Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 15, Number 3, June 2024, pages 153-168

Comparative Efficacy of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in the Treatment of Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Recent Randomized Controlled Trials

Figure 5. Forest plot for incidence of stroke in PCI vs. CABG [22, 23, 25, 29, 32]. CABG: coronary artery bypass grafting; PCI: percutaneous coronary intervention.

**Table 1.** Inclusion and Exclusion Criteria
Criteria	Inclusion	Exclusion
CABG: coronary artery bypass grafting; IHD: ischemic heart disease; PCI: percutaneous coronary intervention.
Language	English, Russian	All other languages
Publication timeframe	2019 - 2024	Older
Type of studies	Randomized controlled trials	Perspective, case study, reviews, grey literature
Region	All	No exclusion
Target population	Patients with IHD suffering from triple-vessel coronary artery disease and left main coronary artery occlusion	Patients with low SYNTAX scores
Context	Evaluation of the efficacy of cardiovascular interventions: PCI and CABG	Other surgical or non-surgical interventions

Table 1. Inclusion and Exclusion Criteria

Criteria

Inclusion

Exclusion

CABG: coronary artery bypass grafting; IHD: ischemic heart disease; PCI: percutaneous coronary intervention.

Language

English, Russian

All other languages

Publication timeframe

2019 - 2024

Older

Type of studies

Randomized controlled trials

Perspective, case study, reviews, grey literature

Region

All

No exclusion

Target population

Patients with IHD suffering from triple-vessel coronary artery disease and left main coronary artery occlusion

Patients with low SYNTAX scores

Context

Evaluation of the efficacy of cardiovascular interventions: PCI and CABG

Other surgical or non-surgical interventions

**Table 2.** Systematic Review Findings
No.	Study	Location	Study design	Participants	Intervention	Key findings
CABG: coronary artery bypass grafting; CI: confidence interval; FFR: fractional flow reserve; GKR: gamma knife radiosurgery; HCR: hybrid coronary revascularization; HR: hazard ratio; MCCEs: major cardiac and cerebrovascular events; MV-PCI: multivessel percutaneous coronary intervention; RR: repeat revascularization; SPECT: single-photon emission computed tomography; SVG: saphenous vein graft; TOs: total occlusions.
1	Stone et al (2019) [22]	New England	Randomized controlled trial	A total of 1,905 patients with left main coronary artery disease were randomly assigned to PCI (948 patients) or CABG (957 patients).	The SYNTAX score was used as an eligibility parameter based on CAD for patients with a score of 32 or less. Patients were eligible to participate in the trial if they had greater than 70% stenosis of the left main coronary artery.	After PCI compared to CABG, ischemia-driven revascularization was more common (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI: 3.7 - 10.0). Regarding the composite outcome of mortality, stroke, or myocardial infarction, there was no statistically significant difference observed between PCI and CABG in individuals with left main coronary artery disease.
2	Thuijs et al (2019) [23]	Germany	Randomized controlled trial	A total of 1,800 patients were randomly assigned to either the PCI (n = 903) or CABG (n = 897) group in a randomized controlled trial conducted in 85 hospitals across 18 North American and European countries.	Over 10 years, patients with de novo three-vessel disease and left main coronary artery disease were randomly assigned in a 1:1 fashion to either the PCI or CABG group.	At the 10-year follow-up, no significant difference in mortality rates was observed between PCI and CABG for patients with left main coronary artery disease. However, significantly lower mortality was found in cases of three-vessel coronary artery disease treated with CABG. Among patients with three-vessel disease, 28% had died after PCI compared to 21% after CABG (HR 1.41 (95% CI: 1.10 - 1.80)). For patients with left main coronary artery disease, 26% had died after PCI, versus 28% after CABG (HR 0.90 (95% CI: 0.68 - 1.20), P-interaction = 0.019).
3	Holm et al (2020) [24]	England	Randomized controlled trial	A total of 1,184 patients, with 592 patients in each group, were included in this analysis.	The NOBLE trial enrolled patients with left main coronary artery disease requiring revascularization and randomized them in a 1:1 ratio to receive either PCI or CABG. The trial was specifically designed to evaluate the comparative effectiveness of these two interventions over 5 years.	All-cause mortality was estimated at 9% after PCI versus 9% after CABG (HR 1.08 (95% CI: 0.74 - 1.59); P = 0.68); non-procedural myocardial infarction was estimated at 8% after PCI versus 3% after CABG (HR 2.99 (95% CI: 1.66 - 5.39); P = 0.0002); and RR was estimated at 17% after PCI versus 10% after CABG (HR 1.73 (95% CI: 1.25 - 2.40); P = 0.0009).
4	Fearon et al (2022) [25]	Belgium, Hungary, Netherlands	Randomized controllded trial	Of the 1,500 patients enrolled, 757 were randomly assigned to undergo PCI and 743 to undergo CABG at multiple centers.	Endpoints were investigated for 1 year. The major inclusion criterion was the presence of three-vessel coronary artery disease, defined as at least 50% diameter stenosis as assessed by visual estimation in each of the three major epicardial vessels.	The incidence of the composite primary endpoint (MCCEs) was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (HR 1.5; 95% CI: 1.1 to 2.2) (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (HR 1.4; 95% CI: 0.9 - 2.1).
5	Wang et al (2023) [26]	Netherlands, Germany	Randomized controlled trial	A total of 1,800 patients were enrolled, with 903 randomly assigned to PCI and 897 assigned to CABG.	Patients with triple-vessel coronary artery disease were included.	Among patients requiring RR, those who underwent PCI as initial revascularization had a higher risk of 10-year mortality compared to those who underwent initial CABG (33.5% vs. 17.6%, adjusted HR: 2.09, 95% CI 1.21 - 3.61, P = 0.008). RRs were recorded at 5 years.
6	Kawashima et al (2021) [27]	USA	Randomized controlled trial	Of the 1,500 patients enrolled, 757 were randomly assigned to undergo PCI and 743 to undergo CABG at multiple centers.	By the protocol design of the SYNTAX trial, patients with acute myocardial infarction were excluded, and patients with TOs were included under the inclusion criteria.	The status of TO revascularization among the treatment groups was as follows: in the PCI group, 29.9% vs. 29.4%; adjusted HR: 0.992; 95% CI: 0.474 - 2.075; P = 0.982; and in the CABG arm, 28.0% vs. 21.4%; adjusted HR: 0.656; 95% CI: 0.281 - 1.533; P = 0.330.
7	Giustino et al (2018) [28]	USA	Randomized controlled trial	A total of 1,905 patients were randomly assigned, with 948 to PCI and 957 to CABG.	All patients were required to have low or intermediate anatomic complexity of coronary artery disease, as defined by a site-determined SYNTAX score of 32 or less. At the time of the present analysis, all patients had completed 3 years of follow-up.	During the 3-year follow-up, there were 346 RR procedures among 185 patients. PCI was associated with higher rates of any RR (12.9% vs. 7.6%; HR: 1.73; 95% CI: 1.28 - 2.33; P = 0.0003).
8	Ganyukov et al (2023) [29]	Kemerovo	Randomized controlled trial	The study included 155 consecutive patients with multivessel coronary artery disease, of whom 53 underwent PCI and 53 underwent CABG.	The primary endpoint of the study was residual ischemia 12 months after revascularization, as determined by data from SPECT.	Statistically significant differences were observed between the CABG and PCI groups in the incidence of myocardial infarction (12.8% and 16.3%; P = 0.12), stroke (4.2% and 10.2%; P = 0.13), and RR (23.4% and 34.7%; P = 0.11).
9	De Winter et al (2023) [30]	Amsterdam, USA	Randomized controlled trial	A total of 584 participants will be randomly assigned in a 1:1 ratio to either a strategy of native coronary artery PCI or SVG PCI, with 292 patients in each group.	Clinical indication for revascularization, as determined by the local Heart Team, was based on symptoms, documented ischemia, and viability.	A 3-year MACE rate of 47% was observed after bypass graft PCI, whereas the event rate for native vessel PCI in these patients was 33%.
10	Ganyukov et al (2020) [32]	Russia	Randomized controlled trial	A total of 155 consecutive patients were randomized to CABG (n = 50), HCR (n = 52), or MV-PCI (n = 53).	The mean age was 62 ± 7 years, and the majority of participants were men (71.6%). The mean follow-up duration was 52.5 months, with a minimum of 36 months.	The occurrence of the study endpoints at 3 years was available for 98% and 94.3% of the included patients for CABG and PCI, respectively.
11	Ganyukov et al (2021) [31]	Russia	Randomized controlled trial	A total of 155 patients with multivessel coronary artery disease were randomized into three groups: CABG (50 patients), HCR (52 patients), and MV-PCI (53 patients).	The primary endpoint was residual ischemia at 12 ± 1 months as determined by SPECT. Approximately one-half of the study patients had 2-vessel disease (50.3%), while the other half had ≥ 3 vessel CAD (49.7%).	Statistically significant differences in the incidence of myocardial infarction between the groups of CABG, GKR, and PCI (12.8%, 8.5%, and 16.3%; P = 0.12), stroke (4.2%, 6.4%, and 10.2%; P = 0.13), and RR according to clinical indications (23.4%, 23.4%, and 34.7%; P = 0.11) were also not observed.

Table 2. Systematic Review Findings

No.

Study

Location

Study design

Participants

Intervention

Key findings

CABG: coronary artery bypass grafting; CI: confidence interval; FFR: fractional flow reserve; GKR: gamma knife radiosurgery; HCR: hybrid coronary revascularization; HR: hazard ratio; MCCEs: major cardiac and cerebrovascular events; MV-PCI: multivessel percutaneous coronary intervention; RR: repeat revascularization; SPECT: single-photon emission computed tomography; SVG: saphenous vein graft; TOs: total occlusions.

Stone et al (2019) [22]

New England

Randomized controlled trial

A total of 1,905 patients with left main coronary artery disease were randomly assigned to PCI (948 patients) or CABG (957 patients).

The SYNTAX score was used as an eligibility parameter based on CAD for patients with a score of 32 or less. Patients were eligible to participate in the trial if they had greater than 70% stenosis of the left main coronary artery.

After PCI compared to CABG, ischemia-driven revascularization was more common (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI: 3.7 - 10.0). Regarding the composite outcome of mortality, stroke, or myocardial infarction, there was no statistically significant difference observed between PCI and CABG in individuals with left main coronary artery disease.

Thuijs et al (2019) [23]

Germany

Randomized controlled trial

A total of 1,800 patients were randomly assigned to either the PCI (n = 903) or CABG (n = 897) group in a randomized controlled trial conducted in 85 hospitals across 18 North American and European countries.

Over 10 years, patients with de novo three-vessel disease and left main coronary artery disease were randomly assigned in a 1:1 fashion to either the PCI or CABG group.

At the 10-year follow-up, no significant difference in mortality rates was observed between PCI and CABG for patients with left main coronary artery disease. However, significantly lower mortality was found in cases of three-vessel coronary artery disease treated with CABG. Among patients with three-vessel disease, 28% had died after PCI compared to 21% after CABG (HR 1.41 (95% CI: 1.10 - 1.80)). For patients with left main coronary artery disease, 26% had died after PCI, versus 28% after CABG (HR 0.90 (95% CI: 0.68 - 1.20), P-interaction = 0.019).

Holm et al (2020) [24]

England

Randomized controlled trial

A total of 1,184 patients, with 592 patients in each group, were included in this analysis.

The NOBLE trial enrolled patients with left main coronary artery disease requiring revascularization and randomized them in a 1:1 ratio to receive either PCI or CABG. The trial was specifically designed to evaluate the comparative effectiveness of these two interventions over 5 years.

All-cause mortality was estimated at 9% after PCI versus 9% after CABG (HR 1.08 (95% CI: 0.74 - 1.59); P = 0.68); non-procedural myocardial infarction was estimated at 8% after PCI versus 3% after CABG (HR 2.99 (95% CI: 1.66 - 5.39); P = 0.0002); and RR was estimated at 17% after PCI versus 10% after CABG (HR 1.73 (95% CI: 1.25 - 2.40); P = 0.0009).

Fearon et al (2022) [25]

Belgium, Hungary, Netherlands

Randomized controllded trial

Of the 1,500 patients enrolled, 757 were randomly assigned to undergo PCI and 743 to undergo CABG at multiple centers.

Endpoints were investigated for 1 year. The major inclusion criterion was the presence of three-vessel coronary artery disease, defined as at least 50% diameter stenosis as assessed by visual estimation in each of the three major epicardial vessels.

The incidence of the composite primary endpoint (MCCEs) was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (HR 1.5; 95% CI: 1.1 to 2.2) (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (HR 1.4; 95% CI: 0.9 - 2.1).

Wang et al (2023) [26]

Netherlands, Germany

Randomized controlled trial

A total of 1,800 patients were enrolled, with 903 randomly assigned to PCI and 897 assigned to CABG.

Patients with triple-vessel coronary artery disease were included.

Among patients requiring RR, those who underwent PCI as initial revascularization had a higher risk of 10-year mortality compared to those who underwent initial CABG (33.5% vs. 17.6%, adjusted HR: 2.09, 95% CI 1.21 - 3.61, P = 0.008). RRs were recorded at 5 years.

Kawashima et al (2021)
[27]

USA

Randomized controlled trial

Of the 1,500 patients enrolled, 757 were randomly assigned to undergo PCI and 743 to undergo CABG at multiple centers.

By the protocol design of the SYNTAX trial, patients with acute myocardial infarction were excluded, and patients with TOs were included under the inclusion criteria.

The status of TO revascularization among the treatment groups was as follows: in the PCI group, 29.9% vs. 29.4%; adjusted HR: 0.992; 95% CI: 0.474 - 2.075; P = 0.982; and in the CABG arm, 28.0% vs. 21.4%; adjusted HR: 0.656; 95% CI: 0.281 - 1.533; P = 0.330.

Giustino et al (2018)
[28]

USA

Randomized controlled trial

A total of 1,905 patients were randomly assigned, with 948 to PCI and 957 to CABG.

All patients were required to have low or intermediate anatomic complexity of coronary artery disease, as defined by a site-determined SYNTAX score of 32 or less. At the time of the present analysis, all patients had completed 3 years of follow-up.

During the 3-year follow-up, there were 346 RR procedures among 185 patients. PCI was associated with higher rates of any RR (12.9% vs. 7.6%; HR: 1.73; 95% CI: 1.28 - 2.33; P = 0.0003).

Ganyukov et al (2023)
[29]

Kemerovo

Randomized controlled trial

The study included 155 consecutive patients with multivessel coronary artery disease, of whom 53 underwent PCI and 53 underwent CABG.

The primary endpoint of the study was residual ischemia 12 months after revascularization, as determined by data from SPECT.

Statistically significant differences were observed between the CABG and PCI groups in the incidence of myocardial infarction (12.8% and 16.3%; P = 0.12), stroke (4.2% and 10.2%; P = 0.13), and RR (23.4% and 34.7%; P = 0.11).

De Winter et al (2023)
[30]

Amsterdam, USA

Randomized controlled trial

A total of 584 participants will be randomly assigned in a 1:1 ratio to either a strategy of native coronary artery PCI or SVG PCI, with 292 patients in each group.

Clinical indication for revascularization, as determined by the local Heart Team, was based on symptoms, documented ischemia, and viability.

A 3-year MACE rate of 47% was observed after bypass graft PCI, whereas the event rate for native vessel PCI in these patients was 33%.

Ganyukov et al (2020) [32]

Russia

Randomized controlled trial

A total of 155 consecutive patients were randomized to CABG (n = 50), HCR (n = 52), or MV-PCI (n = 53).

The mean age was 62 ± 7 years, and the majority of participants were men (71.6%). The mean follow-up duration was 52.5 months, with a minimum of 36 months.

The occurrence of the study endpoints at 3 years was available for 98% and 94.3% of the included patients for CABG and PCI, respectively.

Ganyukov et al (2021) [31]

Russia

Randomized controlled trial

A total of 155 patients with multivessel coronary artery disease were randomized into three groups: CABG (50 patients), HCR (52 patients), and MV-PCI (53 patients).

The primary endpoint was residual ischemia at 12 ± 1 months as determined by SPECT. Approximately one-half of the study patients had 2-vessel disease (50.3%), while the other half had ≥ 3 vessel CAD (49.7%).

Statistically significant differences in the incidence of myocardial infarction between the groups of CABG, GKR, and PCI (12.8%, 8.5%, and 16.3%; P = 0.12), stroke (4.2%, 6.4%, and 10.2%; P = 0.13), and RR according to clinical indications (23.4%, 23.4%, and 34.7%; P = 0.11) were also not observed.

**Table 3.** Patient Demographics and Clinical Characteristics
No.	Study	No. of patients	Mean age (years)	Medical history	% Stenosis	Intervention	Stent thrombosis (no. of events)	Incomplete revascularization
LM-CAD: left main coronary artery disease; MV-CAD: multivessel coronary artery disease; 3VD: three-vessel disease; ACS: acute coronary syndrome.
1	Stone et al (2019) [22]	1,905	66.0 ± 9.6	80.5% of the patients had distal LM-CAD.	NR	Fluoropolymer-based cobalt-chromium everolimus-eluting stents	16	153
2	Thuijs et al (2019) [23]	1,184	> 21	Patients with de novo 3VD and LM-CAD	NR	Paclitaxel-eluting stents	NR	NR
3	Holm et al (2020) [24]	1,201	66.2	Stable angina pectoris, unstable angina pectoris, or ACS; LM-CAD	> 50%	Umirolimus-eluting stents	19	155
4	Fearon et al (2022) [25]	1,500	< 65 or ≥ 65	ACS	NR	Zotarolimus-eluting stents	6	74
5	Wang et al (2023) [26]	1,800	64.6 ± 10.4	3VD and/or LM	NR	Paclitaxel-eluting stents	5.0 ± 2.2	238
6	Giustino et al (2018) [28]	1,905	NR	LM-CAD	≥ 70% visually or 50% to < 70% via CA	Cobalt-chromium fluoropolymer-based everolimus-eluting stents	8	346
7	De Winter et al (2023) [30]	584	> 18	Coronary artery lesion(s) and the SVG lesion(s)	> 50%	Everolimus-eluting stents	NR	NR
8	Ganyukov et al (2020) [32]	155	62 ± 7	Femoropopliteal lesions	NR	Paclitaxel-eluting stents	NR	NR
9	Ganyukov et al (2021) [31]	155	62 ± 7	MV-CAD	≥ 70%	Everolimus-eluting stents	2.6 ± 0.7	9

Table 3. Patient Demographics and Clinical Characteristics

No.

Study

No. of patients

Mean age (years)

Medical history

% Stenosis

Intervention

Stent thrombosis (no. of events)

Incomplete revascularization

LM-CAD: left main coronary artery disease; MV-CAD: multivessel coronary artery disease; 3VD: three-vessel disease; ACS: acute coronary syndrome.

Stone et al (2019) [22]

1,905

66.0 ± 9.6

80.5% of the patients had distal LM-CAD.

Fluoropolymer-based cobalt-chromium everolimus-eluting stents

153

Thuijs et al (2019) [23]

1,184

> 21

Patients with de novo 3VD and LM-CAD

Paclitaxel-eluting stents

Holm et al (2020) [24]

1,201

66.2

Stable angina pectoris, unstable angina pectoris, or ACS; LM-CAD

> 50%

Umirolimus-eluting stents

155

Fearon et al (2022) [25]

1,500

< 65 or ≥ 65

ACS

Zotarolimus-eluting stents

Wang et al (2023) [26]

1,800

64.6 ± 10.4

3VD and/or LM

Paclitaxel-eluting stents

5.0 ± 2.2

238

Giustino et al (2018) [28]

1,905

LM-CAD

≥ 70% visually or 50% to < 70% via CA

Cobalt-chromium fluoropolymer-based everolimus-eluting stents

346

De Winter et al (2023) [30]

584

> 18

Coronary artery lesion(s) and the SVG lesion(s)

> 50%

Everolimus-eluting stents

Ganyukov et al (2020) [32]

155

62 ± 7

Femoropopliteal lesions

Paclitaxel-eluting stents

Ganyukov et al (2021) [31]

155

62 ± 7

MV-CAD

≥ 70%

Everolimus-eluting stents

2.6 ± 0.7