Simple cholesterol is excellent * A small study yielded a big surprise: a few treatments, for a short period of time, produced a significant benefit in the condition of heart patients. Is this a sign of the birth of a new strategy to prevent heart disease?
Gina Coletta New York Times
A small-scale study among heart patients, which tested a very unlikely hypothesis (the lead researcher said he predicted a 1 in 10,000 chance of success), found that just a few treatments of an experimental drug produced a significant benefit, similar in terms of its effect to removing the amount of plaque (plaque) that accumulated over years in the coronary arteries.
The results, published on November 5 in the Journal of the American Medical Association, referred to 47 patients who suffered a heart attack. They received an infusion of a substance that mimics the substance HDL (high density lipoprotein), which removes cholesterol from the arteries. The patients in the control group received an infusion of saline.
After five weekly infusions, there was a 4.2% decrease in plaque volume in the coronary arteries among the patients who received the experimental drug; whereas among those who received saline infusions there was little, if any, increase in plaque volume.
Dr. Steven Neeson, a cardiologist from the Cleveland Clinic who did the research, says that the most powerful drugs from the statin family require years of treatment to achieve milder results. Medicines from this family lower the levels of LDL (low-density lipoprotein) that transports cholesterol to the coronary arteries.
Dr. Daniel Ryder, a lipid expert at the University of Pennsylvania, also expressed surprise: "It's amazing. The biggest and certainly the most surprising thing is that it can happen so quickly. Weekly infusion? It's surprising enough to make us all want to see a replication of the findings in a larger study."
Dr. Brian Brewer, head of the Department of Molecular Diseases at the National Heart, Lung and Blood Institute, said: "No one has seen anything like this in such a period of time. The narrowing of the arteries takes many years. The thought was that if we initiated a treatment to reduce or prevent it, it would take years before it would have an effect. We thought HDL treatment would work, but no one expected it to work within six weeks."
But all the researchers called for caution. This is a small and single study that needs to be verified. After that, it will be necessary to do large studies showing that the reduction as a result of plaque treatment also corresponds to a lower risk of heart attacks.
Heart disease researchers have long wondered what would happen if they increased HDL levels. Many thought this would prevent heart attacks, since epidemiological studies have shown that HDL is associated with a lower risk of heart disease. However, they were unable to go far. According to Dr. Ryder, the pharmaceutical companies were looking for a pill that would activate the HDL genes. "This is more or less the holy grail of the pharmaceutical industry," he says. "He is not found." The experts knew how to treat LDL and thus prevent the transfer of cholesterol to the arteries. This is done with the help of drugs from the statin family, which reduce LDL levels and, according to research, prevent heart attacks.
Regarding the obvious possibility of giving people HDL by intravenous infusion, there was a problem: the idea of waking up normal HDL is in the public domain and is not protected by patents. Therefore the companies were not interested.
There was, however, one type of HDL that was patented, and Dr. Roger Newton, president and CEO of Asperion Therapeutics in Mann Arbor, Michigan, bought the rights to develop it. Dr. Newton developed a drug to lower cholesterol; He is the one who discovered Lipitor, the most prescribed drug from the statin family in the United States. His goal in establishing Esperion in 1998 was to develop HDL treatments.
The story of the patented HDL began more than 20 years ago, when Italian researchers reported that about 40 residents of Limone sul Garda, a town in northern Italy, had unusually low levels of HDL - so low that they were below the measurement scale. Doctors expected them to have a high rate of heart disease, but it has been reported that they actually seem to be protected from these diseases.
Eventually, the researchers discovered that these people have a mutation in the HDL gene. The HDL they produce - known as - apoA-1Milano just breaks down quickly.
One of the first to study apoA-1Milano was Dr. Fardiman Shah, who directs the Atherosclerosis Research Center at Cedars-Sinai Medical Center. He reported that it prevents the accumulation of plaque in the arteries of rabbits and mice - and for only six weeks. "There was still skepticism at this stage," said Dr. Shah, "but we were convinced."
Then Shah wanted to know how quickly the effect would be seen in mice. "My God, what these mice showed in 48 hours," he declares. "The cholesterol content of the plaque decreased by almost 50%. Almost 50% of the lipids disappeared. And the inflammation subsided. The plaque retreated."
After doing preliminary tests of the HDL in humans, to check its safety, the Esperion company contacted Dr. Nissen. He developed a technique called ultrasound of the blood vessels, in which a tiny ultrasound camera is threaded into the arteries and through it directly observes the plaque and measures its size precisely. Esperion asked him to conduct a small-scale study using this method to test the drug's effects on plaque.
Dr. Nissen had his doubts. Most of the studies he participates in take two or three years and 500 or more participants to see an effect. This study was supposed to last five weeks and include about 50 people.
He agreed, but the arrangement was that Dr. Newton of Esperion would not see the results until the article was already in print. He first saw the data on October 31. Dr. Nissan is not financially involved in the company.
"Until now, the paradigm has been to prevent the disease by lowering bad cholesterol levels," said Dr. Nissen, referring to lowering LDL levels. The meaning of the experiment results is that it is possible
Also to remove the disease in the wall of the artery."
There are limitations, notes Dr. Alan Toole, an HDL researcher at Columbia University. The main problem is the small sample of the study. "This is not research that cannot be refuted. But basically I believe in his results", said Dr. Tull. "I think it's exciting."
He and others see the study as a first glimpse of what could become
For a new strategy of preventing heart disease, in which pills will be given to increase HDL levels, a second option is for the treatment to remain in the form of an infusion, which will be reserved for reducing the amount of plaque in severe cases.
Dr. Brewer sees this as a proof of principle. "We only reduced the risk of heart attacks by about 30% with the help of the drugs from the statin family," he says. "Can we reduce it even more? Our goal will be to reduce it by 95%, and this is one of the reasons to investigate HDL treatment. We are certainly at the beginning of the research field, but it is very encouraging."
