TRILOGY ACS Substudy: Prasugrel Post-Angiography Minimizes Risk of Adverse Events

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Diagnostic angiography appears to play a key role in triaging patients with acute coronary syndromes (ACS) to medical therapy; ultimately promoting better long-term outcomes compared with no angiography prior to treatment, according to a substudy of the TRILOGY ACS trial published August 17, 2013, ahead of print in the Lancet. Additionally, prasugrel vs. clopidogrel reduces adverse events in those who receive angiography.

The substudy was originally presented in October 2012 at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in Miami Beach, FL.

TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes), published in the New England Journal of Medicine in October 2012, randomized 9,326 patients with unstable angina or NSTEMI on aspirin to either prasugrel or clopidogrel. Results showed that prasugrel does not reduce the frequency of ischemic events compared with clopidogrel.

For the current paper, Stephen D. Wiviott, MD, of Brigham and Women’s Hospital (Boston, MA), and colleagues analyzed the outcomes of 7,243 subjects (< 75 years old) triaged to medical therapy with (n = 3,085) or without (n = 4,158) prior diagnostic angiography. In both groups, roughly half of patients were assigned to clopidogrel and half to prasugrel.

Angiography in and of Itself Tied to Better Outcomes

At 30 months, patients who underwent angiography prior to randomization had lower rates of the primary endpoint (CV death, MI, stroke) as well as CV death, all-cause death, and MI alone. Neither stroke nor GUSTO and TIMI bleeding differed between groups (table 1).

Table 1. Outcomes by Preenrollment Angiography Status

 

Angiography
(n = 3,085)

No Angiography
(n = 4,158)

P Value

Primary Endpoint

12.8%

16.5%

< 0.0001

CV Death

4.7%

8.2%

0.0007

All-Cause Death

5.8%

9.6%

0.0004

MI

8.7%

9.9%

< 0.0001

Stroke

1.5%

2.1%

0.58

TIMI Major Bleeding

2.0%

1.6%

0.66

GUSTO Severe Bleeding

0.8%

0.7%

0.53


Furthermore, patients in the angiography cohort who received prasugrel rather than clopidogrel saw lower rates of the primary endpoint, MI, and stroke but not CV death (table 2). TIMI major and GUSTO severe bleeding trended higher with prasugrel.

Table 2. Outcomes by Antiplatelet Drug After Angiography

 

Prasugrel
(n = 1,524)

Clopidogrel
(n = 1,561)

P Value

Primary Endpoint

10.7%

14.9%

0.032

CV Death

4.2%

5.2%

0.62

MI

7.2%

10.3%

0.047

Stroke

0.6%

2.4%

0.006


Similar proportions of patients in the angiography and no-angiography groups underwent PCI (6.2% and 5.7%, respectively). CABG was rare and performed in fewer participants who had angiography before enrollment than those who did not (1.3% vs. 3.2%; P < 0.0001). Subsequent angiography during the trial also was uncommon.

 Positive Result from a Neutral Trial

The substudy has 2 take-home messages, according to coauthor Deepak L. Bhatt, MD, MPH, also of Brigham and Women’s Hospital. “First, it confirms the value of coronary angiography as a management and triage strategy in patients with acute coronary syndromes without ST-elevation,” he told TCTMD in a telephone interview. “Of course randomized trials and the guidelines already support an early invasive strategy, but this study shows in a large, real-world population that if someone has an ACS, it’s helpful to have coronary angiography performed.”

Secondly, “the study suggests that more potent antiplatelet therapy is useful in ACS patients even when revascularization or stenting in particular isn’t chosen as the strategy once coronary artery disease has been confirmed,” Dr. Bhatt observed.

Still, “it’s important to acknowledge that this is a positive finding from a trial that was overall neutral in its primary endpoint,” he said, adding that caution is advised before extrapolating the data to clinical practice.

“I wouldn’t go so far as to say the study actually supports the use of prasugrel in ACS patients who are medically managed,” Dr. Bhatt continued, noting that the choice is currently between clopidogrel and ticagrelor depending on the patient’s risk profile and what is affordable.

In an accompanying editorial, Rajesh V. Swaminathan, MD, and Dmitry N. Feldman, MD, both of Weill Cornell Medical College (New York, NY), observe that it is counterintuitive to think that diagnostic angiography would provide clinical benefit. “The reason [why it appears to do so]—and perhaps the most important lesson from this analysis—is that patient selection is crucial,” they write. For example, patients enrolled without angiography were more likely to be older, female, have lower body weight, worse renal function, higher GRACE scores, and present with unstable angina. “Therefore, patients with more comorbidities were more likely to be treated without angiography,” they conclude.

With regard to the advantage for prasugrel, the editorial authors suggest that angiography helps to clarify the cause of the index event and thus identifies a group for whom a more potent antiplatelet drug is likely to be beneficial. They also point out that the patent for prasugrel expires in 2017, so a “randomized trial in such patients is unlikely to be done in the near future, leaving doctors with compelling but inconclusive evidence for use of prasugrel in this heterogeneous and often untreated population.”

When prasugrel does go generic, Dr. Bhatt added, “then I think I would use it in patients with low bleeding risk over clopidogrel if those 2 options were both available and equally priced.”

 


Sources:
1. Wiviott SD, White HD, Ohman EM, et al. 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. Lancet. 2013;382:605-613.

2. Swaminathan RV, Feldman DN. TRILOGY ACS: Prasugrel of benefit only after angiography [editorial]? Lancet. 2013;382:580-582.

 

 

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Disclosures
  • TRILOGY ACS was funded by Daiichi Sankyo and Eli Lilly.
  • Dr. Wiviott reports receiving grant and research support from AstraZeneca, Eisai, Eli Lilly, and Merck and consulting fees and honoraria from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, and Sanofi-Aventis.
  • Dr. Bhatt reports conflicts of interest with multiple device and pharmaceutical companies.
  • Dr. Feldman reports serving as a consultant to or member of the speakers’ bureau for Abbott Vascular, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, and Pfizer.
  • Dr. Swaminathan reports no relevant conflicts of interest.

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