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Abstract

Background:

Patients post-coronary artery bypass graft (CABG) can re-present with acute coronary syndrome (ACS); however, culprit lesion identification, as well as revascularization, is often challenging. Furthermore, the impact of revascularization in this patient group is relatively unknown.

Objectives:

The purpose of our study was to evaluate the efficacy of percutaneous coronary intervention (PCI) in patients with previous CABG surgery presenting with ACS.

Methods:

Using data from the Manitoba Center for Health Policy, we identified patients treated with CABG between April 1979 and March 2018, who subsequently presented with the primary diagnosis of ACS. Patients were divided into four groups: (1) managed medically and not investigated by cardiac catheterization and (2) investigated by cardiac catheterization and treated (2a) medically, (2b) with PCI, and (2c) with redo-CABG. Inverse probability treatment-weighted survival analyses were performed. Ethical approval was obtained from the local research board.

Results:

Nearly 20% of patients treated with CABG presented with ACS at a median of 7.2 years (age at the time of CABG: 66 years (interquartile range: 58–73 years); 75.6% male). Patients treated with PCI (N = 929) demonstrated improved survival compared to the patients investigated by catheterization but treated medically (N = 952; hazard ratio 0.87, 95% confidence interval 0.77–0.97, p = 0.02). Patients who underwent redo CABG (N = 171) experienced 13% mortality within the first year, but subsequently, demonstrated a trend toward improved survival.

Conclusion:

ACS is not uncommon following CABG. Revascularization is associated with prognostic improvement; however, such could be accounted for by inherent group differences, including comorbidities and coronary anatomy These findings should be validated in a prospective randomized study.

Plain language summary

Efficacy of revascularization for ACS in patients with previous CABG

Patients who have had coronary artery bypass graft (CABG) surgery can represent with acute coronary syndrome (ACS). Not only that culprit lesion identification is challenging, but the impact of revascularization remains relatively unknown in this setting. We have reviewed the provincial repository to identify outcomes among patients with previous CABG presenting with ACS and the impact of revascularization.

Keywords

acute coronary syndrome coronary artery bypass surgery revascularization

Introduction

Coronary artery disease is one of the leading causes of morbidity and mortality. Symptomatic patients with obstructive atherosclerotic coronary artery disease are treated with coronary revascularization, either by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Patients with complex coronary artery disease are commonly treated with CABG.¹ As a result of progressive atherosclerosis, nearly 15% of internal mammary arteries and 40% of saphenous venous grafts (SVGs) become occluded 10 years after CABG surgery.² Such patients can present with an acute coronary syndrome (ACS), including unstable angina (UA), ST-elevation myocardial infarction (STEMI), or non-STEMI (NSTEMI).

Multiple studies have demonstrated a mortality benefit for revascularization, either by PCI or CABG, in patients (without previous CABG) presenting with ACS.³ Identifying a culprit lesion in patients with STEMI is relatively straightforward, whereas such identification in patients presenting with NSTEMI or UA who have had a CABG remains challenging, as they often have complex coronary anatomy. Multiple studies have described worse outcomes after ACS in patients with previous CABG, in comparison to those without prior CABG^4–7; however, one reported conflicting findings.⁸ The management of ACS post-CABG is confounded by the fact that patients with previous CABG are more likely to have multiple medical comorbidities, an adverse cardiovascular risk profile, and have more complex coronary anatomy often not suitable for revascularization.^7,9 The current European and American Cardiology Society guidelines support invasive cardiac catheterization and revascularization as the treatment of choice in patients presenting with ACS^10,11; however, this is based on studies that excluded or enrolled only small numbers of patients with previous CABG.^12–14 As a result, the precise impact of revascularization in patients with previous CABG, later presenting with ACS remains largely unknown. We aimed to assess the impact of revascularization in this patient cohort, using a provincial population-based administrative dataset.

Materials and methods

Study design

This is a retrospective, population-based, cohort study utilizing linked clinical and administrative databases collected and stored under the Manitoba Centre for Health Policy, a publicly funded, non-profit research unit, based at the University of Manitoba. These datasets contain a unique scrambled identifier allowing for data linkage to occur at the individual level, across multiple provincial government and healthcare agencies databases, including pharmacy, physician billing, and hospital discharge abstract databases. Such an approach has been described previously.¹⁵ Informed consent was waived by the institutional review board and ethics committee.

Data sources

The Hospital Abstracts Database contains information on all hospital discharges in Manitoba, Canada, and includes an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), or International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada (ICD-10-CA) diagnosis code. This database also contains the ICD-9 Procedure and Canadian Classification of Health Interventions codes, identifying inpatient or day procedures performed at each healthcare facility in Manitoba. The Physician Claims Database contains fee-for-service billings submitted by physicians in the Province of Manitoba, with a catchment area of approximately 1.4 million people. Each submitted billing is also linked to an ICD-9-CM code. The Manitoba Health Insurance Registry contains information on individuals residing in the province of Manitoba, including their birthdate, biological sex, postal code of residence, and the date and reason for termination of their public health insurance coverage, such as death or emigration.

Inclusion criteria

Individuals aged 18 years or older who underwent CABG between April 1, 1979 and March 31, 2018, without a history of prior CABG or PCI, were included in this study. Patients who did not survive their initial hospital stay at the time of CABG were excluded from the analysis. Similarly, individuals investigated by cardiac catheterization following discharge from their initial CABG but before their ACS event were excluded from this analysis, as these individuals might have been treated with revascularization. The Hospital Abstracts Database was used to flag eligible individuals through the use of ICD-9 Procedure Codes and Canadian Classification of Health Interventions codes (Supplemental Table 1).

ACS diagnosis

ACS was defined using ICD-9-CM and ICD-10-CA codes found in the Hospital Abstracts Database (Supplemental Table 2). Primary diagnosis codes of UA and Myocardial Infarction (MI) were flagged for all individuals in the final study cohort who were discharged alive from their initial CABG procedure and experienced the ACS event following their CABG discharge date.

Baseline characteristics

Baseline characteristics were determined using a combination of the data sources mentioned above. These characteristics were assessed for each patient in the study cohort immediately preceding their index CABG procedure, as well as, at the time of their subsequent ACS event. Individual patient household income was extracted by linking the Manitoba Insurance Registry to publicly available household income data from Statistics Canada. This neighborhood-level average income value was then assigned a neighborhood-level income quintile (for urban and rural postal codes, respectively) at the Manitoba Centre for Health Policy. Comorbidities were assessed using the Charlson Comorbidity Index (CHCI)^16–19; as well, important cardiovascular risk factors not part of the CHCI, such as hypertension and dyslipidemia status were assessed for the patient population. Physician Claims and the Hospital Abstracts Database were used to flag the relevant ICD-9 and ICD-10 codes for these comorbidities (Supplemental Table 3).

Statistical analysis

Baseline patient characteristics were summarized using medians and interquartile ranges (IQRs) for continuous variables and counts and percentages for categorical variables. The incidence rates of ACS following discharge from the hospital after the initial CABG procedure were estimated via a cumulative incidence curve, with mortality considered as a competing risk. In addition, factors associated with the time to ACS event were evaluated via a cause-specific Cox Proportional Hazards Model, again considering mortality as a competing risk. Fine and Gray’s method was applied to estimate the rates of ACS.²⁰ The treatment modalities of those who experienced an ACS event following their initial CABG were explored further to examine mortality trends in this patient cohort. Baseline characteristics of patients investigated by cardiac catheterization following their ACS event were compared to those who did not undergo cardiac catheterization using a Mann–Whitney test for continuous variables, and a Chi-square test for categorical variables. For individuals who underwent cardiac catheterization following their ACS diagnosis, the factors associated with survival time were assessed using a Cox-Proportional Hazards Regression Model. This model considered the treatment decision following catheterization (medical management/PCI/CABG) as a time-dependent covariate. Survival rates by treatment decision were visualized using a Kaplan–Meier survival curve. To further evaluate treatment decisions following ACS diagnosis post-CABG in a more contemporary cohort, a subgroup analysis was performed on those who had their ACS diagnosis occur between January 1, 2000 and March 31, 2018. Inverse Probability Treatment Weights (IPTW) were calculated for those who underwent cardiac catheterization followed by medical management and those who underwent cardiac catheterization and subsequent PCI in this cohort of contemporary patients. Unweighted and weighted standardized mean differences were calculated for both cohorts to evaluate the performance of the IPTW. The effect of undergoing PCI following cardiac catheterization on survival time in this cohort was then evaluated by performing an IPTW-adjusted Cox-Proportional Hazards Regression Model, with PCI treatment considered as a time-dependent covariate. In addition, an IPTW-adjusted survival curve was generated to estimate survival rates in these two cohorts of patients. A similar IPTW analysis was conducted to compare survival in the contemporary subgroup of patients who underwent cardiac catheterization and were treated with PCI to those who did not undergo cardiac catheterization.

A final analysis to compare the survival of CABG patients who experienced an ACS (from January 1, 2000 onwards) and were treated with PCI to the general CABG non-ACS population was also performed. A 1:10 propensity score match utilizing a greedy matching algorithm was performed to match one ACS/PCI-treated case to 10 CABG (non-ACS) patients post-discharge. Following this, all cases that had at least two out of 10 matches, and whose follow-up time from their initial CABG discharge was greater than or equal to the number of days from the ACS case’s initial CABG discharge date to their subsequent PCI, were included. For all cases included, two randomly selected controls were considered in the final survival analysis. Follow-up time in this survival analysis was the total follow-up time minus the time from CABG discharge to index PCI. A Kaplan–Meier curve was generated and compared using a log-rank test. All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc. Cary, NC, USA).

Results

Between April 1, 1979 and March 31, 2018, 20,297 patients without prior coronary intervention were treated with CABG, forming the eligible CABG population (Figure 1). The baseline characteristics of the patients at the time of index CABG surgery are shown in Supplemental Table 4. The majority (75.6%) of patients were male with a median age of 66 years (IQR 58–73 years); 17.1% of patients had two or fewer grafts, 38.9% had three grafts, and 37.4% had four or more grafts. Of this population, 4102 (20%) patients presented with an ACS at a median of 7.2 years (IQR 3.4–11.5 years) post-CABG (Figures 1 and 2). Of these, 757/4102 (18%) patients with CABG who presented with ACS were excluded from subsequent analysis, as they underwent cardiac catheterization prior to ACS diagnosis (Figure 1). Predictors of ACS in patients with previous CABG included increased age, female sex, lower income, rural residence, previous MI, peripheral vascular disease, peptic ulcer disease, diabetes without complications and dyslipidemia (Supplemental Table 5).

Figure 1.

CONSORT diagram describing the study cohort.

Figure 2.

Incidence of acute coronary syndrome following coronary artery bypass graft surgery.

Post-CABG ACS patients undergoing cardiac catheterization

Of the patients with previous CABG who presented with an ACS, 2052/3345 (61%) were investigated by cardiac catheterization. Subsequent treatment was medical management (N = 952; 46.4%), PCI (N = 929; 45.3%), or redo CABG (N = 171; 8.3%; Figure 1). Baseline patient demographics for each treatment group investigated with catheterization are displayed in Table 1. Patients treated with redo-CABG were younger (median age 63 years) than those patients treated with PCI (median age 69 years) or medical management (median age 69 years; p < 0.001). Patients treated with PCI had the shortest time to catheterization from ACS diagnosis (median of 2 days), compared to patients who underwent redo-CABG (median of 21 days). Patients treated with medical management alone had more comorbidities, illustrated by a higher weighted CHCI (Table 1).

Table 1.

Characteristics of the study population who underwent cardiac catheterization, stratified based on treatment group.

Characteristics	Medical management, N = 952	PCI, N = 929	Redo-CABG, N = 171	p Value
Demographics
Age at initial cardiac surgery	62 (54–69)	60 (54–67)	55 (49–61)	<0.001
Age at ACS diagnosis	69 (61–75)	69 (61–76)	63 (56–69)	<0.001
Age ⩾75 (ACS diagnosis), n (%)	273 (28.7)	282 (30.4)	16 (9.4)	<0.001
Male, n (%)	704 (74.0)	716 (77.1)	141 (82.5)	0.035
Income quintile, n (%)				0.789
1	183 (19.4)	174 (18.8)	39 (23.2)
2	217 (23.0)	194 (20.9)	39 (23.2)
3	228 (24.2)	223 (24.1)	38 (22.6)
4	184 (19.5)	194 (20.9)	32 (19.1)
5	130 (13.8)	142 (15.3)	20 (11.9)
Urban/rural residence, n (%)				0.713
Urban	570 (60.5)	544 (58.7)	99 (58.9)
Rural	372 (39.5)	383 (41.3)	69 (41.1)
Charlson comorbidities (initial cardiac surgery)
Total Charlson comorbidities	2 (1–4)	2 (1–3)	2 (1–3)	<0.001
Weighted Charlson comorbidities	3 (1–4)	2 (1–4)	2 (1–3)	<0.001
Myocardial infarction, n (%)	498 (52.3)	398 (42.8)	92 (53.8)	<0.001
Congestive heart failure, n (%)	202 (21.2)	148 (15.9)	22 (12.9)	0.002
Peripheral vascular disease, n (%)	155 (16.3)	124 (13.4)	28 (16.4)	0.176
Cerebrovascular disease, n (%)	155 (16.3)	123 (13.2)	17 (9.9)	0.039
Chronic pulmonary disease, n (%)	578 (60.7)	573 (61.7)	82 (48.0)	0.003
Connective tissue disease-rheumatic disease, n (%)	139 (14.6)	102 (11.0)	21 (12.3)	0.062
Peptic ulcer disease, n (%)	247 (26.0)	206 (22.2)	32 (18.7)	0.045
Mild liver disease	—	—	—	—
Diabetes without complications, n (%)	311 (32.7)	344 (37.0)	34 (19.9)	<0.001
Diabetes with complications	—	—	—	—
Paraplegia and hemiplegia	—	—	—	—
Renal disease, n (%)	35 (3.7)	32 (3.4)	0 (0.0)	0.041
Any malignancy, including lymphoma and leukemia, except non-melanoma skin cancer, n (%)	130 (13.7)	138 (14.9)	14 (8.2)	0.066
Moderate or severe liver disease, n (%)	6 (0.5)	8 (0.9)	0 (0.0)	0.438
Metastatic solid tumor	—	—	—	—
HIV/AIDS	—	—	—	—
Hypertension, n (%)	657 (69.0)	644 (69.3)	90 (52.6)	<0.001
Dyslipidemia, n (%)	338 (35.5)	435 (46.8)	28 (16.4)	<0.001
ACS type
Myocardial infarction, n (%)	504 (52.9)	595 (64.1)	92 (53.8)	<0.001
Unstable angina	448 (47.1)	334 (36.0)	79 (46.2)	<0.001
Cardiac surgery hospital discharge to ACS diagnosis (years)	5.8 (2.5–9.8)	7.6 (3.9–11.8)	6.9 (2.9–10.7)	<0.001
ACS diagnosis to cardiac catheterization (days)	4 (0–133)	2 (0–7)	21 (1–821)	<0.001
Cardiac catheterization to PCI/CABG (days)	—	0 (0–0)	34 (0–298)	<0.001

ACS, acute coronary syndrome; AIDS, acquired immunodeficiency syndrome; CABG, coronary artery bypass graft; HIV, human immunodeficiency virus; PCI, percutaneous coronary intervention.

A mortality difference was observed post-cardiac catheterization, which was dependent upon treatment modality (Figure 3). Patients treated with PCI demonstrated improved survival compared to those who underwent catheterization but were treated medically (hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.77–0.97, p = 0.02; Figure 4)). The group treated with redo-CABG demonstrated 13% mortality in the first year; however, for those who survived this initial postoperative period, there was no significant difference in mortality as compared to the medical management group (HR 0.91, 95% CI 0.74–1.11, p = 0.335; Figure 3).

Figure 3.

Survival among patients with ACS post-CABG, stratified by treatment post-cardiac catheterization.

Figure 4.

Impact of coronary revascularization on survival among the contemporary cohort of patients with ACS post-CABG.

Predictors of mortality for CABG patients following ACS diagnosis included increased age, lower income, congestive heart failure, peripheral vascular disease, diabetes without complications, renal disease, hypertension, dyslipidemia, time from CABG to ACS presentation, and presentation with MI versus UA (Table 2).

Table 2.

Predictors of mortality following ACS in the entire cohort of patients with previous CABG surgery.

Characteristic	Hazard ratio	95% CI	p Value
Demographics
Age at ACS diagnosis	1.05	1.04–1.06	<0.001
Male, n (%)	1.05	0.92–1.21	0.475
Income quintile
1 vs 5	1.27	1.03–1.56	0.023
2 vs 5	1.00	0.82–1.23	0.980
3 vs 5	1.02	0.84–1.25	0.828
4 vs 5	1.01	0.82–1.24	0.950
Urban/rural residence
Rural vs Urban	1.07	0.95–1.21	0.272
Charlson comorbidities (initial cardiac surgery)
MI	1.04	0.92–1.17	0.557
Congestive heart failure	1.37	1.19–1.59	<0.001
Peripheral vascular disease	1.21	1.04–1.42	0.015
Cerebrovascular disease	1.14	0.97–1.34	0.107
Dementia	—	—	—
Chronic pulmonary disease	0.99	0.88–1.11	0.846
Connective tissue disease-rheumatic disease	0.98	0.83–1.16	0.786
Peptic ulcer disease	0.95	0.83–1.09	0.485
Mild liver disease	—	—	—
Diabetes without complications	1.65	1.46–1.87	<0.001
Diabetes with complications	—	—	—
Paraplegia and hemiplegia	—	—	—
Renal disease	1.77	1.29–2.45	<0.001
Any malignancy, including lymphoma and leukemia, except non-melanoma skin cancer	0.90	0.76–1.08	0.249
Moderate or severe liver disease	0.77	0.32–1.86	0.556
Metastatic solid tumor	—	—	—
HIV/AIDS	—	—	—
Hypertension	1.15	1.01–1.31	0.033
Dyslipidemia	0.83	0.72–0.95	0.008
Cardiac surgery hospital discharge to ACS diagnosis (years)	1.03	1.01–1.04	<0.001
ACS diagnosis to cardiac catheterization (days)
7–30 Days vs <7 days	1.17	0.97–1.42	0.100
30+ Days vs <7 days	0.94	0.82–1.07	0.349
ACS type MI vs unstable angina	1.35	1.19–1.52	<0.001

ACS, acute coronary syndrome; AIDS, acquired immunodeficiency syndrome; CABG, coronary artery bypass graft; CI, confidence interval; HIV, human immunodeficiency virus; MI, myocardial infarction; PCI, percutaneous coronary intervention.

Finally, the survival of CABG patients who presented with ACS and were subsequently treated with PCI was compared to a control cohort of CABG patients who never presented with ACS. Baseline characteristics of these two populations are shown in Supplemental Table 6. As depicted in Figure 5, the survival of CABG patients treated with PCI was comparable to those who never presented with ACS after CABG surgery (p = 0.225).

Figure 5.

Comparison of survival among patients treated with PCI after their presentation with ACS post-CABG, to the cohort who never experienced ACS post-CABG.

Post-CABG ACS patients not undergoing cardiac catheterization

The group of patients with previous CABG who did not undergo cardiac catheterization on presentation with ACS (N = 1293) were older (median age 75 years, 51.6% age ⩾75 years at ACS diagnosis) than patients investigated with catheterization (median age 68 years, 27.8% age ⩾75 years at ACS diagnosis) (Supplemental Table 7). These patients had a higher likelihood of four or more grafts (p = 0.031) and were more co-comorbid, as suggested by a higher CHCI (Supplemental Table 7). Patients investigated with catheterization and treated with PCI demonstrated improved survival as compared to the patients not investigated with cardiac catheterization, after adjusting for differences in baseline characteristics (HR 0.62, 95% CI 0.56–0.68; p < 0.01); however, after adjustment using a time-dependent definition, statistical significance was not present (HR 0.99, 95% CI 0.90–1.09; p = 0.8) (Supplemental Figure 1).

Discussion

Important findings from our study include the following: (1) nearly one in five patients post-CABG experience an ACS during follow-up, (2) revascularization is associated with improved outcomes in this patient cohort, and (3) in post-CABG patients with ACS treated with PCI, subsequent survival is similar to post-CABG patients who do not re-present with ACS.

Current ACS guidelines recommend investigating patients with previous CABG by cardiac catheterization, followed by revascularization if indicated^10,11; however, this is largely based on trials that excluded patients with prior CABG or only included a small number of CABG patients.^12–14 Data to guide the specific management of patients with previous CABG who present with ACS are sparse. As this is a unique patient population with increased comorbidities, nonspecific presentations, and complex coronary anatomy, extrapolation of outcome data from the non-CABG population may not be appropriate.²¹ Furthermore, reliable culprit lesion identification remains challenging in patients with prior CABG as a result of their typically complex coronary anatomy.²¹ The published literature describes a very low rate of revascularization among ACS patients with previous CABG; however, this may increase over time with advancing techniques in complex and chronic total occlusion PCI.²²

Prior studies have reported conflicting outcomes for patients with previous CABG who present with NSTEMI or UA (Table 3). A subgroup analysis, of the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial, randomized patients with ACS to eptifibatide or placebo compared patients with prior CABG (N = 1134) to those without (N = 8321).⁶ Patients with prior CABG were older, more comorbid, more likely to have a reduced left ventricular ejection fraction, multi-vessel disease, lower thrombolysis in myocardial infarction (TIMI) flow, and more severe culprit stenoses.⁶ Adjusted mortality at 30 and 180 days was higher for patients with previous CABG as compared to those without, with HRs of 1.45 and 1.32, respectively.⁶ In contrast to these findings, Shoaib et al. compared outcomes between those with and without prior CABG using a registry of 287,658 NSTEMI patients.²² Patients with prior CABG (N = 25,296) were similarly older and more comorbid.²² However, all-cause mortality, major bleeding, reinfarction and Major adverse cardiovascular events (MACE) were similar between the two groups after adjustment.²² In addition, Mathew et al. analyzed 15,936 patients with prior CABG who presented with an acute MI.⁸ Patients with prior CABG were less likely to present with ST elevation/left bundle branch block (LBBB) than those without prior CABG.⁸ After adjusting for baseline differences, a history of previous CABG was associated with higher in-hospital mortality in those with ST elevation/LBBB (odds ratio (OR), 1.11, 95% CI 1.00–1.23) but not in those with NSTEMI when compared to patients without prior CABG.⁸ This discrepancy has been attributed to clinical factors such as increased age and the greater prevalence of comorbidities in the CABG population, as excess mortality is often attenuated with statistical adjustment for such factors.²¹

Table 3.

Studies comparing outcomes in patients presenting with ACS, comparing those with previous CABG to those without previous CABG.

Author	Publication year	Total number of patients	Number of patients with previous CABG	Follow-up duration	Outcomes
Al-Aqeedi et al.²³	2012	16,750	693	In hospital	No significant difference in mortality between those with prior CABG to those without (5.8% vs 5.2%, p = 0.52)
Iqbal et al.²⁴	2016	79,295	2658	30 Days	No significant difference in mortality after adjusting for patient risk factors
Kim et al.²⁵	2010	47,557	8790	In hospital	Mortality did not differ between patients with previous CABG vs those without (adjusted OR 0.99, 95% CI 0.87–1.11)
Kleiman et al.⁴	1996	2048	336	1 Year	The composite of death, myocardial infarction, or recurrent ischemia occurred in 39.3% of those with prior CABG, compared to 30.2% in those without (p = 0.002)
Kugelmass et al.⁵	2006	2220	484	6 Months	Prior CABG was associated with:1. Higher readmission rate for ACS (17.4% vs 11.0%, p < 0.001)2. Higher incidence of death, myocardial infarction, or rehospitalization for ACS (22.3% vs 16.4%, p = 0.002)
Labinaz et al.⁶	2002	9455	1134	30 and 180 Days	Patients with previous CABG experienced higher mortality at 30 days (HR 1.45 (95% CI 1.06–1.98); p = 0.019) and at 180 days (HR 1.32 (95% CI 1.04–1.67); p = 0.021)
Mathew et al.⁸	2002	112,697	15,936	In hospital	Prior CABG was not associated with higher mortality in patients without ST elevation/LBBB (OR 0.99, 95% CI 0.92–1.07)
Nikolsky et al.⁷	2012	13,764	2475	1 Year	Patients with prior CABG experienced higher MACE (22.5% vs 15.2%, p < 0.0001)
Ribeiro et al.²⁶	2020	9402	479	1 Year	Mortality was similar between patients with previous CABG as compared to those without after propensity-matching and multivariate analysis (HR 0.63, 95% CI 0.37–1.09, p = 0.098)
Shoaib et al.²²	2021	287,658	25,296	In hospital	MACE (OR, 0.97; 95% CI 0.90–1.04; p = 0.44), all-cause mortality (OR, 0.96; 95% CI 0.88–1.04; p = 0.31), and reinfarction (OR, 1.02; 95% CI 0.89–1.17; p = 0.78), were similar regardless of prior CABG status

ACS, acute coronary syndrome; CABG, coronary artery bypass graft surgery; CI, confidence interval; HR, hazard ratio; LBBB, left bundle branch block; MACE, major adverse cardiac events; NSTEMI, non-ST elevation myocardial infarction; OR, odds ratio; UA, unstable angina.

An important and often challenging component of revascularization in patients with NSTEMI and previous CABG is to determine the culprit lesion. This may explain, in part, why patients with previous CABG are less likely to undergo revascularization. Shoaib et al. demonstrated that even after adjustment for differences in baseline characteristics, patients with a history of CABG who presented with ACS were less likely to undergo revascularization (40%) as compared to those without previous CABG (53%).²² Our study corroborates this finding, as only 61% of the post-CABG population were referred for cardiac catheterization. Moreover, when patients with previous CABG are investigated by cardiac catheterization, complex anatomy may preclude revascularization in a proportion of patients. In fact, Lee et al. reported that a culprit vessel was identified in only half of invasively managed CABG patients presenting with NSTEMI.²⁷ Data from the National Cardiovascular Data Registry (NCDR) cathPCI Registry were used to characterize and determine outcomes in patients with previous CABG, comparing native versus bypass graft PCI.²⁸ In this large registry of over 1 million interventions, PCI in patients with prior CABG comprised only 17.5% of the total procedural volume.²⁸ A native coronary artery was believed to be a culprit in the majority of cases (62.5%), whereas a bypass graft culprit comprised only 37.5% of cases (34.9% SVGs, 2.5% arterial grafts, and 0.2% both SVG and arterial grafts).²⁸ Furthermore, patients with bypass graft PCI had higher contrast volumes and longer fluoroscopy times, lower rates of final TIMI 3 flow, were more likely to require intra-aortic balloon pump support, and experienced higher post-procedural complications and in-hospital mortality, as compared to those with native vessel PCI.²⁸ Additionally, no reflow, peri-procedural MI, and in-stent restenosis were more common when an SVG was treated, as compared to native vessel PCI.²⁸

A number of studies have attempted to determine the prognostic benefit of invasive management for NSTEMI in patients with CABG (Table 4). For example, Shoaib et al. conducted a sensitivity analysis on 25,296 patients with previous CABG who presented with NSTEMI, comparing outcomes between those who underwent PCI versus medical management.²² Those treated medically were older and more likely to have left ventricular dysfunction or chronic kidney disease, similar to our observation.²² PCI was associated with lower inpatient mortality compared to medical management (OR 0.67, 95% CI 0.46–0.98; p = 0.04); however, the odds of in-hospital reinfarction, major bleeding, and MACE did not differ between the two groups.²² This result was supported by a subgroup analysis of 484 patients with previous CABG in the TACTICS-TIMI 18 trial, which randomized patients with NSTEMI to an early invasive versus conservative (selectively invasive) strategy.⁵ Those with prior CABG demonstrated a higher composite of death, MI, or rehospitalization for ACS compared to those without prior CABG (22.3% vs 16.4%, p = 0.002).⁵ In addition, an early invasive strategy in the CABG group trended toward a reduction in death or MI (OR 0.58, 95% CI 0.31–1.0, p = 0.089).⁵ Similarly, Gyenes et al. evaluated outcomes in 7127 patients with previous CABG who underwent coronary angiography for ACS or UA.⁹ Patients treated with revascularization benefited from improved mortality compared to the medically managed group after adjusting for baseline differences (HR 0.81 (95% CI 0.74–0.90); p < 0.001).⁹ These findings contrast a study by Lee et al. which randomized 60 patients with UA or NSTEMI and prior CABG to invasive management or medical care (excluding refractory ischemia or cardiogenic shock).²⁷ The efficacy outcome including all-cause mortality, nonfatal MI, refractory ischemia, and hospitalization for heart failure was equivalent between the two groups (42% invasive group, 45% medical group; HR 0.85, 95% CI 0.39–1.83).²⁷ Furthermore, there was no difference in the composite safety outcome of major bleeding, stroke, procedure-related MI, or worsening renal function, which occurred in 26% of the invasive group and 31% of the medical group (HR 0.87, 95% CI 0.34–2.25).²⁷ Of note, 15/29 (52%) patients assigned to the medical management group underwent catheterization during the follow-up period, of which 7/29 (24%) received PCI, potentially contributing to the negative findings.²⁷ Our results suggest there may be mortality benefit to revascularization in patients with appropriate anatomy, as compared to those treated medically. In addition, our findings demonstrated survival at par for CABG patients treated with PCI to those with CABG who never re-present with ACS, further suggesting the benefit of revascularization in this setting.

Table 4.

Studies evaluating the effects of revascularization in patients with previous CABG presenting with ACS.

Author	Year of publication	Number of patients	Follow-up	Outcomes
Asrar Ul Haq et al.²⁹	2014	117	1 Year	No difference in readmission, recurrent UA/ACS, or mortality between those treated with revascularization vs medical management
Gyenes et al.⁹	2013	7127	14 Years	Mortality was lower in revascularized patients, compared to those treated medically (HR 0.81 (95% CI 0.74–0.90); p < 0.001)
Gurfinkel et al.³⁰	2007	3853	In hospital	The primary composite endpoint of death, non-fatal MI, and recurrent ischemia was similar in medically managed patients compared to those who were revascularized (31% vs 30%, respectively; p = 0.53)
Held et al.³¹	2007	10,469	1 Year	Revascularization was associated with reduced mortality (RR 0.67; 95% CI 0.56–0.81; p < 0.001)
Kugelmass et al.⁵	2006	484	6 Months	An early invasive strategy was associated with a reduction in the composite of death or MI (OR, 0.58; 95% CI 0.31–1.0; p = 0.089)
Lee et al.²⁷	2019	60	2 Years	The composite of all-cause mortality, nonfatal MI, refractory ischemia, and hospitalization for heart failure was equivalent between the invasive and medical treatment groups (HR 0.85, 95% CI 0.39–1.83)
Nikolsky et al.⁷	2012	2475	1 Year	Patients treated with PCI had higher rates of MI (13.5% vs 4.6%; p < 0.0001), unplanned revascularization (17.3% vs 7.7%; p < 0.0001), and MACE (27.8% vs 14.3%; p < 0.0001)
Shoaib et al.²²	2021	25,296	In hospital	Revascularization was associated with lower mortality compared to medical management (OR 0.67, 95% CI 0.46–0.98; p = 0.04)

ACS, acute coronary syndrome; CABG, coronary artery bypass graft surgery; CI, confidence interval; HR, hazard ratio; MACE, major adverse cardiac events MI, myocardial infarction; OR, odds ratio; PCI, percutaneous coronary intervention; RR, relative risk; UA, unstable angina.

The exact mechanism driving the apparent survival advantage from revascularization in the post-CABG population remains unknown, and it remains possible that any differences in outcome are reflective of baseline differences in the patient populations. However, the answer may reside in a recent study by Seraphim et al. that evaluated the prognostic implications of global stress myocardial blood flow and perfusion reserve using cardiac magnetic resonance imaging in 341 patients with prior CABG.³² After adjusting for prognostic factors (age, comorbidities, regional ischemia, extent of previous infarction), both myocardial blood flow and perfusion reserve independently predicted all-cause mortality and MACE.³² Similar conclusions may be drawn from The Outcomes of Percutaneous RevascularizaTIon for Management of SUrgically Ineligible Patients with Multivessel or Left Main Coronary Artery Disease (OPTIMUM) registry.³³ This study described PCI outcomes in 726 patients with complex coronary artery disease, who were ineligible for CABG.³³ 16.4% of patients had a history of prior CABG, and 27.1% presented with an ACS.³³ In this registry, both complete and incomplete revascularization improved symptom and quality of life scores at 6 months, suggesting that any improvement in myocardial blood supply improves patient outcomes.³³ Taken together, these studies imply that the benefit of PCI in cases of ACS following CABG surgery may stem from improved overall myocardial perfusion placing less importance on identifying a specific culprit lesion.

Limitations

The major limitation of our study is the retrospective design, including the lack of individualized patient-level data. Importantly, we were unable to determine why some ACS patients with prior CABG were not referred for cardiac catheterization, a decision made by the treating physician at the time of the ACS presentation. It is possible that this patient cohort may have significant non-cardiac comorbidities, suspected type II MI, known complex coronary anatomy, or other prohibitive risk factors precluding not only invasive assessment but also potentially explaining the higher mortality in this patient group. Given this limitation, this patient cohort was not included in the primary analysis. In addition, those who were referred for catheterization but were ultimately medically managed may have had anatomy that was not suitable for revascularization. What remains unclear is whether the apparent survival benefit in revascularized patients was realized by treating the culprit lesion, by improving overall myocardial perfusion, or was secondary to their fewer medical comorbidities. Finally, despite statistical adjustment for differences within patient groups, unknown confounders may have influenced the observed findings and mortality differences.

Conclusion

Our analysis suggests a prognostic benefit from revascularization in patients with previous CABG presenting with ACS. Although our findings could have been influenced by inherent differences in baseline characteristics, including coronary anatomy and comorbidities, such findings should be validated in a prospective, multicenter study.

Perspectives

Data to guide the management of ACS in patients with a previous CABG are lacking.

We demonstrate a survival advantage for PCI compared to catheterization plus medical management in patients with prior CABG presenting with ACS.

These findings should be validated in future prospective studies.

Supplemental Material

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Supplemental material, sj-docx-1-tak-10.1177_17539447241308047 for Outcomes among patients with coronary artery bypass grafts presenting with acute coronary syndrome: impact of revascularization by Hilary J. Bews, Brett Hiebert, Shuangbo Liu, John Ducas, Amir Ravandi, Kunal Minhas, Malek Kass, Michael P. Love, Harindra C. Wijeysundera and Ashish H. Shah in Therapeutic Advances in Cardiovascular Disease

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Supplemental material, sj-docx-7-tak-10.1177_17539447241308047 for Outcomes among patients with coronary artery bypass grafts presenting with acute coronary syndrome: impact of revascularization by Hilary J. Bews, Brett Hiebert, Shuangbo Liu, John Ducas, Amir Ravandi, Kunal Minhas, Malek Kass, Michael P. Love, Harindra C. Wijeysundera and Ashish H. Shah in Therapeutic Advances in Cardiovascular Disease

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Footnotes

Appendix

Acknowledgements

None.

Declarations

ORCID iD

Ashish H. Shah

Supplemental material

Supplemental material for this article is available online.

References

Head

Milojevic

Daemen

, et al. Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. Lancet 2018; 391(10124): 939–948.

Goldman

Zadina

Moritz

, et al. Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study. J Am Coll Cardiol 2004; 44(11): 2149–2156.

Fox

KAA

Clayton

Damman

, et al. Long-term outcome of a routine versus selective invasive strategy in patients with non–ST-segment elevation acute coronary syndrome. J Am Coll Cardiol 2010; 55(22): 2435–2445.

Kleiman

Theroux

Anderson

, et al. Comparison of outcome of patients with unstable angina and non-Q-wave acute myocardial infarction with and without prior coronary artery bypass grafting (Thrombolysis in Myocardial Ischemia III Registry). Am J Cardiol 1996; 77(4): 227–231.

Kugelmass

Sadanandan

Lakkis

, et al. Early invasive strategy improves outcomes in patients with acute coronary syndrome with previous coronary artery bypass graft surgery: a report from TACTICS-TIMI 18. Crit Pathw Cardiol 2006; 5(3): 167–172.

Labinaz

Kilaru

Pieper

, et al. Outcomes of patients with acute coronary syndromes and prior coronary artery bypass grafting: results from the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial. Circulation 2002; 105(3): 322–327.

Nikolsky

Mclaurin

Cox

, et al. Outcomes of patients with prior coronary artery bypass grafting and acute coronary syndromes: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. JACC Cardiovasc Interv 2012; 5(9): 919–926.

Mathew

Gersh

Barron

, et al. In hospital outcome of acute myocardial infarction in patients with prior coronary artery bypass surgery. Am Heart J 2002; 144(3): 463–469.

Gyenes

Norris

Graham

MM.

Percutaneous revascularization improves outcomes in patients with prior coronary artery bypass surgery. Catheter Cardiovasc Interv 2013; 82(3): E148–E154.

10.

Lawton

Tamis-Holland

Bangalore

, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice guidelines. Circulation 2022; 145(3): e18–e114.

11.

Collet

Thiele

Barbato

, et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021; 42(14): 1289–1367.

12.

The TIMI IIIB Investigators. Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in myocardial ischemia. Circulation 1994; 89(4): 1545–1556.

13.

Fox

Poole-Wilson

Henderson

, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Lancet 2002; 360(9335): 743–751.

14.

Jolly

Faxon

Fox

KAA

, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors or thienopyridines. J Am Coll Cardiol 2009; 54(5): 468–476.

15.

Hiebert

Janzen

Sanjanwala

, et al. Impact of spironolactone exposure on prostate cancer incidence amongst men with heart failure: a pharmacoepidemiological study. Br J Clin Pharmacol 2021; 87(4): 1801–1813.

16.

Deyo

Cherkin

Ciol

MA.

Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992; 45(6): 613–619.

17.

Quan

Sundararajan

Halfon

, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 2005; 43(11): 1130–1139.

18.

Lix

Smith

Pitz

, et al. Cancer data linkage in Manitoba: expanding the infrastructure for research. Winnipeg, MB: Manitoba Centre for Health Policy, 2016.

19.

Garland

Fransoo

Olafson

, et al. The epidemiology and outcomes of critical illness in Manitoba. Winnipeg, MB: Manitoba Centre for Health Policy, 2012.

20.

Fine

Gray

RJ.

A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94(446): 496.

21.

Palm

Drame

Moliterno

, et al. Acute coronary syndromes among patients with prior coronary artery bypass surgery. Curr Cardiol Rep 2022; 24(11): 1755–1763.

22.

Shoaib

Rashid

Berry

, et al. Clinical characteristics, management strategies, and outcomes of non–ST-segment–elevation myocardial infarction patients with and without prior coronary artery bypass grafting. J Am Heart Assoc 2021; 10(20): e018823.

23.

Al-Aqeedi

Asaad

Al-Qahtani

, et al. Acute coronary syndrome in patients with prior coronary artery bypass surgery: observations from a 20-year registry in a middle-eastern country. PLoS One 2012; 7(7): e40571.

24.

Iqbal

Kwok

Kontopantelis

, et al. Outcomes following primary percutaneous coronary intervention in patients with previous coronary artery bypass surgery. Circ Cardiovasc Interv 2016; 9(4): e003151.

25.

Kim

Wang

, et al. Association of prior coronary artery bypass graft surgery with quality of care of patients with non-ST-segment elevation myocardial infarction: a report from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines. Am Heart J 2010; 160(5): 951–957.

26.

Ribeiro

Teixeira

Siserman

, et al. Impact of previous coronary artery bypass grafting in patients presenting with an acute coronary syndrome: current trends and clinical implications. Eur Heart J Acute Cardiovasc Care 2020; 9(7): 731–740.

27.

Lee

MMY

Petrie

Rocchiccioli

, et al. Invasive versus medical management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: a pilot randomized controlled trial. Circ Cardiovasc Interv 2019; 12(8): e007830.

28.

Brilakis

O’Donnell

Penny

, et al. Percutaneous coronary intervention in native coronary arteries versus bypass grafts in patients with prior coronary artery bypass graft surgery. JACC Cardiovasc Interv 2016; 9(9): 884–893.

29.

Asrar

Haq

Rudd

Mian

, et al. Predictors and outcomes of early coronary angiography in patients with prior coronary artery bypass surgery presenting with non-ST elevation myocardial infarction. Open Heart 2014; 1(1): e000059.

30.

Gurfinkel

Perez de la Hoz

Brito

, et al. Invasive vs non-invasive treatment in acute coronary syndromes and prior bypass surgery. Int J Cardiol 2007; 119(1): 65–72.

31.

Held

Tornvall

Stenestrand

Effects of revascularization within 14 days of hospital admission due to acute coronary syndrome on 1-year mortality in patients with previous coronary artery bypass graft surgery. Eur Heart J 2007; 28(3): 316–325.

32.

Seraphim

Dowsing

Rathod

, et al. Quantitative myocardial perfusion predicts outcomes in patients with prior surgical revascularization. J Am Coll Cardiol 2022; 79(12): 1141–1151.

33.

Salisbury

Grantham

Brown

, et al. Outcomes of medical therapy plus PCI for multivessel or left main CAD ineligible for surgery. JACC Cardiovasc Interv 2023; 16(3): 261–273.

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