Impact of Age on the Survival Benefit of a Second Arterial Graft

ABSTRACT

Background

This retrospective propensity matched study investigated the impact of age on the survival benefit from a second arterial conduit to the left sided circulation.

Methods

Data for isolated CABG was collected from October 2004 to March 2014. All patients with an IMA graft to LAD artery and additional arterial or venous graft to the circumflex circulation were included.Propensity matching was used to balance co-variates and generate odds of death for each observation. Odds ratios (venous vs arterial) were charted against age.

Results

The in-hospital mortality rate was 1.12% (arterial) vs 1.24% (venous) (p=0.77). The overall 10-year survival was 74.6% (venous) vs 82.6% (arterial) (p=0.001). A total of 1226 patients were successfully matched to the venous or arterial (second conduit to circumflex territory after LIMA to LAD) cohorts. Odds ratio for death (venous to arterial) showed a linear decremental overall survival benefit for the second arterial graft to circumflex circulation with increasing age.

Conclusions

The survival benefit of a second arterial graft persists through all age groups with a gradual decline with increasing age over the decades. Elderly patients should not be denied a second arterial graft to the circumflex circulation based on age criterion alone.

Keywords: CABG, coronary artery bypass surgery, coronary artery disease, CAD coronary revascularization.

INTRODUCTION

Arterial grafts have been associated with better survival after coronary artery bypass surgery (CABG). There are benefits with a second arterial graft to the circumflex circulation. However it is not clear if these benefits are seen across all age ranges. Previous studies have shown that survival benefits of a second arterial graft may be confined to only younger patients.

This retrospective propensity matched study investigated the impact of age as on the survival benefit from a second arterial conduit to the left sided circulation, and whether this effect is seen in all age groups.

PATIENTS AND METHODS

Data for isolated CABG was retrospectively collected from October 2004 – March 2014 from the hospital database (PATS, Dentrite Clinical Systems Ltd, Henley-on-Thames, UK). Inclusion criteria was 1) an internal mammary artery (IMA) to the left anterior descending artery (LAD), 2) double or triple vessel disease, 3) atleast one additional conduit (venous or arterial) to the circumflex circulation, in addition to an IMA graft to left anterior descending artery. Single vessel disease and those with other concomitant procedures were excluded. Approval was obtained from the departmental review committee. Consent for individual use of data was waived off due to the nature of the study and prior approval for use of such data at the time of consent for operation. Long term survival statistics were collected from NICOR (National Institute of Cardiac Outcomes Research, UK) database (release June 2015) which is linked to Office of National Statistics, UK for mortality data.

Data analysis

Patients were stratified into 2 groups, those with atleast one arterial conduit to the obtuse marginal territory (Group 1) or those with only vein grafts to this territory (Group 2). Baseline demographic characteristics for CABG were stratified for those with at least one arterial conduit or all venous conduits to the circumflex territory in addition to an arterial graft (left or right internal thoracic artery) to the LAD system. Distributions from each variable were visually inspected and normality was tested by a Shapiro-Wilcoxon W test. Categorical and continuous variables were compared using a ² and Mann-Whitney test, respectively. A p≤0.05 was considered statistically significant.

Propensity Score Matching

The propensity score was estimated by logistic regression (p1 for venous and p2 for arterial). Propensity matching was used to balance the co-variates in the nonrandomized, observational data. Covariates used in the propensity match are listed on Supplemental Table 1. The definitions used for these risk factors were as previously described for the calculation of Euroscore (EUROpean System for Cardiac Operative Risk Evaluation) by Roques et al.(1) Treated observations were posteriorly matched in a 1:1 ratio using the nearest-neighbour method (0.2 times caliper width of standard deviation of the propensity score logit). Balance was assured using a Wilcoxon signed-ranks paired test or McNemar´s test for continuous and categorical variables, respectively. The odds of death for each group were calculated p1/(1-p1) for venous and p2/(1-p2) for arterial from the respective propensity scores. Propensities for death calculated for the venous (p1) and arterial (p2) groups using logistic regression for the matched pairs were used to calculate the odds ratio as follows:

Polynomial charts for Odds ratio (odds of death – venous to arterial) against age (abscissa) for the propensity matched pairs were obtained to study the impact of age.

RESULTS

3995 patients with primary CABG were included over 10 years (2004-2014). These included 1238 patients in Group 1 and 2757 patients in Group 2. The mean follow-up period was 74.5 months (group 1) vs 64.5 months (group 2) (Figure 1).  The in-hospital mortality rate was 1.12% (arterial) vs 1.24% (venous) (p = 0.77). The overall 10-year survival was 74.6% (venous) vs 82.6% (arterial) (P = 0.001).

A total of 1226 patients were successfully matched to the venous or arterial (second conduit to circumflex territory after LIMA to LAD) cohorts. The demographic characteristics of the matched cohort are given in Supplemental Table 1.A second arterial conduit, logistic EuroSCORE, diabetes, left ventricular ejection fraction <30%, NYHA Class III–IV and previous myocardial infarction as significant predictors of survival in regression analysis among the matched cohort (Supplemental Table 2).

Odds ratio (odds of death – venous to arterial) plotted against age for the propensity matched pairs (Figure 2) showed a linear decrement in survival benefit for the second arterial graft to circumflex circulation with increasing age.

DISCUSSION

The present analysis tries to define the age cut off beyond which the benefits of a second arterial graft are not seen. We had earlier shown that the second arterial graft to the circumflex circulation significantly improves both early and late survival, although these benefits did not extend to the use of additional arterial grafts to the right sided circulation.(2)^{, 14} Other groups have similarly shown late survival benefits from bilateral internal thoracic arteries and total arterial revascularization in retrospective, observational studies.(3, 4) ART (Arterial Revascularization Trial) is a randomized control trial that has recently failed to show a survival benefit of bilateral internal thoracic arteries at 1, 5 and 10 years of follow up.(5, 6)^{, 21} There was however an additional benefit of a radial artery in 20% of the patients in the single internal thoracic artery group.(7) The trial failed to show any differences, even at 10 years.(8) The trial may not have been adequately powered for differences to emerge in the intention to treat analysis due to large number of cross overs and high attrition.(9, 10) Hidden confounders and metodological flaws of randomized controlled trials and forward frequentist analysis may explain some of the discrepancies between the trial results and observational data.(11, 12) The ROMA trial which is underway may be able to address some of the weaknesses of the ART trial.(13, 14)

There is no consensus on the age at which the survival benefits of additional arterial grafting diminish. Venous grafts have been shown to undergo late accelerated degeneration from the 3^rd to 4^th year onwards due to progressive atherosclerosis.(15-18) The potential survival benefits of a second arterial graft are possibly from improved patency compared to venous grafts. Theoretically at least, patient cohorts with a life expectancy of at last 7-8 years should potentially benefit from absence of a failed second venous graft related morbidity and mortality. It is also likely for these reasons that any potential survival benefits, even in the young, are unlikely to be realized before this late accelerated inflection point in vein graft patency at 4-5 years. Similar considerations may apply to further arterial grafts to the circumflex and right coronary circulations where larger cohorts and longer studies in more elderly age groups may be needed to demonstrate any further benefits.(19) As seen in this analysis, these survival benefits are much greater in younger patients but persist in other age groups albeit with progressively diminishing magnitudes.

Kurlanski et al found significant survival benefit with bilateral IMA (BIMA) in all groups <65 years, 65-70, and >65 years in their retrospective analysis of 4,503 consecutive isolated coronary artery bypass grafting operations (SIMA, n=2,340 and BIMA, n=2,163).(20) Actuarial curves after 23,593 patient-years of follow-up demonstrated improved long-term survival for BIMA versus SIMA patients at 12 years (51.0 ± 1.5% versus 39.0 ± 1.5%) and at 24 years (3.5 ± 0.7% versus 4.5 ± 0.7%; p < 0.001). Similarly, in matched groups of patients age 70 and older, overall survival was also enhanced with BIMA grafting (p < 0.005). In contrast, the APPROACH investigators in the Canadian cardiovascular registry of 5601 patients (mean follow up 7.1 years) could not show any statistically significant benefits of BIMA grafting in patients older than 70 years (HR, 0.87; 95% CI, 0.69 to 1.08; p = 0.2).(21) In an older study (1992-2005), Mohamadi et al similarly found age to be a significant covariate in their statistical model.(22) The cardiac-related survival benefit with BIMA was superior to that of SIMA grafting up to 60 years of age. This benefit decreased over time. Compared to only vein grafts, use of a single ITA was superior for cardiac-related survival in all age groups, including octogenarians.

Benedetto et al used spline analysis to demonstrate the age cut off for benefit from additional arterial grafts in their single institution study.(23) Their analysis was confined to radial artery as a second graft as opposed to saphenous vein grafts. Most of their patients had conventional on-pump CABG. They however did not specify if the radial artery was used as a second conduit to the right or the left coronary circulation (86% had obtuse marginal grafts and 73% had right coronary grafts in the unmatched radial artery group). The benefit was maximum in patients aged 60 years or younger (upper limit of 95% CI,<1). The survival advantage conferred by radial artery use gradually declined with increasing age, and it was no longer present beyond 70 years of age.

Use of BIMA for left-sided grafts in completely an-aortic off-pump technique has previously been shown to confer a small survival advantage especially in high risk and elderly patients possibly from prevention of adverse neurological sequelae.(24, 25)

The age range for the ‘elderly’ has gradually increased as the results of cardiac surgery have improved over the last few decades. The average life expectancy has increased in the developed nation and the demographics of patients referred for CABG has changed over the last few decades. An increasing number of ‘elderly’ patients now have a longer expectant life ahead of them after CABG. Our matched data shows that these survival benefits gradually diminish with increasing age but they are seen across all age groups up to 80 years of age. Elderly patients are also likely to benefit and should not be denied a second arterial graft to circumflex circulation based on sole considerations of age.

Limitations

This is a retrospective single center study. The nature of grafts and their patency were not examined for any of the left or right sided grafts. The results would need to be interpreted cautiosly due to the small number of cases at risk in the cohorts. Larger cohorts and longer follow is required to further substantiate these findings.

CONCLUSIONS

The survival benefit of an additional arterial graft to the circumflex circulation is seen in all age groups. Elderly patients should not be denied the benefits of second arterial grafts based on age criteria alone.

KEY ISSUES

• A second arterial graft to the circumflex circulation significantly improves survival
• This survival benefit of an additional arterial graft to the circumflex circulation persists despite increasing age
• Coronary arterial revascularization should not be denied based on age alone

REFERENCES

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FIGURE LEGENDS

Figure 1. Flow chart for study design

Figure 2. Odds ratio (odds of death venous to arterial) charted against age (abscissa). Table below provides the odds ratios for each age group.