PLATO showed that in patients with acute coronary syndrome, ticagrelor reduced cardiovascular death, MI, or stroke compared with clopidogrel, without a significant increase in overall major bleeding. It did increase non-CABG major bleeding and dyspnea.
Study design
- Multicenter, randomized, double-blind trial
- N = 18,624
- Patients hospitalized with acute coronary syndrome
- Randomized to ticagrelor vs clopidogrel
- Median treatment duration 9 months
- Primary outcome assessed at 12 months
Population
Included
- ACS with or without ST-segment elevation
- Planned invasive or medical management
- Presentation within 24 hours of symptom onset
- Eligible for dual antiplatelet therapy
Excluded
- Need for oral anticoagulation
- Recent fibrinolytic therapy before randomization
- Increased bleeding risk
- Contraindication to clopidogrel or ticagrelor
- Clinically important bradycardia without pacemaker
ACS population
STEMI + NSTEMI/UA
Invasive or medical strategy
DAPT trial
12-month outcome
Interventions
Ticagrelor
- Loading dose 180 mg
- Maintenance dose 90 mg BID
- Given with aspirin
Clopidogrel
- Loading dose 300-600 mg when appropriate
- Maintenance dose 75 mg daily
- Given with aspirin
Primary outcome
- Composite of cardiovascular death, MI, or stroke
- 9.8% with ticagrelor vs 11.7% with clopidogrel at 12 months
- HR 0.84, 95% CI 0.77-0.92
- P < 0.001
- Driven mainly by reductions in MI and cardiovascular death
Ticagrelor vs clopidogrel
Primary composite endpoint at 12 months
15%
11.25%
7.5%
3.75%
0%
9.8% vs 11.7% | HR 0.84 | P < 0.001
Primary composite: cardiovascular death, MI, or stroke at 12 months.
Secondary outcomes
| Outcome | Ticagrelor | Clopidogrel | Effect |
|---|---|---|---|
| Primary composite | 9.8% | 11.7% | HR 0.84, 95% CI 0.77-0.92 |
| MI | 5.8% | 6.9% | HR 0.84, 95% CI 0.75-0.95 |
| Cardiovascular death | 4.0% | 5.1% | HR 0.79, 95% CI 0.69-0.91 |
| All-cause mortality | 4.5% | 5.9% | HR 0.78, 95% CI 0.69-0.89 |
| Stroke | 1.5% | 1.3% | No significant reduction |
Safety
| Safety outcome | Ticagrelor | Clopidogrel | Interpretation |
|---|---|---|---|
| Overall major bleeding | 11.6% | 11.2% | No significant difference |
| Non-CABG major bleeding | 4.5% | 3.8% | Increased with ticagrelor |
| Dyspnea | 13.8% | 7.8% | More common with ticagrelor |
Practical point: ticagrelor has better ischemic efficacy than clopidogrel in ACS, but watch for dyspnea, bradyarrhythmias, bleeding risk, adherence issues with BID dosing, and cost/access barriers.
Interpretation
- Ticagrelor was superior to clopidogrel for ACS patients treated with DAPT.
- The benefit included lower MI, cardiovascular death, and all-cause mortality.
- Overall major bleeding was not significantly higher, but non-CABG major bleeding increased.
- PLATO helped establish ticagrelor as a preferred P2Y12 inhibitor for many ACS patients.
- Clopidogrel remains reasonable when bleeding risk, intolerance, cost, drug interactions, or need for oral anticoagulation make ticagrelor less appropriate.
Citation: Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. New England Journal of Medicine. 2009;361:1045-1057.
NEJM