Lipid-lowering effect of preoperative statin therapy on postoperative major adverse cardiac events after coronary artery bypass surgery

Article Outline

• Abstract
• Materials and Methods
  • Study Design
  • Data Collection
  • Outcome Measures
  • Definitions
  • Statistical Analysis
• Results
• Discussion
• References
• Copyright

Objective

Statins are powerful lipid-lowering drugs that have been proved effective in the prevention of coronary artery disease, clearly reducing the risk of mortality and cardiovascular events. Whether hyperlipidemic patients undergoing coronary artery bypass grafting profit from the lipid-lowering beneficial effects of statins is as yet uncertain. We sought to determine whether preoperative statin therapy may have an effect on outcome among hyperlipidemic patients undergoing coronary artery bypass grafting.

Methods

From January 2000 through March 2006, prospectively recorded clinical data from 3346 consecutive patients undergoing isolated first-time elective coronary artery bypass grafting were analyzed for major adverse cardiac events and all-cause in-hospital mortality. Of these, 167 patients had preoperative statin-untreated hyperlipidemia (group 1), 2592 had statin-treated hyperlipidemia (group 2), and 587 had statin-untreated normolipidemia (group 3).

Results

Risk-adjusted multivariate logistic regression analysis revealed statin-treated hyperlipidemia (odds ratio, 0.42; 95% confidence interval, 0.26-0.69; P = .0007) and statin-untreated normolipidemia (odds ratio, 0.42; confidence interval, 0.26-0.69; P = .0007) to be independently associated with reduced in-hospital major adverse cardiac events but not with in-hospital mortality. To further control for selection bias, a computed propensity score matching based on 14 major preoperative risk factors was performed. After propensity matching, conditional logistic regression analysis confirmed statin-treated hyperlipidemia and statin-untreated normolipidemia to be strongly related to reduced in-hospital major adverse cardiac events (odds ratio, 0.41; 95% confidence interval, 0.24–0.71 [P = .0013] and odds ratio, 0.23; 95% confidence interval, 0.11–0.48 [P = .0001]) but not with in-hospital mortality (odds ratio, 1.18; 95% confidence interval, 0.36–3.87 [P = .79] and odds ratio, 1.10; 95% confidence interval, 0.32–4.41 [P = .80]) after coronary artery bypass grafting surgery.

Conclusions

Hyperlipidemic, but not normolipidemic, patients have an increased risk for in-hospital major adverse cardiac events and therefore clearly benefit from preoperative statin therapy before coronary artery bypass grafting surgery.

CTSNet classification: 16, 23, 30

Abbreviations and Acronyms: CAD, coronary artery disease, CI, confidence interval, LCOS, low cardiac output syndrome, LDL-C, low-density lipoprotein cholesterol, MACE, major adverse cardiac event, PMI, perioperative myocardial infarction, OR, odds ratio

Hyperlipidemia is known as one of the major risk factors associated with vascular endothelial injury, causing atherosclerotic plaque formation and coronary artery disease (CAD) that result in recurrent ischemic cardiovascular events.¹ Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, statins, are recognized as powerful lipid-lowering drugs that have been proved highly effective in primary and secondary prevention of CAD, decreasing low-density lipoprotein cholesterol (LDL-C) levels and thereby reducing the risk of mortality and cardiovascular adverse events in hyperlipidemic and normocholesterolemic patients.² In terms of surgical intervention, preoperative statin therapy has recently been shown to reduce the risk of early mortality in noncardiac³, ⁴, ⁵ and cardiac⁶, ⁷, ⁸, ⁹ operations, suggesting early beneficial effects of statin treatment, irrespective of hyperlipidemia. To further differentiate lipid-dependent early beneficial statin effects, we sought to determine whether preoperative statin therapy might be associated with a reduced risk of postoperative death or major adverse cardiac events (MACEs) in patients with hyperlipidemia undergoing CABG and whether statin-untreated normolipidemic patients might have in turn an increased risk for postoperative death and MACEs after CABG.

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Materials and Methods 

Study Design 

This study was a retrospective single-center cohort study including 3346 consecutive patients who underwent first-time isolated elective CABG at the West German Heart Center Essen between January 2000 and March 2006. Patients were included in and classified into one of 3 groups, depending on whether they had statin-untreated hyperlipidemia (group 1), statin-treated hyperlipidemia (group 2), or statin-untreated normolipidemia (group 3) before CABG surgery. The most recent levels of total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglyceride in serum within 1 month before surgical intervention were recorded. Hyperlipidemia was defined as a serum total cholesterol level of 200 mg/dL or greater and/or a low-density lipoprotein level of 130 mg/dL or greater and/or use of lipid-lowering statin therapy with a history of hyperlipidemia. Preoperative statin therapy consisted of one the following statins before CABG: pravastatin, simvastatin, fluvastatin, atorvastatin, cerivastatin, or lovastatin. Surgical revascularization was routinely performed as previously described¹⁰ in all patients by using a median sternotomy, a standard CPB technique with ascending aortic and 2-stage venous cannulation, mild hypothermia (>32°C), and cold crystalloid cardioplegic arrest. Off-pump coronary operations, emergency or urgent surgical intervention, previous myocardial infarction (<4 weeks) before CABG, reoperative procedures, or concomitant operations were the exclusion criteria. The institutional review board approved the study. All of the patients had previously granted permission for use of their medical records for research purposes.

Data Collection 

Data used in this analysis were retrieved from the West German Heart Center cardiovascular surgical database. This database prospectively collects a comprehensive list of prespecified data points, with more than 1800 data items per patient for all of the consecutive patients undergoing CABG surgery at our institution, including demographic, clinical, and outcome data. Within the database, patients were coded as having statin-untreated hyperlipidemia, statin-treated hyperlipidemia, or statin-untreated normolipidemia.

Outcome Measures 

All outcome measures used in this analysis were prespecified. Given the subject nature of many clinical outcomes, we only prespecified all-cause in-hospital mortality after CABG as the primary study end point. The prespecified secondary end point was the MACE rate, including sudden cardiac death, cardiac death, low cardiac output syndrome (LCOS), and perioperative myocardial infarction (PMI), during the postoperative hospitalization period. An independent review of the medical records of the patients who died after CABG operations was performed, and cardiac versus noncardiac cause of death was adjudicated.

Definitions 

In-hospital death was defined as death after CABG during the index hospitalization. A PMI was considered to have occurred if one of the following diagnostic criteria were present: (1) a cardiac troponin I level of greater than 10.5 ng/mL after CABG, as previously described¹¹; (2) a creatine kinase–MB level 3 times greater than the upper normal level; (3) new persistent ST-segment or T-wave changes (Minnesota code 4-1, 4-2, 5-1, 5-2, or 9-2); or (4) the development of new Q-waves (Minnesota code 1-1-1 to 1-2-7). LCOS was supposed with a cardiac index of less than 2.0 L · min⁻¹ · m⁻² or a systolic arterial pressure of less than 90 mm Hg, despite high-dose inotropic support (intravenous dopamine, ≥8 μg · kg⁻¹ · min⁻¹; dobutamine, ≥6 μg · kg⁻¹ · min⁻¹; epinephrine, >0.1 μg · kg⁻¹ · min⁻¹; or norepinephrine, >0.1 μg · kg⁻¹ · min⁻¹). Death was considered cardiac if it was caused by PMI, significant cardiac arrhythmias, or refractory LCOS. Sudden unexpected death occurring without another explanation was defined as sudden cardiac death.

Statistical Analysis 

Descriptive statistics are summarized for categoric variables as frequencies (percentages) and compared between groups by using the Pearson χ² exact test. Continuous variables, expressed as means ± standard deviations or as medians (interquartile ranges), were compared between groups by using the Kruskal–Wallis test. When a significant overall effect was detected, 2 group comparisons were performed with the Fisher exact test or the Mann–Whitney U test. Univariate and multivariate logistic regression were performed to identify preoperative independent predictors for in-hospital mortality and MACEs. Those variables identified by means of univariate regression analysis with a P value of .05 or less for at least 1 study end point were added to the multivariate logistic regression model. Propensity score matching was performed to control for selection bias as a result of nonrandom assignment to the 3 groups.¹² The propensity scores were calculated separately, comparing group 1 versus group 2 and group 1 versus group 3. The following patient characteristics and major preoperative risk factors were used to calculate propensity scores: age, sex, diabetes, hypertension, hyperlipidemia, left ventricular ejection fraction, renal disease, previous myocardial infarction, left main disease, chronic obstructive pulmonary disease, peripheral vascular disease, angina class III ot IV, aspirin and β-blocker use, and the number of bypassed vessels. For both comparisons, patients with similar propensity scores were combined into 20 matched sets of equal size. Once patients were matched, conditional logistic regression was used.¹³ All statistical analyses were performed with the SAS System, version 8 (SAS Institute, Inc, Cary, NC).

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Results 

Of the 3346 patients included in the present analysis, 167 hyperlipidemic patients underwent CABG surgery without preoperative statin therapy in group 1, whereas 2592 hyperlipidemic patients were taking statin therapy before surgical intervention in group 2, and 587 patients were normolipidemic without statins before surgical intervention in group 3. Preoperative characteristics of the patients are presented in Table 1. Patients were not significantly different according to their demographics, risk factors, and comorbidities, except for age and a higher number of patients with hypertension in group 2 compared with those in groups 1 and 3. Patients did not differ according to their cardiac history and their extent of CAD, but statin-treated patients received significantly more β-blockers and tended to have more aspirin use compared with the statin-untreated hyperlipidemic and normolipidemic patients. Preoperative lipid levels showed a significant difference in the total cholesterol level, as well as the LDL-C levels, of statin-untreated group 1 compared with statin-treated group 2, whereas high-density lipoprotein cholesterol and triglyceride levels did not show any statistical difference between the groups. Intraoperative results did not differ between the groups (Table 2). As a result, the usual postoperative outcome data, such as length of ventilation time and intensive care unit and hospital stay, did not differ between the groups. The incidence of postoperative complications, such as postoperative stroke, supraventricular or ventricular arrhythmias, rethoracotomy, and other complications, were also not different (Table 2).

TABLE 1. Preoperative patient characteristics

	Group 1, statin-untreated HLP (n = 167)	Group 2, statin-treated HLP (n = 2592)	P value (group 1 vs group 2)	Group 3, statin-untreated NLP (n = 587)
Demographics
Age, y	65±9	66±9	<.001	67±9⁎†
Sex, female	37(22)	607(23)	.78	128(22)
Risk factors and comorbidities
Diabetes mellitus	57(34)	857(33)	.80	191(33)
Hypertension	137(82)	2278(88)	.04	423(72)⁎†
Hyperlipidemia	167(100)	2592(100)	1.00	0(0)⁎†
Obesity(BMI >30)	86(52)	1191(46)	.17	253(43)⁎
Smoking past 2 mo	32(19)	448(17)	.53	118(20)
Smoking past 1 y	61(37)	906(35)	.33	185(32)⁎
COPD	24(14)	458(18)	.30	110(19)
Peripheral vascular disease	21(13)	407(16)	.32	72(12)
Renal disease(>1.8 mg/dL)	21(13)	332(13)	1.00	65(11)
Cardiac history
Angina CCS III-IV	21(13)	278(11)	.44	72(12)
Previous MI(>4 wk)	62(37)	935(36)	.80	214(36)
Previous PCI	28(17)	480(19)	.68	91(15)
LVEF, %	58±14	57±14	.94	56±15⁎
Extent of CAD
Triple-vessel disease	124(74)	2047(79)	.60	449(77)
Left main disease	41(25)	768(30)	.19	167(28)
Serum lipid levels
Total cholesterol, mg/dL	219±55	183±64	.02	166±53⁎†
LDL-C, mg/dL	147±54	109±38	.01	103±25⁎†
HDL-C, mg/dL	47±16	46±15	.92	48±16
Triglyceride, mg/dL	190±89	181±105	.77	162±81⁎†
Additional medication
Aspirin	92(55)	1602(62)	.09	311(53)†
β-Blocker	121(73)	2049(79)	.05	408(70)†
ACE inhibitor	107(65)	1703(66)	.17	316(54)⁎
Nitrates	94(56)	1428(55)	.67	331(56)

Data are presented as means±standard deviation or number(percentage). HLP, Hyperlipidemia; NLP, normolipidemia; COPD, chronic obstructive pulmonary disease; CCS, Canadian Cardiovascular Society; MI, myocardial infarction; PCI, percutaneous coronary intervention; LVEF, Left ventricular ejection fraction; LDL-C, low-density lipoprotein cholesterol; HDL-C, High-density lipoprotein cholesterol; ACE, angiotensin-converting enzyme.

TABLE 2. Intraoperative and postoperative characteristics

	Group 1, statin-untreated HLP (n = 167)	Group 2, statin-treated HLP (n = 2592)	P value (group 1 vs group 2)	Group 3, statin-untreated NLP (n = 587)
Intraoperative data
ACC time, min	70±24	72±24	.42	70±23
CPB time, min	112±38	112±38	.11	111±37
Reperfusion time, min	34±17	35±19	.38	34±16
Grafts per patient, n	3.0±0.8	3.0±0.8	.98	3.0±0.8
Mean graft flow, mL/min	54±32	57±31	.13	54±36
Postoperative data
Ventilation time, h	8(6–12)	8(6–12)	.34	8(6–12)
IABP support	10(6)	120(5)	.45	22(4)
ICU stay, d	1(1–3)	1(1–3)	.87	1(1–3)
Hospital stay, d	9(7–13)	8(6–12)	.14	8(7–12)
Postoperative complications
Stroke	3(2)	54(2)	1.00	9(2)
Renal failure(dialysis)	10(3)	92(3)	.13	14(2)
Supraventricular arrhythmia	15(9)	201(8)	.55	46(8)
Ventricular arrhythmia	36(22)	526(20)	.69	112(19)

Data are presented as means±standard deviation, number(percentage), or median and interquartile range(15%-75%). HLP, Hyperlipidemia; NLP, normolipidemia; ACC, aortic crossclamp; CPB, cardiopulmonary bypass; IABP, intra-aortic balloon pump; ICU, intensive care unit.

The postoperative incidence of primary and secondary study end points are presented in Figure 1, Figure 2. The incidence of all-cause in-hospital death did not differ between the groups. The in-hospital MACE rate, however, showed a significant risk reduction in statin-treated hyperlipidemic patients compared with that in statin-untreated hyperlipidemic patients (from 12.6% to 5.7%, P = .001), which was almost comparable with that of statin-untreated normolipidemic patients, who had a MACE rate of 4.3%. By analyzing all secondary end points, no statistical difference was found regarding the incidence of sudden cardiac death and cardiac death. The incidence of postoperative LCOS was halved in the statin-treated group 2 but did not reach statistical significance (P = .07). Postoperative myocardial infarction, however, was significantly less in group 2 (5.1%) compared with that in group 1 (10.2%, P = .01) and therewith reached almost the incidence of the normolipidemic group 3 patients.

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• Figure 1. 

  Incidence of death and major adverse cardiac events (MACE) during the hospital stay. P values indicate overall significance between groups 1 and 2 calculated by using the Pearson χ² exact test. OR, Odds ratio; CI, confidence interval.

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• Figure 2. 

  Incidence of secondary end points during the hospital stay. P values indicate overall significance between groups 1 and 2 calculated by using the Pearson χ² exact test. OR, Odds ratio; CI, confidence interval; LCOS, low cardiac output syndrome; PMI, perioperative myocardial infarction.

A logistic regression analysis model was constructed to evaluate independent preoperative predictors of death, and several univariate factors were found to be predictive of death (Table 3). After risk adjustment, a multivariate logistic regression analysis revealed age, left ventricular function, peripheral vascular disease, and chronic obstructive pulmonary disease to be independently related to in-hospital death, but none of the 3 groups were independent predictors of death. As independent predictors for MACEs, the multivariate regression analysis revealed previous myocardial infarction, renal disease, and the number of grafted vessels as highly related to MACEs, whereas preoperative statin treatment of hyperlipidemic patients of group 2 and normolipidemic patients of group 3 significantly reduced the risk of in-hospital MACEs (Table 4).

TABLE 3. Univariate and multivariate logistic regression analysis of variables associated with in-hospital death

	Univariate analysis		Multivariate analysis
	Odds ratio(95% CI)	P value	Odds ratio(95% CI)	P value
Age, y	1.06(1.03–1.09)	<.0001	1.06(1.02–1.09)	.0006
Sex, female	1.06(0.65–1.74)	.82	—	—
Obesity	1.10(0.82–1.46)	.51	—	—
Left main stem disease	1.11(0.70–1.76)	.67	—	—
LVEF, %	0.98(0.97–0.99)	.01	0.99(0.97–1.00)	.04
Peripheral vascular disease	2.70(1.70–4.33)	<.0001	1.91(1.11–3.29)	.02
COPD	2.82(1.80–4.44)	<.0001	2.24(1.34–3.75)	.002
Diabetes mellitus	1.74(1.13–2.69)	.01	1.53(0.94–2.50)	.09
Hypertension	1.49(0.71–3.10)	.29	—	—
Angina CCS III-IV	1.86(1.09–3.17)	.02	1.24(0.69–2.25)	.47
Previous MI	1.32(0.86–2.04)	.21	—	—
Renal disease	2.02(1.21–3.36)	.007	1.21(0.67–2.21)	.70
Aspirin	1.35(0.84–2.16)	.64	—	—
β-Blockers	0.93(0.68–1.27)	.64	—	—
No. of bypassed vessels	1.22(0.95–1.56)	.12	—	—
Group 1: statin-untreated HLP	Reference	Reference	Reference	Reference
Group 2: statin-treated HLP	1.10(0.40–3.05)	.86	—	—
Group 3: statin-untreated NLP	1.07(0.35–3.27)	.91	—	—

CI, Confidence interval; LVEF, left ventricular ejection fraction; COPD, chronic obstructive pulmonary disease; CCS, Canadian Cardiovascular Society; HLP, hyperlipidemia; NLP, normolipidemia.

TABLE 4. Univariate and multivariate logistic regression analysis of variables associated with MACEs

	Univariate analysis		Multivariate analysis
	Odds ratio(95% CI)	P value	Odds ratio(95% CI)	P value
Age, y	1.01(1.00–1.03)	.05	1.02(0.99–1.04)	.10
Sex, female	1.13(0.81–1.57)	.49	—	—
Obesity	1.10(0.81–1.53)	.51	—	—
Left main stem disease	0.93(0.67–1.28)	.65	—	—
LVEF, %	0.98(0.97–0.99)	.001	0.99(0.98–1.00)	.11
Peripheral vascular disease	1.65(1.16–2.35)	.006	1.26(0.83–1.90)	.28
COPD	1.69(1.21–2.37)	.002	1.33(0.90–1.96)	.16
Diabetes mellitus	1.31(0.97–1.77)	.08	—	—
Hypertension	1.60(0.96–2.67)	.07	—	—
Angina CCS III-IV	1.57(1.11–2.21)	.01	1.36(0.92–2.01)	.12
Previous MI	1.63(1.22–2.19)	.001	1.46(1.04–2.05)	.03
Renal disease	1.70(1.18–2.45)	.005	1.45(0.95–2.22)	.09
Aspirin	0.83(0.62–1.13)	.23	—	—
β-Blockers	0.78(0.59–1.04)	.08	—	—
No. of bypassed vessels	1.29(1.09–1.54)	.004	1.32(1.09–1.59)	.005
Group 1: statin-untreated HLP	Reference	Reference	Reference	Reference
Group 2: statin-treated HLP	0.42(0.26–0.69)	.0005	0.37(0.22–0.63)	.0003
Group 3: statin-untreated NLP	0.31(0.17–0.57)	.0002	0.27(0.14–0.53)	.0001

MACE, Major adverse cardiac event; CI, confidence interval; LVEF, left ventricular ejection fraction; COPD, chronic obstructive pulmonary disease; CCS, Canadian Cardiovascular Society; HLP, hyperlipidemia; NLP, normolipidemia.

In an attempt to further correct for and minimize selection bias, a computed propensity score matching of the study groups based on 14 major preoperative risk factors was performed, comparing group 1 versus group 2 and group 1 versus group 3. The c-index for the propensity score model was 0.82, indicating that the model exhibits very good discrimination in separating dichotomies. Even after propensity score matching, a conditional regression analysis confirmed that there was no risk reduction for death, either with preoperative statins in hyperlipidemic patients (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.36–3.87; P = .79) or in statin-untreated normolipidemic patients (OR, 1.10; 95% CI, 0.32–4.41; P = .80), but as the main result, there was a significant risk reduction for in-hospital MACEs for statin-treated hyperlipidemic patients (OR, 0.42; 95% CI, 0.24–0.71; P = .0013), which was almost at the same level of statin-untreated normolipidemic patients (OR, 0.23; 95% CI, 0.11–0.48; P = .0001).

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Discussion 

The present study is the first to clearly demonstrate that preoperative statin therapy is significantly associated with a risk reduction of in-hospital MACEs, particularly nonfatal PMI, in patients with hyperlipidemia undergoing CABG surgery. However, preoperative statin therapy is not associated with reduced in-hospital mortality compared with that seen in statin-untreated hyperlipidemic or normolipidemic patients. Conversely, the present study also demonstrates that statin-untreated normolipidemic patients are not at any short-term increased risk, either for in-hospital mortality or for MACEs, compared with statin-treated hyperlipidemic patients. Finally, preoperative statin therapy does not seem to be superior in terms of reduced early mortality and MACE rate compared with values seen in statin-untreated normolipidemic patients, suggesting that these early beneficial statin effects predominantly seem to be due to their lipid-lowering properties.

Numerous clinical trials have demonstrated that decreasing LDL-C levels is highly effective in primary and secondary prevention of CAD by substantially reducing the risk of adverse cardiovascular events, particularly in selected groups of patients with hyperlipidemia,² familial atherosclerosis,¹⁴ a previous history of CABG,¹⁵, ¹⁶ or acute coronary syndromes¹⁷ or during coronary interventions,¹⁸ but favorable statin effects are also seen, irrespective of baseline LDL-C levels and the presence or absence of other cardiac risk factors.¹⁹ There is also evidence that coronary plaque’s inflammatory characteristics strongly influence the likelihood of plaque rupture, which is at highest risk in hyperlipidemic patients. Plaque rupture occurs either spontaneously or as a result of coronary manipulation (by means of percutaneous coronary intervention or CABG surgery), causing microinfarctions with myocardial inflammatory response as a result of microembolization,²⁰ which in turn is reduced in patients undergoing statin treatment.¹⁷, ²⁰, ²¹, ²² In the setting of cardiac surgery, preoperative statin therapy has been proved effective in several recent clinical studies by reducing the release of proinflammatory cytokines, thus attenuating postoperative inflammatory reactions after cardiac surgery with cardiopulmonary bypass.²³, ²⁴ Moreover, several recent large-scale observational cohort studies analyzed whether favorable effects of preoperative statins might exist, irrespective of whether patients had preoperatively increased LDL-C levels or hyperlipidemia.⁶, ⁷, ⁸, ⁹ However, most of the recent large-scale clinical trials analyzed the efficacy of preoperative statin treatment by pooling those patients with increased LDL-C levels and statin-untreated hyperlipidemia, which is the primary target of lipid-lowering statin therapy, with statin-untreated normolipidemic patients and therefore failed to define the outcome in statin-untreated normolipidemic patients. Moreover, to date, little is known about the potential early benefit of serum cholesterol reduction in more defined subgroups of patients undergoing CABG with hyperlipidemia and CAD undergoing surgical intervention. The present study therefore precisely defined the study groups, not only focusing on preoperative statin treatment but also considering the preoperative lipid levels, which were not addressed in the previous statin outcome studies performed in patients undergoing CABG surgery.⁶, ⁷, ⁸, ⁹ Thus we could clearly demonstrate that early beneficial effects of preoperative statin therapy, resulting in a significantly reduced incidence of PMI, only exist in statin-treated hyperlipidemic patients after CABG.

Although normolipidemic patients who did not receive preoperative statins had no increase in MACEs in this series, results from other CABG studies⁶, ⁷, ⁸, ⁹, ¹⁶ and those of patients with acute coronary syndromes²⁵ would suggest that all patients undergoing CABG, irrespective of their baseline LDL-C levels, might benefit form perioperative and long-term statin therapy. Although some of those patients might not exhibit immediate short-term benefits, the present study did not examine long-term MACEs and the incidence of future cardiovascular events. It is likely that this cohort of patients will also benefit from the reduction of long-term MACEs by instituting perioperative statin therapy, despite their lower preoperative LDL-C levels.

The major limitation of the present study is its retrospective and nonrandomized design. Additionally, there are several important preoperative group differences in clinical characteristics and risk factors, as well as in the unequal study group size itself. Furthermore, statin-untreated hyperlipidemic patients might well be identified as a surrogate for patients receiving “substandard preoperative medical care” and therefore be vulnerable to other untreated maladies. We therefore accounted for these differences by means of careful statistical adjustment, using multivariate risk-adjusted and propensity score–adjusted regression models. In addition, the small sample size of statin-untreated patients during the observation period of more than 6 years indicates today’s widespread and highly established use of statins. Furthermore, the effect of precise preoperative statin therapy, considering the dose and duration, before CABG was not analyzed and should be addressed in future studies.

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