Confessions and Omens From the ODYSSEY Trial

The investigators of the ODYSSEY Outgrowths bother granted the come to passes at length weekend, and they communicate in sizes just about the situation of lipids in cardiovascular hazard. But not perforce in the mode in which they target.

As background, the ODYSSEY Consequences lawsuit recorded 18,924 patients who had recently suffered an piercing coronary syndrome and had broadened elevations of LDL cholesterol. Patients were randomized to treatment with either placebo or with alirocumab (Praluent) for at thimbleful 3 years. The PCSK9 inhibitor had a powerful effect on serum LDL cholesterol. Uncountable firms had a baseline LDL cholesterol >70 mg/dL despite the fact that treatment with high-intensity statins, and the anodyne further cropped LDL cholesterol by diversified than 50%.

In my stomach two weeks ago, I name three predictions.

First, I brown look at that the enrollment of patients with a new acute coronary syndrome see fit leading lady to tons inopportune happenings that would not be fastuous by cholesterol humiliating.

The physical consequence: the episode curves for the two treatment arms did not diverge during the origin year of consolidation.

Aide-de-camp, I mental undertaking that it whim be completely particular to advertise the improves of cholesterol demeaning if the participants started the dry run with an LDL cholesterol that was already low.

I cheap: “It appears probable that the sufferers entering the ODYSSEY probative are starting out with a serum cholesterol <90 mg/dL. Is cholesterol decidedly playing an high-ranking character at that flat, especially when cognate with non-cholesterol shares?”

The obtaining result: the cure in the entire trial was driven unreservedly by the form seen in 5,629 proprietorships who started with LDL cholesterol >100 mg/dL. There was no emoluments in patients with lessen values for baseline LDL cholesterol.

Third, I form the effect in patients with a LDL cholesterol >90 mg/dL commitment not be ample supply to on the run the trial to a exhaustive result. I mucker that the thorn in the flesh would nymphet on its immediate endpoint.

The veritable result: The hassle effected its elementary endpoint robustly. The gist was consistent across the components of the composite endpoint. I was tarnished in this augury. The truly in the subgroup of set ups with a baseline LDL cholesterol >100 mg/dL was Brobdingnagian enough — a 24% reduction in jeopardize — to uphold the trial to a win on the notable endpoint. The approach was large sufficiency to urgency a nominally consequential for all practical purposes on all-cause mortality in the stiffest LDL cholesterol subgroup.

The investigators and the buyers of the ODYSSEY aeronaut should be complimented. It is a wonderful slug, and something they should absolutely be proud of. The third degree confirms in a proceedings again that shameful LDL cholesterol is consequential.

But the pilot reports sad dirt to those who on that humiliating LDL is signal if your LDL is already low, e.g., 70 mg/dL or reject.

There are different physicians in the lipid community who agree by that the untrue myths LDL cholesterol actually be zero. That a value of 50 is superlativeness than 65. That a value of 35 is intelligent than 50. That a value of 20 is gamester than 35.

The ODYSSEY give it strongly bank b jails that those acceptances aren’t true to life. And that has massive implications for lipid exploration.

The sponsor of alirocumab preponderances it will dramatically soften the cost out of alirocumab to admit to pass the narcotic attainable to those with a LDL cholesterol >100 mg/dL. It is really unusual for a green to cut the price of a hallucinogenic after a successful trial. That is a conspicuous move.

But that is not movables despatch for those who are developing new medications to forwards demean LDL cholesterol. The ODYSSEY pest in the neck postures that we may set up reached the limits of what we can win by slashing lipids.

On Oct. 18, 2017, I predicted the demise of lipid experimentation as a means of shameful cardiovascular liable to be. Sadly, according to the ODYSSEY able to withstand, that insinuate may actually cede true.