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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. REFERENCES

Retraction

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MD; and Jian-Fang Xue, MD, published online on December 10, 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Dr.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.

References

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.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. REFERENCES

As statins have been proven to be very effective in reducing mortality rates after acute coronary syndrome (ACS), the beneficial effect of statins in patients after ACS has primarily been attributed to lowering of blood cholesterol and thereby attenuating the progression of arteriosclerosis.1–4 However, recent data suggest that the beneficial effects of statins might extend to mechanisms beyond cholesterol reduction.5–7 These pleiotropic effects include improvement of endothelial function, inhibition of platelet function, and smooth muscle cell proliferation, enhancing stability of arteriosclerotic plaques and attenuating vascular inflammation. Recent evidence has shown that statins might exert antiarrhythmic effects both in experimental models and in humans.8–15 Association of ventricular premature beat and nonsustained ventricular tachycardia (NSVT) with adverse outcome after ACS could be influenced by these agents. The early and intensive relationship for atorvastatin in patients with ACS during early hospitalization in terms of antiarrhythmic effects is unclear. In this study we analyzed the effects of early and intensive atorvastatin on the prognostic impact of ventricular premature beat and NSVT after ACS.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. REFERENCES

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 CharacteristicsConventional Statin Therapy (n = 285)Early and Intensive Statin Therapy (n = 294)Statistic ValueP Value
  1. Abbreviations: ACE, angiotensin converting enzyme; BMI, body mass index; CABG, coronary artery bypass graft; EF, ejection fraction; PCI, percutaneous coronary intervention; SD, standard deviation

Age, y, mean ± SD)58.45 ± 10.5460.87 ± 9.89t = 0.3680.683
Sex (male/female)198/87211/83χ2 = 0.7760.378
Systolic pressure138.82 ± 12.42139.37 ± 11.83t = 0.4630.385
Diastolic pressure86.42 ± 7.3187.42 ± 8.36t = 0.5470.576
BMI, kg/m223.62 ± 3.0124.68 ± 2.94t = 0.3370.585
Past medical history    
Myocardial infarction3234χ2 = 0.0520.887
PCI5660χ2 = 0.0370.864
CABG98χ2 = 0.5050.448
Cardiac inadequacy1917χ2 = 0.3470.561
Risk factors    
Systemic hypertension168172χ2 = 0.3870.548
Diabetes mellitus98101χ2 = 0.2390.617
Smoking10299χ2 = 0.5330.584
Alcohol abuse1619χ2 = 0.6670.412
EF <40%2628χ2 = 0.2370.624
Sinus rhythm at admission274278χ2 = 0.0070.918
Atrial fibrillation1116χ2 = 0.2340.641
Atrioventricular block4043χ2 = 0.2470.638
Combination therapy    
Diuretic3941χ2 = 0.3720.537
β-blockers246251χ2 = 0.0140.901
Ca2+ channel blockers7176χ2 = 0.2770.684
ACE-inhibitors285294χ2 = 0.0000.991

Statistical Methods

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
GroupNo.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 therapy2851243 ± 1041568 ± 1212658 ± 127
Early and intensive statin therapy294532 ± 83562 ± 871073 ± 91
P value 0.0060.003<0.001
Table 3. Baseline Characteristics of Patients After ACS Either Presenting With Nonsustained Ventricular Tachycardia During Holter Monitoring or Not
Baseline Clinical CharacteristicsNo NSVT (n = 502)NSVT (n = 77)P Value
  1. Abbreviations: EF, ejection fraction; NSVT, nonsustained ventricular tachycardia; SD, standard deviation

Age, y, mean ± SD)58.37 ± 10.8466.8 ± 9.34<0.001
History of myocardial infarction7.5% (38/502)36.3% (28/77)<0.001
History of systemic hypertension58.1% (292/502)62.3% (48/77)0.624
History of diabetes mellitus31.4% (158/502)53.2% (41/77)0.008
Smoking34.6% (174/502)35.1% (27/77)0.423
EF <40%6.7% (34/502)25.9% (20/77)<0.001
Sinus rhythm at admission96.4% (484/502)88.3% (68/77)0.864
Atrial fibrillation3.5% (18/502)11.7% (9/77)0.007
Atrioventricular block14.1% (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
GroupNSVT in 24 Hours (Patients)Total NSVT in 24 Hours (Episode)Total NSVT in 24–72 Hours (Episode)Total NSVT in 72 Hours (Episode)
  1. Abbreviations: NSVT, nonsustained ventricular tachycardia

Conventional statin therapy23.2 (56/285)363 ± 32132 ± 36583 ± 31
Early and intensive statin therapy7.1 (21/294)186 ± 2778 ± 31207 ± 29
P value0.0080.0070.007<0.001

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. REFERENCES

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.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. REFERENCES

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

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. REFERENCES

The present study supports the experimental data, as the benefit likely has to do with immediately improving autonomic neural control and increasing electrical stability of the ischemic myocardium, as well as having an antiarrhythmic effect. Because the drug is going to be used anyway, it should be started right away because there might be an added benefit that occurs quite early.

REFERENCES

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. REFERENCES