PLATFORM: A Prospective Longitudinal Trial of Fractional Flow Reserve CT

Educational Objectives

Evaluate the cost-benefit balance of using CTA-guided fractional flow reserve measurement to evaluate symptomatic patients with intermediate probability of coronary artery disease.

Summary

Interviewer: Alfred A. Bove, MD, PhD, MACC

Take-home Messages:

• Although the CTA-guided strategy for measuring fractional flow reserve (FFRCT) is a relatively new technique, PLATFORM demonstrates that it is feasible and safe in busy clinical settings.
• When used as an alternative diagnostic strategy to guide care in those with planned invasive catheterization, CTA/FFRCT was associated with a significantly lower rate of angiography that showed no obstructive CAD.
• In symptomatic patients with intermediate probability of CAD, evaluation strategies based on FFRCT can be achieved at lower cost than invasive coronary angiography, with greater improvement in quality of life than usual non-invasive testing.

The optimal approach to evaluating new-onset stable chest pain is uncertain, but the goals of evaluation are more clear. Testing should clarify the diagnosis, document the presence or absence of CAD, and guide subsequent care (whether revascularization, intensified medical treatment, or both) while maximizing efficiency and patient safety.

Recent data suggest that an evaluation strategy based on coronary CTA increases diagnostic certainty, improves efficiency of triage to invasive catheterization, and may reduce radiation exposure when compared with functional stress testing, with similar rates of cardiac events.^1,2 In the PROMISE trial, as noted above, CTA increased the rate of invasive catheterization by almost 50% compared with functional testing, but more than a quarter of these patients did not have obstructive CAD identified by invasive angiography.

One issue is that CTA provides anatomic information and is highly sensitive, but it does not define the functional significance of lesions. A CTA strategy by itself, then, is at variance with current guidelines that recommend determining the functional significance of coronary stenoses.

PLATFORM

The PLATFORM (Prospective Longitudinal Trial of FFRCT: Outcome and Resource Impacts) study was designed to test the hypothesis that evaluating patients with suspected CAD using a strategy of CTA guidance to determine fractional flow reserve (FFRCT) would lead to fewer invasive angiograms than evaluating patients with standard practice, and would produce similar low rates of major cardiac events. (FFRCT was recently approved by the U.S. Food and Drug Administration [FDA].)

Patients enrolled in the study had stable symptoms, intermediate probability of CAD, and no established CAD diagnosis. They were referred for planned invasive or noninvasive evaluation at 11 European centers. There were two consecutive cohorts: usual care or CTA plus FFRCT. Each cohort was subdivided into two groups based on the evaluation plan decided upon before enrollment: noninvasive testing (any form of stress testing or CTA [without FFRCT]) or invasive coronary angiography (ICA).

Overall, 90% of CTAs had acceptable image quality for analysis.³ Among those with intended ICA (FFRCT-guided = 193; usual care = 187), no obstructive CAD was found at ICA in 24 (12%) of the CTA/FFRCT arm versus 137 (73%) in the usual care arm (risk difference 61%; 95% confidence interval: 53 to 69; p < 0.0001). This was achieved with similar mean cumulative radiation exposure (9.9 vs. 9.4 mSv, respectively; p = 0.20; which is less than the average level of 14 mSv noted in the literature for nuclear stress testing). Invasive coronary angiography was canceled in 61% of patients after receiving CTA/FFRCT results.

Among those with intended noninvasive testing (the noninvasive stratum), the rates of finding no obstructive CAD at ICA were 13% (CTA/FFRCT) and 6% (usual care; p = 0.95). Clinical event rates within 90 days were similarly low in both usual care and CTA/FFRCT arms.

Cost and quality of life (QOL) outcomes from the PLATFORM trial (Table) were reported at the 2015 Transcatheter Cardiovascular Therapeutics (TCT) scientific sessions and published simultaneously in JACC.⁴ In the planned invasive stratum, mean costs were 32% lower among the FFRCT patients than among the usual care patients who typically underwent ICA ($7,343 vs. $10,734; p < 0.0001). In the noninvasive stratum, mean costs were not significantly different between the FFRCT patients and the usual care patients who underwent traditional noninvasive risk stratification ($2,679 vs. $2,137; p = 0.26).

Each QOL score improved in the overall study population (p < 0.0001). In the noninvasive stratum, QOL scores improved more in FFRCT patients than in usual care patients: with the Seattle Angina Questionnaire, the score was 19.5 versus. 11.4, respectively (p = 0.003); with the European QOL score, it was 0.08 versus 0.03 (p = 0.002); and for the visual analog scale, 4.1 versus 2.3 ( p = 0.82). In the invasive cohort, QOL improvements were similar in FFRCT and usual care patients.

PLATFORM: 90-day Economic and QOL Outcomes of an FFRCT Diagnostic Strategy in Suspected CAD

	Planned Invasive		p Value	Planned Noninvasive		p Value
	Usual Care (n = 187)	FFRCT (n = 193)		Usual Care (n = 100)	FFRCT (n = 104)
Costs	$10,734	$7,343	<0.0001	$2,137	$2,679	0.26
Change in QOL*	+15.5	+16.9	0.54	+11.4	+19.5	0.003

*Seattle Angina Questionnaire, 7-item version

PLATFORM = Prospective Longitudinal Trial of FFRCT: Outcomes and Resource Impacts; QOL = quality of life; CAD = coronary artery disease; FFRCT = fractional flow reserve obtained noninvasively from computed tomography

In an editorial comment accompanying the publication of the data in JACC, Hulten and Di Carli noted that like all cohort data, the PLATFORM observations do not imply causality, and it is difficult to rectify why QOL was improved in the noninvasive but not invasive subgroup, while cost showed the opposite result.⁵

A Solid Foundation or Thin Ice?

PLATFORM suggests that FFR can be estimated without coronary catheterization at a level of accuracy and reliability appropriate for individual decision making.

Mark Hlatky, MD, professor of health research and policy and medicine, Stanford University School of Medicine, was lead researcher of the study. He told the press, “In this nonrandomized study, we found that in symptomatic patients with intermittent probability of coronary artery disease, the evaluation strategy based on FFRCT had lower costs than invasive angiography and greater improvement in quality of life than usual noninvasive testing. The effect here is so big that I do not think this was by chance. If you do a CT angiogram and it’s normal, because it is so sensitive, people are happy with that result. But if you see something you are not sure if it’s significant, then the estimated FFR, if normal, is extremely reassuring that what you are seeing is not obstructing flow. This would be best tested using a randomized trial, but I think it is going to show the same thing.”

Here is a second opinion from Bernard De Bruyne, MD, PhD, associate director, Cardiovascular Center Aalst, Belgium: “I believe if these data can be confirmed by outcome data, this kind of an approach will probably largely replace the presently available noninvasive approach: stress testing. It is really a game changer, which we are already seeing used in practice in Europe; you get anatomy and physiology at the same time and same place; it is a very important paradigm change.”

However, in an editorial comment accompanying the QOL and economic analysis,⁵ Edward Hulten, MD, MPH (Brigham and Women’s Hospital and Harvard Medical School, Boston), and Marcelo F. Di Carli, MD (Walter Reed National Military Medical Center, Bethesda, Maryland), wrote: “Translating these results to clinical practice might prove challenging. First, clinicians will not choose between FFRCT versus direct referral to ICA for patient care decisions, especially among low-intermediate risk patients with stable symptoms as those enrolled in PLATFORM. Rather, the clinical choice would be between CCTA + FFRCT versus stress testing, which was not used in patients not receiving FFRCT.” They argue that stress testing would have resulted in a similar reduction in the number of unnecessary ICAs, as shown in the planned noninvasive stratum of PLATFORM and in other studies, and even lower costs than testing with CCTA + FFRCT. Therefore, they added, “The clinical utility of the observed lower cost with CCTA + FFRCT versus direct ICA for low-intermediate risk patients with SIHD (stable ischemic heart disease) is uncertain.”

“To routinely consider FFRCT,” they concluded, “clinicians should be confident that sending patient data to a data processing center for a 1- to 2-day wait and additional significant cost has some value beyond what could be accomplished by conventional coronary CTA or combining CTA with functional testing, such as exercise testing or stress imaging.”

Readings

1. Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med 2015;372:1291-1300.

2. Newby DE on behalf of the SCOT-HEART Investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet 2015;385:2383-91.

3. Douglas PS, Pontone G, Hlatky MA, et al. Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFRct: outcome and resource impacts study. Eur Heart J 2015 Sep 1. [Epub ahead of print]

4. Hlatky MA, De Bruyne B, Pontone G, et al. Quality-of-Life and Economic Outcomes of Assessing Fractional Flow Reserve with Computed Tomography Angiography: PLATFORM. J Am Coll Cardiol 2015;66:2315-23. http://content.onlinejacc.org/article.aspx?articleID=2462067

5. Hulten E, Di Carli MF. FFRCT: Solid PLATFORM or Thin Ice? J Am Coll Cardiol 2015;66:2324-8. http://content.onlinejacc.org/article.aspx?articleID=2462068

 

Disclosures

Pamela S. Douglas, MD, MACC, Durham, NC
Pappas Ventures (C, Spouse); UpToDate Inc (C); Elsevier BV (C, Spouse); Mallinckrodt plc (C); CardioDx Inc (C,E, spouse); Edwards Lifesciences Corp (G); Bristol-Myers Squibb Co (G); ABIOMED (G); Boston Scientific Corp (G); Novartis AG (C, Spouse); F. Hoffman-LaRoche Ltd (G); Gilead (G); ResMed (G); Achillion Pharmaceuticals Inc (G); Miracor Medical Systems GmbH (G); HeartFlow Inc (G)

Interviewer: Alfred A. Bove, MD, PhD, MACC
World Health­Networks, Inc (C); Merck & Co Inc (G); Insight Telehealth Systems Inc (C,E)

The planning committee reported nothing to disclose.

A = Advisory panel B = Speakers’ bureau C = Consultant fees/honoraria D = Data and Safety Monitoring Board E = Equity interests/stock options F = Fellowship support G = Grant support L = Licensing Agreement O = Other relationship R = Royalties S = Salary W = Expert witness

Acknowledgements

CME/CE INFO

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