Cholesterol Targets Now Demand Multi-drug Strategies - World Congress Of Cardiology 2006 (2-6 September) Barcelona, Spain

Main Category: Statins
Also Included In: Cholesterol;  Cardiovascular / Cardiology
Article Date: 09 Sep 2006 - 10:00 PDT

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Statin therapy alone is failing to bring patients to the target levels of blood cholesterol required by guidelines to minimize their health risk. Cardiologists attending the World Congress of Cardiology in Barcelona advocate multi-drug strategies to get patients to target.

The new ' lower is better' approach increasingly advocated is manifest in the trend towards lower low-density-lipoprotein cholesterol (LDL-C) targets in guidelines. Specialists believe that this requires more intensive therapy earlier. Only 51% of patients on lipid lowering therapy achieve the goal of total cholesterol <150mg/dL [5mmol/L] in practice(1). Standard doses of statins achieve LDL-C <2.6 mmol/L (<100mg/dL) in little more than half of high-risk patients.

Dr Evan Stein, Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio, USA, speaking at a session in the congress, said: 'The statins are the most powerful and consistent LDL reducers, and by far the best tolerated. They provide very predictable response. Every time you double a dose of a statin, you get an additional 6% LDL decrease.' However, he added, 'We also know that physicians are reluctant to titrate a dose once that dose has started'.

Professor Alberico Catapano, professor of pharmacology, University of Milan, Italy, said, 'The significant gap between the recommended treatment goals of guidelines and the lipid levels actually achieved in clinical practice highlights the urgent need for new management strategies, particularly for high-risk patients'. Professor Catapano was speaking at an industry press briefing.

Dr Stein said that other strategies to add to the LDL lowering power of statins are needed. He said, 'The most effective way and the easiest way which we now use is to use a cholesterol transport inhibitor'. The strategy, he explained, is to combine two drugs: the statin stops cholesterol synthesis in the liver while ezetimibe stops cholesterol absorption from the intestine. Ezetimibe is the first in the class of cholesterol absorption inhibitors to come to market. Treating two sources of cholesterol by co-administration provides greater LDL-C lowering efficacy than inhibition of either pathway alone, said Dr Stein.

Professor Catapano presented part of a large study of patients with high cholesterol, recently accepted for publication, comparing different doses of ezetimibe/simvastatin with different doses of rosuvastatin, the most potent of the statins.

For a target of LDL-C 100mg/dL, the following results were seen:

-- 72% of 475 patients on rosuvastatin 10mg achieved goal, while 84% of the 476 patients on ezetimibe/simvastatin 10mg/20mg attained goal (P<0.001 vs rosuvastatin).

-- However, the differences with rosuvastatin 20mg and 40mg doses compared with ezetimibe/simvastatin 10mg/40mg and 10mg/80mg) failed to reach statistical significance.

But for a tougher target of LDL-C 70mg/dL, results were consistently dramatic:

-- 9% of 475 patients on rosuvastatin 10 mg reached target, while 24% of 476 patients on ezetimibe/simvastatin 10mg/20mg reached target (P?0.05 vs rosuvastatin);

-- 30% of 478 patients on rosuvastatin 20mg attained goal while 41% of 477 patients on ezetimibe/simvastatin 10mg/40mg attained goal. (P?0.05 vs rosuvastatin);

-- 50% of 475 patients on rosuvastatin 40mg attained goal, while 66% of 474 patients attained goal on ezetimibe/simvastatin 10mg/80mg (P?0.05 vs rosuvastatin)

Concluded Professor Catapano: 'This study shows that attaining LDL cholesterol is most likely when you use this type of combination than the most effective statin that is currently available.'

Reference
1.EUROASPIRE II Study Group Eur Heart J 2001;22:554-572

World Congress of Cardiology, Barcelona, Spain

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