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Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial
Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial
The Lancet, June 8 2010
doi:10.1016/S0140-6736(10)60391-1
Original Text
Awsan Noman MB et al
Summary
Background
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.
Methods
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.
Findings
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.
Interpretation
Allopurinol seems to be a useful, inexpensive, well tolerated, and safe anti-ischaemic drug for patients with angina.
Funding
British Heart Foundation.
Featured Angina| Acute Coronary Syndrome and Heart Disease Interviews
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Author Interview: Claes Held MD
Associate professor at Uppsala Clinical Research Center and the
Cardiology department at Uppsala University Hospital in Sweden
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Publication:
Physical activity levels, ownership of goods promoting sedentary behaviour and risk of myocardial infarction: results of the INTERHEART study
Eur Heart J first published online January 11, 2012 doi:10.1093/eurheartj/ehr432
2012 doi:10.1093/eurheartj/ehr432
Claes Held, Romaina Iqbal, Scott A. Lear, Annika Rosengren, Shofiqul Islam,James Mathew, and Salim Yusuf
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What are the main findings of the study?
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The main findings are he following:
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It is well known that physical inactivity is a risk factor for developing cardiovascular disease.
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Our study shows that being physically active reduces the risk of having a heart attack.
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Older studies have mostly studied people in the developed countries. This study which has a global perspective and includes 52 countries from all continents, shows that physical inactivity reduces the risk also in both low- middle-and high-income countries.
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We also found that ownership of a car and TV was associated with a more than doubled risk of being sedentary and that in low- and middle income the risk for a heart attack was increased with 27 %.
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We can however, not conclude from this study that there is a causal relationship but it is an interesting finding.
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Were any of the findings unexpected?
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We looked at the relationship between physical activity both at work and during leisure time.
A bit surprising was that people with heavy physical labor did not have a reduction in the risk of heart attacks, whereas people with both mild and moderate intensity did.
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What should clinicians and patients take away from this study?
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The main findings above and also that physical activity with duration below the recommended 30 minutes/day does seem to prevent from heart attacks as well although not as much as when you do it according to guidelines.
This may be a comfort to those who are completely sedentary and feel that it would be a too big step to move to the 30 minutes/day right away.
All PA does a good job for the heart as compared to not doing anything at all!
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What recommendations do you have for cardiology health care providers as a result of your study?
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It would be interesting to follow up on the ownership of car and TV and do a prospective study to see if the theory holds true.
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Abstract
Background— Despite data showing the benefits of implantable cardioverter-defibrillator (ICD) insertion for primary prevention in populations at risk for sudden death, professional society guidelines recommending primary prevention, and recognition by payers of the clinical value of ICDs in these populations, ICDs for primary prevention remain underused. We sought to determine whether implementing a screening tool would increase appropriate identification of patients showing clinical evidence of ICD benefit and prompt referral to an electrophysiologist for ICD implantation.
Methods and Results— Screening tools were affixed to medical records for patients seen in 2 outpatient cardiology offices that queried ejection fraction and whether referral to an electrophysiologist was made (N=6632).
The number of appropriate referrals in the screening period were compared with analogous data collected before implementation of the screening tool (control period) through retrospective record review (n=3606). Significantly more eligible patients were offered referral during the screening period than during the control period at both sites, 80% (8/10 eligible) versus 33% (5/15) at site 1 (P<0.02) and 100% (44/44) versus 60% (21/35) at site 2 (P<0.001). Of all patients offered referral, 41% (32/78) accepted.
Conclusions— The use of a screening tool increases referral to electrophysiology for patients in whom placement of an ICD confers the benefit of sudden cardiac death primary prevention. Barriers to referral include both physician and patient factors. Verification of these findings on a larger scale as well as studies defining the foundation of these barriers may further improve use of ICDs in patients for whom their mortality benefit is well described.
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Amazon.com 's Editorial Reviews
Angina: New Ways to Treat
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Part of the award winning public television series Healthy head
/Healthy Mind. It's one of the scariest medical symptoms for people who are generally healthy: a tightening, painful feeling in the chest known as Angina. In some cases this chest pain can be a serious warning that requires immediate treatment. But for the millions of people with chronic, stable angina the discomfort is something that can be readily managed with a variety of treatments. In this program we take a look at what generally causes angina, what can be done to prevent it and how it can be effectively treated with lifestyle changes, innovative drug therapies and medical procedures.
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