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. 2024 Jan 25;7(1):e2352427. doi: 10.1001/jamanetworkopen.2023.52427

Cost-Effectiveness of Fractional Flow Reserve–Guided Treatment for Acute Myocardial Infarction and Multivessel Disease

A Prespecified Analysis of the FRAME-AMI Randomized Clinical Trial

David Hong 1, Seung Hun Lee 2, Jin Lee 3,4, Hankil Lee 5, Doosup Shin 6, Hyun Kuk Kim 7, Keun Ho Park 7, Eun Ho Choo 8, Chan Joon Kim 9, Min Chul Kim 2, Young Joon Hong 2, Myung Ho Jeong 2, Sung Gyun Ahn 10, Joon-Hyung Doh 11, Sang Yeub Lee 12, Sang Don Park 13, Hyun-Jong Lee 14, Min Gyu Kang 15, Jin-Sin Koh 15, Yun-Kyeong Cho 16, Chang-Wook Nam 16, Ki Hong Choi 1, Taek Kyu Park 1, Jeong Hoon Yang 1, Young Bin Song 1, Seung-Hyuk Choi 1, Hyeon-Cheol Gwon 1, Eliseo Guallar 17, Juhee Cho 3,4, Joo-Yong Hahn 1, Danbee Kang 3,4,✉, Joo Myung Lee 1,✉, for the FRAME-AMI Investigators
PMCID: PMC10811558  PMID: 38270954

Key Points

Question

Is fractional flow reserve (FFR)–guided treatment for non–infarct-related artery (IRA) percutaneous coronary intervention (PCI) more cost-effective than angiography-guided treatment for patients with acute myocardial infarction and multivessel disease?

Findings

In this prespecified analysis of the FRAME-AMI randomized clinical trial with 562 patients, FFR-guided PCI increased quality-adjusted life-years by 0.06 and decreased the total cumulative cost per patient (in US dollars) by $1208 compared with angiography-guided PCI. The incremental cost-effectiveness ratio was −$19 484 and the incremental net monetary benefit was $3378.

Meaning

This study found that FFR–guided PCI for non-IRA lesions saved medical costs and increased quality of life better than angiography-guided PCI in patients with acute myocardial infarction and multivessel disease.

This prespecified analysis of a randomized clinical trial evaluates the cost-effectiveness of fractional flow reserve–guided vs angiography-guided percutaneous coronary intervention for patients with acute myocardial infarction and multivessel disease.

Abstract

Importance

Complete revascularization by non–infarct-related artery (IRA) percutaneous coronary intervention (PCI) in patients with acute myocardial infarction is standard practice to improve patient prognosis. However, it is unclear whether a fractional flow reserve (FFR)–guided or angiography-guided treatment strategy for non-IRA PCI would be more cost-effective.

Objective

To evaluate the cost-effectiveness of FFR-guided compared with angiography-guided PCI in patients with acute myocardial infarction and multivessel disease.

Design, Setting, and Participants

In this prespecified cost-effectiveness analysis of the FRAME-AMI randomized clinical trial, patients were randomly allocated to either FFR-guided or angiography-guided PCI for non-IRA lesions between August 19, 2016, and December 24, 2020. Patients were aged 19 years or older, had ST-segment elevation myocardial infarction (STEMI) or non-STEMI and underwent successful primary or urgent PCI, and had at least 1 non-IRA lesion (diameter stenosis >50% in a major epicardial coronary artery or major side branch with a vessel diameter of ≥2.0 mm). Data analysis was performed on August 27, 2023.

Intervention

Fractional flow reserve–guided vs angiography-guided PCI for non-IRA lesions.

Main Outcomes and Measures

The model simulated death, myocardial infarction, and repeat revascularization. Future medical costs and benefits were discounted by 4.5% per year. The main outcomes were quality-adjusted life-years (QALYs), direct medical costs, incremental cost-effectiveness ratio (ICER), and incremental net monetary benefit (INB) of FFR-guided PCI compared with angiography-guided PCI. State-transition Markov models were applied to the Korean, US, and European health care systems using medical cost (presented in US dollars), utilities data, and transition probabilities from meta-analysis of previous trials.

Results

The FRAME-AMI trial randomized 562 patients, with a mean (SD) age of 63.3 (11.4) years. Most patients were men (474 [84.3%]). Fractional flow reserve–guided PCI increased QALYs by 0.06 compared with angiography-guided PCI. The total cumulative cost per patient was estimated as $1208 less for FFR-guided compared with angiography-guided PCI. The ICER was −$19 484 and the INB was $3378, indicating that FFR-guided PCI was more cost-effective for patients with acute myocardial infarction and multivessel disease. Probabilistic sensitivity analysis showed consistent results and the likelihood iteration of cost-effectiveness in FFR-guided PCI was 97%. When transition probabilities from the pairwise meta-analysis of the FLOWER-MI and FRAME-AMI trials were used, FFR-guided PCI was more cost-effective than angiography-guided PCI in the Korean, US, and European health care systems, with an INB of $3910, $8557, and $2210, respectively. In probabilistic sensitivity analysis, the likelihood iteration of cost-effectiveness with FFR-guided PCI was 85%, 82%, and 31% for the Korean, US, and European health care systems, respectively.

Conclusions and Relevance

This cost-effectiveness analysis suggests that FFR-guided PCI for non-IRA lesions saved medical costs and increased quality of life better than angiography-guided PCI for patients with acute myocardial infarction and multivessel disease. Fractional flow reserve–guided PCI should be considered in determining the treatment strategy for non-IRA stenoses in these patients.

Trial Registration

ClinicalTrials.gov Identifier: NCT02715518

Introduction

Previous randomized clinical trials and registry data have shown that percutaneous coronary intervention (PCI) of non–infarct-related artery (IRA) lesions in patients with acute myocardial infarction with multivessel disease improves patient prognosis.1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17 Based on these results, 2021 guidelines from the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions and 2018 guidelines from the European Society of Cardiology and European Association of Percutaneous Cardiovascular Interventions for myocardial revascularization recommend revascularization of non-IRA lesions before hospital discharge for patients with acute myocardial infarction with multivessel disease.18,19,20

The criteria for performing non-IRA PCI have not been clarified. Revascularization of non-IRA lesions based on angiographic severity assessed by visual estimation or quantitative coronary angiography4,11,12 or functional significance assessed by fractional flow reserve (FFR)7,9 had better clinical outcomes than IRA-only PCI. Two recent trials, FLOWER-MI (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction)14 and FRAME-AMI (Fractional Flow Reserve vs Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction),15 evaluated the comparative prognosis between FFR-guided vs angiography-guided PCI for non-IRA lesions in patients with acute myocardial infarction and multivessel disease. In both trials, FFR-guided PCI resulted in substantially lower rates of non-IRA PCI with fewer stents used than angiography-guided PCI. However, there were conflicting results regarding clinical outcomes between the 2 groups in both trials.14,15 In the FLOWER-MI trial, FFR-guided PCI had similar risk in a composite of death, myocardial infarction, or unplanned hospitalization leading to urgent revascularization with angiography-guided PCI; in the FRAME-AMI trial, FFR-guided PCI substantially reduced risk in a composite of death, myocardial infarction, and repeat revascularization.

Given the heterogenous results in previous trials regarding which treatment provides better clinical outcomes, it is important to evaluate these strategies from a cost-effectiveness standpoint. Therefore, this prespecified analysis of the FRAME-AMI trial evaluated comparative cost-effectiveness between FFR-guided and angiography-guided PCI for non-IRA lesions among patients with acute myocardial infarction and multivessel disease.

Methods

This prespecified analysis used data from the FRAME-AMI investigator-initiated, randomized, open-label, multicenter randomized clinical trial, which was conducted at 14 sites in Korea. The design and primary results of the FRAME-AMI trial have been published previously.15 The trial protocol was approved by the institutional review board at each participating site (Supplement 1). All patients provided written informed consent before randomization. For patients presenting with conditions that precluded their understanding of the trial process, informed consent was obtained after stabilization by revascularization of IRA and a subsequent procedure for non-IRA was performed in a staged manner during the index hospitalization. Otherwise, informed consent was acquired before diagnostic coronary angiography and randomization was performed after successful primary or urgent PCI for IRA in patients that met the eligibility criteria.15 eAppendices 1 to 4 in Supplement 2 provide detailed information on all participating centers and trial personnel, inclusion and exclusion criteria, definition of clinical events, and Seattle Angina Questionnaire analysis of FRAME-AMI. This study is reported according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guideline. The network and pairwise meta-analysis conducted both complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline.

Data Source

Briefly, patients aged 19 years or older with ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who underwent successful primary or urgent PCI of an IRA between August 19, 2016, and December 24, 2020, were candidates for enrollment. Patients were also required to have at least 1 non-IRA lesion with diameter stenosis greater than 50% in a major epicardial coronary artery or major side branch with a vessel diameter of 2.0 mm or greater by visual estimation judged to be amenable to PCI by operators. Key exclusion criteria were single-vessel disease, flow-limiting stenosis with a Thrombolysis in Myocardial Infarction flow grade of 2 or less in the non-IRA, target lesion located in the left main coronary artery, cardiogenic shock, and chronic total occlusion in non-IRA lesions. A total of 562 patients were randomly assigned to either FFR-guided PCI or angiography-guided PCI for non-IRA lesions. In the FFR-guided PCI group, FFR was measured in all non-IRA lesions with stenosis greater than 50% on visual estimation and only stenoses with an FFR of 0.80 or lower were treated with PCI. In the angiography group, any lesions with diameter stenosis greater than 50% on visual estimation were treated with PCI. The primary end point was a composite of time to death, MI, or repeat revascularization.

Statistical Analysis

Statistical analysis was planned in 2 ways. One analysis used actual individual patient data from the FRAME-AMI trial, and the other was based on the Markov model using previously published evidence.12,14,15,21,22,23,24,25,26,27,28,29,30,31

Cost-Effectiveness Analysis Using Trial Data

The primary economic evaluation was a within-trial cost-effectiveness analysis using the FRAME-AMI trial data undertaken from a health care system perspective. This cost-effectiveness analysis of the FRAME-AMI trial was prespecified and described in the trial protocol (Supplement 1) and at ClinicalTrials.gov (NCT02715518). A time horizon of 4 years was applied considering the median follow-up duration of the FRAME-AMI trial.

We calculated medical costs based on resource use during the index hospitalization and clinical events that occurred during subsequent follow-ups. Medical cost at the index hospitalization was calculated using the unit cost from the Korea Health Insurance Review and Assessment Service as well as from individual data regarding the number of guiding catheters, coronary guide wires, balloon catheters, stents, intravascular imaging devices, and hospital days for each patient in the trial log. Performance fees for IRA PCI, immediate non-IRA PCI, and staged non-IRA PCI from the Korea Health Insurance Review and Assessment Service were also included in the medical cost (Table 1). To calculate the medical cost at event, we assigned costs to postdischarge events based on previous studies (Table 1). Procedure-related myocardial infarction was not assigned a cost. In the analysis, costs are presented in US dollars (US$1 = ₩1200 and €1.07).

Table 1. Key Inputs in the Model.
Input Korean population US population European population
Value, $ Source Value, $ Source Value, $ Source
Cost a
Medical cost at index hospitalization
Angiography-guided PCI 9842 Lee et al,15 2023 14 878 Fearon et al,21 2010 7226 Le Bras et al,29 2022
FFR-guided PCI 9326 13 182 7647
Unit cost per service or product, $
IRA PCI performance fee 2126 Lee et al,15 2023 2005 Fearon et al,23 2013 202 Le Bras et al,29 2022
Immediate non-IRA PCI performance fee 435 796 Fearon et al,26 2018 202
Staged non-IRA PCI performance fee 1357 567 Fearon et al,22 2013 194
Drug-eluting stent, 1 each 1431 1656 613
Pressure wire 709 650 Fearon et al,21 2010 428
Guide wire 16 85 50
Intensive care unit cost per day 74 2877 346-863
Hospitalization cost per day 15 2000 578-820
Medical cost at event
Death from any cause 9235 Hwang et al,30 2023 35 818 Kazi et al,24 2014 1586 Le Bras et al,29 2022
Nonfatal MI 7338 16 544 Fearon et al,21 2010 5370
Repeat revascularization 7292 12 780 4633
Utility
After PCI 0.79 Kodera et al,27 2019 0.92 Shaw et al,31 2008 0.85 Pocock et al,28 2021
Recurrent MI (disutility) −0.06 Lewis et al,25 2014 −0.06 Lewis et al,25 2014 −0.06 Lewis et al,25 2014
Transition probability
Death
Angiography-guided PCI 0.02 Lee et al,15 2023 0.02 Mehta et al,12 2019 0.02 Puymirat et al,14 2021
FFR-guided PCI 0.007 0.01 0.01
Angiography-guided vs FFR-guided PCI, HR (95% CI) 0.30 (0.11-0.83) 0.86 (0.50-1.83) eFigure in Supplement 2 0.89 (0.36-2.20)
Recurrent MI
Angiography-guided PCI 0.01 Lee et al,15 2023 0.02 Mehta et al,12 2019 0.02 Puymirat et al,14 2021
FFR-guided PCI 0.008 0.03 0.03
Angiography-guided vs FFR-guided PCI, HR (95% CI) 0.32 (0.13-0.75) 1.31 (0.51-4.21) eFigure in Supplement 2 1.77 (0.82-3.84)
Repeat revascularization
Angiography-guided PCI 0.01 Lee et al,15 2023 0.005 Mehta et al,12 2019 0.02 Puymirat et al,14 2021
FFR-guided PCI 0.009 0.004 0.03
Angiography-guided vs FFR-guided PCI, HR (95% CI) 0.61 (0.28-1.34) 0.87 (0.37-2.09) eFigure in Supplement 2 1.34 (0.62-2.92)
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Abbreviations: FFR, fractional flow reserve; HR, hazard ratio; IRA, infarct-related artery; MI, myocardial infarction; PCI, percutaneous coronary intervention.

a

Exchange rate calculated with ratios between $1 and ₩1200 and between $1 and €1.07.

Utility is expressed as the difference in quality-adjusted life-years (QALYs) between the 2 strategies. Quality-adjusted life-years represent patient survival time weighted by quality of life, represented by a utility function. Quality-of-life indexes (utilities) were evaluated at 12 months using the Seattle Angina Questionnaire. Questionnaire scores were translated to European Quality of Life–5 Dimensions scores using a mapping algorithm.32 The trial protocol did not mandate Seattle Angina Questionnaire completion, and 60% of patients completed the questionnaire at 1-year follow-up. We performed multiple imputations to account for the missing values. To estimate Seattle Angina Questionnaire scores, a linear regression model was constructed among patients who were measured for utility and did not experience recurrent myocardial infarction until 1-year follow-up with the following variables: assigned treatment group (FFR-guided or angiography-guided PCI), intended timing of non-IRA PCI (immediate or staged non-IRA PCI during index hospitalization), location of non-IRA (left anterior descending artery or non-left anterior descending artery), initial presentation (STEMI or NSTEMI), sex (male or female), age (<65 or ≥65 years), diabetes, left ventricular ejection fraction (<50% or ≥50%), and P2Y12 inhibitor type (clopidogrel, ticagrelor, or prasugrel). The estimated coefficients were used to generate utility values for patients who did not have utility data. If the patient experienced recurrent myocardial infarction, the score was adjusted using disutility. Both utilities estimated from trial data and from the previous study were used.27 The disutility weight of the state after recurrent myocardial infarction was obtained from a previous study in both analyses (Table 1).25

The cost-effectiveness of FFR-guided PCI was expressed as the incremental cost-effectiveness ratio (ICER), defined as the difference in cumulative costs divided by the difference in cumulative QALYs. We computed CIs for differences in costs and QALYs and in ICERs using the bootstrap technique with the percentile method with 25 000 replications. We also calculated the incremental net monetary benefit (INB).33 The INB can be computed as the difference between incremental QALYs multiplied by the willingness-to-pay (WTP) threshold and incremental cost: INB = (ΔQALY × WTP) − ΔCost.33 A positive INB (>0) indicates that the FFR-guided PCI is cost-effective compared with angiography-guided PCI at the given threshold of WTP, whereas a negative INB indicates that FFR-guided PCI is not cost-effective relative to angiography-guided PCI.33

Multiple sensitivity analyses were conducted to assess the robustness of the findings. First, probabilistic sensitivity analysis using Monte Carlo simulation was performed to further assess intraindividual and parameter uncertainties.34 In the probabilistic sensitivity analysis, patients were randomly sampled and simulations were repeated 25 000 times. Using bayesian statistical principles, we used a prior distribution that is commonly specified depending on the characteristics of the model parameters. As for the input variable ranges in the simulation, a log-normal distribution was used for transitional probabilities with a 95% CI from the previous literature (Table 1), a β distribution for utilities with values between 0 and 1 and a range variation of 10%, and a γ distribution for costs (ie, costs could not be <0), with a range variation the same as the mean, to accurately represent cost variability.35 Second, utility data were extrapolated from previous studies and the same analysis was performed to compensate for the incompleteness of calculating utility through the Seattle Angina Questionnaire.25,27 Third, planned subgroup analyses regarding cost-effectiveness of FFR-guided PCI were performed according to the intended timing of non-IRA PCI, location of non-IRA, initial presentation, sex, age, diabetes, left ventricular ejection fraction, and P2Y12 inhibitor type.

Cost-Effectiveness Analysis Using a Markov Model

In the secondary analysis, we performed a cost-effectiveness analysis of FFR-guided PCI in 3 different health care systems (Korean, US, and European) using a Markov model. We used a 2-state Markov model in which the simulated patients can exist in either (1) myocardial infarction or (2) death. Patients initially allocated to myocardial infarction could either remain in that same state or transition to death in every cycle, according to transition probability. Patients who experienced recurrent myocardial infarction or repeat revascularization remained in the same state, and disutility was only applied in the case of recurrent myocardial infarction. A time horizon of 4 years was applied for the model, as done for the within-trial cost-effectiveness analysis.

Medical costs at index hospitalization were obtained from the FRAME-AMI trial15 for the Korean population, the FAME and FAME 2 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trials21,26 for the US population, and the FLOWER-MI trial14 for the European population. We assigned costs to postdischarge events based on previous studies (Table 1). Cost and utility data were discounted by an annual rate of 4.5%, according to the Korean Guidelines of Methodological Standards for economic evaluation, and by 3.5% for US and European cost and utility based on previous literature.36 We projected the discounted lifetime health care cost by multiplying the number of patients with the sum of the costs in every health status. Total QALYs were accumulated from the QALY values in each cycle. In the Korean, US, and European health care systems, values of $35 000, $60 000, and $40 000 per QALY were considered a reasonable WTP threshold based on the gross domestic product per capita.

Transition probability for the Korean population was acquired from the FRAME-AMI trial.15 Since there was no head-to-head trial comparing FFR-guided and angiography-guided PCI in patients with acute myocardial infarction and multivessel disease in the US, transition probabilities for the US population were obtained from the COMPLETE trial (Complete Versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease After Early PCI for STEMI) for angiography-guided PCI.12 The transition probability of FFR-guided PCI was obtained by multiplying the transition probability of angiography-guided PCI and the odds ratio (OR) between FFR-guided and angiography-guided PCI calculated from a network meta-analysis of 14 trials. For the European population, transition probabilities were obtained from the FLOWER-MI trial.14 To confirm the robustness of cost-effectiveness analysis, 2 models with different transition probabilities were constructed: model 1 used transition probabilities from the network meta-analysis of 14 trials (eTable 1 in Supplement 2),1,2,3,4,5,6,7,8,9,10,11,12,13,14,15 and model 2 used transition probabilities from a pairwise meta-analysis of the FRAME-AMI and FLOWER-MI trials.

For the network meta-analysis, a bayesian random-effects model was used to calculate ORs with 95% credible intervals (CRIs), which were calculated with the gemtc package in R, version 4.1.0 (R Project for Statistical Computing). We ran Markov chain Monte Carlo samplers, running 4 chains with different starting values. A burn-in phase of 10 000 iterations was followed by 50 000 updates, in which the number of burn-in iterations was chosen according to the Brooks-Gelman-Rubin method for convergence checks.37 For the pairwise meta-analysis, pooled ORs with 95% CIs were calculated using the DerSimonian and Laird method for the random-effects model. The probabilistic sensitivity analysis was conducted with the same method as the within-trial cost-effective analysis. All analyses were performed using R, version 4.1.0, and Stata, version 16 (StataCorp LP). Data analysis was performed on August 27, 2023.

Results

A total of 562 FRAME-AMI patients with acute myocardial infarction and multivessel disease underwent randomization: 284 to receive FFR-guided PCI and 278 to receive angiography-guided PCI for non-IRA lesions. Their mean (SD) age was 63.3 (11.4) years, and there were 474 men (84.3%) and 88 women (15.7%). A total of 265 patients (47.2%) presented with STEMI and 297 patients (52.8%) presented with NSTEMI. Non-IRA lesions were treated with immediate PCI after successful treatment of IRA in 337 patients (60.0%) and with a staged procedure during the same hospitalization in 225 patients (40.0%). In the FFR-guided PCI group, PCI was performed in 182 patients (64.1%) and deferred in 102 patients (35.9%) with non-IRA lesions, whereas 270 patients (97.1%) underwent PCI for non-IRA lesions in the angiography-guided PCI group. In the FFR-guided PCI group, FFR was measured in 83.2% of non-IRA lesions and the treatment decision was made based on the FFR value. Among the non-IRA lesions evaluated with FFR, 49.5% of interrogated lesions had an FFR greater than 0.80 and 50.5% had an FFR of 0.80 or less. In 16.8% of non-IRA lesions, PCI was performed without FFR measurement due to diameter stenosis greater than 90% in non-IRA lesions. The mean (SD) number of stents used per patient for non-IRA lesions was 0.9 (0.9) in the FFR-guided PCI group and 1.3 (0.7) in the angiography-guided PCI group (P < .001). The total mean (SD) number of stents used per patient for both IRA and non-IRA PCI was 2.2 (1.1) in the FFR-guided PCI group and 2.5 (0.9) in the angiography-guided PCI group (P < .001).

At a median follow-up of 3.5 years (IQR, 2.7-4.1 years), the FFR-guided PCI group had a significantly lower risk of the primary end point than the angiography-guided PCI group (Kaplan-Meier event rates at 4 years, 7.4% vs 19.7%; hazard ratio [HR], 0.43 [95% CI, 0.25-0.75]; P = .003). Kaplan-Meier event rates for death at 4 years were 2.1% vs 8.5% (HR, 0.30 [95% CI, 0.11-0.83]; P = .02) and those for myocardial infarction were 2.5% vs 8.9% (HR, 0.32 [95% CI, 0.13-0.75]; P = .009) in the FFR-guided and angiography-guided PCI groups, respectively. There was no significant difference in repeat revascularization between the 2 groups (4.3% vs 9.0%; HR, 0.61 [95% CI, 0.28-1.34]; P = .22) (Table 1).

Within-Trial Cost-Effectiveness Analysis

The 4-year QALY was 3.46 vs 3.40 for the FFR-guided and angiography-guided PCI groups, respectively. Regarding the effectiveness, there was a gain of 0.06 QALYs in the FFR-guided PCI group compared with the angiography-guided PCI group at 4 years. The total cumulative cost per patient in the FFR-guided PCI group was estimated as $1208 less than that for the angiography-guided PCI group. Consequently, the INB was $3378, suggesting that FFR-guided PCI was more cost-effective than angiography-guided PCI. Overall, the ICER was −$19 484, indicating that FFR-guided PCI was the dominant strategy for patients with acute myocardial infarction and multivessel disease (Table 2). The probabilistic sensitivity analysis showed consistent results and the likelihood iteration of cost-effectiveness in FFR-guided PCI was 97% (Figure 1). Similar results were also shown, with an INB of $4253 and ICER of −$13 885 when different utilities from the previous literature were applied (Table 2). The cost-effectiveness of FFR-guided PCI relative to angiography-guided PCI was consistent across various subgroups (eTable 2 in Supplement 2).

Table 2. Cost-Effectiveness of FFR-Guided PCI Relative to Angiography-Guided PCI in the FRAME-AMI Trial.

Utilities Cost, $a QALYs Cost-effectiveness, ICER ($/QALY) INB, $
Total Incremental Total Incremental
Estimated from data
Angiography-guided PCI 11 057 Reference 3.40 Reference NA NA
FFR-guided PCI 9849 −1208 3.46 0.062 −19 484 3378
Extrapolated
Angiography-guided PCI 11 057 Reference 3.12 Reference NA NA
FFR-guided PCI 9849 −1208 3.21 0.087 −13 885 4253
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Abbreviations: FFR, fractional flow reserve; FRAME-AMI, Fractional Flow Reserve vs Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction; ICER, incremental cost-effectiveness ratio; INB, incremental net monetary benefit; NA, not applicable; PCI, percutaneous coronary intervention; QALY, quality-adjusted life-year.

a

Exchange rate calculated with ratio between $1 and ₩1200.

Figure 1. Cost-Effectiveness of Fractional Flow Reserve (FFR)–Guided vs Angiography-Guided Percutaneous Coronary Intervention (PCI) in the FRAME-AMI Trial.

Figure 1.

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Replications of incremental cost-effectiveness of FFR-guided PCI compared with angiography-guided PCI. The incremental cost-effectiveness plane presents the impact of FFR-guided compared with angiography-guided PCI on the difference in quality-adjusted life-years (QALYs; until 4 years after PCI) and accompanying medical costs within this 4-year time period. Each of the 25 000 dots represents the results of 1 bootstrap replication. The diagonal dotted blue line indicates the willingness-to-pay (WTP) threshold of $35 000 per QALY added. The vertical dashed line represents the mean effectiveness difference; the horizontal dashed line, the mean cost difference.

Cost-Effectiveness Analysis Using a Markov Model

The network meta-analysis of 14 previous trials showed that there was no significant difference in the risk of death (OR, 0.86 [95% CRI, 0.50-1.83]), myocardial infarction (OR, 1.31 [95% CRI, 0.51-4.21]), and repeat revascularization (OR, 0.87 [95% CRI, 0.37-2.09]) between FFR-guided and angiography-guided PCI (eFigure in Supplement 2). When transition probabilities from the network meta-analysis were applied, FFR-guided PCI was accompanied by higher QALYs and lower medical costs in the Korean and US health care systems, represented by an INB of $1114 and $2451, respectively (Table 3). Conversely, FFR-guided PCI resulted in higher medical costs and similar QALYs with angiography-guided PCI in the European health care system. In probabilistic sensitivity analysis, the likelihood iteration of cost-effectiveness in FFR-guided PCI was 75%, 71%, and 40% in the Korean, US, and European health care systems, respectively (Figure 2).

Table 3. Cost-Effectiveness of FFR-Guided PCI Relative to Angiography-Guided PCI Across 3 Different Health Care Systems.

Health care system Cost, $ QALYsa INB, $
Angiography-guided PCI FFR-guided PCI Incremental Angiography-guided PCI FFR-guided PCI Incremental
Model 1b
Korea 12 437 11 956 −480 2.68 2.70 0.02 1114
US 22 718 21 156 −1562 3.24 3.25 0.01 2451
Europe 8288 8916 627 2.99 3.00 0.01 −154
Model 2c
Korea 12 437 10 928 −1509 2.68 2.75 0.07 3910
US 22 718 18.014 −4703 3.24 3.30 0.06 8557
Europe 8288 8405 116 2.99 3.05 0.06 2210
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Abbreviations: FFR, fractional flow reserve; INB, incremental net monetary benefit; PCI, percutaneous coronary intervention; QALY, quality-adjusted life-year.

a

In the Korean, US, and European health care systems, values of $35 000, $60 000, and $40 000 per QALY were considered a reasonable willingness-to-pay threshold based on the gross domestic product per capita.

b

Transition probabilities were estimated from a network meta-analysis of 14 trials, including FLOWER-MI (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) and FRAME-AMI (Fractional Flow Reserve vs Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction).

c

Transition probabilities were estimated from pairwise meta-analysis of the FLOWER-MI and FRAME-AMI trials.

Figure 2. Cost-Effectiveness of Fractional Flow Reserve (FFR)–Guided vs Angiography-Guided Percutaneous Coronary Intervention (PCI) in 3 Health Care Systems.

Figure 2.

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Transition probabilities from the network meta-analysis of 14 trials, including the FLOWER-MI and FRAME-AMI trials (A) and with pairwise meta-analysis of the FLOWER-MI and FRAME-AMI trials (B), were used in the cost-effectiveness analysis. The incremental cost-effectiveness plane illustrates the impact of FFR-guided PCI compared with angiography-guided PCI on the difference in quality-adjusted life-years (QALYs; up to 4 years after PCI) and the associated medical costs within this 4-year period. A Monte Carlo simulation was conducted, in which patients were randomly selected and simulations were repeated 25 000 times to generate the outcomes (represented as dots). The difference in cumulative costs is displayed on the vertical axis, and the difference in QALYs is displayed on the horizontal axis. Graphs display the Korean willingness-to-pay (WTP) thresholds for the Korean ($35 000/QALY), US ($65 000/QALY), and European ($45 000/QALY) health care systems. Red dots represent mean incremental cost-effectiveness ratios.

In the pairwise meta-analysis of the FLOWER-MI and FRAME-AMI trials, pooled ORs for death, MI, and repeat revascularization were 0.53 (95% CI, 0.18-1.54), 0.76 (95% CI, 0.14-4.07), and 0.99 (95% CI, 0.42-2.37), respectively (eFigure in Supplement 2). When transition probabilities from the pairwise meta-analysis of the FLOWER-MI and FRAME-AMI trials were used, FFR-guided PCI was the dominant treatment in all 3 health care systems, with an INB of $3910, $8557, and $2210, respectively (Table 3). In the probabilistic sensitivity analysis, the likelihood iteration of cost-effectiveness in FFR-guided PCI was 85%, 82%, and 31% in the Korean, US, and European health care systems, respectively (Figure 2).

Discussion

This prespecified analysis of the FRAME-AMI trial showed that FFR-guided PCI saved medical costs and increased quality of life better than angiography-guided PCI in patients with acute myocardial infarction and multivessel disease. The greater cost-effectiveness of FFR-guided PCI was similarly observed across various planned subgroup analysis. A sensitivity analysis with Markov models using medical costs from individual trials and transition probabilities from meta-analyses suggested that FFR-guided PCI would be more cost-effective than angiography-guided PCI across the Korean, US, and European health care systems.

Complete revascularization for non-IRA decreases adverse clinical events compared with IRA-only PCI in patients with acute myocardial infarction and multivessel disease. However, whether selective FFR-guided non-IRA PCI or routine non-IRA PCI based on angiographic findings is better for patient prognosis is still debated. Previous studies have consistently shown that most intermediate coronary artery stenoses viewed with angiography do not have functional significance,38 and the angiographic severity of non-IRA lesions can be overestimated in the acute phase of MI, leading to stenting hemodynamically insignificant lesions.39 Furthermore, the prognostic benefit of non-IRA PCI was observed only in patients with non-IRA stenosis with diameter stenosis of 80% or greater by visual assessment or 60% or greater on laboratory assessment in the COMPLETE trial.12 Moreover, total infarct size and ischemic burden were similar between angiography-guided complete revascularization and IRA-only PCI in the cardiac magnetic resonance substudy of the CvLPRIT trial (Complete Versus Lesion-Only Primary PCI Pilot Study).40 Therefore, routine angiography-guided PCI for all non-IRA lesions with diameter stenosis greater than 50%, even without inducible myocardial ischemia, may be accompanied by unnecessary procedures with additional stents, greater contrast media use, and increased risk of procedure-related complications, which may result in worse long-term patient prognosis. In this regard, FFR-guided PCI would reduce unnecessary PCI for functionally insignificant stenosis and would be superior to angiography-guided PCI for patients with stable ischemic heart disease and for those with acute myocardial infarction and multivessel disease.18,19,20 However, 2 recent trials that directly compared FFR-guided and angiography-guided PCI in patients with acute myocardial infarction and multivessel disease showed conflicting results.14,15 Based on the heterogenous results from these 2 trials, it is important to clarify the cost-effectiveness of each strategy.

This study evaluated the cost-effectiveness of FFR-guided PCI in multiple ways. By using actual medical cost and utility values in the FRAME-AMI trial data, FFR-guided PCI was deemed the dominant strategy compared with angiography-guided PCI. Consistent results were observed when utility values were extrapolated from a previous study,27 probabilistic sensitivity analysis, and multiple subgroup analyses. In addition, cost-effectiveness of FFR-guided PCI was also shown across 3 different health care systems using Markov models. The cost-effectiveness of FFR-based PCI was more remarkable for the US health care system, which has higher medical costs than the Korean and European health care systems. This difference in cost-effectiveness was mainly attributable to relatively higher medical costs incurred when adverse clinical events were treated in the US. It should be noted that the results of the network meta-analysis and pairwise meta-analysis were slightly different for the European health care system; this was due to the different transition probability, especially for myocardial infarction, between the network meta-analysis (OR, 1.31 [95% CRI, 0.51-4.21]) and pairwise meta-analysis (OR, 0.76 [95% CI, 0.14-4.07]), originating from the discordant results between the FLOWER-MI and FRAME-AMI trials.

Nevertheless, the overall analysis results support that FFR-guided PCI was the dominant strategy compared with angiography-guided PCI. Of note, deferral of PCI for non-IRA based on FFR provided at least comparable clinical outcomes in the FLOWER-MI trial or superior clinical outcomes in the FRAME-AMI trial compared with angiography-guided PCI. Considering that FFR-guided PCI resulted in much lower rates of non-IRA PCI than angiography-guided PCI in both trials, it should be noted that FFR-guided PCI would save additional medical resources and costs without an apparent safety signal for patient prognosis. Further trials with larger sample sizes, such as FULL REVASC,41 OPTION-STEMI,42 and COMPLETE 2,43 would further clarify the role of FFR-guided PCI in patients with acute myocardial infarction and multivessel disease.

Limitations

The following limitations of this study should be considered. First, the results of the cost-effectiveness analysis were dependent on key input values, such as transition probability, medical costs, and utilities, which were obtained through limited previous studies. Therefore, application of our results to other health care systems is limited. Second, all of the previous trials excluded patients with left main coronary artery disease or chronic total occlusion in non-IRA lesions. Further trials are required to clarify whether complete revascularization, including chronic total occlusion in non-IRA, would have prognostic benefit and cost-effectiveness over IRA-only PCI in patients with acute myocardial infarction and multivessel disease. Third, the FRAME-AMI trial was terminated earlier than initially planned due to the COVID-19 pandemic; therefore, potential overestimation of the treatment effect as well as a resulting loss of power should be considered in interpreting our results. Fourth, we used a published approach to convert Seattle Angina Questionnaire scores to quality-of-life measures, but these instruments measure different aspects of quality of life.

Conclusions

This cost-effectiveness prespecified analysis of the FRAME-AMI randomized clinical trial suggests that FFR-guided PCI for non-IRA lesions saved medical costs and increased quality of life compared with angiography-guided PCI in patients with acute myocardial infarction and multivessel disease. In conclusion, FFR-guided PCI should be considered when determining the treatment strategy for non-IRA stenoses in these patients.

Supplement 1.

Trial Protocol

Click here for additional data file. (1.5MB, pdf)
Supplement 2.

eAppendix 1. Investigators and Collaborators

eAppendix 2. Inclusion and Exclusion Criteria

eAppendix 3. Definition of Clinical Events

eAppendix 4. Seattle Angina Questionnaire Analysis

eFigure. Network and Pairwise Meta-Analysis Comparing IRA-Only PCI and FFR-Guided and Angiography-Guided PCI for Non-IRA Lesions

eTable 1. Characteristics of Trials Included in the Network Meta-Analysis

eTable 2. Subgroup Analysis for Cost-Effectiveness of FFR-Guided PCI Relative to Angiography-Guided PCI in the FRAME-AMI Trial

eReferences

Click here for additional data file. (414.3KB, pdf)
Supplement 3.

Data Sharing Statement

Click here for additional data file. (18.7KB, pdf)

References

  • 1.Di Mario C, Mara S, Flavio A, et al. Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised Hepacoat for Culprit or Multivessel Stenting for Acute Myocardial Infarction (HELP AMI) study. Int J Cardiovasc Intervent. 2004;6(3-4):128-133. doi: 10.1080/14628840310030441 [DOI] [PubMed] [Google Scholar]
  • 2.Politi L, Sgura F, Rossi R, et al. A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up. Heart. 2010;96(9):662-667. doi: 10.1136/hrt.2009.177162 [DOI] [PubMed] [Google Scholar]
  • 3.Ghani A, Dambrink JH, van ’t Hof AW, Ottervanger JP, Gosselink AT, Hoorntje JC. Treatment of non-culprit lesions detected during primary PCI: long-term follow-up of a randomised clinical trial. Neth Heart J. 2012;20(9):347-353. doi: 10.1007/s12471-012-0281-y [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Wald DS, Morris JK, Wald NJ, et al. ; PRAMI Investigators . Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med. 2013;369(12):1115-1123. doi: 10.1056/NEJMoa1305520 [DOI] [PubMed] [Google Scholar]
  • 5.Hlinomaz AO, Groch L, Poloková K, et al. Multivessel coronary disease diagnosed at the time of primary PCI for STEMI: complete revascularisation versus conservative strategy. Prague-13 trial. Kardiol Rev Int Med. 2015;17(3):214-220. [Google Scholar]
  • 6.Zhang J, Wang Q, Yang H, et al. [Evaluation of different revascularization strategies for patients with acute myocardial infarction with lesions of multiple coronary arteries after primary percutaneous coronary intervention and its economic evaluation]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015;27(3):169-174. [DOI] [PubMed] [Google Scholar]
  • 7.Engstrøm T, Kelbæk H, Helqvist S, et al. ; DANAMI-3—PRIMULTI Investigators . Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial. Lancet. 2015;386(9994):665-671. doi: 10.1016/S0140-6736(15)60648-1 [DOI] [PubMed] [Google Scholar]
  • 8.Hamza M, Mahmoud N, Elgendy IY. A randomized trial of complete versus culprit-only revascularization during primary percutaneous coronary intervention in diabetic patients with acute ST elevation myocardial infarction and multi vessel disease. J Interv Cardiol. 2016;29(3):241-247. doi: 10.1111/joic.12293 [DOI] [PubMed] [Google Scholar]
  • 9.Smits PC, Abdel-Wahab M, Neumann FJ, et al. ; Compare-Acute Investigators . Fractional flow reserve-guided multivessel angioplasty in myocardial infarction. N Engl J Med. 2017;376(13):1234-1244. doi: 10.1056/NEJMoa1701067 [DOI] [PubMed] [Google Scholar]
  • 10.Smits PC, Laforgia PL, Abdel-Wahab M, et al. Fractional flow reserve-guided multivessel angioplasty in myocardial infarction: three-year follow-up with cost benefit analysis of the Compare-Acute trial. EuroIntervention. 2020;16(3):225-232. doi: 10.4244/EIJ-D-20-00012 [DOI] [PubMed] [Google Scholar]
  • 11.Gershlick AH, Banning AS, Parker E, et al. Long-term follow-up of complete versus lesion-only revascularization in STEMI and multivessel disease: the CvLPRIT trial. J Am Coll Cardiol. 2019;74(25):3083-3094. doi: 10.1016/j.jacc.2019.10.033 [DOI] [PubMed] [Google Scholar]
  • 12.Mehta SR, Wood DA, Storey RF, et al. ; COMPLETE Trial Steering Committee and Investigators . Complete revascularization with multivessel PCI for myocardial infarction. N Engl J Med. 2019;381(15):1411-1421. doi: 10.1056/NEJMoa1907775 [DOI] [PubMed] [Google Scholar]
  • 13.Calviño-Santos R, Estévez-Loureiro R, Peteiro-Vázquez J, et al. Angiographically guided complete revascularization versus selective stress echocardiography-guided revascularization in patients with ST-segment-elevation myocardial infarction and multivessel disease: the CROSS-AMI randomized clinical trial. Circ Cardiovasc Interv. 2019;12(10):e007924. doi: 10.1161/CIRCINTERVENTIONS.119.007924 [DOI] [PubMed] [Google Scholar]
  • 14.Puymirat E, Cayla G, Simon T, et al. ; FLOWER-MI Study Investigators . Multivessel PCI guided by FFR or angiography for myocardial infarction. N Engl J Med. 2021;385(4):297-308. doi: 10.1056/NEJMoa2104650 [DOI] [PubMed] [Google Scholar]
  • 15.Lee JM, Kim HK, Park KH, et al. ; FRAME-AMI Investigators . Fractional flow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease: a randomized trial. Eur Heart J. 2023;44(6):473-484. doi: 10.1093/eurheartj/ehac763 [DOI] [PubMed] [Google Scholar]
  • 16.Rathod KS, Koganti S, Jain AK, et al. Complete versus culprit-only lesion intervention in patients with acute coronary syndromes. J Am Coll Cardiol. 2018;72(17):1989-1999. doi: 10.1016/j.jacc.2018.07.089 [DOI] [PubMed] [Google Scholar]
  • 17.Kim MC, Hyun JY, Ahn Y, et al. Optimal revascularization strategy in non-ST-segment-elevation myocardial infarction with multivessel coronary artery disease: culprit-only versus one-stage versus multistage revascularization. J Am Heart Assoc. 2020;9(15):e016575. doi: 10.1161/JAHA.120.016575 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Neumann FJ, Sousa-Uva M, Ahlsson A, et al. ; ESC Scientific Document Group . 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165. doi: 10.1093/eurheartj/ehy394 [DOI] [PubMed] [Google Scholar]
  • 19.Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(3):e18-e114. doi: 10.1161/CIR.0000000000001038 [DOI] [PubMed] [Google Scholar]
  • 20.Collet JP, Thiele H, Barbato E, et al. ; ESC Scientific Document Group . 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42(14):1289-1367. doi: 10.1093/eurheartj/ehaa575 [DOI] [PubMed] [Google Scholar]
  • 21.Fearon WF, Bornschein B, Tonino PAL, et al. ; Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) Study Investigators . Economic evaluation of fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease. Circulation. 2010;122(24):2545-2550. doi: 10.1161/CIRCULATIONAHA.109.925396 [DOI] [PubMed] [Google Scholar]
  • 22.Fearon WF, Low AF, Yong AS, et al. Prognostic value of the index of microcirculatory resistance measured after primary percutaneous coronary intervention. Circulation. 2013;127(24):2436-2441. doi: 10.1161/CIRCULATIONAHA.112.000298 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Fearon WF, Shilane D, Pijls NHJ, et al. ; Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 2 (FAME 2) Investigators . Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve. Circulation. 2013;128(12):1335-1340. doi: 10.1161/CIRCULATIONAHA.113.003059 [DOI] [PubMed] [Google Scholar]
  • 24.Kazi DS, Garber AM, Shah RU, et al. Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome. Ann Intern Med. 2014;160(4):221-232. doi: 10.7326/M13-1999 [DOI] [PubMed] [Google Scholar]
  • 25.Lewis EF, Li Y, Pfeffer MA, et al. Impact of cardiovascular events on change in quality of life and utilities in patients after myocardial infarction: a VALIANT study (valsartan in acute myocardial infarction). JACC Heart Fail. 2014;2(2):159-165. doi: 10.1016/j.jchf.2013.12.003 [DOI] [PubMed] [Google Scholar]
  • 26.Fearon WF, Nishi T, De Bruyne B, et al. ; FAME 2 Trial Investigators . Clinical outcomes and cost-effectiveness of fractional flow reserve-guided percutaneous coronary intervention in patients with stable coronary artery disease: three-year follow-up of the FAME 2 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation). Circulation. 2018;137(5):480-487. doi: 10.1161/CIRCULATIONAHA.117.031907 [DOI] [PubMed] [Google Scholar]
  • 27.Kodera S, Morita H, Kiyosue A, Ando J, Komuro I. Cost-effectiveness of percutaneous coronary intervention compared with medical therapy for ischemic heart disease in Japan. Circ J. 2019;83(7):1498-1505. doi: 10.1253/circj.CJ-19-0148 [DOI] [PubMed] [Google Scholar]
  • 28.Pocock S, Brieger DB, Owen R, et al. Health-related quality of life 1-3 years post-myocardial infarction: its impact on prognosis. Open Heart. 2021;8(1):e001499. doi: 10.1136/openhrt-2020-001499 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Le Bras A, Puymirat E, Rabetrano H, et al. Economic evaluation of fractional flow reserve-guided versus angiography-guided multivessel revascularisation in ST-segment elevation myocardial infarction patients in the FLOWER-MI randomised trial. EuroIntervention. 2022;18(3):235-241. doi: 10.4244/EIJ-D-21-00867 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Hwang D, Kim HL, Koo BK, et al. ; HOST-EXAM Investigators . Cost-effectiveness of clopidogrel vs aspirin monotherapy after percutaneous coronary intervention: results from the HOST-EXAM study. JACC Asia. 2023;3(2):198-207. doi: 10.1016/j.jacasi.2022.12.007 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Shaw LJ, Berman DS, Maron DJ, et al. ; COURAGE Investigators . Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation. 2008;117(10):1283-1291. doi: 10.1161/CIRCULATIONAHA.107.743963 [DOI] [PubMed] [Google Scholar]
  • 32.Wijeysundera HC, Farshchi-Zarabi S, Witteman W, Bennell MC. Conversion of the Seattle Angina Questionnaire into EQ-5D utilities for ischemic heart disease: a systematic review and catalog of the literature. Clinicoecon Outcomes Res. 2014;6:253-268. doi: 10.2147/CEOR.S63187 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Reed SD. Statistical considerations in economic evaluations: a guide for cardiologists. Eur Heart J. 2014;35(25):1652-1656. doi: 10.1093/eurheartj/ehu174 [DOI] [PubMed] [Google Scholar]
  • 34.Briggs AH, Ades AE, Price MJ. Probabilistic sensitivity analysis for decision trees with multiple branches: use of the Dirichlet distribution in a bayesian framework. Med Decis Making. 2003;23(4):341-350. doi: 10.1177/0272989X03255922 [DOI] [PubMed] [Google Scholar]
  • 35.Briggs AH. Handling uncertainty in cost-effectiveness models. Pharmacoeconomics. 2000;17(5):479-500. doi: 10.2165/00019053-200017050-00006 [DOI] [PubMed] [Google Scholar]
  • 36.Husereau D, Drummond M, Petrou S, et al. ; ISPOR Health Economic Evaluation Publication Guidelines-CHEERS Good Reporting Practices Task Force . Consolidated Health Economic Evaluation Reporting Standards (CHEERS)–explanation and elaboration: a report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force. Value Health. 2013;16(2):231-250. doi: 10.1016/j.jval.2013.02.002 [DOI] [PubMed] [Google Scholar]
  • 37.Gelman A, Rubin DB. Inference from iterative simulation using multiple sequences. Stat Sci. 1992;7(4):457-472. doi: 10.1214/ss/1177011136 [DOI] [Google Scholar]
  • 38.Lee JM, Koo BK, Shin ES, et al. Clinical implications of three-vessel fractional flow reserve measurement in patients with coronary artery disease. Eur Heart J. 2018;39(11):945-951. doi: 10.1093/eurheartj/ehx458 [DOI] [PubMed] [Google Scholar]
  • 39.Thim T, van der Hoeven NW, Musto C, et al. Evaluation and management of nonculprit lesions in STEMI. JACC Cardiovasc Interv. 2020;13(10):1145-1154. doi: 10.1016/j.jcin.2020.02.030 [DOI] [PubMed] [Google Scholar]
  • 40.McCann GP, Khan JN, Greenwood JP, et al. Complete versus lesion-only primary PCI: the randomized cardiovascular MR CvLPRIT substudy. J Am Coll Cardiol. 2015;66(24):2713-2724. doi: 10.1016/j.jacc.2015.09.099 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Ffr-guidance for complete non-culprit revascularization (FULL REVASC). ClinicalTrials.gov identifier: NCT02862119. Updated October 4, 2023. Accessed March 27, 2023. https://clinicaltrials.gov/study/NCT02862119
  • 42.Timing FFR-guided PCI for non-IRA in STEMI and MBD (OPTION-STEMI). ClinicalTrials.gov identifier: NCT04626882. Updated October 31, 2023. Accessed March 27, 2023. https://clinicaltrials.gov/study/NCT04626882
  • 43.Physiology-guided vs angiography-guided non-culprit lesion complete revascularization for acute MI & multivessel disease (COMPLETE-2). ClinicalTrials.gov identifier: NCT05701358. Updated August 24, 2023. Accessed March 27, 2023. https://clinicaltrials.gov/study/NCT05701358

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement 1.

Trial Protocol

Click here for additional data file. (1.5MB, pdf)
Supplement 2.

eAppendix 1. Investigators and Collaborators

eAppendix 2. Inclusion and Exclusion Criteria

eAppendix 3. Definition of Clinical Events

eAppendix 4. Seattle Angina Questionnaire Analysis

eFigure. Network and Pairwise Meta-Analysis Comparing IRA-Only PCI and FFR-Guided and Angiography-Guided PCI for Non-IRA Lesions

eTable 1. Characteristics of Trials Included in the Network Meta-Analysis

eTable 2. Subgroup Analysis for Cost-Effectiveness of FFR-Guided PCI Relative to Angiography-Guided PCI in the FRAME-AMI Trial

eReferences

Click here for additional data file. (414.3KB, pdf)
Supplement 3.

Data Sharing Statement

Click here for additional data file. (18.7KB, pdf)

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