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Give blood pressure drugs to all - Criticism/Commentary
  MAY 22, 2009 Fran Lowry
London, UK - Blood-pressure-lowering drugs should be offered to everyone, regardless of their blood-pressure level, as a safeguard against coronary heart disease and stroke, researchers who conducted a meta-analysis of 147 randomized trials (comprising 958 000 people) conclude in the May 19, 2009 issue ofBMJ [1]. "Guidelines on the use of blood-pressure-lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure," write Drs Malcolm R Law and Nicholas Wald (Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Queen Mary University of London, UK). "Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some." "Whatever your blood pressure, you benefit from lowering it further," Law told heartwire. "Everyone benefits from taking blood-pressure-lowering drugs. There is no one who does not benefit because their blood pressure is so-called normal."
Six years ago, Law and Wald advocated the use of a polypill-containing a statin, three blood-pressure-lowering drugs (each at half the standard dose), folic acid, and aspirin-which they maintained could prevent heart attacks and stroke if taken by everyone 55 years and older and by everyone with existing cardiovascular disease [2].
In the current meta-analysis, which included people aged 60 to 69, they singled out blood-pressure-lowering drugs to determine the quantitative efficacy of different classes of antihypertensive agents in preventing coronary heart disease (CHD) and stroke. They also sought to determine who should receive treatment.
All antihypertensives prevent CHD and stroke
Overall, the results of the meta-analysis showed that in people aged 60 to 69 with a diastolic blood pressure before treatment of 90 mm Hg or a systolic blood pressure of 150 mm Hg, three drugs at half standard dose in combination (as in the polypill) reduced the risk of CHD by approximately 46% and of stroke by 62%. However, when used individually, a single antihypertensive agent at standard dose had about half this effect.
The five main classes of blood-pressure-lowering drugs-thiazides, beta blockers, ACE inhibitors, angiotensin-receptor blockers, and calcium-channel blockers-were similarly effective in preventing CHD events and strokes, with the exception of calcium-channel blockers, which had a greater preventive effect on stroke than the other four agents (relative risk 0.92, 95% CI 0.85-0.98).
People with and without cardiovascular disease derived equal benefit, with similar percentage reductions in CHD events and stroke, and regardless of what their blood pressure was before treatment. Even patients with blood pressures considered to be low-110 mm Hg systolic and 70 mm Hg diastolic-showed fewer CHD events and a reduced incidence of stroke when taking an antihypertensive. Law and Wald also report that calcium-channel blockers reduced the incidence of heart failure by 19% and that the other antihypertensive agents reduced heart failure by 24%.
In an accompanying editorial [3], Dr Richard McManus (University of Birmingham, UK) and Dr Jonathan Mant (University of Cambridge, UK) write that the findings of Law and Wald will contribute to debate on the management of hypertension in several areas. "Taken at face value, these findings provide tacit support for the use of a 'polypill' to lower the risk of cardiovascular disease in people likely to be at high risk (such as all people over the age of 55) without first checking their blood pressure."
In a comment to heartwire, McManus added that he believes that the findings reinforce the view that treatment to lower blood pressure should be offered on the basis of risk, regardless of blood pressure.
Throwing the baby out with the bathwater
On the other side of the Atlantic, hypertension experts were not so sanguine in their opinion of Law and Wald's conclusions.
Commenting on this study for heartwire, Dr James Elliott (Rush Medical College, Chicago, IL) said he took issue with the authors' suggestion that the measuring of blood pressure was unnecessary.
"Profs Wald and Law made the revolutionary comment some years ago that we should abandon blood pressure and simply treat everyone at high CVD risk with their magic polypill, which they claimed reduced heart disease and stroke by 90%.This meta-analysis is an unusual compilation of data that supports that hypothesis." Abandoning blood-pressure measuring is like throwing the baby out with the bathwater, Elliott said.
Elliott also took issue with the meta-analysis, which he called "old-fashioned." "I think Wald and Law have become the ultimate lumpers. They have included the 37 studies where beta blockers were used against placebo in people with heart attacks, and they have lumped those in with all the other kinds of therapies that we use to lower blood pressure and prevent other events. Nobody, as far as I can remember, has ever included that set of 37 trials in with the other antihypertensive trials because it represents such a different population. They have done the old-fashioned, simple meta-analysis. But there are better ways to understand the data."
A meta-analysis is like a sausage
Adding his opinion, Dr Franz Messerli (St Luke's-Roosevelt Hospital Center, New York City) said that by including 147 trials in their meta-analysis, the authors had to make numerous assumptions, "some possibly valid, others clearly not." Because the "blood pressure fall was not reported in patients with a history of coronary heart disease, they estimated this fall from a meta-analysis of blood-pressure trials. This is clearly inappropriate, since the fall in blood pressure depends on the pretreatment level, and patients with coronary heart disease who often are hypotensive (particularly post-MI) will not respond the same way as do patients with hypertension," he told heartwire.
It is little surprise that beta blockers now, all of a sudden, look better than in any other review ever done, Messerli added. "Numerous meta-analyses have clearly demonstrated that beta blockers do not reduce the risk of coronary heart disease in hypertension, despite the fact that they lower blood pressure. Thus, despite its appearance of being bigger and better, this study is yet another example of my dictum: A meta-analysis is like a sausage; only God and the butcher know what goes in it, and neither would ever eat any."
Law and Wald disclosed that they hold patents (granted and pending) on the formulation of a combined pill to simultaneously reduce four cardiovascular risk factors, including blood pressure. McManus disclosed that he has a financial relationship withSanofi-Aventis, Pfizer, A. Menarini Pharma, and Merck Sharp & Dohme. Elliott and Messerli have disclosed no relevant financial conflicts of interest.
1 Law MR, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338:b1665.
2 Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326:1419.
3 McManus RJ, Mant J. Management of blood pressure in primary care. BMJ 2009; 338:b940.
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