Revised cholesterol treatment guidelines could result in increased use of combination lipid-lowering therapies as Merck/Schering-Plough's Vytorin enters the market.

The recommendations could aid the launch of Vytorin, a fixed-dose combination of Zocor (simvastatin) and Zetia (ezetimibe). Vytorin has an estimated user fee date of July 24 (¹ Also see "Schering/Merck Ready For Vytorin; Lipid Market Growth Returns" - Pink Sheet, 26 April, 2004., p. 9).

The updated National Cholesterol Education Program clinical practice guidelines take a more aggressive approach to lowering LDL-C levels in people at high and moderately high risk for having a heart attack.

NCEP not only lowers the drug treatment thresholds for high- and moderately high-risk individuals but also suggests ambitious "therapeutic options" for subsets of those populations.

In particular, NCEP now recommends that drug therapy should achieve at least a 30% to 40% reduction in LDL-C levels in such individuals.

"To use minimal drug therapy just to produce a small LDL reduction that will barely attain the LDL-C goal would not be a prudent use of LDL-lowering drugs," NCEP says.

The 2001 guidelines (Adult Treatment Panel III) did not emphasize a target for LDL-C percentage decreases.

The revised guidelines note a 30%-40% reduction can be achieved through "standard doses" of currently available statins: Pfizer's Lipitor (atorvastatin); Merck's Zocor (simvastatin) and Mevacor (lovastatin); Bristol-Myers Squibb's Pravachol (pravastatin); AstraZeneca's Crestor (rosuvastatin); and Novartis' Lescol (fluvastatin).

The LDL-lowering target also can be reached "by combining lower doses of statins with other drugs or products," such as ezetimibe, bile acid sequestrants or nicotinic acid, according to the guidelines published in the July 13 issue of Circulation.

Merck said Vytorin will be positioned as a first-line therapy while Zetia, which was approved in November 2002 for use as monotherapy or in combination with statins, will be targeted to those patients who have not reached their cholesterol goals (² Also see "Zetia/Zocor Market Will Be First-Line Patients, Not Switches, Merck Says" - Pink Sheet, 22 December, 2003., p. 23).

However, the new NCEP guidelines makes those goals significantly more ambitious for many patients, opening the door for positioning the combination product as a convenient answer for those who cannot achieve the new targets with statins alone.

Zetia and all the single-agent statins should get a boost from the revised guidelines as well.

The new guidelines reflect results from the five major clinical trials on statins published since release of ATP III. These include the Bristol-funded PROVE-IT study, which found intensive lipid lowering therapy (Lipitor 80 mg) was linked with significantly better prevention of acute coronary outcomes than a standard therapeutic dose (Pravachol 40 mg) (³ Also see "Statin Studies May Dampen Enthusiasm For Cost-Effectiveness Trials – AARP" - Pink Sheet, 15 March, 2004., p. 10).

The update retains ATP III parameters for determining "high risk": patients who have coronary heart disease, blood vessel disease or diabetes, or two or more risk factors that give them a 20% chance of having a heart attack in 10 years (⁴ Also see "Cholesterol Therapy Guidelines Stress Need To Consider Cost, Treat To Goal" - Pink Sheet, 21 May, 2001., p. 15).

NCEP defines "very high risk" patients as those with cardiovascular disease and multiple or poorly controlled risk factors or metabolic syndrome.

The update retains an LDL goal of <100 mg/dl="" for="" high="" risk="" patients.="" however,="" "when="" the="" risk="" is="" very="" high,="" an="" ldl-c="" goal="" of=""><70 mg/dl="" is="" a="" therapeutic="" option,="" i.e.,="" a="" reasonable="" clinical="" strategy,="" on="" the="" basis="" of="" available="" clinical="" trial="" evidence,"="" ncep="">

In addition, the threshold for initiating drug therapy in high-risk patients is now an LDL of 100 mg/dL or higher, down from the previous threshold of 130 mg/dL or higher.

For moderately high-risk individuals, the LDL goal remains <130 mg/dl,="" but="" the="" update="" adds="" a="" therapeutic="" option="" of=""><100>

"For people in lower risk categories, there are no proposed changes to the treatment goals and cutpoints," NCEP states.

Merck/Schering Vytorin Launch Could Be Aided By New Cholesterol Guidelines

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