CLEVELAND, July 3 -- Beta-blocker therapy can provide statistically significant regression of coronary artery plaque, found a review here of four intravascular ultrasound (IVUS) studies.
Atheroma volume decreased by an average of 2.4 mm3/y among beta blocker-treated patients, compared with 0.4 mm3/y among those who did not receive beta-blockers (P=0.034), reported Steven E. Nissen, M.D., of the Cleveland Clinic, and colleagues, in the July 3 issue of the Annals of Internal Medicine.
The volume of coronary plaque decreased significantly from baseline to the end of the evaluation period in patients who received beta-blockers (P<0.001) but not in patients whose therapy did not include beta-blockers (P=0.86).
"The analysis demonstrates that beta-blockers can slow progression of coronary atherosclerosis," concluded Dr. Nissen and colleagues. "The findings provide additional support for the current clinical guidelines advocating long-term use of beta-blockers to treat most forms of coronary artery disease."
The authors pointed out that beneficial effects on recurrent myocardial infarction, sudden cardiac death, and total mortality in MI patients emerged primarily from studies done two decades ago. Whether beta-blockers provide the same benefits in the current era of aggressive reperfusion for MI had not been clear.
To examine the effects of beta-blockers in contemporary patients, the investigators reviewed data from four clinical trials that used IVUS to evaluate the impact of medical interventions on coronary atherosclerosis volume. The four studies analyzed were:
REVERSAL, a randomized comparison of moderate versus aggressive lipid-lowering therapy with statin drugs
CAMELOT IVUS, a randomized comparison of a calcium-channel blocker and an ACE inhibitor
ACTIVATE, which evaluated lipid modification with a CoA-cholesterol acyltlransferase inhibitor
ASTEROID, a trial of high-intensity lipid-lowering therapy with a statin
The same IVUS technique was used in all four trials, and patients in each trial had IVUS at baseline and at the study's end.
The trials involved a total of 1,515 patients with coronary artery disease, including 1,154 who received beta-blockers as a component of their treatment. On average, patients treated with beta-blockers received the agents for 91% of the trials' duration. More patients in the beta-blocker group had a history of MI, angina, and hypertension.
Patients treated with beta-blockers had a significantly greater reduction in atheroma volume in a univariate analysis and a multivariate analysis that controlled for MI, angina, and hypertension. Adjustments for LDL-cholesterol level, concomitant medications, and clinical trial did not change the results.
The investigators said that antiatherosclerotic effects of beta-blockers have been demonstrated in multiple animal models but not in human coronary arteries. However, a meta-analysis of randomized controlled trials last year found that long-term beta-blocker therapy was associated with a significant slowing of carotid intima-media thickening in hypertensive patients with diabetes or coronary heart disease and asymptomatic carotid artery disease.
Dr. Nissen and colleagues pointed out that beta-blockers reduce heart rate and slow blood velocity, leading to less turbulent blood flow and less intramural stress. However, adjustment for average heart rate during therapy did not change the results. The investigators also cited evidence that beta-blockers may reduce the affinity of LDL cholesterol for vessel wall proteoglycans and blunt catecholamine-induced endothelial permeability to lipoproteins.
Limitations of the study include its nonrandomized nature and the imbalance between treated and untreated patients. Additionally, the authors acknowledge that IVUS findings are a surrogate endpoint for coronary artery disease. Whether IVUS-detected changes in atheroma volume predict cardiovascular outcomes is unknown.
The original IVUS-based studies were supported by Pfizer, Sankyo, and AstraZeneca. The study sponsors contributed to data collection for the pooled analysis but did not participate in the planning or conduct of the analysis. The authors reported multiple associations with the sponsors and with other companies unrelated to the study.Additional source: Annals of Internal MedicineSource reference: Sipahi I et al. "Beta-blockers and coronary atherosclerosis: Pooled analysis of 4 intravascular ultrasonography trials." Ann Intern Med. 2007;147:10-18. Additional source: StrokeSource reference: Wang JG, Staessen JA, Li Y, et al. "Carotid intima-media thickness and antihypertensive treatment: a meta-analysis of randomized controlled trials." Stroke 2006, 37:1933-49.
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