The literature search including manual bibliography checks yielded 4885 citations. The vast majority were rejected immediately for reasons such as ineligible language or patient population. Full papers were retrieved for 596 abstracts that had no apparent reason for exclusion. Of these, 388 were subsequently rejected for reasons of absence of reporting of AEs of interest, unclear timing of AEs, or mixing of data of patients undergoing CABG and data of patients having valve replacement or other concomitant procedures, or because only late (after 30 days) postoperative AEs were reported. In addition, several publications reported on the same patient population (kin studies), and these were extracted as one study to avoid double counting of results. Therefore, 176 primary and 32 kin studies were found to satisfy all inclusion criteria and were included in this review. A citation list of 176 primary studies is provided in the appendix on the Heart website.
The accepted studies were conducted in Europe (k = 54, n = 34 437) and North America (k = 91, n = 154 524), and 31 (n = 16 706) were multinational trials or studies conducted in other geographic locations. There were 69 RCTs (n = 9598), 13 non-RCTs (n = 2019), and 94 cohort studies (n = 194 050). The majority of studies were conducted in a single centre (k = 146, n = 105 104) and 30 studies (n = 100 563) were multicentre trials evaluating in total approximately the same number of patients as all the single centre studies. Most of the studies were published very recently, after 1995 (k = 135).
Patient and treatment characteristics
Table 1 summarises baseline and operative patient characteristics. There were 176 treatment groups overall, comprising 205 667 patients. The majority of patients in all studies were men (81.6%). The average age of all patients ranged from 35–71.3 years with the overall mean being 62.8 years. In the 31 studies reporting New York Heart Association (NYHA) classification, more than half of all patients (67.6%) were in NYHA class III or IV. Approximately 10% of patients in this set of studies had low left ventricular ejection fraction (< 35–40%).
Table 1 also shows the prevalence of comorbid conditions and risk factors among patients in these studies. More than 50% of patients in groups reporting this information had hypertension or high cholesterol concentration (52.1% and 54.2%, respectively). Previous MI was reported by 46.7% and unstable angina by 32.1% of patients in groups reporting these histories. There was also a significant proportion of patients who had previous CABG or revascularisation (5.8% and 6.1%, respectively).
CABG surgery was urgent or an emergency in 28% of patients in 115 studies. During CABG, patients received an average of 3.2 grafts (range of means 1–4.5). Only two studies were single graft studies.
In-hospital adverse events
Table 2 displays the incidences of in-hospital AEs. MI, both all MIs
and non-fatal MIs
, was the most prevalent AE in the overall CABG population and across all stratified categories. Because of the various diagnostic criteria used to define MI, the incidence of MI
differs widely across the studies, from 0–29.2% with the average of 3.9% (median 2.9%). In five studies (all RCTs) it was greater than 10% (Carrier 1998, Menashe 1995, Multicenter Study of Perioperative Ischemia 1995, Mullis-Jansson 1999, and Searle 1996). The incidence of MI differed significantly between RCTs and cohort studies (6.3% v
2.7%, p < 0.05) and between single centre and multicentre studies (2.8% v
7.9%, p < 0.01). A greater incidence of MI was found in studies enrolling patients with prior CABG than in those without prior CABG (6.5% v
2.7%), but this did not reach significance. Non-fatal MI occurred on average in 2.4% (median 2.4%, range 0–13.9%) of the overall CABG patients and was slightly lower in elective CABG than in mixed (2.3% v
2.6%). Interestingly, older age (> 60 years) and lower mean ejection fraction (
50%) were not associated with a higher incidence of MI.
Post-CABG adverse event incidence and mortality
occurred in 1.3% (median 1.3%, range 0–3.2%) of patients and the incidence was lower in groups with elective surgery (1.0% v
1.5%) and no prior CABG (1.0% v
1.8%), and it was significantly lower in RCTs than in cohort studies (1.0% v
1.5%, p < 0.01). Surprisingly, in studies that did not distinguish between fatal and non-fatal strokes (strokes
), the rate appeared to be higher in younger groups (mean age
60 years, 2.8% v
1.9%), but it was not significant.
Gastrointestinal bleeding was reported by only eight studies. Overall, the incidence of gastrointestinal bleeding after CABG among 12 897 patients was 1.5% (median 1.2%, range 0.7–2.7%). Patients without prior CABG appeared to have a higher incidence of gastrointestinal bleeding than the groups where some patients had prior bypass surgery (2.6% v 1.5%). But, with so few studies, no differences were significant in the incidence of gastrointestinal bleeding with respect to any of the variables assessed.
The incidence of renal failure requiring dialysis was low. In 23 studies (n = 22 798) on average 0.8% (median 0.7%, range 0–6.2%) of patients needed dialysis after CABG. The frequency was higher in studies enrolling patients with urgent or emergency CABG than in elective CABG only (0.9% v 0.5%) and it was significantly higher in cohort studies than in RCTs (1.0% v 0.4%, p < 0.05).
Postoperative mortality rate during hospital stay was 1.7% (median 1.5%) in the overall CABG population and ranged from 0–6.6%. When studies were stratified as elective versus mixed (including patients with urgent or emergency CABG), the mortality rate was significantly lower in the elective CABG (1.5% v 1.8%, p < 0.05). In-hospital mortality rate was higher in studies enrolling older patients (mean age > 60 years, 1.8% v 1.2%) and in patients with no history of prior CABG (1.2% v 1.9%). A significantly lower incidence of death was also noted in RCTs than in cohort studies (1.5% v 1.8%, p < 0.05) and in single centre studies than in multicentre studies (1.5% v 2.5%, p < 0.05).
30 Day adverse events
Except for deaths, AEs at 30 days after surgery were not commonly reported. There were 70 studies that reported a mortality rate for death in hospital or within 30 days after surgery. An average 2.1% (median 2.0%, range 0–7.7%) of all CABG patients died within 30 days (table 2). In the overall CABG category the 30 day mortality rate was higher than the overall in-hospital death rate (2.1% v
1.7%). Among stratified categories 30 day mortality incidence differed significantly with respect to number of study sites (single versus multicentre), elective versus mixed CABG groups, and mean age (
60 or > 60 years), with the greater incidence in the latter category in each instance.
The 30 day outcomes for MI, stroke, gastrointestinal bleeding, and renal failure were reported too infrequently; therefore, a meta-analysis of the incidence of these events was not performed.
Since the incidence of major AEs after CABG surgery appears to differ in RCTs and cohort studies, we performed similar stratified analyses for all outcomes of interest separately for RCTs and cohort studies. These findings were consistent with the overall analysis of the incidence of major AEs after CABG and further confirmed the potential influence of some study (geographic location, number of study centres) and group variables (elective CABG only versus some patients with urgent of emergency CABG, some patients with a history of prior CABG versus primary CABG).
The potential impact of cardiopulmonary bypass duration on patient outcomes was tested in the meta-regression analysis. A weak but significant positive relation (p = 0.02) was noted between cardiopulmonary bypass duration and incidence of non-fatal MI. There was no significant relation between cardiopulmonary bypass duration and any of the other outcomes. It should be noted that the lack of significant findings does not imply that there is no relation between cardiopulmonary bypass duration and increased risk of AEs at the patient level. The metaregression can only investigate the study level relation between mean cardiopulmonary bypass duration and incidence of AEs, and thus this investigation has much lower power than an individual patient analysis would have.
Analysis of risk factors
In the set of 176 studies accepted in this review, there were 22 studies in which either risk factor odds ratios were reported for the AEs of interest or the information on these was available and it was possible to calculate the odds ratio of interest. Table 3 shows the individual study odds ratios and meta-analytical results for 30 day mortality by risk factors. These results clearly suggest that old age, female sex, presence of diabetes and hypertension, and history of prior heart surgery and MI are associated with increased risk of death after CABG. Except for diabetes (too few studies), the same is true for stroke (data not shown). The data were too sparse to perform similar meta-analyses for MI and renal failure; however, evidence suggests that female sex, age, and diabetes are positively related to incidence of renal failure after CABG.
Odds ratios for 30 day mortality after CABG