None of the 66 pharmaceutical drugs currently licensed as treatment for high blood pressure, or hypertension, are any better than 'water pills', according to a new breakthrough study. This means that doctors will need to seek out alternatives to treat one of the most common medical conditions in the West.
This damning conclusion also throws into doubt the effectiveness of many of the most financially lucrative types of drugs on the market today, including alpha-blockers, beta-blockers, calcium-channel blockers (or calcium antagonists), angiotensin-II receptor blockers, and angiotensin-converting enzyme (ACE) inhibitors. Each of these drug types includes a number of competing products from different manufacturers.
This remarkable expos'e of this set of the 'Emperor's new clothes' has come from Australian mathematician Thomas Lumley, who has developed a new kind of medical analysis. Indeed, the American Medical Association has been so impressed by his analytical methodology that it has published his findings in its own prestigious journal (JAMA, 2003; 289: 2534- 44).
This may prove to be a brave watershed gesture for a peer-reviewed journal that has enjoyed enormous streams of revenue from drug-company advertising, and has itself, in the past, often championed one of the very antihypertensive drugs condemned in Lumley's report
Although still only in his 30s, Lumley has developed a whole new way of analysing medical data from clinical trials. It's a breakthrough in statistical analysis that enables results from very differently designed medical trials to be pooled, thus allowing the maximum amount of information to be extracted.
Until now, the normal way of pooling medical-trial data has been by what's called meta-analysis. This was a method proposed in 1976 by Gene Glass, now a professor at the College of Education at Arizona State University, to integrate and summarise the findings from a body of research.
'Meta-analysis refers to the analysis of analyses. I use it to refer to the statistical analysis of a large collection of results from individual studies for the purpose of integrating the findings,' said Glass.
But the technique is limited as it cannot easily distill information from drug trials that have been set up for different purposes. For example, new drugs may be tested against a placebo or they may be compared with existing drugs. But the two types of trials are, statistically speaking, apples and oranges and so not truly comparable.
Lumley's new technique - which he calls 'network meta-analysis - is a way of linking the data from all drug trials, whatever their purpose, so that a clear picture emerges from what has hitherto been a statistical fog.
Lumley's network meta-analysis is tailormade for today's drug-dependent conventional medicine, and the internecine competition among dozens of different drugs for the same medical condition.
Antihypertensives are a highly profitable group of drugs - largely because the 'condition' of high blood pressure is considered to require constant pharmaceutical management. As a result, many people are given antihypertensive drugs for years on end, making these products the most commonly prescribed medications in the world.
Over the years, as their original product patents have begun to expire, drug manufacturers have brought out newer drugs with different modes of action - and, of course, higher price tags.
Drug companies have also waged a successful behind-the-scenes campaign to make more of us officially victims of hypertension - and, thus, potential drug recipients.
The US official health organisation the National Institutes of Health (NIH) recently revised its definition of high blood pressure downwards. Until earlier this year, a blood pressure reading of 130/85 mmHg (systolic/diastolic, respectively) was considered normal. But now, the acceptably normal systolic figure is 120 mmHg. Anyone with a blood pressure that is above that figure is now considered 'prehypertensive' - a new category of blood pressure 'patient'.
Full-blown hypertension is said to begin at a systolic level of 140 mmHg (the diastolic blood pressure is now thought to be relatively unimportant).
The upshot is that the developed countries are spending billions of pounds and dollars a year on antihypertensive drugs. But is it all necessary? Network meta-analysis says 'no'.
Even accepting the premise that high blood pressure needs to be treated with drugs (see box, p 4), Lumley's findings indicate that most blood-pressure drugs are largely a waste of money - particularly the highly sophisticated (and expensive) new ones.
To arrive at this subversive conclusion, Lumley took as his starting point the simplest and cheapest hypertension drugs on the market - the diuretics (see box below). These drugs have been in use for over a generation and, in low doses, have shown some benefit in terms of reducing heart disease and death rates.
Lumley proceeded to collect the data from every clinical trial that had tested either low-dose diuretics or the newer antihypertensive drugs. His database eventually totalled 42 clinical trials, involving nearly 200,000 patients with high blood pressure. After applying his network meta-analysis system, it was like scales falling from the eyes. 'For the first time, we could now view the totality of the evidence, rather than a patchwork of data,' says Lumley.
What his analyses revealed shot a huge hole in all that seductive drug company marketing hype. Drugs that had been described as 'breakthroughs', 'revolutions' and 'final answers' were exposed as being no better than the old cheap diuretics and, in most cases, were actually worse. For example, compared with diuretics, there were twice as many cases of heart failure with either beta-blockers or calcium-channel blockers. More people suffered a stroke with an ACE inhibitor than with a diuretic, and patients taking the costly angiotensin-II receptor blockers ended up with more heart disease.
'This is compelling evidence that the most effective drug is the least expensive,' says Professor Bruce Psaty, one of Lumley's co-authors. 'Low dose diuretics should be the first-line treatment for simple hypertension,' he concluded.
This is not the first attack aimed at the antihypertensives. Three years ago, an official Canadian survey came to precisely the same conclusion (Can Med Assoc J, 2000; 163: 57-60). 'Low dose diuretics are as good as and often better than other drugs', said the author of that report, blood-pressure specialist Dr James Wright. 'We've been brainwashed into thinking new is better, mainly because of heavy marketing by drug companies of what are costly but unproven drugs.'
So, are diuretics the answer to high blood pressure? Although that's the current official recommendation, there's considerable evidence that they, too, are not the miracle solution they're cracked up to be (see lower box, p 2).
Another issue is the overwhelming evidence that high blood pressure is related to lifestyle - in particular, diet - and that lifestyle changes can produce far greater reductions in blood pressure than diuretic drugs (see box, p 4).
One of the roadblocks is that many doctors who treat high blood pressure turn to drugs without ever considering diet and lifestyle. Another problem is that the patients themselves often prefer to take a pill than change their life habits.
High blood pressure is popularly associated with high stress levels. The scientific research does indeed confirm that reducing stress levels will reduce blood pressure - again obviating the need for drugs.
One of the oldest de-stressing techniques is meditation. Eastern practitioners have used it for thousands of years to achieve spiritual enlightenment, but Westerners cottoned on to it in the 1960s as a fashionable means of 'mental detox'.
Since then, a number of scientific studies has shown it to be a very effective way of reducing blood pressure and its associated problems. In one clinical trial, over 100 middle-aged and elderly Americans with severe high blood pressure (up to 179 mmHg systolic) were persuaded to practise Transcendental Meditation for three months. At the end of the study, their systolic blood pressure was as much as 12 mmHg lower than before (Hypertension, 1996; 28: 228-37).
Other Eastern meditative practices are equally effective antihypertensive techniques. Several studies have found that yoga can significantly lower blood pressure (Ind J Physiol Pharmacol, 1998; 42: 205-13; Aviat Space Environ Sci, 1989; 60: 684-7) as can Chi Gong (J Alt Complement Med, 1999; 5: 383-9). In one long-term study (lasting more than 22 years), patients with high blood pressure who practised Chi Gong lived 18 per cent longer than other hypertensives (J Trad Chin Med, 1986; 6: 235-8).
Exercise and losing weight can also reduce high blood pressure (Ann Intern Med, 1983; 98: 855-9).
Finally, an effective strategy is to keep a pet. When 24 New York unmarried stockbrokers taking antihypertensives looked after a pet at home, then had to give a speech and do mental arithmetic, their blood pressure rose. But compared with a matched set of controls without pets, the pet-owners' blood pressure went up by 10 mmHg less (Hypertension, 2001; 38: 815-20). 'When we told the group that didn't have pets about the findings, many went out and bought animals,' said lead investigator Dr Karen Allen. 'This study shows that, if you have high blood pressure, a pet is very good for you when you're under stress.'
Better, she might have added, than drugs.