40-Year-Old Gout Drug Shows Promise Against Angina
Could be a less expensive treatment for the painful heart condition, study says
MONDAY, June 7 (HealthDay News) -- A new British study suggests that a standard treatment for gout, already in use for four decades, could be an effective and less expensive alternative to conventional drugs targeting chronic stable angina.
Following work with 65 heart disease patients between the ages of 18 and 85, the research team noted that six weeks of high doses (600 milligrams per day) of the gout drug allopurinol appeared to curtail the activity of a particular enzyme called xanthine oxidase, and in so doing cut back on the amount of energy the heart needs to exert whenever it beats.
Exercise tests further revealed that allopurinol enabled the angina patients to get more oxygen to heart tissue plagued by blood and oxygen deprivation due to the arterial narrowing that characterizes coronary heart disease. Without treatment, this oxygen supply issue -- called ischaemia -- often leads to the onset of severe chest pain, sometimes as often as once a week.
The findings were published online June 8 in The Lancet.
"Allopurinol is inexpensive compared with some other antianginal drugs such as ranolazine and ivabradine, and has a favourable long-term safety record for the treatment of gout," the study authors, led by Allan D. Struthers of the University of Dundee, said in a news release.
Referring to standard angina treatment, Struthers said "allopurinol is better tolerated because it does not reduce blood pressure or heart rate, and does not cause many side effects, such as headaches and tiredness, that occur frequently with nitrates and beta-blockers."
The study authors concluded that "on the basis of our results, allopurinol is a useful anti-ischaemic treatment option in patients with angina that has the advantage of being inexpensive, well tolerated and safe in the long term."
"The precise place of allopurinol in the management of angina pectoris now needs to be explored further," the researchers added. "But this drug might be especially appealing for use in developing countries where coronary artery disease is rapidly increasing in frequency and where access to expensive drugs or invasive treatments (angioplasty and bypass surgery) is often restricted."
Dr. Kirk Garratt, clinical director of interventional cardiovascular research at Lenox Hill Hospital in New York City, said the "mechanism of angina relief with allopurinol is mysterious, but the clinical findings are supported by earlier work. The fact that this is a low cost drug with few side effects and a great safety profile will drive interest."
"The few patients that dropped out of the study seemed to have worse baseline angina and were taking more daily nitroglycerin pills," he said. "This makes me wonder if allopurinol will be better suited for patients with moderate, rather than severe, chest pains.
"This was a very small study, but the results were impressive. If allopurinol still had patent protection, we'd likely see a large-scale trial. But that won't happen now that it's a generic drug, so clinicians must decide if this small trial is convincing enough," he added.
Gout drug 'can prevent angina pain of heart disease'
Page last updated at 00:00 GMT, Tuesday, 8 June 2010 01:00 UK
Allopurinol Allopurinol has been available for the last 40 years to treat gout
A drug commonly used to treat gout can also relieve angina, researchers say.
Allopurinol is inexpensive compared with some other angina drugs and appears to work by reducing the energy needs of the heart, the Lancet reports.
The severe chest pain of angina occurs when the heart muscle is deprived of blood - and therefore oxygen.
The Dundee University study involving 65 angina patients found those on allopurinol could exercise for longer without getting chest pain.
Angina affects about two million people in the UK and is the most common symptom of heart disease.
It substantially reduces quality of life, with one in three patients with chronic stable angina having an angina "attack" at least once a week.
Effective treatments already exist, but for some patients they may not work and for others they can be too expensive.
Continue reading the main story
It's helpful for doctors to have another option to turn to for patients who don't respond well to existing drugs
Professor Peter Weissberg Medical director of the British Heart Foundation
Professor Allan Struthers and his team believe allopurinol could plug this gap.
They told the Lancet journal: "On the basis of our results, allopurinol is a useful anti-ischaemic treatment option in patients with angina that has the advantage of being inexpensive, well tolerated and safe in the long term.
"The precise place of allopurinol in the management of angina pectoris now needs to be explored further, but this drug might be especially appealing for use in developing countries where coronary artery disease is rapidly increasing in frequency and where access to expensive drugs or invasive treatments (angioplasty and bypass surgery) is often restricted."
The researchers suspect that allopurinol blocks an enzyme called xanthine oxidase, which in turn reduces the energy used by the heart in each beat or "stroke".
In their small study, those who received allopurinol treatment as opposed to a placebo were able to walk for 25% longer before they complained of chest pain.
Electrical recordings of the heart showed that allopurinol enabled the heart to work for longer before showing signs of oxygen starvation.
Prof Peter Weissberg, medical director of the British Heart Foundation, said the findings were promising.
"Allopurinol has been used to treat gout for decades, so we know it's safe and it's relatively cheap.
"There are several effective medicines out there for controlling angina, but it's helpful for doctors to have another option to turn to for patients who don't respond well to existing drugs."
He said people with angina should continue taking medicines as prescribed and talk to their doctor if they have any concerns.
"What is exciting is that it looks as if allopurinol may work by protecting the heart from oxygen starvation.
"If that is the case, then it raises the possibility that it could help the heart in other situations as well, such as after a heart attack."
The Lancet, Early Online Publication, 8 June 2010
doi:10.1016/S0140-6736(10)60391-1Cite or Link Using DOI
Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial
Awsan Noman MB a, Donald SC Ang MD a, Simon Ogston PhD b, Prof Chim C Lang MD a, Prof Allan D Struthers MD a Corresponding AuthorEmail Address
Experimental evidence suggests that xanthine oxidase inhibitors can reduce myocardial oxygen consumption for a particular stroke volume. If such an effect also occurs in man, this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris. We ascertained whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina.
65 patients (aged 18―85 years) with angiographically documented coronary artery disease, a positive exercise tolerance test, and stable chronic angina pectoris (for at least 2 months) were recruited into a double-blind, randomised, placebo-controlled, crossover study in a hospital and two infirmaries in the UK. We used computer-generated randomisation to assign patients to allopurinol (600 mg per day) or placebo for 6 weeks before crossover. Our primary endpoint was the time to ST depression, and the secondary endpoints were total exercise time and time to chest pain. We did a completed case analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 82040078.
In the first treatment period, 31 patients were allocated to allopurinol and 28 were analysed, and 34 were allocated to placebo and 32 were analysed. In the second period, all 60 patients were analysed. Allopurinol increased the median time to ST depression to 298 s (IQR 211―408) from a baseline of 232 s (182―380), and placebo increased it to 249 s (200―375; p=0?0002). The point estimate (absolute difference between allopurinol and placebo) was 43 s (95% CI 31―58). Allopurinol increased median total exercise time to 393 s (IQR 280―519) from a baseline of 301 s (251―447), and placebo increased it to 307 s (232―430; p=0?0003); the point estimate was 58 s (95% CI 45―77). Allopurinol increased the time to chest pain from a baseline of 234 s (IQR 189―382) to 304 s (222―421), and placebo increased it to 272 s (200―380; p=0?001); the point estimate was 38 s (95% CI 17―55). No adverse effects of treatment were reported.
Allopurinol seems to be a useful, inexpensive, well tolerated, and safe anti-ischaemic drug for patients with angina.
British Heart Foundation.
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