CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Franz H. Messerli, MD, FACC, FACP* and
Sripal Bangalore, MD, MHA
* Director, Hypertension Program, Division of Cardiology, St. Luke’s-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, 1000 10th Avenue, Suite 3B-30, New York, New York 10019 (Email: fmesserl{at}chpnet.org).
We thank Dr. Giles and colleagues for their interest in our paper (1) and completely agree with their contention that "recommendations for the use of beta-blockers in the individual with hypertension should be made after reviewing the totality of the data." Unfortunately, the totality in this case is completely negative. Ever since our meta-analysis about a decade ago, study after study has attested to the inefficacy of beta-blockers in hypertension. Why would any physician expose a hypertensive patient to a drug that reduces mortality no better than placebo, as evidenced in the thorough Cochrane meta-analysis (2), and yet leads to a withdrawal rate that is twice as high as the one seen with diuretics (which are certainly not the best-tolerated drug class for the treatment of hypertension)? We are puzzled by our colleagues’ cherrypicking of the STOP-1 and -2 (Swedish Trial in Old Patients with Hypertension-1 and -2). Neither of those studies dared to conclude that beta-blockers per se reduce morbidity and mortality. The reason for this is very simply that neither one analyzed the effects of diuretics and beta-blockers separately. Thus, STOP-1 and -2 studies are classical examples of gin-and-tonic studies in which about two-thirds of patients treated with a beta-blocker also received a thiazide diuretic.
The INVEST (International Verapamil-Trandolapril Study) is a landmark trial in which an atenolol (given mostly twice a day)-based regimen was compared with a verapamil-based regimen, as Dr. Giles and colleagues point out. However, all of the patients in the INVEST study had well defined coronary artery disease, and an extrapolation from such a high-risk population to uncomplicated hypertension is not appropriate. As can be seen in our Figure 3 (1) we are convinced that coronary artery disease is an acceptable indication for the use of beta-blockers.
We use the term pseudoantihypertensive efficacy to describe the observation in the CAFE (Conduit Artery Function Evaluation) study (3) that, for a given brachial blood pressure, atenolol lowered central aortic blood pressure significantly less than did amlodipine. Therefore, practicing physicians may wrongly conclude that the patient has well controlled hypertension when central aortic pressure is still significantly elevated. The term pseudoantihypertensive efficacy aptly describes this phenomenon.
We certainly agree with our colleagues, and we have stated so (4), that vasodilating beta-blockers have a different hemodynamic profile and a different metabolic/endocrine profile, induce less weight gain (5), and are better tolerated than the traditional beta-blockers. Thus, nebivolol and carvedilol are not only better tolerated but also have the potential to be more beneficial in terms of morbidity and mortality reduction than traditional beta-blockers. However, this potential remains hypothetic as long as we have no conclusive outcome studies attesting to this. If indeed the companies manufacturing these drugs are concerned about this issue they should mount outcome studies in hypertension. This does not need to be an exceedingly expensive endeavour, as is evidenced by the fact that it only took 1,473 patients with cerebrovascular disease to show that stroke reduction was no better with atenolol than with placebo (6).
We agree that many patients with increased blood pressure have some degree of nonobstructive coronary disease. However, neither our nor the Cochrane meta-analysis showed any efficacy of beta-blockers for primary prevention of coronary disease. The Cochrane meta-analysis specifically stated that "the absence of an effect on heart disease [compared with] placebo or no treatment" led to the conclusion that beta-blockers should not be used as first-line drugs in the treatment of hypertension.
We are not particularly concerned about "throwing out the baby with the bathwater." In 2006 more than 100 million prescriptions for beta-blockers were written in the U.S. Atenolol remains the fourth most prescribed drug, and most of these prescriptions are for atenolol given once a day for the treatment of hypertension. This is a sad state of the art, given the fact that atenolol has never shown to reduce morbidity and mortality in hypertension. One may also want to consider that treatment of 1,000 patients with beta-blockers for 4.4 years will result in 14 extra cases of diabetes, 3 extra deaths, and 5 extra strokes (7). This means that in the U.S. alone, beta-blocker therapy may account for 70,000 new cases of diabetes, 15,000 deaths, and 25,000 strokes every year.
Thus, many more gallons of bathwater can be thrown out before the baby runs any risk of being harmed.
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References
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1. Bangalore S, Messerli F, Kostis J, Pepine C. Cardiovascular protection using beta-blockersA critical review of the evidence. J Am Coll Cardiol 2007;50:563-572.[Abstract/Free Full Text]2. Wiysonge CS, Bradley H, Mayosi BM, et al. Beta-blockers for hypertension Cochrane Database Syst Rev 2007CD002003. 3. Williams B, Lacy PS, Thom SM, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study Circulation 2006;113:1213-1225.[Abstract/Free Full Text] 4. Messerli FH, Grossman E. β-blockers in hypertension: is carvedilol different? Am J Cardiol 2004;93(Suppl):7B-12B.[CrossRef][Web of Science][Medline] 5. Messerli FH, Bell DS, Fonseca V, et al. Body weight changes with beta-blocker use: results from GEMINI Am J Med 2007;120:610-615.[CrossRef][Medline] 6. Dutch TIA Trial Study Group Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke Stroke 1993;24:543-548.[Abstract/Free Full Text] 7. Bangalore S, Parkar S, Grossman E, Messerli F. A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus Am J Cardiol 2007;100:1254-1262.[CrossRef][Web of Science][Medline]
Related Article
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Beta-Blocker Therapy in Hypertension: A Need to Pause and Reflect
- Thomas D. Giles, George L. Bakris, and Michael A. Weber
J. Am. Coll. Cardiol. 2008 51: 516-517.
[Full Text]
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