A Closer Look at the P4 Trial and CCTA-Guided PCI

The recently published P4 trial is a landmark study, a major step forward for coronary computed tomography angiography (CCTA) and a perfect opportunity for some spectacular overinterpretation.¹

Let's separate the science from the marketing.

Here is the good news.

• The P4 trial demonstrated that CCTA-guided PCI is noninferior to IVUS-guided PCI in selected patients.Researchers noted a 4.1 percent vs. a 4.6 percent target-vessel failure at 12 months.

• Shorter procedures. Less contrast during PCI. Comprehensive planning before entering the catheterization laboratory.

• This is a major achievement for coronary CT.

What Are the Key Caveats with the P4 Trial?

Now let’s discuss the uncomfortable parts of the study.

1. Noninferiority is not equivalence.The 4.5 percent noninferiority margin was almost as large as the observed event rate in the control group.

2. FFRct was not independently validated.All patients required stenosis >70% and FFRct ≤ 0.80. But nobody tested whether adding FFRct to anatomical CT planning actually improved outcomes.

3. Abnormal FFRct does not mean PCI is necessary. Even in this highly selected population, 8.1 percent received medical therapy alone. In the broader ADVANCE registry, approximately 55 percent of patients with stenosis ≥ 50% and FFRct ≤ 0.80 were not revascularized at one year.² These are certainly different populations, but this is nonetheless a rather inconvenient reminder that physiological significance and clinical benefit from PCI are not synonyms.

4. What about photon counting CT (PCCT)?Only 4.1 percent of examinations used PCCT. Imagine what improved spatial resolution, calcium characterization and quantitative coronary assessment might contribute.

But let's generate evidence before generating headlines.

What is the Real Take-Home Message with the P4 Trial?

• The P4 trial validates a comprehensive CT-guided PCI strategy.
• It does not prove that every component of that strategy is indispensable.
• It does not prove that FFRct independently improves outcomes.
• It certainly does not mean every physiologically significant stenosis should be stented.

The future is not about CT defeating IVUS. It is about moving coronary decision-making upstream, integrating anatomy and physiology, and finally distinguishing between:

• having a stenosis;
• having ischemia;
• having atherosclerotic disease; and
• actually benefiting from PCI.

These are four different concepts that are still confused far too often.

The P4 trial is a landmark study but let's not turn it into a marketing brochure.

Dr. Cademartiri is the director of advanced cardiovascular imaging and photon-counting CT at the Scientific Institute for Research, Hospitalization, and Healthcare Synlab Diagnostic Network in Naples, Italy. He is also a consultant in advanced cardiovascular imaging at CDI/Centro Diagnostico Italiano in Milan, Italy.

References

1. Collet C, Mizukami T, Bouisset F, et al. Coronary CT angiography versus intravascular ultrasound guidance for PCI. N Engl J Med. 2026 Nov 1. doi: 10.1056/NEJMoa2610771. Online ahead of print.
2. Patel MR, Norgaard BL, Fairbairn TA, et al. 1-year impact on medical practice and clinical outcomes of FFR_CT: the ADVANCE registry. JACC Cardiovasc Imaging. 2020;13(1 Pt 1):97-105. Doi: 10.1016/j.jcmg.2019.03.003.

(Editor’s note: This blog is adapted with permission from Dr. Cademartiri’s original LinkedIn post available at https://www.linkedin.com/feed/update/urn:li:activity:7523969854622773248/