The US Food and Drug Administration has controversially given the green light to Merck & Co's Liptruzet, a combination of the company’s Zetia and Pfizer's off-patent cholesterol-lower Lipitor.

The agency has approved Liptruzet (ezetimibe and atorvastatin) tablets for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patients with primary or mixed hyperlipidaemia as adjunctive therapy to diet. Taken once-daily, Merck says the combo inhibits both the absorption of cholesterol in the digestive tract, through Zetia, and its production in the liver, with atorvastatin.

The company quoted Peter Jones of Baylor College of Medicine as saying that "a significant percentage of patients are unable to lower their LDL cholesterol to recommended levels despite treatment" and Liptruzet is an effective new lipid-lowering treatment option "that may help address this unmet need". He added that "the complementary actions of its components can provide significant additional LDL-lowering beyond atorvastatin therapy alone".

Merck cited data from a variety of studies showing that the combo was better at reducing LDL, or 'bad' cholesterol, than taking atorvastatin alone but admitted that "no incremental benefit of Liptruzet on cardiovascular morbidity and mortality over and above that demonstrated for atorvastatin has been established". This has caused some experts to question the FDA's decision to approve the new treatment.

Approval 'doesn't make any sense' - Nissen

Steven Nissen, head of cardiology at the Cleveland Clinic and a critic of Zetia, was quoted by Forbes as saying that the move "just doesn’t make any sense". He added that “I find it astonishing that after all the controversy about ezetimibe the FDA would approve another combination product with a drug that has been on the market for a decade and has not been shown to improve cardiovascular outcomes".

Dr Nissen went on to say that "it seems like the agency is just tone deaf to the concerns raised by many members of the community about approving drugs with surrogate endpoints like cholesterol without evidence of a benefit for the disease we are truly trying to treat - cardiovascular disease".

Zetia is already sold in combination with Zocor (simvastatin) as Vytorin, which itself is under close scrutiny for not preventing heart attacks and is the subject of a closely-watched trial, the IMPROVE-IT study, which has raised questions over whether Vytorin worked any better than simvastatin on its own. That trial will continue until September 2014.

Commenting on the approval of Liptruzet, Tim Anderson, an analyst at Sanford Bernstein, issued a research note saying that "this is certainly not a ‘high science’ product, yet there is something to be said for a drug that can boast the best LDL cholesterol lowering of any single oral agent currently available", even better than AstraZeneca's Crestor (atorvastatin).