Prasugrel superior to clopidogrel in unstable angina and in NSTEMI patients

De Servi S, Goedicke J, Schirmer A, Widimsky P
Eur Heart J Acute Cardiovasc Care. 2014 May 12

Background

The new P2Y12 inhibitors have been shown to be superior to clopidogrel in reducing thrombotic CV events in patients with acute coronary syndrome (ACS) in the TRial to assess Improvement in Therapeutic outcomes by Optimizing platelet inhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38) and the PLATelet inhibition and patient Outcomes (PLATO) trial [1,2].
Three typical subgroups of ACS can be distinguished: unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI). Detailed analysis of clinical outcomes with these new agents in biomarker-negative ACS-patients (UA) and biomarker-positive NSTEMI patients are not available.
This analysis therefore addressed the clinical outcomes for prasugrel vs clopidogrel in the UA and NSTEMI subgroups in the TRITON-TIMI 38 trial. An additional analysis was limited to UA and NSTEMI patients who met the European Union (EU)-label for use of prasugrel. In TRITON-TIMI 38, patients with ACS and scheduled for percutaneous coronary intervention (PCI) were randomised to prasugrel or clopidogrel, on a background of aspirin, for a median of 14.5 months.  Of 10074 non-ST segment elevation (NSTE)-ACS patients, 7541 were classified as entering the study with a NSTEMI and 2528 with UA.

Main results

• In the entire ACS study population prasugrel lowered the rate of the primary efficacy endpoint as compared with clopidogrel (HR: 0.81, 95%CI: 0.73-0.90, P<0.001). HR for UA was 0.75 (95%CI: 0.58-0.96, P=0.021) and for NSTEMI patients it was 0.85 (95%CI: 0.73-0.97, P=0.019).
• In the EU-label cohort, reduced rates of the primary endpoint were also observed with prasugrel vs. clopidogrel, in NSTE-ACS patients (HR: 0.73, 95%CI: 0.63-0.85,), UA (HR: 0.72, 95%CI: 0.53-0.98) and NSTEMI (HR: 0.73, 95%CI: 0.62-0.87) subgroups (P(interaction): 0.93).
• In the overall NSTE-ACS population, the reduction in the primary endpoint was mainly driven by a lower rate of MI, both within three days after the procedure, and later in follow-up. Definite stent thrombosis was also significantly reduced with prasugrel in NSTE-ACS, and in UA and in NSTEMI patients, both in all NSTE-ACS and in the EU-label cohort.
• TIMI major bleeding not related to CABG was increased with prasugrel in the all-NSTE-ACS population (HR: 1.40, 95%CI: 1.05-1.88), consistently in UA and NSTEMI groups (P(interaction)=0.84). In the EU-label cohort, the difference in bleeding rate between prasugrel and clopidogrel was no longer significant (HR: 1.11, 95%CI: 0.77-1.60, P=0.57), again consistent for UA and NSTEMI (P(interaction)=0.52).
• Fatal bleedings occurred more often in prasugrel-treated patients in the all-NSTE-ACS population (14 (0.28%) vs. 3 (0.06%), HR: 4.66, 95%CI: 1.34-16.23, P=0.008). In the EU-label cohort, numbers were 5 (0.13%) in the prasugrel group and 2 (0.05%) for clopidogrel.
• HR for net clinical benefit was in favour of prasugrel (HR: 0.89, 95%ci: 0.80-1.00, P=0.04) in the NSTE-ACS population, and in the EU-label cohort (HR: 0.79, 95%CI: 0.69-0.91, P=0.008), consistent for UA and NSTEMI (P(interaction)= 0.72 and 0.94).

Conclusion

This analysis shows that the benefits of prasugrel are consistent among NSTEMI and UA patients, and consistent with those previously reported for the full study population. Decreasing the number of MIs is the driving factor behind reducing ischaemic events, both peri-procedural MI, and MI during long-term follow-up. Thus, prasugrel is superior to clopidogrel both in the acute interventional phase and for chronic management after PCI.
Although the rate of non-CABG-related TIMI major bleedings was higher with prasugrel, in patients treated according to the EU-label this effect was attenuated. Thus the EU-label cohort showed numerically more favourable net clinical benefit with prasugrel than in the all-NSTE-ACS population.

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References

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