International Journal of Cardiology 187 (2015) 334–337
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Fractional flow-guided management in patients with acute coronary syndromes: A systematic review and meta-analysis Alexandros Briasoulis ⁎, Mohan Palla, Ashraf Mostafa, Luis Afonso, Cindy Grines Wayne State University, Detroit Medical Center, Department of Cardiology, Detroit, IL 48226, USA
a r t i c l e
i n f o
Article history: Received 20 January 2015 Accepted 20 March 2015 Available online 21 March 2015 Keywords: Fractional flow reserve Non-ST-elevation myocardial infarction Meta-analysis
Dear Editor, In acute coronary syndrome (ACS) patients, the decision of revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) depends upon the severity of coronary artery disease (CAD) assessed by coronary angiography (CA) [1]. Treatment decisions made based on coronary artery stenosis measured by visual assessment of the lesion are tend to be incorrect leading to inappropriate coronary interventions [2,3]. This is most likely to occur in ACS patients presenting with non-ST segment elevation myocardial infarction (NSTEMI), who have unstable CAD. Fractional flow reserve (FFR) ≤ 0.75 was found to strongly correlate with the cardiac ischemia
diagnosed using noninvasive testing [4–6]. Severity of CAD assessed through CA was found to weakly correlate with FFR. Therefore, visual assessment of coronary artery stenosis cannot be used to predict the function of diseased coronary artery [2,7–9]. We intended to perform a systematic review and meta-analysis to explore the differences in outcomes of NSTEMI patients with moderate coronary artery stenosis who were managed with FFR guided approach in comparison to the CA/SPS guided approach. We searched databases – MEDLINE, PUBMED, EMBASE and the Cochrane central registry of controlled trials – with no language limitations. We used Key words — NSTEMI, FFR, coronary angiography, revascularization, PCI and CABG. A total of 3 RCTs have been identified by two reviewers after the independent electronic search. We included randomized controlled trials of NSTEMI patients who underwent FFR guided revascularization in comparison with standard of care, CA or SPS guided revascularization. Inclusion criteria for study selection include: the randomized control trials performed in NSTEMI patients with continuing ischemic symptoms and scheduled for CA, coronary artery stenosis of N30%, with an intervention of FFR in comparison to CA or SPS to guide the decision of revascularization. We excluded studies that are not randomized control trials, studies involving patients with stable CAD or STEMI, and studies that do not report long term follow-up outcomes. We did not restrict eligibility based on study outcomes.
Fig. 1. Fixed-effect meta-analysis for myocardial infarction. The figure presents number of events, number of patients in treatment and control groups, odds ratio (OR) and 95% confidence interval (CI) for each trial, overall OR estimate with 95% CI and P value for association test, P value for heterogeneity test, and between trial inconsistency (I2) measures.
⁎ Corresponding author. E-mail address: [email protected] (A. Briasoulis).
http://dx.doi.org/10.1016/j.ijcard.2015.03.325 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
A. Briasoulis et al. / International Journal of Cardiology 187 (2015) 334–337
335
Table 1 Baseline characteristics of randomized studies. Randomized Year studies
Sample size
Inclusion criteria
Exclusion criteria
Primary end points
Secondary end points
Mean follow-up period
The feasibility and safety of routine FFR measurement. The relationship between FFR and coronary stenosis severity by visual assessment of the angiogram. Major adverse cardiac events (MACE) defined as cardiac death or hospitalization for myocardial infarction or heart failure after randomization. Cardiovascular death, stroke, transient ischemic attack, contrast nephropathy, and bleeding were also prospectively recorded. Index hospitalization resource use including: material, procedure, hospitalization, and in-hospital event costs. Health-related quality of life.
12 months
Intervention Control (FFR guided (CA or SPS approach) guided approach)
FAMOUS– NSTEMI
2014 176
174
Patients with a clinical diagnosis of recent NSTEMI and with at least one risk factor for coronary artery disease and has planned invasive management within 72 h of the index episode of event or history of recurrent ischemic symptoms within 5 days of NSTEMI. At least one coronary stenosis ≥30% severity with normal coronary blood flow [Thrombolysis in Myocardial Infarction (TIMI) grade III] in which FFR measurement might have a diagnostic value.
Presence of ischemic symptoms that were not controlled by medical therapy, hemodynamic instability, MI with persistent ST elevation, intolerance to anti-platelet drugs, ineligible for coronary revascularization, a treatment plan for non-coronary heart surgery (e.g., valve surgery), a history of prior CABG, angiographic evidence of severe (e.g., diffuse calcification) or mild (30% severity) coronary disease, and a life expectancy of b1 year.
Between-group difference in the proportion of patients allocated to medical management.
FAME
2011 150
178
Left main disease, previous CABG, and ST-segment elevation myocardial infarction (STEMI) 5 days before.
Major adverse cardiac events (MACE) defined as composite of death from any cause, myocardial infarction (MI), any repeat revascularization and their individual components.
24 months
Leesar et al.
2002
Patients with multi vessel coronary artery disease undergoing PCI by stenting with drug-eluting stents, UA (whether or not with transient ST-segment changes) and NSTEMI with positive troponin but total creatine kinase of b1000 U/l. An episode of angina lasting
Incessant chest pain not responding to medical therapy; left main or multi-vessel coronary artery disease; prior coronary artery bypass grafting (CABG); vessels that were totally occluded or supplying an akinetic territory by visual assessment of the left ventricular angiogram.
Death, MI, CABG, PCI, and readmission because of UA.
13 months
35
35
N 20 min or recurrent episodes of angina at rest and had at least one of the following criteria: a new finding of ST-segment depression; transient (b20 min) ST-segment elevation; a new finding of T-wave inversion in at least two leads; elevated levels of cardiac markers; history of MI, including a Q-wave on the electrocardiogram or previous admission with a diagnosis of MI; and evidence of prior coronary artery disease or history of percutaneous coronary intervention (PCI).
The outcomes assessed include myocardial infarction (MI) – both fatal and non-fatal, death or all-cause mortality, major adverse cardiovascular events (MACE) – cardiac death or unplanned hospitalization for MI or heart failure, target vessel revascularization, and duration of index hospitalization. Target vessel revascularization was included only in two studies [10,11]. Cochrane's risk of bias tool has been utilized in order to assess the individual risk of bias of each study [12]. Data analysis was done in accordance with the Cochrane Collaboration and the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Meta-analyses were performed by using the Review Manager (RevMan) 5.1. Chi-square test of heterogeneity and I2 statistic of inconsistency were used to assess heterogeneity between studies. I2 values of 25%, 50%, and 75% indicate low, moderate, and high heterogeneity, respectively [13]. Pooled estimates of odd risks (ORs) with their 95% confidence intervals (CIs) were calculated using the Mantel– Haenszel method. Reported values are two-tailed, and hypothesistesting results were considered statistically significant at P b 0.05.
336
A. Briasoulis et al. / International Journal of Cardiology 187 (2015) 334–337
Table 2 Patient characteristics in each randomized trail. Demographics
Age, mean Male sex (n) Smoking history (n) Prior CAD (n) Hypertension (n) Diabetes mellitus (n) Hyperlipidemia (n)
FAMOUS–NSTEMI
FAME
Leesar et al.
FFR guided (n = 176)
CA guided (n = 174)
FFR guided (n = 150)
CA guided (n = 178)
FFR guided (n = 35)
SPS guided (n = 35)
62.3 133 127 22 78 26 71
61.6 127 118 22 81 26 56
65.6 110 43 66 90 33 101
64.2 116 55 78 122 38 129
59 24 20 9 25 13 19
55 22 15 14 26 11 22
The small study effect, including publication bias, was tested using funnel plot, the Begg's log-rank test and the Egger's test. Literature search of fractional flow reserve (FFR) and coronary arteries resulted in total of 463 studies. A total of 3 studies were finally included in the meta-analysis. Mean age of the study population was 61 years; 60 years in CA guided revascularization and 62 years in FFR guided revascularization. The baseline study characteristics are represented in Table 1. The patient characteristics in each trail are represented in Table 2. On the basis of quality assessment, two [9,11] were deemed to be at low risk of bias and the remaining study to be at low risk [10]. The incidence of MI during the follow up period was 6.6% in group of patients managed with FFR guided approach vs 10.4% in CA/SPS guided approach. FFR guided revascularization was associated with significant reduction in incidence of MI compared to CA guided revascularization (OR: 0.63, 95% CI: 0.37–1.07; P = 0.09; I2 = 0%). As the heterogeneity was low, fixed effects model was used to compute the statistics. Publication bias was assessed used Egger's and Begg's test (Fig. 1). The incidence of all-cause mortality was 2.5% in patients managed with FFR guided approach vs 2.8% in CA/SPS guided approach. There was no significant difference between two groups in case of all-cause mortality (OR: 0.9, 95% CI: 0.37–2.21; P = 0.82; I2 = 16%) without significant heterogeneity among trials (Fig. 2). The incidence of MACE was 14.1% in patients managed with FFR guided approach vs 17.6% in CA guided approach. No significant difference was found between two groups in case of all-cause mortality
(OR: 0.8, 95% CI: 0.52–1.23; P = 0.31; I2 = 0%) without significant heterogeneity among trials (Fig. 3). The percent of patients underwent target vessel revascularization were 11.9% in FFR guided approach and 12.2% in CA/SPS guided approach. There was no significant difference between two groups in total number of patients who underwent target vessel revascularization (OR: 0.99, 95% CI: 0.54–1.83; P = 0.98; I2 = 0%) without significant heterogeneity among trials (Fig. 4). The funnel plot did not show asymmetry consistent with publication bias, and the Egger's test was not significant for the outcomes studied. Our meta-analysis showed that FFR guided management of NSTEMI patients was associated with modest reduction in incidence of MI during the follow up period. There were no significant differences in incidence of MACE, death or all cause mortality, and target vessel revascularization between the FFR guided approach in comparison with CA or SPS guided approach. FFR has been extensively studied and validated in determining the functional significance of moderate coronary artery stenosis [14,15]. In patients with moderate coronary artery disease, FFR guided treatment showed decreased rate of revascularization and cardiovascular events compared to coronary angiographic assessment [16,17]. In case of NSTEMI patients with moderate stenos is of coronary arteries, the decision of revascularization is based on anatomical assessment of severity of CAD rather than functional assessment. We found decreased incidence of MI in case of FFR guided revascularization. FFR helps to determine the NSTEMI patients who require intervention and avoid
Fig. 2. Fixed-effect meta-analysis for all-cause mortality.
Fig. 3. Fixed-effect meta-analysis for MACE.
A. Briasoulis et al. / International Journal of Cardiology 187 (2015) 334–337
337
Fig. 4. Fixed-effect meta-analysis for target vessel revascularization.
the unnecessary intervention. FFR guided revascularization might help in more judicious use of stents and decreased health care costs. MACE and all cause mortality were not significantly different between FFR guided revascularization and CA guided revascularization. Based on limited data from randomized studies we conclude that FFR guided management of NSTEMI patients was associated with modest reduction in incidence of MI and no significant differences in incidence of MACE, death or all cause mortality, and target vessel revascularization. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] C.W. Hamm, et al., ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the Management of Acute Coronary Syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC), Eur. Heart J. 32 (23) (2011) 2999–3054. [2] C.W. White, et al., Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N. Engl. J. Med. 310 (13) (1984) 819–824. [3] C.J. Terkelsen, et al., Mortality rates in patients with ST-elevation vs. non-STelevation acute myocardial infarction: observations from an unselected cohort, Eur. Heart J. 26 (1) (2005) 18–26. [4] N.H. Pijls, et al., Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses, N. Engl. J. Med. 334 (26) (1996) 1703–1708.
[5] B. De Bruyne, et al., Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography, Circulation 89 (3) (1994) 1013–1022. [6] B. De Bruyne, et al., Fractional flow reserve in patients with prior myocardial infarction, Circulation 104 (2) (2001) 157–162. [7] E.J. Topol, S.E. Nissen, Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease, Circulation 92 (8) (1995) 2333–2342. [8] M.L. Marcus, et al., Visual estimates of percent diameter coronary stenosis: “a battered gold standard”, J. Am. Coll. Cardiol. 11 (4) (1988) 882–885. [9] J. Layland, et al., Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS–NSTEMI randomized trial, Eur. Heart J. 36 (2) (2015) 100–111. [10] M.A. Leesar, et al., Use of fractional flow reserve versus stress perfusion scintigraphy after unstable angina. Effect on duration of hospitalization, cost, procedural characteristics, and clinical outcome, J. Am. Coll. Cardiol. 41 (7) (2003) 1115–1121. [11] J.W. Sels, et al., Fractional flow reserve in unstable angina and non-ST-segment elevation myocardial infarction experience from the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study, JACC Cardiovasc. Interv. 4 (11) (2011) 1183–1189. [12] J.P. Higgins, et al., The Cochrane Collaboration's tool for assessing risk of bias in randomised trials, BMJ 343 (2011) d5928. [13] J.P. Higgins, et al., Measuring inconsistency in meta-analyses, BMJ 327 (7414) (2003) 557–560. [14] B. de Bruyne, et al., Simultaneous coronary pressure and flow velocity measurements in humans. Feasibility, reproducibility, and hemodynamic dependence of coronary flow velocity reserve, hyperemic flow versus pressure slope index, and fractional flow reserve, Circulation 94 (8) (1996) 1842–1849. [15] N.H. Pijls, et al., Fractional flow reserve. A useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow, Circulation 92 (11) (1995) 3183–3193. [16] P.A. Tonino, et al., Fractional flow reserve versus angiography for guiding percutaneous coronary intervention, N. Engl. J. Med. 360 (3) (2009) 213–224. [17] B. De Bruyne, et al., Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease, N. Engl. J. Med. 367 (11) (2012) 991–1001.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Fractional flow-guided management in patients with acute coronary syndromes: A systematic review and meta-analysis Alexandros Briasoulis ⁎, Mohan Palla, Ashraf Mostafa, Luis Afonso, Cindy Grines Wayne State University, Detroit Medical Center, Department of Cardiology, Detroit, IL 48226, USA
a r t i c l e
i n f o
Article history: Received 20 January 2015 Accepted 20 March 2015 Available online 21 March 2015 Keywords: Fractional flow reserve Non-ST-elevation myocardial infarction Meta-analysis
Dear Editor, In acute coronary syndrome (ACS) patients, the decision of revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) depends upon the severity of coronary artery disease (CAD) assessed by coronary angiography (CA) [1]. Treatment decisions made based on coronary artery stenosis measured by visual assessment of the lesion are tend to be incorrect leading to inappropriate coronary interventions [2,3]. This is most likely to occur in ACS patients presenting with non-ST segment elevation myocardial infarction (NSTEMI), who have unstable CAD. Fractional flow reserve (FFR) ≤ 0.75 was found to strongly correlate with the cardiac ischemia
diagnosed using noninvasive testing [4–6]. Severity of CAD assessed through CA was found to weakly correlate with FFR. Therefore, visual assessment of coronary artery stenosis cannot be used to predict the function of diseased coronary artery [2,7–9]. We intended to perform a systematic review and meta-analysis to explore the differences in outcomes of NSTEMI patients with moderate coronary artery stenosis who were managed with FFR guided approach in comparison to the CA/SPS guided approach. We searched databases – MEDLINE, PUBMED, EMBASE and the Cochrane central registry of controlled trials – with no language limitations. We used Key words — NSTEMI, FFR, coronary angiography, revascularization, PCI and CABG. A total of 3 RCTs have been identified by two reviewers after the independent electronic search. We included randomized controlled trials of NSTEMI patients who underwent FFR guided revascularization in comparison with standard of care, CA or SPS guided revascularization. Inclusion criteria for study selection include: the randomized control trials performed in NSTEMI patients with continuing ischemic symptoms and scheduled for CA, coronary artery stenosis of N30%, with an intervention of FFR in comparison to CA or SPS to guide the decision of revascularization. We excluded studies that are not randomized control trials, studies involving patients with stable CAD or STEMI, and studies that do not report long term follow-up outcomes. We did not restrict eligibility based on study outcomes.
Fig. 1. Fixed-effect meta-analysis for myocardial infarction. The figure presents number of events, number of patients in treatment and control groups, odds ratio (OR) and 95% confidence interval (CI) for each trial, overall OR estimate with 95% CI and P value for association test, P value for heterogeneity test, and between trial inconsistency (I2) measures.
⁎ Corresponding author. E-mail address: [email protected] (A. Briasoulis).
http://dx.doi.org/10.1016/j.ijcard.2015.03.325 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
A. Briasoulis et al. / International Journal of Cardiology 187 (2015) 334–337
335
Table 1 Baseline characteristics of randomized studies. Randomized Year studies
Sample size
Inclusion criteria
Exclusion criteria
Primary end points
Secondary end points
Mean follow-up period
The feasibility and safety of routine FFR measurement. The relationship between FFR and coronary stenosis severity by visual assessment of the angiogram. Major adverse cardiac events (MACE) defined as cardiac death or hospitalization for myocardial infarction or heart failure after randomization. Cardiovascular death, stroke, transient ischemic attack, contrast nephropathy, and bleeding were also prospectively recorded. Index hospitalization resource use including: material, procedure, hospitalization, and in-hospital event costs. Health-related quality of life.
12 months
Intervention Control (FFR guided (CA or SPS approach) guided approach)
FAMOUS– NSTEMI
2014 176
174
Patients with a clinical diagnosis of recent NSTEMI and with at least one risk factor for coronary artery disease and has planned invasive management within 72 h of the index episode of event or history of recurrent ischemic symptoms within 5 days of NSTEMI. At least one coronary stenosis ≥30% severity with normal coronary blood flow [Thrombolysis in Myocardial Infarction (TIMI) grade III] in which FFR measurement might have a diagnostic value.
Presence of ischemic symptoms that were not controlled by medical therapy, hemodynamic instability, MI with persistent ST elevation, intolerance to anti-platelet drugs, ineligible for coronary revascularization, a treatment plan for non-coronary heart surgery (e.g., valve surgery), a history of prior CABG, angiographic evidence of severe (e.g., diffuse calcification) or mild (30% severity) coronary disease, and a life expectancy of b1 year.
Between-group difference in the proportion of patients allocated to medical management.
FAME
2011 150
178
Left main disease, previous CABG, and ST-segment elevation myocardial infarction (STEMI) 5 days before.
Major adverse cardiac events (MACE) defined as composite of death from any cause, myocardial infarction (MI), any repeat revascularization and their individual components.
24 months
Leesar et al.
2002
Patients with multi vessel coronary artery disease undergoing PCI by stenting with drug-eluting stents, UA (whether or not with transient ST-segment changes) and NSTEMI with positive troponin but total creatine kinase of b1000 U/l. An episode of angina lasting
Incessant chest pain not responding to medical therapy; left main or multi-vessel coronary artery disease; prior coronary artery bypass grafting (CABG); vessels that were totally occluded or supplying an akinetic territory by visual assessment of the left ventricular angiogram.
Death, MI, CABG, PCI, and readmission because of UA.
13 months
35
35
N 20 min or recurrent episodes of angina at rest and had at least one of the following criteria: a new finding of ST-segment depression; transient (b20 min) ST-segment elevation; a new finding of T-wave inversion in at least two leads; elevated levels of cardiac markers; history of MI, including a Q-wave on the electrocardiogram or previous admission with a diagnosis of MI; and evidence of prior coronary artery disease or history of percutaneous coronary intervention (PCI).
The outcomes assessed include myocardial infarction (MI) – both fatal and non-fatal, death or all-cause mortality, major adverse cardiovascular events (MACE) – cardiac death or unplanned hospitalization for MI or heart failure, target vessel revascularization, and duration of index hospitalization. Target vessel revascularization was included only in two studies [10,11]. Cochrane's risk of bias tool has been utilized in order to assess the individual risk of bias of each study [12]. Data analysis was done in accordance with the Cochrane Collaboration and the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Meta-analyses were performed by using the Review Manager (RevMan) 5.1. Chi-square test of heterogeneity and I2 statistic of inconsistency were used to assess heterogeneity between studies. I2 values of 25%, 50%, and 75% indicate low, moderate, and high heterogeneity, respectively [13]. Pooled estimates of odd risks (ORs) with their 95% confidence intervals (CIs) were calculated using the Mantel– Haenszel method. Reported values are two-tailed, and hypothesistesting results were considered statistically significant at P b 0.05.
336
A. Briasoulis et al. / International Journal of Cardiology 187 (2015) 334–337
Table 2 Patient characteristics in each randomized trail. Demographics
Age, mean Male sex (n) Smoking history (n) Prior CAD (n) Hypertension (n) Diabetes mellitus (n) Hyperlipidemia (n)
FAMOUS–NSTEMI
FAME
Leesar et al.
FFR guided (n = 176)
CA guided (n = 174)
FFR guided (n = 150)
CA guided (n = 178)
FFR guided (n = 35)
SPS guided (n = 35)
62.3 133 127 22 78 26 71
61.6 127 118 22 81 26 56
65.6 110 43 66 90 33 101
64.2 116 55 78 122 38 129
59 24 20 9 25 13 19
55 22 15 14 26 11 22
The small study effect, including publication bias, was tested using funnel plot, the Begg's log-rank test and the Egger's test. Literature search of fractional flow reserve (FFR) and coronary arteries resulted in total of 463 studies. A total of 3 studies were finally included in the meta-analysis. Mean age of the study population was 61 years; 60 years in CA guided revascularization and 62 years in FFR guided revascularization. The baseline study characteristics are represented in Table 1. The patient characteristics in each trail are represented in Table 2. On the basis of quality assessment, two [9,11] were deemed to be at low risk of bias and the remaining study to be at low risk [10]. The incidence of MI during the follow up period was 6.6% in group of patients managed with FFR guided approach vs 10.4% in CA/SPS guided approach. FFR guided revascularization was associated with significant reduction in incidence of MI compared to CA guided revascularization (OR: 0.63, 95% CI: 0.37–1.07; P = 0.09; I2 = 0%). As the heterogeneity was low, fixed effects model was used to compute the statistics. Publication bias was assessed used Egger's and Begg's test (Fig. 1). The incidence of all-cause mortality was 2.5% in patients managed with FFR guided approach vs 2.8% in CA/SPS guided approach. There was no significant difference between two groups in case of all-cause mortality (OR: 0.9, 95% CI: 0.37–2.21; P = 0.82; I2 = 16%) without significant heterogeneity among trials (Fig. 2). The incidence of MACE was 14.1% in patients managed with FFR guided approach vs 17.6% in CA guided approach. No significant difference was found between two groups in case of all-cause mortality
(OR: 0.8, 95% CI: 0.52–1.23; P = 0.31; I2 = 0%) without significant heterogeneity among trials (Fig. 3). The percent of patients underwent target vessel revascularization were 11.9% in FFR guided approach and 12.2% in CA/SPS guided approach. There was no significant difference between two groups in total number of patients who underwent target vessel revascularization (OR: 0.99, 95% CI: 0.54–1.83; P = 0.98; I2 = 0%) without significant heterogeneity among trials (Fig. 4). The funnel plot did not show asymmetry consistent with publication bias, and the Egger's test was not significant for the outcomes studied. Our meta-analysis showed that FFR guided management of NSTEMI patients was associated with modest reduction in incidence of MI during the follow up period. There were no significant differences in incidence of MACE, death or all cause mortality, and target vessel revascularization between the FFR guided approach in comparison with CA or SPS guided approach. FFR has been extensively studied and validated in determining the functional significance of moderate coronary artery stenosis [14,15]. In patients with moderate coronary artery disease, FFR guided treatment showed decreased rate of revascularization and cardiovascular events compared to coronary angiographic assessment [16,17]. In case of NSTEMI patients with moderate stenos is of coronary arteries, the decision of revascularization is based on anatomical assessment of severity of CAD rather than functional assessment. We found decreased incidence of MI in case of FFR guided revascularization. FFR helps to determine the NSTEMI patients who require intervention and avoid
Fig. 2. Fixed-effect meta-analysis for all-cause mortality.
Fig. 3. Fixed-effect meta-analysis for MACE.
A. Briasoulis et al. / International Journal of Cardiology 187 (2015) 334–337
337
Fig. 4. Fixed-effect meta-analysis for target vessel revascularization.
the unnecessary intervention. FFR guided revascularization might help in more judicious use of stents and decreased health care costs. MACE and all cause mortality were not significantly different between FFR guided revascularization and CA guided revascularization. Based on limited data from randomized studies we conclude that FFR guided management of NSTEMI patients was associated with modest reduction in incidence of MI and no significant differences in incidence of MACE, death or all cause mortality, and target vessel revascularization. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] C.W. Hamm, et al., ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the Management of Acute Coronary Syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC), Eur. Heart J. 32 (23) (2011) 2999–3054. [2] C.W. White, et al., Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N. Engl. J. Med. 310 (13) (1984) 819–824. [3] C.J. Terkelsen, et al., Mortality rates in patients with ST-elevation vs. non-STelevation acute myocardial infarction: observations from an unselected cohort, Eur. Heart J. 26 (1) (2005) 18–26. [4] N.H. Pijls, et al., Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses, N. Engl. J. Med. 334 (26) (1996) 1703–1708.
[5] B. De Bruyne, et al., Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography, Circulation 89 (3) (1994) 1013–1022. [6] B. De Bruyne, et al., Fractional flow reserve in patients with prior myocardial infarction, Circulation 104 (2) (2001) 157–162. [7] E.J. Topol, S.E. Nissen, Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease, Circulation 92 (8) (1995) 2333–2342. [8] M.L. Marcus, et al., Visual estimates of percent diameter coronary stenosis: “a battered gold standard”, J. Am. Coll. Cardiol. 11 (4) (1988) 882–885. [9] J. Layland, et al., Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS–NSTEMI randomized trial, Eur. Heart J. 36 (2) (2015) 100–111. [10] M.A. Leesar, et al., Use of fractional flow reserve versus stress perfusion scintigraphy after unstable angina. Effect on duration of hospitalization, cost, procedural characteristics, and clinical outcome, J. Am. Coll. Cardiol. 41 (7) (2003) 1115–1121. [11] J.W. Sels, et al., Fractional flow reserve in unstable angina and non-ST-segment elevation myocardial infarction experience from the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study, JACC Cardiovasc. Interv. 4 (11) (2011) 1183–1189. [12] J.P. Higgins, et al., The Cochrane Collaboration's tool for assessing risk of bias in randomised trials, BMJ 343 (2011) d5928. [13] J.P. Higgins, et al., Measuring inconsistency in meta-analyses, BMJ 327 (7414) (2003) 557–560. [14] B. de Bruyne, et al., Simultaneous coronary pressure and flow velocity measurements in humans. Feasibility, reproducibility, and hemodynamic dependence of coronary flow velocity reserve, hyperemic flow versus pressure slope index, and fractional flow reserve, Circulation 94 (8) (1996) 1842–1849. [15] N.H. Pijls, et al., Fractional flow reserve. A useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow, Circulation 92 (11) (1995) 3183–3193. [16] P.A. Tonino, et al., Fractional flow reserve versus angiography for guiding percutaneous coronary intervention, N. Engl. J. Med. 360 (3) (2009) 213–224. [17] B. De Bruyne, et al., Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease, N. Engl. J. Med. 367 (11) (2012) 991–1001.
