Tuesday June 8 2010
Allopurinol is used to treat gout
“A drug commonly used to treat gout can also relieve angina,” BBC News reported. It said that, although effective drugs for angina already exist, allopurinol could be a cheaper option.
This study looked at the effects of allopurinol in 65 people with stable angina – a condition where chest pain or discomfort occurs during exercise or stress. It found that, after taking the drug for six weeks, participants could exercise for about 58 seconds longer on average and experienced chest pain about 38 seconds later than after six weeks of taking 'dummy’ pills. Based on this study, it is not possible to say how allopurinol compares to other anti-angina drugs.
Overall, this study suggests that allopurinol may have the short-term effect of increasing exercise tolerance in people with stable angina. Larger, longer studies would ideally be needed to confirm the findings and determine whether allopurinol has any effect on longer-term outcomes such as the risk of cardiovascular events. People taking angina drugs should continue taking them as prescribed and contact their GP with any queries.
Where did the story come from?
The study was carried out by researchers from the University of Dundee and was funded by the British Heart Foundation. The research was published in the peer-reviewed medical journal The Lancet.
The study was reported by BBC News and The Daily Telegraph. Both reports are generally accurate. However, both papers report that when people received allopurinol they could walk for 25% longer before they complained of chest pain than when they received placebo. This relative risk is not reported in the study itself, in which the authors only report the absolute increase in walking times.
What kind of research was this?
This crossover randomised controlled trial (RCT) investigated the effect of allopurinol on the exercise ability of people with chronic stable angina. Allopurinol is a drug commonly used to treat gout. Chronic stable angina involves chest pain that usually occurs during exercise or when a person is stressed, and goes away when they are resting or calm. The condition is caused by a narrowing of the arteries that supply the heart with oxygen (coronary artery disease), meaning that the heart muscle does not get enough oxygen during exercise. Allopurinol may be able to reduce chest pain caused by exercise in people with stable angina by reducing the amount of oxygen their heart needs during exercise.
An RCT is the best way to look at the effects of a treatment. This study was a crossover RCT, where all participants receive both treatments being tested in a random order. One limitation is the absence of a ‘no treatment’ break between the two treatment periods in this study, which could mean that the treatment taken first could still be having an effect during the second treatment period. However, this is less of a concern because this study compared allopurinol to placebo.
If the effects of allopurinol ‘carried over’ into the placebo period, then this would make placebo look more effective than it truly was, rather than making allopurinol look more effective than it was. Also, the researchers carried out statistical tests to monitor this, and the tests suggested that there had been no ‘carry over’ of treatment effects from the first period into the second period.
This study was double blinded, meaning that the participants and the researchers did not know who had been given which treatment (allopurinol or placebo) and, therefore, their expectations about the effects of these treatments could not affect their outcomes.
What did the research involve?
The researchers enrolled 65 adults with stable angina that had lasted for at least two months. Participants were randomly assigned to receive either high-dose allopurinol or placebo for six weeks before switching over to the other treatment. The researchers tested the participants’ exercise capabilities and heart function on a treadmill after both six-week periods and compared their performance after taking allopurinol or placebo.
Participants in the study had to have confirmed coronary artery disease and were recruited from three hospitals in Scotland. The researchers discounted people with gout, back or leg problems, those who had had a heart attack, surgery to treat coronary artery disease in the past six months, or had angina at rest. Participants could continue taking their anti-angina medications during the study. All participants had to be well enough to be able to do an exercise tolerance test (ETT). In the ETT, participants walked on a treadmill while attached to an electrocardiogram (ECG) that monitored the electrical activity of their heart. During the ETT, the speed and incline of the treadmill increased and the researchers monitored what effect this had on the heart and any chest pain or discomfort.
The participants performed the ETT at least twice before the start of the study, and these tests had to show that exercise affected the electrical activity of their heart in a way called ST segment depression that is typical of stable angina. ST segment depression shows that the heart muscle is not getting enough oxygen. The researchers were mainly interested in whether allopurinol affected the time it took for the ST segment to become depressed. If allopurinol delayed ST segment depression during the test, it would suggest that it was improving the angina. The researchers also assessed how long it took for participants to experience chest pain, and how long they could exercise for.
When the participants were on allopurinol, they received 100mg once a day in the first week, 300mg once a day in the second week and then 300mg twice a day for four weeks. During the placebo period, the participants took identical-looking and tasting ‘dummy’ tablets for six weeks. At the end of each six-week period the participants did another ETT. Blood samples were also taken, and the participants were asked to record any attacks of angina they had during the study in a diary.
What were the basic results?
Five participants dropped out of the study, leaving 60 participants whose results were analysed.
The researchers found that allopurinol appeared to delay ST segment depression according to ECG during the tests. When the participants were taking allopurinol, half of them took 296 seconds or longer to show ST depression (the median measurement), compared with 232 seconds before they started the study and 249 seconds when they were taking placebo.
Participants on allopurinol could also exercise for about 58 seconds longer than when they were on placebo. Half could exercise for 393 seconds or longer, compared with 301 seconds before they started the study and 307 seconds when they were taking placebo. Participants also took longer on average to experience chest pain in the exercise test when taking allopurinol than when they were taking placebo (median 304 seconds with allopurinol versus 272 seconds with placebo).
The 43 participants who returned their angina diaries reported having fewer angina attacks during the six weeks when they were taking allopurinol than in the placebo period, but this reduction was not large enough to be statistically significant.
The participants did not report any side effects of taking allopurinol.
How did the researchers interpret the results?
The researchers conclude that, “allopurinol seems to be a useful, inexpensive, well tolerated, and safe anti-ischaemic drug for patients with angina”.
They suggest that it “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”.
This study had a good design, and its results suggest that allopurinol may increase exercise tolerance in people with stable angina. There are some points to note:
- The study was relatively small, and a larger study would be useful to confirm the results.
- Participants only took allopurinol for six weeks. Longer-term trials would be needed to determine its longer-term effects, for example, whether it has any effect on the risk of having cardiovascular events.
- The study cannot tell us how allopurinol compares to other anti-angina medications as it was only compared to placebo. The researchers say that an indirect comparison to other drugs used for angina suggests that the increase in median (average) time to ST depression is similar.
- It also cannot tell us whether allopurinol will be effective in people for whom other anti-angina medications have not been effective, as this was not the population tested in this trial.
This somewhat surprising finding will no doubt be explored further in studies designed to define the place of this drug in angina management. People taking angina drugs should continue taking them as prescribed and contact their GP with any queries.