Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial

Wiviott SD, White HD, Ohman EM et al
Lancet, Volume 382, Issue 9892, Pages 605 - 613

Background

Many patients with unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI) are managed without revascularization [1,2] , despite it being recommended [3,4]. Treatment with two antiplatelet drugs is also a cornerstone of management of UA/NSTEMI. Often a combination of aspirin and a PsY12 antagonist is given, irrespective of whether treatment involves revascularisation. This combination was found to be better in comparison to clopidogrel and aspirin [5,6].
In the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial, patients were assigned randomly to treatment with clopidogrel or prasugrel. This study assessed outcomes based on assigned treatment and whether or not patients had pre-enrolment coronary angiography. The primary endpoint was cardiovascular death, myocardial infarction (MI) or stroke at 30 months.

Main results

• Baseline characteristics  differed between those who received coronary angiography and those who did not.
• Patients who had angiography before enrolment (281/3085, 12.8%)more often reached the primary endpoint than did patients who did have angiography (480/4158, 16.5%, adj HR for angiography: 0.63, 95%CI: 0.53-0.75, P<0.0001). Patients who had angiography also showed less cardiovascular death or all-cause death, and MI, while GUSTO and TIMI bleeding were not different between groups.
• Subsequent angiography and revascularisation during the trial did not occur often, in either group. Percutaneous coronary intervention was also similarly rare in both groups. Coronary artery bypass graft was performed less frequent in patients who had angiography before enrolment (1.3% vs. 3.2%, HR: 0.39, 95%CI: 0.27-0.56, P<0.0001).
• Of the patients who received angiography, fewer patients assigned to prasugrel reached the primary endpoint at 30 months, as compared to those receiving clopidogrel (10.7% vs. 14.9%, HR: 0.77, 95%CI: 0.61-0.98, P=0.032). No difference between treatments was seen for patients who had no angiography.
• When assessing all events, prasugrel was associated with fewer events in patients who had received angiography, while no difference was seen in patients who did not have angiography. Similar results were seen when considering MI and stroke as endpoints. Risk of cardiovascular death was not different between treatments, irrespective of whether patients had had angiography.
• The proportion of patients with bleeding events was higher among those who received prasugrel, with or without angiography, but no difference between treatment groups was seen for frequency of severe GUSTO and TIMI bleedings.

Conclusion

Among patients who had angiography, those treated with prasugrel had fewer CV deaths, MI or stroke than those who took clopidogrel. Differences in baseline characteristics likely contributed to the differences in clinical outcomes: higher rates of post-acute coronary syndrome events are seen, but not events that are modifiable by antiplatelet drugs. Angiography without revascularisation is not expected to reduce CV events, thus the difference in recurrent CV events seems to be a result of the different risk profiles, rather than the effect of treatment.
Therefore, these data do not suggest that giving angiography to more patients will improve CV outcome. Angiography may however help to identify patients who have coronary disease. When angiography has confirmed anatomic coronary disease, the benefits and risks of intensive antiplatelet treatment remain, whether drug treatment of PCI is chosen.

References

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