Beta blockers are busted أ¢â‚¬â€œ what happens next?
2012-11-14 09:05:43
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.
Comments