This randomized clinical trial compares 12-month event rates using quantitative coronary angiography guidance during percutaneous coronary intervention with those after intravascular ultrasonography–guided stent implantation.
Key Points
Question
Could systematic implementation of quantitative coronary angiography (QCA) to assist angiography-guided percutaneous coronary intervention (PCI) be an alternative to intravascular ultrasonography (IVUS)?
Findings
In this randomized clinical trial including 1528 patients with coronary artery stenosis undergoing PCI, rates of target lesion failure at 12 months were similarly low in both QCA- and IVUS-guided PCI groups. Guidance via QCA resulted in a similar post-PCI minimum lumen diameter as IVUS guidance.
Meaning
Findings of this study suggest that a standardized QCA-based PCI algorithm may be an acceptable alternative to IVUS-guided PCI, and warrants further research.
Abstract
Importance
Although intravascular ultrasonography (IVUS) guidance promotes favorable outcomes after percutaneous coronary intervention (PCI), many catheterization laboratories worldwide lack access.
Objective
To investigate whether systematic implementation of quantitative coronary angiography (QCA) to assist angiography-guided PCI could be an alternative strategy to IVUS guidance during stent implantation.
Design, Setting, and Participants
This randomized, open-label, noninferiority clinical trial enrolled adults (aged ≥18 years) with chronic or acute coronary syndrome and angiographically confirmed native coronary artery stenosis requiring PCI. Patients were enrolled in 6 cardiac centers in Korea from February 23, 2017, to August 23, 2021, and follow-up occurred through August 25, 2022. All principal analyses were performed according to the intention-to-treat principle.
Interventions
After successful guidewire crossing of the first target lesion, patients were randomized in a 1:1 ratio to receive either QCA- or IVUS-guided PCI.
Main Outcomes and Measures
The primary outcome was target lesion failure at 12 months, defined as a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. The trial was designed assuming an event rate of 8%, with the upper limit of the 1-sided 97.5% CI of the absolute difference in 12-month target lesion failure (QCA-guided PCI minus IVUS-guided PCI) to be less than 3.5 percentage points for noninferiority.
Results
The trial included 1528 patients who underwent PCI with QCA guidance (763; mean [SD] age, 64.1 [9.9] years; 574 males [75.2%]) or IVUS guidance (765; mean [SD] age, 64.6 [9.5] years; 622 males [81.3%]). The post-PCI mean (SD) minimum lumen diameter was similar between the QCA- and IVUS-guided PCI groups (2.57 [0.55] vs 2.60 [0.58] mm, P = .26). Target lesion failure at 12 months occurred in 29 of 763 patients (3.81%) in the QCA-guided PCI group and 29 of 765 patients (3.80%) in the IVUS-guided PCI group (absolute risk difference, 0.01 percentage points [95% CI, –1.91 to 1.93 percentage points]; hazard ratio, 1.00 [95% CI, 0.60-1.68]; P = .99). There was no difference in the rates of stent edge dissection (1.2% vs 0.7%, P = .25), coronary perforation (0.2% vs 0.4%, P = .41), or stent thrombosis (0.53% vs 0.66%, P = .74) between the QCA- and IVUS-guided PCI groups. The risk of the primary end point was consistent regardless of subgroup, with no significant interaction.
Conclusions and Relevance
Findings of this randomized clinical trial indicate that QCA and IVUS guidance during PCI showed similar rates of target lesion failure at 12 months. However, due to the lower-than-expected rates of target lesion failure in this trial, the findings should be interpreted with caution.
Trial Registration
ClinicalTrials.gov Identifier: NCT02978456
Introduction
Coronary angiography is the most frequently used technique for guiding stent implantation. However, angiography-guided percutaneous coronary intervention (PCI) relies on visual estimation, thereby suffering from subjectivity and often resulting in underestimation of vessel size and stent expansion.1,2,3,4 Intravascular ultrasonography (IVUS) can provide reliable qualitative and quantitative information regarding the vessel, lumen, plaque, and deployed stents. Considering the concept of stent optimization established by intracoronary imaging studies,5,6,7 2 large randomized clinical trials were conducted; compared with angiography-guided PCI, IVUS-guided PCI was associated with improved device-oriented outcomes in long coronary lesions and the all-comers population.8,9 Despite the evidence supporting the use of IVUS to improve post-PCI outcomes and proctoring programs on IVUS image interpretation,10,11 the method has not become a routine tool worldwide, with the estimated proportion of intravascular imaging use for PCI being approximately 20% in China, 1.8% in India, less than 10% in the US, 2% in Indonesia, and 12% in the UK.12,13 This is likely owing to inaccessibility related to reimbursement policies and high device cost.14 Thus, a way to improve stent outcomes during PCI in typical circumstances when IVUS is unavailable is needed.
Quantitative coronary angiography (QCA) is readily available at every catheterization laboratory and provides reliable and reproducible quantitative measures of coronary vessels. On the basis of available evidence examining the correlation between QCA and IVUS lumen diameters,15,16 we developed a size selection algorithm based on QCA measurements. Incorporating other essential technical considerations,17,18,19,20 we established a protocol regarding QCA-guided PCI. In this Quantitative Coronary Angiography vs Intravascular Ultrasound Guidance for Drug-Eluting Stent Implantation (GUIDE-DES) trial, we investigated whether this novel, on-site, QCA-guided PCI strategy is noninferior to the IVUS-guided PCI strategy in patients with significant coronary artery stenosis.
Methods
Trial Design and Oversight
This prospective, randomized, open-label, multicenter, noninferiority clinical trial was conducted at 6 cardiac centers in Korea (eAppendix in Supplement 2) between February 23, 2017, and August 23, 2021. Details regarding the trial design have been previously described.21 The protocol was approved by the institutional review boards of Asan Medical Center and each participating center. An independent data safety and monitoring board had full access to the trial data and monitored patient safety. A centralized clinical events committee, composed of interventional and noninterventional cardiologists who were masked to treatment allocations, adjudicated all clinical events. This trial followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.
Participants and Randomization
Patients aged 18 years or older with a clinical diagnosis of chronic or acute coronary syndrome and angiographically confirmed native coronary artery stenosis suitable for stent implantation were screened for trial eligibility. Target lesions were required to have 70% or greater diameter stenosis on visual estimation or 50% to 69% diameter stenosis with objective evidence of ischemia (positive noninvasive stress test or fractional flow reserve of ≤0.8). Major exclusion criteria were bypass graft lesions (for which the utility of QCA is less established) and lesions for which IVUS delivery is deemed impaired (eg, extreme angulation or tortuosity and heavy calcification proximal to or within the target lesion). Details regarding the inclusion and exclusion criteria are provided in the eMethods in Supplement 2.
Written informed consent was obtained before the PCI procedure from eligible patients. After confirmation of angiographic eligibility and successful guidewire crossing of the first target lesion, patients were centrally randomized in a 1:1 ratio to receive either QCA- or IVUS-guided PCI. Information regarding treatment assignment was available to treating investigators, patients, catheterization laboratory members, and follow-up staff. The allocation of the study participants was processed through an interactive web response system in a permutated block size of 6 without stratification. Patients were regarded as enrolled after determining eligibility and randomization. All lesions within the same individual that fulfilled the inclusion criteria were to be managed with the treatment to which the patient was randomized.
Procedures
In the QCA-guided PCI group, investigators and catheterization laboratory members in each participating site were educated and trained in person before enrollment of the first patient. In brief, after selecting the best angle for an image that corresponded to the lesion location with the least foreshortening, an angiogram of a vessel adequately filled with contrast medium after the administration of intracoronary nitroglycerin was acquired. Thereafter, using the automatic calibration software embedded in angiography systems, lumen diameters were measured at the optimal proximal and distal reference segments. The final target diameters for the reference segments were determined using a simple calculation table provided to each participating center (eMethods in Supplement 2). Stent size was then selected on the basis of the target diameter of the distal reference segment, and stent length was determined with the aid of a radiopaque guidewire tip (30 mm) for long lesions or an uninflated balloon (15 or 20 mm) for short lesions. Dilation after stenting using a properly sized noncompliant balloon was mandatory, with proximal and distal stent edges dilated up to the target diameters. The goal was to achieve residual diameter stenosis of less than 10% by visual estimation in the absence of angiographically detected dissection.22 The trial did not set a nonapplicable restriction of this QCA-based PCI algorithm according to lesion location (eg, main epicardial arteries, side branches), severity (eg, chronic total occlusions), or stenting techniques (eg, 2-stent technique).
In the IVUS-guided PCI group, stent size and length were determined using on-site IVUS measurements. Adjunctive balloon dilation was left to the operator’s discretion based on the IVUS findings. It was mandatory to perform IVUS after PCI to assess stent optimization. Stent optimization was defined as the achievement of an in-stent minimal lumen cross-sectional area larger than the distal reference segment’s lumen cross-sectional area, complete stent apposition, and no clinically significant proximal or distal edge dissection.5,8
Pharmacological treatments were optimized early after randomization under the established standards of practice.23,24 Biodegradable polymer sirolimus-eluting stents (Orsiro or Orsiro Mission; Biotronik) were exclusively used in both trial arms. Patients were followed up by clinic visits or telephone interviews at 1, 6, and 12 months after randomization.
Outcomes
The primary end point was target lesion failure, defined as a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization at 12 months. Secondary end points included 12-month rates of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, target lesion revascularization, and any revascularization. End points were assessed from the time of randomization to the day of the first occurrence of an end point event, the day of the last office or telephone visit, or the day of death. Detailed definitions of clinical events are provided in the eMethods in Supplement 2.
Statistical Analysis
This trial was designed to establish the noninferiority of QCA-guided PCI, compared with IVUS-guided PCI, for the primary end point of target lesion failure at 12 months. We assumed a 12-month rate of 8% for the primary end point events for each group according to 2 multicenter studies, allowing unrestricted use of contemporary drug-eluting stents.25,26 Randomization of 1528 patients was estimated to provide 80% power at a 1-sided type I error of 2.5% to show the noninferiority of QCA-guided PCI, with a noninferiority margin of 3.5% for the between-group differences in event rates and an assumed 5% attrition.
Data were collected and analyzed according to the predefined statistical analysis plan (Supplement 1). All principal analyses were done on an intention-to-treat basis. Sensitivity analyses were performed in the per-protocol population, which excluded patients for any inconsistency between the intended treatment plan and actual treatment, for failure of final IVUS evaluation in the IVUS-guided PCI group, and for stent deployment failure. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. Given the much lower-than-expected absolute event rate, noninferiority testing was not performed, and comparisons between randomized groups are presented as absolute risk differences in percentage points and hazard ratios (HRs) with 95% CIs. Hazard ratios with 95% CIs were estimated using the Cox proportional hazards model.
Baseline characteristics of the study patients are presented as means and SDs for continuous variables and as numbers and percentages for categorical variables. Patient-level intergroup differences were evaluated by Pearson χ2 test, Fisher exact test, or t test, as appropriate. Lesion-level intergroup differences were compared using a generalized estimating equation approach. Subgroup analysis of the primary end point was conducted according to the type of PCI strategy and patient age, sex, diabetes status, acute vs chronic coronary syndrome, and lesion and stent characteristics (eFigure 2 in Supplement 2). A 2-sided P < .05 indicated statistical significance. Data were analyzed using SAS, version 9.4 (SAS Institute Inc).
Results
Between February 23, 2017, and August 23, 2021, 1528 patients who underwent PCI were enrolled and randomly assigned to either the QCA-guided PCI group (n = 763; mean [SD] age, 64.1 [9.9] years; 574 males [75.2%] and 189 females [24.8%]) or the IVUS-guided PCI group (n = 765; mean [SD] age, 64.6 [9.5] years; 622 males [81.3%] and 143 females [18.7%]) (Figure 1). Approximately one-third of patients in both groups had diabetes mellitus, and 30% presented with acute coronary syndromes (Table 1). The proportion of patients with dual antiplatelet and statin therapy after PCI was high (approximately 99%) in both groups.
Figure 1. Flow Diagram of Patients in the GUIDE-DES Trial.
GUIDE-DES indicates Quantitative Coronary Angiography vs Intravascular Ultrasound Guidance for Drug-Eluting Stent Implantation; IVUS, intravascular ultrasonography; PCI, percutaneous coronary intervention; and QCA, quantitative coronary angiography.
aAll patients were randomized after successful guidewire crossing of the target lesion.
Table 1. Baseline Clinical Characteristics of Patients Undergoing QCA-Guided PCI or IVUS-Guided PCI.
| Characteristic | Mean (%) | |
|---|---|---|
| QCA-guided PCI (n = 763) | IVUS-guided PCI (n = 765) | |
| Age, mean (SD), y | 64.1 (9.9) | 64.6 (9.5) |
| Sex | ||
| Male | 574 (75.2) | 622 (81.3) |
| Female | 189 (24.8) | 143 (18.7) |
| BMI, mean (SD) | 24.8 (3.1) | 24.9 (2.7) |
| Risk factors | ||
| Current smoker | 203 (26.6) | 178 (23.3) |
| Diabetes mellitus | 257 (33.7) | 237 (31.0) |
| Dyslipidemia | 655 (85.8) | 649 (84.8) |
| Hypertension | 480 (62.9) | 488 (63.8) |
| Clinical presentation | ||
| CCS | 544 (71.3) | 538 (70.3) |
| NSTE-ACS | 166 (21.8) | 171 (22.4) |
| STEMI | 53 (6.9) | 56 (7.3) |
| Chronic kidney disease | 35 (4.6) | 40 (5.2) |
| Previous myocardial infarction | 47 (6.2) | 56 (7.3) |
| Previous stroke | 42 (5.5) | 44 (5.8) |
| Previous PCI | 117 (15.3) | 119 (15.6) |
| Previous bypass surgery | 7 (0.9) | 6 (0.8) |
| Medications at discharge | ||
| Aspirin | 758 (99.3) | 762 (99.6) |
| P2Y12 inhibitors | 756 (99.1) | 759 (99.2) |
| Statins | 749 (98.2) | 754 (98.6) |
| ARBs or ACEIs | 256 (33.6) | 285 (37.3) |
| β-Blockers | 290 (38.0) | 303 (39.6) |
| Calcium channel blockers | 458 (60.0) | 465 (60.8) |
Abbreviations: ACEIs, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CCS, chronic coronary syndrome; NSTE-ACS, non–ST-segment elevation acute coronary syndrome; IVUS, intravascular ultrasonography; PCI, percutaneous coronary intervention; QCA, quantitative coronary angiography; STEMI, ST-segment elevation myocardial infarction.
Table 2 describes the angiographic and procedural characteristics at index PCI. The mean (SD) number of lesions treated per patient was 1.2 (0.5), and 267 patients (17.5%) received multivessel stenting. Among 1825 treated lesions, the left anterior descending artery was the most commonly stented vessel (n = 856 [46.9%]). Overall, 1097 lesions (60.1%) were bifurcation lesions, of which 249 (13.6%) were true bifurcation lesions according to the Medina classification; 96 (5.3%) were chronic total occlusion lesions; 232 (12.7%) were lesions of the left main coronary artery; and 139 (7.6%) had moderate to severe calcification. Overall, the mean (SD) number of stents implanted was 1.6 (0.9) per patient, the mean (SD) stent diameter per lesion was 3.1 (0.4) mm, and the mean (SD) stent length per lesion was 37.0 (18.9) mm. During the procedure, IVUS was used in 7 patients in the QCA-guided PCI group to evaluate potential complications, whereas final IVUS evaluation could not be completed in 6 patients in the IVUS-guided PCI group. Adjunct balloon dilation after stent deployment was common in both groups, with maximal inflation pressure reaching up to 20 atm. Notably, in the IVUS-guided PCI group, the proportion of patients who met the IVUS criteria for stent optimization was 66.6% according to the core laboratory analysis (eTable 1 in Supplement 2). On postprocedural offline analysis, the proximal reference diameter was larger and the degree of diameter stenosis was higher in the IVUS-guided PCI group than in the QCA-guided PCI group. Accordingly, the maximum size of the balloon selected for post-dilation and the diameter of the proximal reference segment was larger in the IVUS-guided PCI group than in the QCA-guided PCI group. However, the balloon-to-vessel ratio was 1.1 in both groups, and other procedural characteristics were similar between the QCA- and IVUS-guided PCI groups, including the final minimum lumen diameter (mean [SD], 2.57 [0.55] vs 2.60 [0.58] mm; P = .26) and the minimum lumen diameter to reference vessel diameter ratio (mean [SD] 0.81 [0.09] vs 0.81 [0.10]; P = .79).
Table 2. Angiographic and Procedural Characteristics of Patients Undergoing QCA-Guided PCI or IVUS-Guided PCI.
| Characteristic | No. (%) | P value | |
|---|---|---|---|
| QCA-guided PCI (n = 763) | IVUS-guided PCI (n = 765) | ||
| Patients | |||
| Multivessel disease | 383 (50.2) | 381 (49.8) | .88 |
| SYNTAX score, mean (SD)a | 13.3 (8.4) | 13.0 (8.6) | .58 |
| Treated arteries | |||
| Left main coronary artery | 118 (12.8) | 114 (12.7) | .68 |
| Left anterior descending artery | 432 (46.7) | 424 (47.1) | |
| Left circumflex artery | 117 (12.7) | 118 (13.1) | |
| Right coronary artery | 258 (27.9) | 242 (26.9) | |
| Ramus intermedius | 0 | 2 (0.2) | |
| Treated lesions per patient, mean (SD) | 1.2 (0.5) | 1.2 (0.4) | .15 |
| Stents per patient, mean (SD) | 1.7 (0.9) | 1.6 (0.8) | .54 |
| Treated lesions | |||
| Adjunct post-dilatation | 900 (97.3) | 879 (97.7) | .73 |
| Maximum balloon size, mean (SD), mm | 3.5 (0.6) | 3.6 (0.6) | .003 |
| Maximum inflation pressure, mean (SD), atm | 19.9 (4.9) | 20.0 (4.7) | .75 |
| Overlapped stents | 272 (29.4) | 279 (31.0) | .46 |
| Stent edge dissection | 11 (1.2) | 6 (0.7) | .25 |
| Coronary perforation | 2 (0.2) | 4 (0.4) | .41 |
| Preintervention QCA | |||
| Reference vessel diameter, mean (SD), mm | |||
| Proximal | 3.58 (0.56) | 3.66 (0.56) | .009 |
| Distal | 2.66 (0.54) | 2.70 (0.54) | .19 |
| Lesion length, mean (SD), mm | 29.2 (16.6) | 30.5 (17.2) | .11 |
| Minimum lumen diameter, mean (SD), mm | 0.71 (0.47) | 0.63 (0.44) | <.001 |
| Diameter stenosis, mean (SD), % | 77.99 (13.62) | 80.32 (13.18) | <.001 |
| Postintervention QCA | |||
| Proximal reference vessel diameter, mean (SD), mm | 3.63 (0.55) | 3.72 (0.55) | .002 |
| Distal reference vessel diameter, mean (SD), mm | 2.71 (0.55) | 2.75 (0.57) | .11 |
| Total stented length, mean (SD), mm | 34.4 (16.9) | 35.8 (17.6) | .08 |
| Minimum lumen diameter, mean (SD), mm | 2.57 (0.55) | 2.60 (0.58) | .26 |
| Diameter stenosis, mean (SD), % | 12.87 (9.14) | 12.82 (9.47) | .91 |
Abbreviations: IVUS, intravascular ultrasonography; PCI, percutaneous coronary intervention; QCA, quantitative coronary angiography; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery.
The SYNTAX score assesses the complexity of coronary artery disease. Scores range from 0 to greater than 40, with higher scores suggesting more complex coronary artery disease.
At 12 months, 734 patients (96.2%) in the QCA-guided PCI group and 739 patients (96.6%) in the IVUS-guided PCI group completed clinical follow-up. The primary end point occurred in 29 patients (3.81%) in the QCA-guided PCI group and 29 patients (3.80%) in the IVUS-guided PCI group (absolute risk difference, 0.01 percentage points [95% CI, –1.91 to 1.93 percentage points]; HR, 1.00 [95% CI, 0.60-1.68]; P = .99) (Figure 2). The incidence of the primary end point was thus lower than the assumed 8% event rate. A per-protocol analysis, including 754 patients from the QCA-guided PCI group and 757 patients from the IVUS-guided PCI group, yielded similar results for the primary end point (absolute risk difference, −0.12 percentage points [95% CI, –2.01 to 1.77 percentage points]; HR, 0.97 [95% CI, 0.57-1.64]; P = .91) (eTable 2 in Supplement 2). Secondary clinical events were infrequent and similar in both groups (Table 3; eFigure 1 in Supplement 2). Nine cases of definite or probable stent thrombosis occurred, of which 4 cases occurred in the subacute phase (>24 hours to 30 days after PCI) and 5 in the later phase. The rate of minor or major bleeding, assessed by the Thrombolysis in Myocardial Infarction bleeding criteria,27 was not significantly different between the 2 groups (2.24% in the QCA-guided PCI group vs 2.34% in the IVUS-guided PCI group; HR, 0.95 [95% CI, 0.49-1.83]; P = .87). In post hoc subgroup analyses, the risk of the primary end point was consistent regardless of the subgroup, with no significant interactions (eFigure 2 in Supplement 2).
Figure 2. Cumulative Incidence of Target Lesion Failure After Quantitative Coronary Angiography (QCA)–Guided and Intravascular Ultrasonography (IVUS)–Guided Percutaneous Coronary Intervention (PCI).
Table 3. Clinical Outcomes at 12 Months in the QCA-Guided PCI or IVUS-Guided PCI Groups.
| Outcome | No. (%) | Difference in event rates, percentage points (95% CI) | P value | |
|---|---|---|---|---|
| QCA-guided PCI (n = 763) | IVUS-guided PCI (n = 765) | |||
| Primary end point | ||||
| Target lesion failurea | 29 (3.81) | 29 (3.80) | 0.01 (−1.91 to 1.93) | .99 |
| Secondary end points | ||||
| Death | 7 (0.92) | 6 (0.79) | 0.13 (−0.79 to 1.06) | .78 |
| Cardiac | 2 (0.27) | 2 (0.26) | 0.00 (−0.51 to 0.52) | >.99 |
| Noncardiac | 5 (0.66) | 4 (0.53) | 0.13 (−0.64 to 0.91) | .73 |
| Myocardial infarction | 26 (3.41) | 25 (3.27) | 0.14 (−1.66 to 1.94) | .88 |
| Target vessel | 25 (3.28) | 24 (3.14) | 0.14 (−1.63 to 1.91) | .88 |
| Procedural | 21 (2.75) | 18 (2.35) | 0.40 (−1.18 to 1.98) | .62 |
| Nonprocedural | 4 (0.53) | 6 (0.79) | −0.26 (−1.08 to 0.55) | .53 |
| Nontarget vessel | 1 (0.13) | 1 (0.13) | 0.00 (−0.36 to 0.37) | >.99 |
| Any revascularization | 10 (1.33) | 18 (2.37) | −1.05 (−2.40 to 0.31) | .13 |
| Target vessel | 4 (0.53) | 7 (0.92) | −0.40 (−1.25 to 0.46) | .37 |
| Target lesion | 4 (0.53) | 6 (0.79) | −0.26 (−1.08 to 0.55) | .53 |
| Nontarget lesion | 0 | 1 (0.13) | −0.13 (−0.39 to 0.13) | .32 |
| Nontarget vessel | 7 (0.93) | 13 (1.72) | −0.79 (−1.94 to 0.36) | .19 |
| Stroke | 6 (0.79) | 6 (0.79) | 0.00 (−0.89 to 0.90) | >.99 |
| Stent thrombosis | 4 (0.53) | 5 (0.66) | −0.13 (−0.90 to 0.64) | .74 |
| Minor or major bleeding | 17 (2.24) | 18 (2.34) | −0.12 (−1.63 to 1.39) | .87 |
Abbreviations: IVUS, intravascular ultrasonography; PCI, percutaneous coronary intervention; QCA, quantitative coronary angiography.
Defined as the composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization.
Discussion
To our knowledge, the GUIDE-DES trial is the first trial to assess the feasibility and efficacy of a protocolized angiography-guided PCI strategy incorporating simple real-time QCA measures. Although the overall event rates were much lower than expected among these patients who underwent stent implantation (3.8% vs an expected 8%), QCA-guided PCI compared with IVUS guidance showed similar results regarding the primary composite end point of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization at 12 months. Results were consistent between the intention-to-treat and per-protocol populations, and no safety concerns were raised for QCA-guided PCI.
Accomplishing complete stent apposition and an appropriate stent area, which are impossible to assess solely by angiography, are the desired PCI results5,6,7 most commonly evaluated by IVUS in clinical practice. Two adequately powered clinical trials have shown the benefit and legacy effect of IVUS-guided stent implantation over angiography guidance on clinical outcomes.28,29 These data support that the key mechanism behind these findings was not only the higher frequency of post-dilatation in the IVUS-guided group, but also that IVUS permits the selection of an adequately sized stent and postdilation balloon to maximize the final stent area.30 Ironically, these studies highlight the downside of the comparator—angiography-guided PCI—which remains the current de facto standard of care worldwide. Angiography-based PCI requires visual estimation by the operators during every step of the procedure, potentially leading to an undersized stent or balloon and suboptimal results. Therefore, practical and standardized angiography guidance to overcome the drawback of visual estimation is needed.
In this trial, we incorporated QCA into the clinical context and used a target size selection algorithm based on the real-time QCA measurements of proximal and distal reference segments. Using a relatively objective QCA, we sought to minimize the operators’ dependency and interindividual variability on the initial determination of the reference vessel size. By subsequently adjusting this size 5% to 10% with the sizing algorithm, we aimed to determine a standardized reference to upsize the target diameter for stent and postdilation balloon selection, further offsetting the operators’ erroneous decisions during this step. Finally, sequential in-stent post-dilation up to the pressure that reached at least the settled target diameter was mandatory to ensure stent apposition and expansion.17,20,31 These unique features of QCA-guided PCI in our trial address the lingering issue of lack of standardization and reproducibility of the conventional angiography-guided PCI process.1,2
Accordingly, several distinct procedural aspects in our trial should be taken into consideration. Although the proximal reference diameter of the target lesions tended to be smaller in the QCA-guided PCI group than in the IVUS-guided PCI group, the postdilatation balloon pressure was applied up to the size that accommodated the target diameter, resulting in a QCA-assessed balloon-to-vessel ratio of 1.1, similar to that of the IVUS-guided PCI group. Ultimately, post-PCI minimum lumen diameter (2.57 vs 2.60 mm) and the minimum lumen diameter to reference vessel diameter ratio (0.81 vs 0.81) with QCA guidance approximated those with IVUS guidance. These results contrast with those of the IVUS-XPL (Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions) and ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions) trials,8,9 wherein the post-PCI minimum lumen diameter was substantially smaller with angiography guidance than with IVUS guidance. Considering that a smaller minimum lumen diameter is the major contributing factor for post-PCI adverse cardiac events,31 a standardized QCA-based strategy may have offset the benefit of IVUS guidance in our trial.
The benefit of IVUS guidance also largely depends on the interpretation of the acquired images and operators’ reactions to them. Stent underexpansion is a major factor in stent failure, and several absolute and relative expansion targets have been proposed for final stent results with IVUS.6,7,32 A minimum stent cross-sectional area of greater than 5.5 mm2 is commonly recommended for non–left main artery lesions; however, a relative criterion would be more relevant in small vessels or complex long lesions. In the IVUS-XPL trial, in which the prespecified expansion criterion was a final minimum stent cross-sectional area greater than the distal reference lumen area, patients who met the IVUS criteria for stent optimization had a low adverse event rate (4.0% at 5 years).28 In a pooled analysis of the IVUS-guided PCI populations from the IVUS-XPL and ULTIMATE trials, achievement of several stent expansion cutoffs was associated with approximately 70% decreased risk of 3-year outcomes of cardiac death, target lesion–related myocardial infarction, or stent thrombosis compared with their counterparts.33 Notwithstanding the benefit of achieving optimization end points, the proportion of procedures that meet the prespecified expansion target has been reported to be 40% to 70%, which is in line with the 66.6% optimization rate in our IVUS-guided PCI group.5,33 Because there seems to be substantial heterogeneity regarding the immediate stenting results and subsequent outcomes with IVUS guidance, developing a practical guide on appropriate lesion preparation based on pre-PCI imaging, selection of the best stent or balloon size and length, criteria to complete the procedure depending on the vessel characteristics, and differential medical therapy according to the final stent result should be subjects of future investigation.
Limitations
This trial has limitations. First, the degrees of adjusting measured QCA to the target diameter that we used cannot be regarded as optimal. We set a uniform 10% adjustment for QCA values of 3.5 mm or less and 5% to 9% for values greater than 3.5 mm, decremental to higher QCA values. The consensus of these cutoffs was derived on the basis of existing evidence of the correlation between lumen diameters determined by QCA and IVUS, experience and advice from IVUS specialists, and consideration of the safety of implementing a systematic QCA-guided procedure. Despite our comprehensive and prudent approach, these adjustment percentages cannot be claimed to be definitive, and future studies are necessary for refinement. Second, severely calcified and angulated lesions were likely to be excluded by the study protocol. Particular lesion subsets, such as chronic total occlusions and left main disease, were represented less frequently; thus, the results may not apply to complex lesions that require advanced PCI techniques. Third, the incidence of the primary end point was much lower than assumed, affecting the robustness of the comparative results. The expected event rate was based on the all-comers PCI studies,25,26 which were considered when our trial was designed; however, the actual rate was in line with recent trials8,9 that exclusively used IVUS. Apart from the use of IVUS and potentially including less complex lesions in our trial, additional factors, such as the exclusive use of the ultrathin strut stent, frequent use of antiplatelet and statin therapy, and relatively high IVUS optimization rate (67% vs 54% in the IVUS-XPL trial and 53% in the ULTIMATE trial), could have lowered the event rates we found. Fourth, our trial lacked a third conventional angiography-guided PCI arm or a blinded post-PCI IVUS examination in the QCA guidance group; thus, precise mechanisms underlying the findings remain elusive. Comparison with a conventional angiography-guided PCI arm would have provided clearer insights into the practical role of QCA-guided PCI. Fifth, the PCI operators were aware of the group assignments, potentially introducing procedural bias. Since QCA guidance was a new approach, physicians may have been unintentionally biased toward greater attentiveness and carefulness on encountering QCA-guided PCI. However, enticing operators into reacting in a positive way could be regarded as an inherent effect of QCA guidance. Finally, we verified that follow-up procedures were minimally affected by the COVID-19 pandemic during patient enrollment. However, because patients were not blinded to treatment allocation, a potential ascertainment bias that may have been introduced from patients cannot be excluded.
Conclusions
In the GUIDE-DES randomized clinical trial, PCI with QCA and IVUS guidance showed similar rates of the composite end point of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization at 12 months after PCI. However, the study was limited by lower-than-expected rates of the primary end point. The role of QCA-guided PCI should be further determined by meticulously designed clinical trials.
Trial Protocol
eAppendix. Participating Sites and Committees
eMethods. Supplementary Methods
eTable 1. Core Laboratory IVUS Analysis of Target Lesions
eTable 2. Per-Protocol Analysis of Clinical Outcomes at 12 Months
eFigure 1. Kaplan-Meier Graphs of Hazard Ratios for Cardiac Death, Myocardial Infarction, Target Lesion Revascularization, and Stent Thrombosis in the QCA-Guided PCI Group, Compared With the IVUS-Guided PCI Group
eFigure 2. Subgroup Analyses for Target Lesion Failure at 12 Months in the QCA-Guided PCI and IVUS-Guided PCI Groups
Nonauthor Collaborators
Data Sharing Statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Trial Protocol
eAppendix. Participating Sites and Committees
eMethods. Supplementary Methods
eTable 1. Core Laboratory IVUS Analysis of Target Lesions
eTable 2. Per-Protocol Analysis of Clinical Outcomes at 12 Months
eFigure 1. Kaplan-Meier Graphs of Hazard Ratios for Cardiac Death, Myocardial Infarction, Target Lesion Revascularization, and Stent Thrombosis in the QCA-Guided PCI Group, Compared With the IVUS-Guided PCI Group
eFigure 2. Subgroup Analyses for Target Lesion Failure at 12 Months in the QCA-Guided PCI and IVUS-Guided PCI Groups
Nonauthor Collaborators
Data Sharing Statement
