The Impact of Myocardial Revascularization After Acute Coronary Syndromes on One-Year Cardiovascular Mortality

Correspondence to I. Milvidaitė, Department of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Eivenių 2, 50028 Kaunas, Lithuania E-mail: irena.milvidaite@kaunoklinikos.lt Adresas susirašinėti: I. Milvidaitė, LSMU MA Kardiologijos klinika, Eivenių 2, 50028 Kaunas El. paštas: irena.milvidaite@kaunoklinikos.lt The Impact of Myocardial Revascularization After Acute Coronary Syndromes on One-Year Cardiovascular Mortality


Introduction
During the last decades, myocardial revascularization (MR) applied in cases of acute coronary syndromes (ACSs) has signifi cantly reduced cardiovascular mortality during in-hospital period compared with those receiving only pharmacological treatment.Data comparing the impact of pharmacotherapy and MR on cardiovascular mortality during the posthospitalization in patients with ACSs are scarce and inconclusive.It has been reported that early invasive treatment in patients with ST-segment elevation myocardial infarction (MI) reduces mortality not only during in-hospital period, but also later, while in those with non-Q-wave ACSs, the positive impact of MR during one year after ACSs was observed only in high-risk patients (1)(2)(3)(4)(5).
The aim of our observation study was to evaluate the impact of MR performed after ACSs on cardiovascular mortality within one-year period.

Material and Methods
The study population comprised 1226 consecutive patients with signifi cant (≥70%) coronary artery (CA) stenoses, admitted to the Clinic of Cardiology, Hospital of Lithuanian University of Health Sciences (former Kaunas University of Medicine) because of ACSs.After one year, survival data of 1222 patients (99.7%) were collected.
The evaluation of patients' condition was performed using the data from the database of the Heart Center covering the period of hospitalization, and the obtained information was verifi ed using the patients' case histories.Demographic and clinical characteristics, selected laboratory fi ndings, cardiac medications and procedures, cardiovascular events, and outcomes were recorded on a standardized case report form by a study coordinator.The fi nal discharge diagnosis was made by the attending physician using one of the following categories: Q-wave MI, non-Q-wave MI, and unstable angina pectoris (UAP).The course and outcomes of the disease during one year were evaluated using the patients' records taken from the outpatient unit of the Department of Cardiology, data of the standardized questionnaire (postal or via phone), and information from the Residents' Register Service under the Ministry of the Interior and the Civil Registry Offi ce of Kaunas city.In case of hospitalization, new data were gathered by a systematic review of the patients' discharge lists.Data on patient's status and used medications were recorded on the standardized case report form.Information on procedures, including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG), accomplished during the follow-up was collected.
Myocardial infarction was diagnosed based on angina pain and its equivalents, markers of ischemic damage on ECG (new-onset Q wave, ST-segment and T-wave alterations), and an increase of more than 0.2 μg/L in troponin I levels.The diagnosis of UAP was confi rmed in the presence of the angina syndrome and ischemic changes on ECG without an increase in blood levels of troponin I.The degree of acute heart failure (HF) was evaluated according to the Killip classifi cation, and renal failure was considered as signifi cant when the peak creatinine clearance was <60 mL/min.During inpatient treatment, echocardiography was performed and echocardiographic fi ndings were assessed according to the guidelines of the American Society of Echocardiography and the European Association of Echocardiography (2005).The European System for Cardiac Operative Risk Evaluation (EuroSCORE) was used to assess patients' status, and risk was defi ned as high when score was more than 6.
Myocardial revascularization included successful (TIMI 3) PTCA performed during the inpatient period and CABG provided at the time of ACS and performed within 60 days from an acute MI episode.If the patient underwent PTCA during the early period and later CABG, the effectiveness of the latter procedure was evaluated.
The death registered during the period of one year following ACSs was defi ned as cardiovascular when the cause of death was one of MI complications (heart rupture, arrhythmias, conductional disorders, or acute HF), chronic HF, or stroke or when death occurred suddenly within the fi rst 6 hours from the onset of symptoms during the posthospitalization period.
Statistical Analysis.Statistical analysis was carried out with the SPSS statistical software for Windows, version 13.0.The comparison of continuous variables between groups was done using the Student t test.The Pearson chi-square test was used to evaluate differences for categorized variables.Logistic regression analysis was performed to relate power of MR to cardiovascular mortality during one year.Unadjusted odds ratio (OR) with 95% confi dence intervals was used to measure crude associations between the predictive variable and cardiovascular mortality.Age, previous MI, previous myocardial revascularization, arterial hypertension, Q-wave MI, Killip class, renal failure, paroxysmal atrial fi brillation, ventricular fi brillation, mitral insuffi ciency of second or higher degree, left ventricular ejection fraction (LVEF), number of diseased coronary vessels, peripheral artery disease, and previous stroke were included as confounding variables in multivariate models.Adjusted OR and 95% confi dence intervals were calculated for each independent variable.Patient survival was evaluated using the Kaplan-Meier method.Survival curves were compared using a log-rank test; the difference was considered statistically signifi cant if P<0.05.

Results
Among 1226 patients with ACSs, 540 had Qwave MI and 686 ACSs (339 had non-Q-wave MI and 347 had UAP).Invasive treatment was applied in 81.1% of patients with Q-wave MI and in 62.8% of patients with non-Q-wave ACSs (Table 1).
In case of Q-wave MI, PTCA was applied more frequently than CABG; in the presence of UAP, CABG was performed more commonly; and in case of non-Q-wave MI, both methods were applied in similar numbers of patients.In patients with Q-wave MI, in 79.5% of cases, PTCA was performed within the fi rst 12 hours; in 2.9% of cases, CABG was performed within the fi rst day; and in patients with non-Q-wave ACS, in 20.6% of cases, MR was performed within the fi rst 3 days.In total, invasive treatment was applied in 869 patients (70.9%): 496 patients underwent PTCA; 35, PTCA and CABG; 338, CABG; 357 patients (29.1%) received pharmacological treatment alone.Stents were implanted in 204 patients (41.1%) during PTCA.
Clinical characteristics of patients with ACSs who underwent myocardial MR during the inpatient period and those who received pharmacotherapy alone were compared (Table 2).
There were no age differences between patients who underwent MR during hospitalization and those who received only pharmacologic treatment; more than half of the patients were men.Patients who received pharmacotherapy alone signifi cantly more frequently had previously experienced MI, more frequently had previously undergone MR, and more frequently had arterial hypertension, diabetes mellitus, peripheral artery disease, or stroke.
Their clinical condition during the hospitalization was more severe, i.e., they more frequently had Killip class 3-4, paroxysmal atrial fi brillation, LVEF of <40%, eccentric LV hypertrophy, creatinine clearance of <60 mL/min, and EuroSCORE of more than 6.The patients who underwent MR more frequently had Q-wave MI and blood level of troponin I >10 μg/L as compared with the patients who received pharmacotherapy alone.More than half of the patients in both groups were at high operative risk.
During hospitalization, all patients received standard treatment with nitrates, heparin, betaadrenoreceptor blockers, angiotensin-converting enzyme inhibitors, antiplatelet agents, and statins.Data on medication use at 1 year were gathered for 1004 survivors (in 17.8% of cases, data were unavailable).Table 3 presents the comparison of medication usage between the different treatment strategy groups during 1 year after acute coronary syndromes.
There were no signifi cant differences in medication usage and performed PTCA rate between the groups (4.2% and 3.5%), but CABG was performed more frequently in patients who received pharma- During the inpatient period, cardiovascular death occurred in 61 patients (5.0%).Cardiovascular death occurred in 42 (7.8%) of the 540 patients with Q-wave MI and in 19 (2.8%) of the 686 patients with non-Q-wave ACS (P<0.001).During the hospitalization, cardiovascular mortality was signifi cantly lower in patients with Q-wave MI who underwent MR as compared with patients treated with medications only (5.7% and 16.7% of patients, respectively; P<0.001); there was no signifi cant difference in cardiovascular mortality among patients with non-Q-wave ACSs between the two treatment groups (2.8% and 2.7%, respectively) (Fig. 1).During the hospitalization, cardiovascular mortality was similar among patients with Q-wave MI who underwent PTCA or CABG (5.6% and 5.9%, respectively), but among patients with non-Q-wave ACSs, it was signifi cantly higher in patients who underwent CABG in comparison with PTCA (4.6% vs. 0.5%, P<0.01).In-hospital mortality among patients with Q-wave MI was signifi cantly increased due to deaths of patients admitted to the Clinic in severe condition (63 patients had cardiogenic shock during hospitalization, and 28 of them died).
The data of 1161 patients (of the 1165 survivors after ACSs) were available for analysis at one year.Cardiovascular death during the posthospitalization period occurred in 44 patients (3.8%): in 19 patients with Q-wave MI and in 25 patients with non-Q-wave ACSs.There was no signifi cant difference in cardiovascular mortality among patients with Q-wave MI and those with non-Q-wave ACSs (3.8% and 3.8%, respectively), while the comparison of the MR and pharmacotherapy groups showed signifi cantly higher cardiovascular mortality in patients treated with medications only both in patients with Q-wave MI and non-Q-wave ACSs (P<0.05) (Fig. 2).Posthospitalization cardiovascular mortality after PTCA and CABG did not differ signifi cantly among patients with Q-wave MI (2.4% and 2.9%, respectively; P>0.05) and non-Q-wave ACSs (0.5% and 2.2%, respectively; P>0.05).
The Kaplan-Meier estimates of overall one-year cardiovascular mortality irrespectively of the ACS type showed that the probability of death was significantly higher in patients who received pharmacological treatment during their hospitalization period than those who underwent PTCA or CABG (14.3% vs. 5.4% and 7.8%, P<0.05) (Fig. 3).

Discussion
Our study analyzed the rate of MR procedures among 1226 consecutive patients with ACSs treated in 2005 in a single cardiology center, and the impact of these procedures on one-year cardiovascular mortality.During hospitalization, MR procedures were applied in approximately two-thirds of the patients studied.
According to the published articles, during the last decade, a considerable increase in the rate of MR procedures applied within the early period of ACSs has been reported.According to the data of the Canadian Acute Coronary Syndromes Registry (2004), MR was performed in 23.5% to 19.5% of patients with ACSs, according to the GRACE study (2005), the rate of performed MR procedures was 65% and 37% in patients with ST-segment elevation and non-ST-segment elevation ACSs, respectively, and according to the Australian Registry (2008), early invasive treatment was applied in 70.0% to 89.7% of patients with MI and in 44.8% of patients with UAP (6)(7)(8).The published studies provide markedly varying frequencies of CABG procedures performed during the inpatient period (2.8% to 21%) (9)(10)(11)(12).
In our study, the frequency of MR procedures for ACS was considerably higher as compared with the fi ndings of other studies: MR was performed in 81.1% of cases with Q-wave MI, in 70.2% of cases with non-Q-wave MI, and in more than half (56%) of patients with UAP.
The guidelines of the European Association of Management of Acute Coronary Syndrome (2007) indicate that in case of ACSs, in-hospital mortality reaches 7% to 5%; in cases of ST-elevation MI, this mortality may be signifi cantly reduced by applying PTCA (13).According to different published data, in-hospital or 30-day mortality following PTCA reaches 3.1% to 8.5%, and the impact of this procedure depends on the duration of the symptoms before PTCA (14)(15)(16).If PTCA is performed within 2 hours from the onset of the symptoms, in-hospital mortality accounts for 1.3% to 2.7%, and if later − 4.6% to 6.2% (17)(18)(19).Early myocardial reperfusion is associated not only with better survival, but also with higher probability of the normalization of the  The Impact of Myocardial Revascularization on Cardiovascular Mortality left ventricular function and lower rate of cardiac events during the posthospitalization period (20,21).According to our fi ndings, more than twothirds of patients with Q-wave MI underwent PTCA within the fi rst 12 hours from the onset, and their in-hospital mortality was 5.6%.
According to the data of the European Heart Survey, 30-day mortality in patients with ST-segment elevation MI was higher after CABG (8.0%) than PTCA (4.0%) or pharmacotherapy (5.0%) (9).Other authors indicate lower in-hospital mortality (1.1% to 3.7%) following CABG in patients with ST-segment elevation MI, but the data are scarce and incomparable (10,11).In our study, in-hospital mortality following CABG among patients with Qwave MI was 5.9%.Signifi cantly higher in-hospital mortality (16.7%) among patients with Q-wave MI and treated with medications alone might have been infl uenced by a complicated clinical situation when patients were in cardiogenic shock on admission, and MR was either not performed or ineffective.In our study, posthospitalization cardiovascular mortality among patients with Q-wave MI who underwent MR was similar to that indicated in literature (22)(23)(24): cardiac death occurred in 2.4% to 2.9% of patients after MR procedure, and in 9.5% of patients who received pharmacological treatment alone.
It is noteworthy that when comparing cardiovascular mortality in patients with Q-wave MI (our fi ndings) and patients with ST-segment elevation MI (literature data), one should keep in mind that these are not equivalent forms of MI.It has been indicated that if PTCA is performed within 2 hours from the onset of ST-segment elevation ACSs, MI area is reduced by 31%, in 15% of MI cases, Q wave does not emerge, and thus the percentage of patients with Q-wave MI becomes lower than the number of patients with ST-segment elevation MI (25,26).This has also been confi rmed by the data of the Canadian ACS Registry: 21.3% of patients treated for non-Q-wave MI were hospitalized for ST-segment elevation ACSs (6).
According to the literature, MR performed in patients with non-ST-segment elevation ACSs has no signifi cant impact on survival during the hospitalization period: in-hospital mortality reached 2% to 3% irrespectively of whether the patients were treated with PTCA, CABG, or pharmacotherapy (9).During the posthospitalization period, the impact of MR on the survival of these patients is controversial.According to the European Heart Survey, the total one-year mortality in patients with non-Q-wave ACSs following PTCA and CABG was 4% and following pharmacotherapy − 7% (9).According to the VANQWISH study, there was no signifi cant difference in the 23-month mortality between the invasive and the pharmacological treatment groups (17% and 14%, respectively) (27).Other authors who analyzed a number of randomized studies did not fi nd any signifi cant difference in the survival of patients routinely and selectively treated using invasive techniques either (28).Bavry et al. performed a meta-analysis of 5 randomized studies and reported that the application of early invasive treatment in patients with non-ST-segment elevation ACSs reduced the overall 12-month and 24-month mortality by 20% to 23% as compared with that in the conservative treatment group (29).
Our observational fi ndings are in agreement with those presented in literature.There was no signifi cant difference in in-hospital mortality among patients with non-Q-wave ACSs between the MR and conservatively treated groups (2.8% and 2.7%, respectively).However, MR performed during hospitalization signifi cantly reduced one-year mortality compared with mortality observed in patients treated with medications alone (1.4% and 7.7%, respectively; P<0.001).On the other hand, it is noteworthy that the condition of the patients who received conservative treatment was worse, and the EuroSCORE risk score in this group was significantly higher.
Evaluation of the impact of MR on the overall (in-hospital and posthospitalization) cardiovascular mortality adjusting for clinical risk variables showed that MR had a positive impact on disease prognosis as compared with pharmacological treatment.

Conclusions
Percutaneous transluminal coronary angioplasty performed during hospitalization and coronary artery bypass grafting within 60 days after acute coronary syndromes were signifi cantly associated with the reduction of cardiovascular mortality within one-year period independently of clinical risk variables (adjusted OR, 0.304; 95% CI, 0.18 to 0.53; P<0.001 and adjusted OR, 0.540; 95% CI, 0.32 to 0.90; P=0.018).
In the assurance of timely invasive treatment, greater attention should be focused on the early transfer of patients with acute coronary syndromes to a tertiary cardiac clinic as well as on education of the population about the importance of early seeking for medical assistance in the presence of acute myocardial ischemia.

Statement of Conflict of Interest
The authors state no confl ict of interest.

Table 1 .
Rate of the Application of Invasive Inpatient Treatment in Different Acute Coronary Syndromes

Table 2 .
Clinical Characteristics of Patients With Acute Coronary Syndromes by the Treatment Strategy Applied During the Acute Period Values are percentage except where noted.MI, myocardial infarction; PTCA, percutaneous transluminal coronary angioplasty; CABG, coronary artery bypass grafting; LVEF, left ventricular ejection fraction; CA, coronary artery.cotherapy than those who underwent revascularization (8.7% and 2.5%, respectively) (P<0.001).

Table 3 .
Treatment of the Surviving Patients During the First Year After Acute Coronary Syndromes

Table 4 .
The Risk of Cardiovascular Death During a One-Year Period in Patients With Acute Coronary Syndromes