A new cholesterol blocking drug, pactimibe, has been tested on patients at high risk of heart disease.  Unfortunately it did not reduce progress of atherosclerosis and even increase the risk of heart attack and stroke.

Summary

A new drug called pactimibe, which blocks a cholesterol enzyme, did not slow down the thickening of the artery that sets the scene for heart disease, when tested in patients with high cholesterol. Those on the drug were also more likely to have a heart attack or stroke than those on the placebo. Therefore, these new drugs do not seem to live up to the promise they originally offered.

Introduction

People with familial hypercholesterolemia are born with a genetic defect that means their cholesterol levels are high. Other people have high cholesterol because of their diet and lack of exercise. In both groups, it’s important to get the cholesterol down to avoid a heart attack. Statins are one group of drug proven to have benefit in this respect. But others are being developed. One type is the ACAT inhibitors which block an enzyme involved in cholesterol accumulation. In animal tests, these drugs looked promising, so it was time to test them in humans.

What was done

Researchers in Amsterdam carried out a large clinical trial with 892 patients who had a family history of high cholesterol. Named CAPTIVATE (Carotid Atherosclerosis Progression Trial Investigating Vascular ACAT Inhibition Treatment Effects) it was randomised, placebo-controlled and carried out in the US, Canada, Europe, Israel and South Africa. Patients received either the ACAT inhibitor pactimibe or placebo. Atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (CIMT) which is, put simply, the thickness of the artery serving the head and neck. As it thickens, atherosclerosis progresses.

What was found

The trial was discontinued because the efficacy of pactimibe could not be demonstrated. First, low density lipoprotein, the ‘bad’ form of cholesterol, actually increased by 7.4% in the pactimibe group. Also average CIMT increased in the first year in the pactimibe group. And 6.3% of those in the active treatment group had a heart attack or stroke, compared with 3.4% in the placebo group.

What this study means

Pactimibe clearly did not live up to its promise. In fact, it even seemed to cause harm by performing worse that placebo. The future of this class of drugs is now in question. Patients with high cholesterol should look to a combination of statins and lifestyle changes to reduce their risk of heart attack or stroke.

Source

Meuwese MJ, de Groot E et al ACAT inhibition and progression of atherosclerosis in patients with familial hypercholesterolemia: The CAPTIVATE randomized trial Journal of the American Medical Association March 18 2009;301:1131-1139be