Wednesday, November 14, 2012

Beta blockers are busted ? what happens next?

They have treated heart disease for 40 years, but it now seems that beta blockers don?t work. What went wrong?

IT IS very rare for new evidence to question or even negate the utility of a well-established class of drugs. But after four decades as a standard therapy for heart disease and high blood pressure, it looks like this fate will befall beta blockers. Two major studies published within about a week of each other suggest that the drugs do not work for these conditions. This is a big surprise, with big implications.

The first beta blocker, Inderal, was launched in 1964 by Imperial Chemical Industries for treatment of angina. This drug has been hailed as one of great medical advances of the 20th century. Its inventor, James Black, was awarded the Nobel prize in medicine in 1988.

The 20 or so beta blockers now on the market are very widely used - almost 200 million prescriptions were written for them in the US in 2010. They are standard issue for most people with heart disease or high blood pressure. This may now change.

A large study published last month in The Journal of the American Medical Association found that beta blockers did not prolong the lives of patients - a revelation that must have left many cardiologists shaking their heads (JAMA, vol 308, p 1340).

The researchers followed almost 45,000 heart patients over three-and-a-half years and found that beta blockers did not reduce the risk of heart attacks, deaths from heart attacks, or stroke.

While this is not definitive, it's pretty damning, especially when another study - published just days earlier - found pretty much the same thing (Journal of the American Geriatrics Society, vol 60, p 1854).

The goal of this second study was to examine the effect of drug compliance on death rates in patients who had had heart attacks. About half of patients complied with their drug regimen. Unsurprisingly, these people were nearly 30 per cent less likely to die than those who did not comply.

This was to be expected, but there was one big surprise. While the result held for the standard classes of heart drugs - statins, anticoagulants and antihypertensives - it did not for beta blockers. Regardless of whether or not patients stuck to their regimen, their risk of dying was the same. Taken together with the JAMA study, it becomes very reasonable to question the benefit of beta blockers for treating these conditions.

To understand what is going on, consider how they work. Like many drugs, beta blockers target receptors embedded in the surface of cells. Receptors are "molecular switches" - when a specific molecule binds to them, they change shape and send a signal to the cell to perform a certain function. Beta blockers target beta receptors, which respond to the "fight or flight" hormones adrenalin and noradrenalin.

In humans, there are two principle types of beta-receptor - beta-1, primarily found in the heart, and beta-2, located at multiple sites, including the smooth-muscle cells of the bronchial tubes and in veins.

When adrenalin and noradrenalin bind to beta-1 receptors, they signal the heart to beat faster and pump harder. Binding to beta-2 receptors causes smooth muscle relaxation, especially in the airways, explaining why beta-2 activators are used as asthma drugs.

Beta blockers bind to both types of receptor, but do not activate the cellular response. This blocks adrenalin and noradrenalin from reaching their target and activating the response. By preventing the normal hormone-receptor interaction, the beta blockers slow the heart and cause it to pump less forcefully, lowering blood pressure.

The premise of beta-blocker therapy has been that giving the heart a rest will diminish the frequency of heart attacks. In the light of the two new studies, it is clearly time to question this.

Which raises the question: why has it taken so long to find out? It is worth noting at this point that this is not yet another case of a drug entering the market only to be withdrawn later because of lack of efficacy or even adverse reactions which could have been noticed with longer or larger trials. It is simply a new medical revelation. The authors of the JAMA paper provide a reasonable explanation of the conflict between their results and earlier studies.

The key word is "earlier". Most clinical trials on beta blockers took place before reperfusion therapy became standard treatment following heart attacks. Reperfusion involves opening the blocked artery by surgery or pharmaceuticals, and has been shown to significantly reduce damage to the heart.

Damaged hearts are more prone to fatal irregular beats, and beta blockers are useful in controlling this. But with the advent of reperfusion therapy, people who survived heart attacks suffered less cardiac damage, so the frequency of fatal arrhythmias was lower. Put simply, the beta blocker effect was significant before the advent of this improved treatment, but the beneficial effect has since disappeared.

Additionally, newer and better drugs such as anticoagulants, statins and antihypertensives are now routinely used in heart disease. These more effective therapies swamp any smaller benefit that the beta blockers might provide, minimising any measurable effect.

What comes next is impossible to predict, but we may well be seeing a rare case of medical wisdom being overturned almost overnight. Beta blockers are not dangerous and have been in use for such a long time that it is unlikely that we will see an immediate cessation. But these results are hard to ignore, and cardiologists will be paying careful attention.

Josh Bloom is the director of chemical and pharmaceutical sciences at the American Council on Science and Health, a consumer-education consortium based in New York CityJosh Bloom

If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.

Have your say

Only subscribers may leave comments on this article. Please log in.

Only personal subscribers may leave comments on this article

Subscribe now to comment.

All comments should respect the New Scientist House Rules. If you think a particular comment breaks these rules then please use the "Report" link in that comment to report it to us.

If you are having a technical problem posting a comment, please contact technical support.

Source: http://feeds.newscientist.com/c/749/f/10897/s/257ca186/l/0L0Snewscientist0N0Carticle0Cmg2162890A0A0B20A0A0Ebeta0Eblockers0Eare0Ebusted0E0Ewhat0Ehappens0Enext0Bhtml0Dcmpid0FRSS0QNSNS0Q20A120EGLOBAL0Qonline0Enews/story01.htm

stacey dash christopher columbus columbus day columbus day Stacy Dash Amber Tamblyn Lilit Avagyan

No comments:

Post a Comment

Note: Only a member of this blog may post a comment.