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LIPIDS
MANAGEMENT
Amber Briggs, Section Advisor
Combination lipid-lowering therapy no better than high-dose statin
monotherapy
Key point: In a systematic review of 102 trials,
researchers found limited evidence suggesting that combination
lipid-lowering therapy is no better than high-dose statin monotherapy in
improving clinical outcomes in high-risk patients. However, data do
suggest that high-risk patients receiving combination therapy with a
statin and ezetimibe (Zetia—Merck, Schering-Plough) are more
likely to attain low-density lipoprotein (LDL) goals compared with
patients receiving high-dose statin monotherapy.
Finer points: A systematic review of 102 clinical
trials, including 98 randomized controlled trials and 4 nonrandomized
studies, comparing use of a statin plus another lipid-modifying agent
with statin monotherapy was published online by the Annals of
Internal Medicine on September 1. The combination regimens included
a statin plus bile-acid sequestrants, fibrates, ezetimibe, niacin, or
omega-3 fatty acids. The investigators compared efficacy outcomes
(mortality rates, vascular events, and lipid levels), serious adverse
events, and cancer incidence among trials that were at least 24 weeks in
duration. The primary analysis focused on high-risk patients who
required intensive lipid-lowering therapy. High-risk patients were
defined as those with a 10-year coronary heart disease risk greater than
20%, mean baseline LDL of at least 190 mg/dL, or both.
The investigators noted that the overall quality of the evidence is
weak, with many studies having a short duration and only evaluating
surrogate outcomes. Only three trials assessed the effects of
combination therapy (two statin–ezetimibe trials and one
statin–fibrate trial) versus high-dose statin monotherapy on
mortality in high-risk patients; no statistically significant difference
was noted between the groups (odds ratio 0.61 [95% CI 0.22–1.71]).
No significant difference in mortality was noted in lower risk patients.
None of the studies compared the effects of combination therapy with
high-dose statin monotherapy on outcomes such as myocardial infarction,
stroke, transient ischemic attacks, or revascularization procedures, so
analyses on these outcomes could not be performed. An analysis of two
trials that compared statin–ezetimibe therapy to high-dose statin
monotherapy showed that high-risk patients who received combination
therapy were more likely to meet their LDL goal. In addition, the
investigators commented that an analysis of the overall evidence
suggests that a greater reduction in LDL is seen with combination
therapy compared with high-dose statin monotherapy in high-risk
patients. No statistical differences were noted for serious adverse
events or the incidence of cancer among groups.
What you need to know: The investigators repeatedly
pointed out that the strength of their evidence was very low or limited;
therefore, the results of this analysis must be interpreted cautiously.
Two major trials are currently evaluating the effects of combination
therapy versus statin monotherapy on clinical endpoints. AIM-HIGH
(Atherothrombosis Intervention in Metabolic Syndrome with Low HDL
[High-Density Lipoprotein]/High Triglycerides and Impact on Global
Health Outcomes) is designed to test whether the combination of
simvastatin plus extended release niacin is superior to simvastatin
alone for delaying the time to a first major cardiovascular disease
outcome over a 4-year median follow-up period. IMPROVE-IT (Improved
Reduction of Outcomes: Vytorin Efficacy International Trial) is designed
to evaluate the effects of combination therapy with simvastatin plus
ezetimibe compared with simvastatin monotherapy on the occurrence of the
composite endpoint of cardiovascular death, major coronary event, and
stroke over a minimum follow-up period of 2.5 years. The results of
these two major outcome trials should help shed some light on
combination therapy versus monotherapy.
What your patients need to know: Tell patients that
a recent review suggests that monotherapy with a high-dose statin
appears to be just as effective and safe as combination lipid-lowering
therapy. Counsel patients on the benefits of a low-fat, low-cholesterol
diet and lifestyle modifications such as daily physical activity,
moderate consumption of alcohol, and smoking cessation.
Source
Related resources on www.pharmacist.com
Carli Richard (crichard@aphanet.org)
Posted October 22, 2009
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