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The following article from Clinical Cardiology, “The Effect of Early and Intensive Statin Therapy on Ventricular Premature Beat or Nonsustained Ventricular Tachycardia in Patients With Acute Coronary Syndrome,”1 by Xian-Zhi He, MD; Sheng-Hua Zhou, MD; Xin-Hong Wan, MD; Hai-Yu Wang, MD; Qing-Hua Zhong, MD; and Jian-Fang Xue, MD, published online on December 10, 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Dr. A.J. Camm, and Wiley Periodicals, Inc. The retraction has been agreed due to significant overlap with a similar article2 previously published by the same authors in the Cardiology Journal.
1. He X.-Z., Zhou S.-H., Wan X.-H., Wang H.-Y., Zhong Q.-H. and Xue J.-F. The effect of early and intensive statin therapy on ventricular premature beat or nonsustained ventricular tachycardia in patients with acute coronary syndrome. Clin Cardiol. 34(1):59–63. doi: 10.1002/clc.20818
2. He XZ, Zhou SH, Wan XH, Wang HY, Zhong QH, Xue JF. The effect of early and intensive statin therapy on ventricular premature beat or non-sustained ventricular tachycardia in patients with acute coronary syndrome. Cardiol J. 2010;17(4):381–385.
The authors have no funding, financial relationships, or conflicts of interest to disclose.
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In the present study all data were recorded. Demographic data, patient's history, procedural information, outcomes, and follow-up data were recorded using 4 case report forms. The first form recorded the data necessary for diagnosis and specification of ACS (symptoms, electrocardiography, and cardiac enzymes). The second form included the patient's history (concomitant disease and previous cardiovascular events), and acute therapy (medication, coronary angiography, and reperfusion therapy). The third case report form included elective diagnostic and therapeutic procedures (echocardiography, Holter monitoring, and medication), and clinical events until discharge of the patient.
Evaluation of Holter monitoring was performed by 1 professional physician 3 times. Diagnostic procedures for Holter monitoring for at least 72 hours of continuous registration was required, and mean heart rate, total number of ventricular premature beats, and total number of ventricular tachycardias had to be registered in the corresponding case report form. NSVT was defined as 3 or more consecutive premature ventricular beats with a rate of more than 100 beats per minute. Left ventricular function was measured by angiography or semiquantitatively by echocardiography (4-chamber view).
There were 586 consecutive patients with ACS who were admitted to our institution and were randomly assigned, in a double-blind manner, to receive atorvastatin treatment. Group A (with conventional statin therapy, n = 289) received 10 mg/day atorvastatin within the first 24 hours of admission, and group B (early and intensive statin therapy, n = 297) received 60 mg immediately and then 40 mg/day atorvastatin after admission. A total of 579 patients completed the study. Furthermore, 4 patients in group A and 3 patients in group B were excluded after completion because they died. Excluded patients were evenly distributed over both treatment groups (χ2, 0.58; P = 0.75). There were no differences between the 2 groups for the comparison of baseline clinical characteristics adjusted for age, gender, body mass index, prior myocardial infarction (MI), blood pressure, prior percutaneous coronary intervention (PCI), coronary artery bypass graft, history of heart failure, hypertension, diabetes mellitus, smoking, alcohol abuse, ejection fraction < 40%, sinus rhythm at admission, atrial fibrillation, atrioventricular block, beta-blocker use, calcium-blockers, or angiotensin converting enzyme (ACE) inhibitor use (Table 1). The protocol was approved by the institutional review board at our institution and informed consent was obtained from all study patients.
Table 1. Comparison of Baseline Clinical Characteristics Between the 2 Groups
|Baseline Clinical Characteristics||Conventional Statin Therapy (n = 285)||Early and Intensive Statin Therapy (n = 294)||Statistic Value||P Value |
|Age, y, mean ± SD)||58.45 ± 10.54||60.87 ± 9.89||t = 0.368||0.683|
|Sex (male/female)||198/87||211/83||χ2 = 0.776||0.378|
|Systolic pressure||138.82 ± 12.42||139.37 ± 11.83||t = 0.463||0.385|
|Diastolic pressure||86.42 ± 7.31||87.42 ± 8.36||t = 0.547||0.576|
|BMI, kg/m2||23.62 ± 3.01||24.68 ± 2.94||t = 0.337||0.585|
|Past medical history|| || || || |
|Myocardial infarction||32||34||χ2 = 0.052||0.887|
|PCI||56||60||χ2 = 0.037||0.864|
|CABG||9||8||χ2 = 0.505||0.448|
|Cardiac inadequacy||19||17||χ2 = 0.347||0.561|
|Risk factors|| || || || |
|Systemic hypertension||168||172||χ2 = 0.387||0.548|
|Diabetes mellitus||98||101||χ2 = 0.239||0.617|
|Smoking||102||99||χ2 = 0.533||0.584|
|Alcohol abuse||16||19||χ2 = 0.667||0.412|
|EF <40%||26||28||χ2 = 0.237||0.624|
|Sinus rhythm at admission||274||278||χ2 = 0.007||0.918|
|Atrial fibrillation||11||16||χ2 = 0.234||0.641|
|Atrioventricular block||40||43||χ2 = 0.247||0.638|
|Combination therapy|| || || || |
|Diuretic||39||41||χ2 = 0.372||0.537|
|β-blockers||246||251||χ2 = 0.014||0.901|
|Ca2+ channel blockers||71||76||χ2 = 0.277||0.684|
|ACE-inhibitors||285||294||χ2 = 0.000||0.991|
The aim of the study was first to investigate the association of ventricular premature beat and NSVT with adverse prognosis after ACS under the conditions of modern medical treatment. The second step was to test the hypothesis based on recent scientific data that statins might influence this association. Absolute numbers, percent, mean, and standard deviation were computed to describe the patient population. Categorical variables were compared using the χ2 or Fisher exact test. Evaluating the baseline characteristics, P values were only used in a descriptive way to show differences between the 2 groups under investigation (Tables 1–4). In this analysis, adjustment was performed for the following variables: age, history of myocardial infarction, systemic hypertension, diabetes mellitus, smoking, ejection fraction < 40%, sinus rhythm at admission, atrial fibrillation, and atrioventricular block. These variables were selected according to their clinical relevance. A P value < 0.05 was considered to be statistically significant. All statistical analyses were carried out with the Statistical Package for Social Science version 12.0.2 (SPSS, Inc., Chicago, IL).
Table 2. Comparison of the Numbers of Ventricular Premature Beats Between the 2 Groups
|Group||No.||Ventricular Premature Beats in 24 Hours (Episode)||Ventricular Premature Beats in 24–72 Hours (Episode)||Total Ventricular Premature Beats in 72 Hours (Episode) |
|Conventional statin therapy||285||1243 ± 104||1568 ± 121||2658 ± 127|
|Early and intensive statin therapy||294||532 ± 83||562 ± 87||1073 ± 91|
|P value|| ||0.006||0.003||<0.001|
Table 3. Baseline Characteristics of Patients After ACS Either Presenting With Nonsustained Ventricular Tachycardia During Holter Monitoring or Not
|Baseline Clinical Characteristics||No NSVT (n = 502)||NSVT (n = 77)||P Value |
|Age, y, mean ± SD)||58.37 ± 10.84||66.8 ± 9.34||<0.001|
|History of myocardial infarction||7.5% (38/502)||36.3% (28/77)||<0.001|
|History of systemic hypertension||58.1% (292/502)||62.3% (48/77)||0.624|
|History of diabetes mellitus||31.4% (158/502)||53.2% (41/77)||0.008|
|Smoking||34.6% (174/502)||35.1% (27/77)||0.423|
|EF <40%||6.7% (34/502)||25.9% (20/77)||<0.001|
|Sinus rhythm at admission||96.4% (484/502)||88.3% (68/77)||0.864|
|Atrial fibrillation||3.5% (18/502)||11.7% (9/77)||0.007|
|Atrioventricular block||14.1% (71/502)||15.6% (12/77)||0.495|
Table 4. Comparison of the Number of Patients With Nonsustained Ventricular Tachycardia and the Number of Nonsustained Ventricular Tachycardias Between the 2 Groups
|Group||NSVT in 24 Hours (Patients)||Total NSVT in 24 Hours (Episode)||Total NSVT in 24–72 Hours (Episode)||Total NSVT in 72 Hours (Episode) |
|Conventional statin therapy||23.2 (56/285)||363 ± 32||132 ± 36||583 ± 31|
|Early and intensive statin therapy||7.1 (21/294)||186 ± 27||78 ± 31||207 ± 29|
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For this study, 579 patients with ACS were randomly divided into 2 groups: group A (with conventional statin therapy, to receive 10 mg/day atorvastatin, n = 289) and group B (early and intensive statin therapy, 60 mg immediately, 40 mg/day atorvastatin, n = 297). The results show that early and intensive statin therapy compared with conventional statin therapy can significantly reduce the ventricular premature beats in 24 hours or in 24 to 72 hours (P = 0.006; P = 0.003). The statistic for total ventricular premature beats in 72 hours was P < 0.001, suggesting statistical significance. The mean heart rate in the 2 groups was for group A, 81.3 ± 6.7; and for group B, 79.6 ± 6.4; P = 0.783), suggesting no statistical significance.
Table 3 shows the baseline characteristics of patients with and without NSVT during Holter monitoring either under early and intensive statin therapy or conventional statin therapy. In general, patients with NSVT were older (66.8 ± 9.34 vs 58.37 ± 10.84 years, P < 0.001), more often had myocardial infarction in their history (36.3% vs 7.5%, P < 0.001), had an ejection fraction < 40% (25.9% vs 6.7%, P < 0.001), and had atrial fibrillation more often (11.7% vs 3.5%, P = 0.007) at admission.
Table 4 shows that early and intensive statin therapy compared with conventional statin therapy can significantly reduce the cases with NSVT (P = 0.008) and NSVT in 24 hours or in 24 to 72 hours(P = 0.007). The statistic for total NSVT in 72 hours was P < 0.001, suggesting statistical significance. Almost all patients showed good tolerance of 20 mg/day atorvastatin. All of these results of the present study indicate that early and intensive statin therapy with (60 mg immediately, 40 mg/day) atorvastatin is more efficacious than and as safe as 10 mg/day atorvastatin when administered to patients during early hospitalization for ACS.
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It is well known that a significant portion of the patients who die after ACS, die from sudden death because of severe arrhythmias.13 In some early experimental animal models, researchers have demonstrated that statins can significantly decrease reperfusion injury and limit MI size.5, 6 Many studies show that patients with ACS who are treated with statins early—within 24 hours of hospitalization—have lower in-hospital morbidity and mortality risks than patients not treated with statins,2–4 but the effectiveness of antiarrhythmias in the patients with ACS receiving immediate and intensive statin therapy were not clear. The present study shows that the occurrence of ventricular premature beats and NSVT after ACS is associated with increased mortality. However, this adverse effect only applies for patients not on statin therapy. Atorvastatin significantly reduces mortality irrespective of the absence or presence of ventricular premature beats and NSVT. The present study also shows that atorvastatin is able to markedly attenuate the association of ventricular premature beats and NSVT with adverse outcomes after ACS.16 Patients with or without ventricular premature beats and NSVT did not largely differ in medication, including ACE-inhibitors and beta-blockers. As expected, however, patients with ventricular premature beats and NSVT were older and more often had previous myocardial infarction, severely reduced left ventricular function, and atrial fibrillation. Taking these parameters into account, only ventricular premature beats and NSVT were associated with a trend toward an adverse prognosis. Indeed, the independent prognostic value of ventricular premature beats and NSVT in the era of modern treatment of myocardial infarction, including thrombolysis, PCI, beta-blockers, and statins is controversial and has been questioned previously. The situation completely changes if the prognostic value of ventricular premature beats and NSVT is evaluated within the patients receiving immediate and intensive statin therapy.17–19 In the present study, early and intensive atorvastatin therapy can significantly decrease the recurrence of ventricular premature beats and NSVT. It might therefore be suggested that one of the beneficial mechanisms of statins could be to rapidly affect signaling pathways in cell membranes of the myocardium and/or the autonomic nervous system, thereby protecting patients from life-threatening arrhythmias.20–22 This assumption would be in line with recent data showing statins to improve autonomic neural control and increase electrical stability of the myocardium. Atorvastatin is a highly lipophilic drug that becomes easily embedded in the membrane having overlapping locations in the hydrocarbon core adjacent to the phospholipid head groups.23–26 Moreover, the blocking effects could be attributed to an effect on the lipid content of the membrane.27