Beta Blockers: From Nice to Nasty

After using beta-blockers as the drug of choice to treat hypertension (high blood pressure) for 30 years, doctors have finally been warned that the drugs are ineffective and dangerous.

The drugs come with ‘an unacceptable risk’ of causing type 2 diabetes, and they are only half as effective as newer hypertension drugs such as the ACE inhibitors, according to practice guidelines issued by the National Institute for Health and Clinical Excellence (NICE) last month.

The announcement, described as the ‘most significant’ in NICE’s history, was forced on the advisory group by reports last autumn that beta-blockers had killed tens of thousands of hypertension patients when a more benign and effective therapy was available.

The dangers of beta-blockers were already being highlighted 16 years ago.

One study discovered that hypertension patients who suddenly stopped taking a beta-blocker were very likely to suffer a heart attack and death (JAMA, 1990; 263), while another study, published eight years ago, discovered they were no more effective than a sugar pill (JAMA, 1998; 279: 1903–7).

But it has been the continued revelations from ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) that finally forced NICE’s hand. ASCOT, which recruited 19,257 hypertension patients aged between 40 and 79 years, has been pointing out for years both the dangers and shortcomings of the beta-blockers, but NICE decided to form a review committee only after a damning study was published in September 2005 (Lancet, 2005; 366: 895–906).

This trial established that the beta-blockers were reducing the risk of stroke by 19 per cent compared with the 38 per cent effectiveness of the ACE inhibitors. Beta-blockers were also responsible for the deaths of 3 per cent more patients than other anti-hypertensives.

Beta-blockers (beta-adrenergic antagonists) are designed to decrease the heart’s need for blood and oxygen by reducing its workload. They also help the heart to beat more regularly.

Nobel prize winner Sir James Black developed the drug in the 1950s as a way of combating heart diseases such as angina after he realized that adrenaline, our ‘fight or flight’ hormone, puts a sudden demand on the heart.

Adrenaline triggers the release of glucose reserves into the blood. They bind to receptors on the membrane of the heart cells that cause the heart to beat faster. The hormone also constricts arteries to increase the rate at which blood is pumped around the body.

It took another ten years before the first beta-blocker—propranolol—was licensed for use. Ironically, Black and his team at Glasgow never developed it as an antihypertensive, but it was quickly used as this and for many other conditions that can be worsened by a sudden restriction of the arteries.

Within just a few years of it appearing on the market, propranolol was being used to treat migraine, glaucoma, tremor, hyperthyroidism, and performance anxiety and enhancement.

Propranolol quickly established itself as the beta-blocker for all ills. Not surprisingly, the American Association of Poison Control Centers (AAPCC) each year receives reports of 2.4 million adverse reactions to the drug in the USA alone, and 1,184 fatalities associated with the drug.

Tragically, it is also the ‘drug of choice’ for people attempting suicide, while its widespread use means that almost every home has some, and 510 children under the age of six die every year after swallowing drugs prescribed for their parents.

What now for the beta-blocker? The drug industry has a wonderful way of reinventing drugs that have been finally discredited, and the beta-blockers are no exception.

One researcher at Baylor College of Medicine in Houston, Texas, believes they could be the answer to osteoporosis. Prof Gerard Karsenty believes that the drug could block bone destruction (Nature, 20 Feb 2005), a theory that has been supported by another trial, which found that people taking beta-blockers also suffered fewer fractures (JAMA, 2004; 292: 1326–32).

And psychiatrists at Cornell University believe they could be used to help suppress disturbing memories in people who witnessed a traumatic event such as 9/11 or the London terrorist bombings. Propanolol has the ability to block the neurotransmitters involved in laying down memory, and so it could be used for victims of post-traumatic stress disorder (PTSD), the researchers postulate.

The Cornell team wants to recruit 60 volunteers who would be prepared to take the drug whenever they experienced a PTSD symptom, such as increased heart rate or breathing difficulties.

It’s a therapy that has not been met with universal approval.

Dr Paul McHugh, a psychiatrist at Johns Hopkins University in Baltimore, says: “If soldiers did something that ended up with children getting killed, do you want to give them beta-blockers so that they can do it again?”

Bryan Hubbard