Comparing the adverse clinical outcomes associated with fraction flow reserve-guided versus angiography-guided percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials
In this study, we aimed to compare the adverse clinical outcomes associated with FFR-guided versus standard angiography-guided PCI. Results of this study showed that FFR-guided PCI was not associated with a significantly lower rate of mortality or MACEs. The results for repeated revascularization were also not significantly different. However, FFR-guided PCI was associated with a significantly lower rate of re-infarction (MI).
Similar to the results of this current study, the DKCRUSH-VI trial which was a multi-centered randomized trial, also showed results which supported this current analysis [7]. Mortality and MACEs (18.1% in both groups) were similarly reported at one year follow up. The DEFER-DES trial also showed no difference in MACEs at five years follow up [6]. However, this current analysis showed a different result when MI was analyzed. In addition, the result for MI also varied during sensitivity analyses, especially when study FAME [5] was excluded from the analysis, showing that data from the study FAME could possibly have had an influence on the result analyzing MI in this current analysis.
Moreover, the meta-analysis published by Mallidi et al. which involved prospective cohort studies with a total number of 525 patients showed no significant difference in clinical outcomes between these two groups [11]. However, the main focus of that study was on patients with left main coronary artery disease. In addition, another systematic review and meta-analysis published by Xiu et al. supported the result of this current analysis and showed no difference in secondary outcomes including death, MACEs and MI reported between the FFR-guided and angiography guided PCI [12].
However, another meta-analysis, published by Zhang et al., which also involved a similar number of studies and patients to that of the above-mentioned study published by Xiu et al., showed FFR-guided PCI to be associated with a lower rate of MACEs, death, MI and repeated revascularization with a high level of heterogeneity reported among several subgroups analyzed, compared to the standard angiography-guided PCI [13]. This current study showed results which were completely different due to the fact that the meta-analysis by Zhang et al. involved data which were obtained only from observational studies whereas this current study involved mainly randomized patients.
Nevertheless, the study by Serafino et al. also showed FFR-guided PCI to be associated with a significantly lower rate of major adverse cardiovascular and cerebrovascular events which deviated completely from the results of this analysis [14]. However, their study also involved non-randomized patients who underwent coronary artery bypass surgery.
This current analysis has reported results which were completely different from the FAME study. Moreover, results obtained from the sensitivity analyses did not affect our results at all. Even after excluding the PERFORM study which was an observational study, thinking that it might have affected this current result, no significant change was observed. Also, including patients with bifurcation lesions which were thought to affect our result, did not show any significant change in the main results when trial DKCRUSH VI (consisting of the patients with bifurcation lesions) were excluded.
Recent studies have shown an increased application of FFR in clinical medicine. Several randomized trials and clinical guidelines in interventional cardiology support the implementation of FFR in daily clinical practice [15, 16]. FFR-guided interventions are practiced in conditions such as left intermediate stenosis, also as a guidance during coronary artery bypass surgery, for the evaluation of coronary arteries after stents implantation, and in acute coronary syndrome [3]. Certain centers have even shifted from ‘operator dependent’ to FFR-dependent’ in the evaluation of intermediate coronary artery obstruction in order to improve the prognosis in patients. In addition, invasive imaging for the assessment of the severity of the left main coronary artery demonstrated excellent correlation with FFR [17]. Therefore, it is high time to consider these facts and possibly include FFR among the decision-making tools in interventional cardiology among certain subgroups of patients.
However, there are conditions which might also restrict or limit the use of FFR. Conditions such as chronic kidney disease (CKD) might impair microcirculation and increase cardiovascular risk. The FREAK study recently showed that the index measurement obtained from FFR and microcirculatory resistance differed significantly between normal patients and those who suffered from CKD [18]. The study demonstrated that flow-limiting FFR was less frequent in patients who had a creatinine clearance of less or equal to 45 ml per minute. In addition, Hakeem et al. concluded that strict cautions should be taken when interpreting FFR values obtained from patients with stable coronary artery diseases for clinical decision making in patients with acute coronary syndrome [19].
Novelty
This study is new in several ways. First of all, it is among the first meta-analyses involving a large number of randomized patients obtained from recently published trials. Moreover, no observed heterogeneity was present among all the subgroups analyzed. Other meta-analyses reported a high level of heterogeneity among several subgroups analyzed. This current analysis showed a heterogeneity I2 with 0% in all the subgroups analyzed. Even when sensitivity analyses were conducted, almost all the subgroups showed consistent results. Since the assessment of heterogeneity is becoming more and more important in clinical practice, recently Cochrane reviews strictly started including the value of I2 in order to help readers assess the consistency of results obtained from the studies included in meta-analyses so that convincing and reliable results are produced with evidence. I2 also does not inherently depend on the number of studies included in a meta-analysis which further enhance its use even with a small sample size. This study might also be of interest to readers in the way that they can have an idea to what extent, FFR-guided PCI should be recommended. Moreover, the use of FFR to assess prognosis could also be taken into consideration.
Limitations
Similar to many other studies, this current study also has limitations. Due to the limited number of patients, this analysis might not provide robust results. The PLATFORM study which was included in this meta-analysis, was a prospective study that involved non-randomized patients. However, even if it did not include randomized patients, this PLATFORM study satisfied several features that were considered relevant to a randomized controlled trial. This might further contribute to the limitation in this study.