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.

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.

QFR Assessment and Prognosis After Nonculprit PCI in Patients With Acute Myocardial Infarction.

BACKGROUND: Complete revascularization using either angiography-guided or fractional flow reserve (FFR)-guided strategy can improve clinical outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, there is concern that angiography-guided percutaneous coronary intervention (PCI) may result in un-necessary PCI of the non-infarct-related artery (non-IRA), and its long-term prognosis is still unclear. OBJECTIVES: This study sought to evaluate clinical outcomes after non-IRA PCI according to the quantitative flow ratio (QFR). METHODS: We performed post hoc QFR analysis of non-IRA lesions of AMI patients enrolled in the FRAME-AMI (FFR Versus Angiography-Guided Strategy for Management of AMI With Multivessel Disease) trial, which randomly allocated 562 patients into either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis >50%) for non-IRA lesions. Patients were classified by non-IRA QFR values into the QFR ≤0.80 and QFR >0.80 groups. The primary outcome was a major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, and repeat revascularization. RESULTS: A total of 443 patients (552 lesions) were eligible for QFR analysis. Of 209 patients in the angiography-guided PCI group, 30.0% (n = 60) underwent non-IRA PCI despite having QFR >0.80 in the non-IRA. Conversely, only 2.7% (n = 4) among 209 patients in the FFR-guided PCI group had QFR >0.80 in the non-IRA. At a median follow-up of 3.5 years, the rate of MACEs was significantly higher among patients with non-IRA PCI despite QFR >0.80 than in patients with deferred PCI for non-IRA lesions (12.9% vs 3.1%; HR: 4.13; 95% CI: 1.10-15.57; P = 0.036). Non-IRA PCI despite QFR >0.80 was associated with a higher risk of non-IRA MACEs than patients with deferred PCI for non-IRA lesions (12.9% vs 2.1%; HR: 5.44; 95% CI: 1.13-26.19; P = 0.035). CONCLUSIONS: In AMI patients with multivessel disease, 30.0% of angiography-guided PCI resulted in un-necessary PCI for the non-IRA with QFR >0.80, which was significantly associated with an increased risk of MACEs than in those with deferred PCI for non-IRA lesions. (FFR Versus Angiography-Guided Strategy for Management of AMI With Multivessel Disease [FRAME-AMI] ClinicalTrials.gov number; NCT02715518).

Post-PCI Risk Assessment by Inflammation Activity According to Disease Acuity and Time from Procedure.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) has been proposed as an indicator of inflammation and cardiovascular risk. However, little is known of the comparative temporal profile of hs-CRP and its relation to outcomes according to the disease acuity. METHODS: We enrolled 4,263 East Asian patients who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) and stable disease. hs-CRP was measured at baseline and 1 month post-PCI. Major adverse cardiovascular events (MACE: the composite occurrence of death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. RESULT: The AMI group (n = 2,376; 55.7%) had higher hs-CRPbaseline than the non-AMI group (n = 1,887; 44.3%) (median: 1.5 vs. 1.0 mg/L; p < 0.001), which remained higher at 1 month post-PCI (median: 1.0 vs. 0.9 mg/L; p = 0.001). During 1 month, a high inflammatory-risk phenotype (upper tertile: hs-CRPbaseline ≥ 2.4 mg/L) was associated with a greater MACE in the AMI group (adjusted hazard ratio [HRadj]: 7.66; 95% confidence interval [CI]: 2.29-25.59; p < 0.001), but not in the non-AMI group (HRadj: 0.74; 95% CI: 0.12-4.40; p = 0.736). Between 1 month and 4 years, a high inflammatory-risk phenotype (upper tertile: hs-CRP1 month ≥ 1.6 mg/L) was associated with greater MACE compared to the other phenotype in both the AMI (HRadj: 2.40; 95% CI: 1.73-3.45; p < 0.001) and non-AMI groups (HRadj: 2.67; 95% CI: 1.80-3.94; p < 0.001). CONCLUSION: AMI patients have greater inflammation during the early and late phases than non-AMI patients. Risk phenotype of hs-CRPbaseline correlates with 1-month outcomes only in AMI patients. However, the prognostic implications of this risk phenotype appears similar during the late phase, irrespective of the disease acuity.

Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial.

BACKGROUND: Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease. METHODS: In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed. RESULTS: No significant differences in ΔSAQ angina frequency scores (P=0.53) or Duke Activity Status Index (P=0.76) were observed between ranolazine versus placebo, although patients on ranolazine had lesser improvement in SAQ physical limitation scores (P=0.02) compared with placebo at 3 months. There were no significant differences in ΔCFR or Δhyperemic myocardial resistance between ranolazine and placebo groups. Patients treated with ranolazine, compared with placebo, had no significant improvement in maximum rate of oxygen consumption measured during incremental exercise (VO2 max) and peak metabolic equivalents of task. Interestingly, in the ranolazine group, patients with baseline CFR<2.0 demonstrated greater gain in CFR compared with those with baseline CFR≥2.0 (P=0.02). CONCLUSIONS: Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147067.

Robustness of Fractional Flow Reserve for Lesion Assessment in Non-Infarct-Related Arteries of Patients With Myocardial Infarction.

See Article Mejía-Rentería et al.

Carriage of cytochrome 2C19 polymorphism is associated with risk of high post-treatment platelet reactivity on high maintenance-dose clopidogrel of 150 mg/day: results of the ACCEL-DOUBLE (Accelerated Platelet Inhibition by a Double Dose of Clopidogrel According to Gene Polymorphism) study.

OBJECTIVES: This study sought to determine the impact of gene polymorphisms on platelet reactivity (PR) after clopidogrel 150 mg/day in patients treated with percutaneous coronary intervention (PCI). BACKGROUND: Although high maintenance-dose (MD) clopidogrel reduces PR, it is unknown whether gene polymorphisms are related with the risk of high post-treatment PR (HPPR) after high-MD clopidogrel. METHODS: We included mostly patients receiving high-MD clopidogrel after PCI from previously registered Gyeongsang National University Hospital data. A total of 126 PCI-treated patients receiving high-MD clopidogrel were enrolled. Platelet reactivity was assessed with conventional aggregometry and VerifyNow (Accumetrics Inc., San Diego, California) after receiving clopidogrel 150 mg/day for at least 1 month. CYP3A5, CYP2C19, and ABCB1 genotyping was performed. We defined HPPR as 5 micromol/l adenosine diphosphate (ADP)-induced maximal PR (PR(max)) >50%. RESULTS: CYP3A5 and ABCB1 polymorphisms did not influence PR. Carriers of CYP2C19 variant (*2 or *3) (n = 80) had significantly higher 5 and 20 micromol/l ADP-induced PR(max) than did noncarriers (n = 46) (40.7 +/- 16.8% vs. 30.3 +/- 12.6%, p < 0.001; 54.2 +/- 16.2% vs. 40.5 +/- 15.8%, p < 0.001, respectively). Late PR and VerifyNow results indicated consistently greater measures in carriers versus noncarriers of CYP2C19 variant. All platelet measures proportionally increased according to the number of CYP2C19 variant alleles. Twenty-seven (21.4%) patients met the criteria for HPPR. Prevalence of HPPR was 8.7%, 21.7%, and 50.0% in carriers of 0, 1, and 2 CYP2C19 variant alleles, respectively (p < 0.001). By multivariate analysis, carriage of CYP2C19 variant was a significant predictor of HPPR (odds ratio: 5.525, 95% confidence interval: 1.333 to 23.256, p = 0.018). CONCLUSIONS: Among PCI-treated patients receiving high-MD clopidogrel, carriage of CYP2C19 variant relates to increased PR and predicts risk of HPPR. (Adjunctive Cilostazol Versus High Maintenance-dose ClopidogrEL in Acute Myocardial Infarction [AMI] Patients According to CYP2C19 Polymorphism [ACCELAMI2C19]; NCT00915733; and Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism [ACCEL2C19]; NCT00891670).