Ilke Sipahi, MD; E. Murat Tuzcu, MD; Katherine E. Wolski, MPH; Stephen J. Nicholls, MBBS, PhD; Paul Schoenhagen, MD; Bo Hu, PhD; Craig Balog, BS; Mehdi Shishehbor, DO; William A. Magyar, BS; Timothy D. Crowe, BS; Samir Kapadia, MD; Steven E. Nissen, MD
Acknowledgments: The authors thank Jordan Andrews, Eva Balazs, Sorin Brener, Tammy Churchill, Anne Colagiovanni, Kelly Emerick, Teresa Fonk, Jessica Fox, Marlene Goormastic, Thomas Ivanc, Karilane King, Aaron Loyd, Kara McInturff, Roman Poliszczuk, Rhiannon Regal, Troy Schweitzer, Andrea Winkhart, and Jay Zhitnik at the Cleveland Clinic Cardiovascular Coordinating Center; David J. Frid, Michele Norton, Fady Ntanios, Harry Shi, and Kamlesh Thakker at Pfizer; James Hanyok and Laurent Kassalow at Sankyo Pharma; and Valerie Cain and Joel Raichlen at AstraZeneca for their contributions.
Grant Support: The REVERSAL and CAMELOT studies were funded by Pfizer. The ACTIVATE study was funded by Sankyo. The ASTEROID study was funded by AstraZeneca. Dr. Nicholls is supported by a Ralph Reader Overseas Research Fellowship from the National Heart Foundation of Australia.
Potential Financial Conflicts of Interest: Dr. Sipahi has received an educational grant from Pfizer and lecture honoraria from AstraZeneca. All honoraria are paid directly to charity so that neither income nor any tax deduction is received. Dr. Tuzcu received grant support from Pfizer and Takeda and lecture honoraria from Pfizer. Dr. Nicholls has received lecture honoraria from Pfizer and AstraZeneca. Dr. Schoenhagen has consulted for Takeda without financial compensation. All honoraria are paid directly to higher education so that neither income nor any tax deduction is received. Dr. Nissen has received research support from AstraZeneca, Eli Lilly, Pfizer, Takeda, Sankyo, and Sanofi-Aventis. He has also consulted for a number of pharmaceutical companies without financial compensation. All honoraria, consulting fees, or other payments from any for-profit entity are paid directly to charity so that neither income nor any tax deduction is received.
Requests for Single Reprints: Steven E. Nissen, MD, The Cleveland Clinic Foundation, Department of Cardiovascular Medicine, 9500 Euclid Avenue, Desk F15, Cleveland, OH 44195; e-mail, email@example.com.
Current Author Addresses: Drs. Sipahi, Nicholls, and Schoenhagen; Ms. Wolski; Mr. Balog; Mr. Magyar; and Mr. Crowe: The Cleveland Clinic Foundation, Department of Cardiovascular Medicine, 9500 Euclid Avenue, Desk JJ65, Cleveland, OH 44195.
Drs. Tuzcu and Kapadia: The Cleveland Clinic Foundation, Department of Cardiovascular Medicine, 9500 Euclid Avenue, Desk F25, Cleveland, OH 44195.
Dr. Hu: The Cleveland Clinic Foundation, Department of Quantitative Health Sciences, 9500 Euclid Avenue, Desk Wb4, Cleveland, OH 44195.
Drs. Shishehbor and Nissen: The Cleveland Clinic Foundation, Department of Cardiovascular Medicine, 9500 Euclid Avenue, Desk F15, Cleveland, OH 44195.
Author Contributions: Conception and design: I. Sipahi, E.M. Tuzcu, S.J. Nicholls, S. Kapadia.
Analysis and interpretation of the data: I. Sipahi, E.M. Tuzcu, K.E. Wolski, S.J. Nicholls, B. Hu, S. Kapadia.
Drafting of the article: I. Sipahi, S.J. Nicholls, P. Schoenhagen, S. Kapadia.
Critical revision of the article for important intellectual content: I. Sipahi, E.M. Tuzcu, S.J. Nicholls, P. Schoenhagen, M. Shishehbor, T.D. Crowe, S. Kapadia, S.E. Nissen.
Final approval of the article: I. Sipahi, E.M. Tuzcu, K.E. Wolski, S.J. Nicholls, P. Schoenhagen, C. Balog, M. Shishehbor, W.A. Magyar, T.D. Crowe, S. Kapadia, S.E. Nissen.
Provision of study materials or patients: I. Sipahi, E.M. Tuzcu, W.A. Magyar.
Statistical expertise: I. Sipahi, K.E. Wolski, B. Hu, C. Balog.
Administrative, technical, or logistic support: E.M. Tuzcu, W.A. Magyar.
Collection and assembly of data: I. Sipahi, W.A. Magyar.
In patients with myocardial infarction, β-adrenergic blockers reduce recurrent myocardial infarction and total mortality rates. However, whether a direct influence of β-blockers on coronary atherosclerosis contributes to reduced recurrent myocardial infarction and total mortality rates is not known.
To assess whether β-blocker therapy is associated with reduced atheroma progression in adults with known coronary artery disease.
Post hoc, pooled analysis of individual patient data from 4 intravascular ultrasonography (IVUS) trials.
Four IVUS trials conducted in the United States, Europe, and Australia.
1515 patients with coronary artery disease.
The original trials used 3 different statins, a calcium-channel blocker, an angiotensin-converting enzyme inhibitor, or an acyl coenzyme A–cholesterol acyltransferase inhibitor.
Changes in atheroma volume, as determined by IVUS after adjustment for possible confounders by using linear mixed-effects models, were compared in patients who did and did not receive concomitant β-blocker treatment.
Patients who received β-blockers (n = 1154) were more likely to have histories of myocardial infarction, angina, and hypertension than were patients who did not receive β-blockers (n = 361). The estimated annual change in atheroma volume was statistically significantly less in patients who received β-blockers. This was true for univariate and multivariable analyses that controlled for history of myocardial infarction, angina, and hypertension (mean [±SE] atheroma volume, −2.4 ± 0.5 mm3/y in treated patients vs. −0.4 ± 0.8 mm3/y in untreated patients; P = 0.034). Accordingly, atheroma volume statistically significantly decreased at follow-up IVUS in patients who received β-blockers (P < 0.001) and did not change in patients who did not receive β-blockers (P = 0.86). Additional adjustments for low-density lipoprotein cholesterol level, concomitant medications, and clinical trial did not change the results.
Patients were not randomly assigned to β-blocker therapy, and interventions other than β-blocker therapy could have influenced the changes in atheroma volume. Whether progression rate of atherosclerosis as detected by IVUS predicts cardiovascular outcomes is unknown.
The analysis demonstrates that β-blockers can slow progression of coronary atherosclerosis. The findings provide additional support for the current clinical guidelines advocating long-term use of β-blockers to treat most forms of coronary artery disease.
Sipahi I, Tuzcu EM, Wolski KE, Nicholls SJ, Schoenhagen P, Hu B, et al. β-Blockers and Progression of Coronary Atherosclerosis: Pooled Analysis of 4 Intravascular Ultrasonography Trials. Ann Intern Med. 2007;147:10–18. doi: 10.7326/0003-4819-147-1-200707030-00003
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Published: Ann Intern Med. 2007;147(1):10-18.
Cardiology, Coronary Heart Disease, Coronary Risk Factors, Dyslipidemia.
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