As I said the other day, I see this one as a "put it in the water supply" drug.
Gout drug allopurinol promising in chronic stable angina
June 7, 2010 | Lisa Nainggolan
Dundee, UK - A 40-year-old gout drug has been shown to have anti-ischemic properties and could be an alternative new treatment for the symptoms of chronic stable angina, UK researchers have discovered [1]. In a small six-week study published online June 7, 2010 in the Lancet, Dr Awsan Norman (University of Dundee, Scotland) and colleagues show that allopurinol enabled angina sufferers to exercise for 25% longer before they complained of chest pain or had ST depression on ECG, compared with placebo.
"Allopurinol prolonged quite a lot of the distance that angina patients could walk before they either got chest pain or had ECG signs of oxygen deprivation," senior author of the study, Dr Allan D Struthers (University of Dundee), told heartwire. It seems to be at least as effective as any other antianginal drug, says Struthers, noting that, while larger-scale studies are needed to determine the full potential of allopurinol for angina and to compare and contrast it with other treatment options, he feels it would be "perfectly legitimate" to use it now in a patient who has angina that is proving difficult to treat.
"Around a third of angina patients still get angina pain at least once a week despite what we do, including angioplasty, so a new treatment that is cheap and reduces their pain is very valuable. In an age of austerity, finding new uses for old drugs that are inexpensive and very safe is quite important," he says.
And since allopurinol is thought to protect the heart from oxygen deprivation, Struthers says the drug could even have potential in MI, although this needs to be further investigated.
In an accompanying editorial [2], Drs Renjith Antony (Golden Jubilee National Hospital, Clydebank, UK) and Henry J Dargie (Western Infirmary, Glasgow, Scotland) say: "Although further work is needed to confirm allopurinol's putative anti-ischemic effects and to better understand its mechanism of action, allopurinol joins a growing list of compounds that tests the conventional wisdom on what constitutes antianginal therapy."
Xanthine-oxidase activity contributes to exercise-induced ischemia
In their double-blind, placebo-controlled, crossover study, Norman et al randomized 65 patients with angiographically documented coronary artery disease, a positive exercise-tolerance test, and stable chronic angina pectoris (for at least two months) to either allopurinol, titrated up to 600 mg per day, or placebo for six weeks before crossover. Participants then received the other treatment for a further six weeks. The primary end point was the time to ST depression, and the secondary end points were total exercise time and time to chest pain.
Struthers explained that allopurinol is usually taken chronically to prevent gout and works by blocking the enzyme that forms uric acid, xanthine oxidase. It is generally taken at doses of up to 300 mg per day in the UK, so the 600-mg dose used in this instance is twice that generally prescribed. However, he said that allopurinol is approved for use in doses of up to 800 mg per day for gout in the US. His team chose 600 mg for their study after previous work showed this dose improved endothelial function and oxidative stress much more than 300 mg per day.
In the first treatment period, 31 patients were allocated to allopurinol and 28 were analyzed, and 34 were allocated to placebo and 32 were analyzed. In the second treatment period, all 60 patients were analyzed.
Allopurinol increased the median time to ST depression to 298 seconds compared with an increase to 249 seconds with placebo from a baseline of 232 seconds (p=0.0002). Allopurinol increased median total exercise time to 393 seconds from a baseline of 301, whereas placebo increased it to 307 seconds (p=0.003). And allopurinol increased the time to chest pain from a baseline of 234 seconds to 304 seconds compared with 272 seconds for placebo (p=0.001).
The researchers say that although the study is limited by its small sample size, the size of the effects and the p values "are impressive."
"High-dose allopurinol significantly prolonged the time to ST depression, the total exercise time, and the time to angina in patients with chronic stable angina during a standard exercise test, suggesting that endogenous xanthine-oxidase activity contributes somehow to exercise-induced myocardial ischemia," they state.
Allopurinol could be another second agent option for angina symptoms
Struthers explains that the relief of symptoms (chest pain on exertion) in chronic stable angina is generally treated with angioplasty or beta blockers plus a second drug such as nitrates, calcium antagonists, or newer agents such as ranolazine (Ranexa, Gilead) or ivabradine (Procoralan, Servier). If the second drug is ineffective, it is stopped and another second agent is tried. Allopurinol "could be another second drug to use as an option," he suggests.
It is inexpensive compared with the newer agents, has a favorable long-term safety record for the treatment of gout, and is better tolerated because it does not reduce blood pressure or heart rate and therefore does not cause many of the side effects associated with older antianginal therapies such as beta blockers and nitrates, he adds.
Dr Peter Weissberg, medical director of the British Heart Foundation, which funded the study of allopurinol, agrees. In a University of Dundee statement, he says: "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."
And Struthers says allopurinol may be especially appealing for use in the treatment of angina symptoms in developing countries, where access to expensive therapies such as angioplasty or newer drugs is restricted."
theheart.org |
