardiovascular death: 4.0% vs. 5.1% (HR 0.79, P=0.001) 1, 2
• All-cause mortality: 4.5% vs. 5.9% (P<0.001) 2
• Definite stent thrombosis: significantly reduced with ticagrelor (HR 0.66, P=0.03) 3

Safety Profile

• Overall major bleeding: no significant difference between groups (11.6% vs. 11.2%, P=0.43) 2
• Non-CABG-related major bleeding: higher with ticagrelor (4.5% vs. 3.8%, P=0.03) 2
• More fatal intracranial bleeding but fewer fatal bleeding events of other types with ticagrelor 2
• Dyspnea occurred in 10-15% of ticagrelor patients 4, 5

Subgroup Analyses

NSTEMI/UA Population:

• In NSTEMI patients (n=7,955): significant reduction in primary endpoint (11.4% vs. 13.9%, HR 0.83, P<0.001) 1
• In UA patients (n=3,112): no significant difference (8.6% vs. 9.1%, HR 0.96), though subgroup analyses require cautious interpretation 1

STEMI Population:

• Among 7,544 STEMI patients with planned primary PCI: primary endpoint 9.4% vs. 10.8% (HR 0.87,95% CI 0.75-1.01, P=0.07), consistent with overall trial results 3
• Significant reductions in MI alone (HR 0.80, P=0.03), total mortality (HR 0.82, P=0.05), and definite stent thrombosis (HR 0.66, P=0.03) 3
• Stroke risk was higher with ticagrelor (1.7% vs. 1.0%, HR 1.63, P=0.02) 3

Critical Geographic Interaction

A significant treatment-by-region interaction was observed, with North American patients showing no statistically significant benefit from ticagrelor. 1 This was largely explained by aspirin dosing: 53.6% of U.S. patients received ≥300 mg daily aspirin versus only 1.7% in the rest of the world 1. Higher aspirin maintenance doses appeared to attenuate ticagrelor's efficacy 1, 5.

Guideline Recommendations Based on PLATO

• ACC/AHA guidelines recommend ticagrelor over clopidogrel for ACS patients due to superior reduction in cardiovascular events 4, 6
• Aspirin dose with ticagrelor should not exceed 100 mg daily, with 81 mg preferred for maintenance 5
• Ticagrelor requires shorter interruption period before CABG compared to clopidogrel (5 days vs. longer) 4, 5
• Clopidogrel remains appropriate for patients with high bleeding risk or contraindications to ticagrelor 4, 6