Arteriosclerosis – New Brooms sweep clean

17. December 2008

Whoever relies only on cholesterol values when it comes to his or her risk for heart and vascular system – is out of luck. New studies with surprising results show that drugs for a favourable HDL- and LDL value do not always stem arteriosclerosis.

Every student of medicine learns that stuff early in his studies. Every general practitioner determines the risk for heart attack or stroke by blood values. And just like in an old Western movie, there are the bad guys and the good Sheriffs. Supported by drugs – some of the top selling drugs worldwide – the good HDl shoots its way through the arteries whilst the bad LDL blocks the vessels and leads directly to a heart attack.

ENHANCE: Low LDL is no heart insurance

Until a few years ago, everyone had his particular role in this drama. Now it turns out that obviously there are more influential players, accomplices and snipers in the game than known.
Still in the 90s a number of large studies showed that statine lower the “bad” LDL and reduces the number of cardio-vascular diseases. So far so good. More and more cholesterol lowering drugs entered the market. Most of the time, the proven effect for LDL was enough for the regulatory authorities to give the new player their “go”.

But why did stroke and heart attack claim many victims among those who had good cholesterol values all their lives? In the course of this year several new studies ask the arteriosclerosis researchers new riddles time and again. Indeed, a combination drug of the established Simvastatin and the cholesterol-absorption inhibitor Ezetimib did lower the LDL level in patients with familiar hypercholesteremia considerably and better than Statin alone. But the ENHANCE-study also showed: The combination drug did not reduce the production of plaques more effective than the therapy with the Statin alone. An additional study of the combination drug was published in the New England Journal of Medicine last September. The new data proves that a significantly lowered LDL level does not protect against the progress of an aortic stenosis. Although the disease pattern varies from arteriosclerosis but the two of them are closely connected as shown in recent research.

Torcetrapib: More victim than therapied patient

Pfizer went through an economic catastrophe with its largest beacon of hope: Torcetrapib. The active ingredient inhibits the Cholesterylester Transfer Protein (CETP) and thus increases the HDL-level. In 2006, the pharmaceutical company stopped a phase III study with 15000 participants. Although Torcetrapib does cause good cholesterol values, it does not hem or stop arteriosclerosis. And even worse: Compared to the established Statin Atorvastatin, 60 percent more test persons died during the study. “The pill killed more people than it could save lives”, describes John Kastelein at the Amsterdam University the unwanted side effects. There seem to be a whole lot more co-players and potential targets in the game if you want to inhibit the generation of the dangerous plaques. Anne Tybjørg-Hansen of the University Hospital Copenhagen thinks: “HDL is a ‘Bystander’, a lipide transporter in the body. But I don’t believe that it has anything to do wit the risk for cardiac diseases”.

JUPITER: Statins lower CRP

One of the new actors on stage is CRP (C-Reactive Protein). Current data point towards it that the factor does not only join the game with overweight and diabetes but also causes stuffed up vessels. From the point of view of Paul Ridker at the Brigham and Women’s Hospital in Boston, a low CRP level averts that instabile plaques come off. A few days ago he was able to prove the thesis with the results of the “JUPITER”-study during the American Cardiology Congress. He and his colleagues in 26 countries studied in 17000 participants whether Statins help patients with normal cholesterol but increased CRP values as well. Merck cancelled the study in spring. The results were already clear in the interim analysis. The active ingredient lowered the LDL value for about 50 percent to around 55mg/dl, the ones of CRP for about 37 percent. Compared to the placebo-group, the risk of myocardial infarct, stroke or arterial revascularization, the risks was reduced to half. And the Statin lowers mortality significantly.

The results in 2008 clearly point towards the end of times of forecasting the future for heart and vessels by looking at HDL and LDL. Maybe the CRP test will be routine soon and new brooms clean our vascular wiring system better.

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