CARDIOVASCULAR DISEASES

Health Evidence Bulletins - Wales (logo)
Team Leader: Dr David Fone

Date of completion: 30.9.98

1: Primary prevention of cardiovascular disease

This bulletin is a supplement to, not a substitute for, professional skills and experience. Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation.

The Statements The Evidence
1.1 Smoking
1.1a. Cigarette smoking is associated with a two to three-fold increase in coronary heart diseasei (CHD) and peripheral vascular diseaseii risk in the whole adult population. The risk rises with the number of cigarettes smoked per day. In 1990, smoking accounted for 28% of male and 26% of female all-cause vascular deaths aged 35 to 69iii. Smoking is associated with a doubling of the relative risk of ischaemic strokeiv.
Health gain notation - 6 "harmful")
i. Dawber TR. The Framingham Study. The Epidemiology of atherosclerotic disease. Cambridge, MA: Havard University Press, 1980
(Type IV evidence - summary of results from prospective cohort study of 5127 persons with 24 year follow-up)
ii. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. Journal of the American Geriatric Society 1985;33:13-18
(Type IV evidence - prospective cohort study of 5209 subjects with 26 year follow-up)
iii. Peto R, Lopez AC, Boreham J, Thun M, Heath C. Mortality from smoking in developed countries 1950-2000. Oxford: Oxford University Press (Oxford Medical Publications), 1994
(Type IV evidence - summary of indirect estimates of mortality from National Vital Statistics)
iv. Marmot MG, Poulter NR. Primary prevention of stroke. Lancet 1992;339:344-47
(Type IV evidence - summary of observational studies)
1.1b. In non-smokers, self-reported exposure levels to environmental tobacco smoke ("passive smoking") and serum cotinine levels are associated with diagnosed ischaemic heart diseasei. The best estimate of the reversible (cause and effect) component of the association is a relative risk of 1.23; 95% CI: 1.14, 1.33ii, iii.
(Health gain notation - 6 "harmful")
i. Tunstall-Pedoe H, Brown CA, Woodward M, Tavendale R. Passive smoking by self report and serum cotinine and the prevalence of respiratory and coronary heart disease in the Scottish heart study. Journal of Epidemiology and Community Health 1995;49:139-43
(Type IV evidence - cross-sectional survey of 786 men and 1492 women aged 40-59 years who reported never having smoked)
ii. Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence. British Medical Journal 1997;315:973-80
(Type IV evidence – systematic review and meta-analysis of 19 observational studies)
iii. Poswillo D, Chairman. Department of Health, Department of Health and Social Services, Northern Ireland, The Scottish Office Department of Health, Welsh Office. Report of the Scientific Committee on Tobacco and Health. London: The Stationery Office, 1998
(Type V evidence - expert opinion)
1.2 Air pollution
1.2a. Air pollution is associated with cardio-respiratory morbidity and mortalityi.
(Health gain notation - 6 "harmful")
i. See Healthy Environments bulletin in this series

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1.3 Cholesterol
1.3a. The relationship between serum cholesterol and CHD mortality is continuous and curvilinear. The strength of this relationship is greatest in younger people: a 10% reduction in serum cholesterol is associated at five year follow-up with a 54% reduction in the incidence of CHD at 40 years, 27% at 60 years and a 19% reduction at 80 yearsi.
(Health gain notation - 1 "beneficial")
i. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? British Medical Journal 1994;308:367-72
http://www.bmj.com/cgi/content/full/308/6925/367
(Type II evidence - review of randomised controlled trials and prospective cohort studies)
1.3b. Pravastatin therapy in men aged 45 to 64, with no history of myocardial infarction (MI), a non-fasting plasma cholesterol = 6.5 mmol/l and a trial entry fasting LDL cholesterol of between 4.5 to 6.0 mmol/l, significantly reduced the risk of non-fatal MI or death from definite CHD by 31% (95% CI: 17%, 43%; p<0.001), with non-significant reductions in the risk of death from any cause of 22% (95% CI: 0%, 40%; p=0.051) and fatal or non-fatal stroke of 11% (95% CI: -33%, 40%; p=0.57)i. Reductions in the risk of non-fatal MI and CHD death were seen in all subgroups of patients, including classification by cholesterol level and smoking statusi.

A further analysisii of a systematic review and meta-analysis of three primary prevention trialsiii found to prevent one combined endpoint of death from any cause, non-fatal MI or non-fatal stroke, 35 people (95% CI: 24, 63) with elevated lipids (defined above)i have to be treated with a statin for 4.6 yearsii.
(Health gain notation - 1 "beneficial")

Caveat: Five percent of subjects in the WOSCOP primary prevention triali had a history of stable angina.

i. Shepherd J, Cobbe SM, Ford I, et al, for the West of Scotland Coronary Prevention Study Group (WOSCOP). Prevention of coronary heart disease with pravastatin in men with hypercholesterolaemia. New England Journal of Medicine 1995;333:1301-7
(Type II evidence - randomised controlled trial of 6595 men aged 45 to 64 with mean plasma cholesterol of 7.0 mmol/l randomised to pravastatin 40 mg daily or placebo, mean 4.9 year follow-up)
ii. Statins. Bandolier 1997, Number 47. Volume 5 Issue 1
http://www.jr2.ox.ac.uk/bandolier/band47/b47-2.html
(Type I evidence - NNT calculations using data from three randomised controlled primary prevention trials (reference iii) involving 7961 patients, mean 4.6 year follow-up)
iii. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomised trials. Journal of the American Medical Association 1997;278:313-21. In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of three randomised controlled primary prevention trials involving 7961 patients, mean 4.6 year follow-up)

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1.3c. Lovastatin therapy 20-40mg in men aged 45 to 73 and women aged 55 to 73 with a trial entry total cholesterol of 4.65 to 6.82mmol/l, average LDL-C, below average HDL-C and no clinically evident atherosclerotic cardiovascular disease, significantly reduced the incidence of a first acute major coronary event (primary endpoint defined as fatal or non-fatal MI, unstable angina, or sudden cardiac death): relative risk 0.63; 95% CI: 0.50, 0.79; p<0.001i. Significant reductions in the secondary endpoints of revascularisation (relative risk 0.67; 95% CI: 0.52, 0.85; p=0.001), unstable angina (relative risk 0.68; 95%CI: 0.49, 0.95; p=0.02), and fatal or non-fatal MI (relative risk 0.60; 95% CI: 0.43, 0.83; p=0.002). There were no statistical differences in treatment effects between the sexes.
(Health gain notation - 1 "beneficial")

Caveat: High drop-out rates (29% lovastatin, 37% placebo). Placebo group subjects were more likely to be withdrawn from study as a result of developing CHD or starting cholesterol lowering medication.

i. Downs JR, Clearfield M, Weis S, et al. Women with average cholesterol levels. Results of AFCAPS/TexCAPS. Journal of the American Medical Association 1998;279:1615-22
(Type II evidence - randomised controlled trial of 5608 men aged 45 to 73 and 997 women aged 55 to 73 with entry total cholesterol of 4.65 to 6.82mmol/l randomised to lovastatin 20 mg daily or placebo, mean 5.2 year follow-up)
1.3d. Cost-effectiveness studies suggest that statins should only be used in primary prevention of MI in high risk patients after using other more cost-effective interventions, including aspirin, smoking cessation, dietary change and exercise, and antihypertensive therapyi.
(Health gain notation - 3 "balance of risk and cost-benefit")
i. Cholesterol and coronary heart disease: screening and treatment. Effective Health Care Volume 4 Number 1. University of York: NHS Centre for Reviews and Dissemination, 1998
http://www.york.ac.uk/inst/crd/ehc41.htm
(Type II evidence - systematic literature review of cost-effectiveness studies based on randomised controlled trial data)

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1.4 Hypertension
1.4a. Hypertension is a major risk factor for strokei and CHDii; 40% of strokes are attributable to a systolic blood pressure of >140mmHgi. Drug therapy to reduce blood pressure reduces the risk of mortality from stroke (odds ratio 0.60; 95% CI: 0.46, 0.79), equivalent to eight deaths prevented /1000 patients treated over five years (95% CI: 2, 13) and mortality from CHD (odds ratio 0.74; 95% CI: 0.64, 0.86), equivalent to eight deaths prevented /1000 patients treated over five years (95% CI: 4, 13)iii. Benefits apply to all ages but the five year absolute morbidity and mortality benefits are greater for older age-groups, particularly aged 60-80 yearsiii,iv.
(Health gain notation - 1 "beneficial")
i. Marmot MG. Primary prevention of stroke. Lancet 1992;339:344-47
(Type IV evidence - narrative summary of observational studies)
ii. Dawber TR. The Framingham Study. The epidemiology of atherosclerotic disease. Cambridge, MA: Havard University Press, 1980
(Type IV evidence - summary of results from prospective cohort study of 5127 persons with 24 year follow-up)
iii. Mulrow C, Lau J, Cornell J, Brand M. Antihypertensive drug therapy in the elderly. Cochrane Review [updated 1 December 1997]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 21,908 hypertensive patients aged 60 and over in 15 trials evaluating the effects of drug treatment on morbidity and mortality outcomes)
iv. Lievre M, Leizorovicz A. Treatment of high blood pressure in patients aged over 60 years: lessons from randomised clinical trials. Cardiology in the Elderly 1995;3:217-22. In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 12,483 patients aged over 60 years in five randomised controlled trials and 24,230 patients in 11 randomised controlled trials)
1.4b. Sodium intake is a determinant of population blood pressure: sensitivity to salt increases with age and higher initial blood pressurei-iv. A reduction of sodium intake of 100mmol/24hrs is associated with a significant decrease in systolic blood pressure of 3.7mmHg (95% CI: 2.35, 5.05; p<0.001), but not diastolic blood pressure, 0.9mmHg (95% CI: -0.13, 1.85; p=0.09)iv. This reduction is estimated to reduce the incidence of stroke by 39% and that of ischaemic heart disease by 30%iii.
(Health gain potential - 1 "beneficial")

Caveat: The evidence for dietary sodium restriction in the younger normotensive population is not conclusiveiii,iv, and the validity of the meta-analysis is affected by publication bias and significant heterogeneity among trials in the effect of dietary sodium restriction on blood pressure.

i. Intersalt Co-operative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hours urinary sodium and potassium excretion. British Medical Journal 1988;297:319-28
(
Type IV evidence - cross-sectional study of 10,079 men and women aged 20-59 from 52 centres from 32 countries around the world)
ii. Elliott P, Stamler R, Nichols R, et al for the Intersalt Co-operative Research Group. Intersalt revisited: further analysis of 24 hour sodium excretion and blood pressure within and across populations. British Medical Journal 1996;312:1249-53
(Type IV evidence - reanalysis of data from Intersalt)
iii. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? I-Analysis of observational data among populations, II-Analysis of observational data within populations, III- Analysis of data from trials of salt reduction. British Medical Journal 1991;302:811-24
(Type IV evidence - analysis of data from studies recording blood pressure and sodium intake in geographically defined populations: I - 47,000 subjects aged between 15 to 69 years from 24 communities, II - 14 population studies, III - 68 crossover trials and 10 randomised controlled trials of dietary salt reduction)
iv. Midgley JP, Matthew AG, Greenwood CM, Logan AG. Effect of reduced dietary sodium on blood pressure. A meta-analysis of randomised controlled trials. Journal of the American Medical Association 1996;275:1590-97. In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 1131 hypertensive subjects in 28 randomised controlled trials and 2374 normotensive subjects in 28 randomised controlled trials)

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1.4c. Oral potassium supplements significantly reduce systolic blood pressure (pooled estimate of effect = -3.11mmHg, 95% CI: -1.91, -4.31) and diastolic blood pressure (-1.97mmHg, 95% CI: -0.52, -3.42), particularly in patients with high sodium intakei. Calcium supplementation has also been shown to significantly reduce systolic blood pressure (pooled estimate of effect = -1.27mmHg; 95% CI: -0.29, -0.92)ii.
(Health gain potential - 2 "likely to be beneficial")

Caveat: No studies with mortality outcomes have been identified.

i. Whelton PK, He J, Cutler JA, et al. Effects of oral potassium on blood pressure: meta-analysis of randomised controlled clinical trials. Journal of the American Medical Association 1997;277:1624-32. In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 1560 hypertensive and 1005 non-hypertensive subjects in 33 trials of potassium supplementation of median 75mmol per day with maximum three year follow-up)
ii. Bucher H, Cook RJ, Guyatt GH, et al. Effects of dietary calcium supplementation on blood pressure: a meta-analysis of randomised controlled trials. Journal of the American Medical Association 1996;275:1016-22. In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 2412 hypertensive and non-hypertensive subjects in 33 trials of calcium supplementation)
1.4d. Evidence-based guidelines for the management of essential hypertension are availablei,ii and due to be updated in 1999i.
(Health gain notation - 1 "beneficial")

i. Management guidelines in essential hypertension: modified recommendations based on the report by the second working party of the British Hypertension Society. British Hypertension Society: London, 1997
(Type V evidence - expert opinion)
ii. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Archives of Internal Medicine 1997;157:2413-46
http://www.nhlbi.nih.gov/new/press/nhlbi-06.htm
(Type V evidence - expert opinion)

1.5 Diabetes
1.5a. Diabetes is a major risk factor for CHD, ischaemic stroke and peripheral vascular diseasei: evidence-based guidelines for the management of diabetic cardiovascular disease are availablei. Intensive glycaemic control in non-insulin dependent diabetes has not been shown to be associated with reduced all-cause or cardiovascular disease mortalityii.
(Health gain notation - 4 "unknown")

Caveat: UKPDSii was unlikely to answer whether intensive glycaemic control influences macrovascular disease due to the use of aggregate endpoints.

i. Scottish Intercollegiate Guidelines Network (SIGN). Management of Diabetic Cardiovascular Disease. Edinburgh: Royal College of Physicians,1997
http://www.show.scot.nhs.uk/sign/pdf/sign19.pdf
[Adobe Acrobat reader required]
(Type V evidence - expert opinion)
ii. Intensive blood-glucose control with sulponylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53
(Type II evidence - randomised controlled trial of 3867 newly diagnosed patients with type 2 diabetes, median age 54 years, randomised to conventional or intensive therapy with 10 year follow-up)

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1.5b. There is significant benefit from treatment of hypertension in the primary prevention of cardiovascular mortality in diabetic subjects (odds ratio 0.64; 95% CI: 0.50, 0.82)i. Secondary prevention trials show a reduction of all-cause mortality: short-term follow-up of less than one year odds ratio 0.64; 95% CI: 0.50, 0.83; long-term odds ratio 0.82; 95% CI: 0.69, 0.99i. In the UKPDS trial, tight blood pressure control (mean BP 144/82) with a beta-blocker or ACE inhibitor was associated in a 34% reduction (p=0.019) in risk of the combined endpoint of myocardial infarction, sudden death, stroke and peripheral vascular diseaseii.
(Health gain notation - 1 "beneficial")

Caveat: Data are taken from the hypertension trials with defined diabetic sub-groupsi. Lack of information in these trials on cardiovascular outcomes reduced the power of the meta-analysis to detect possible benefits of the interventions.

i. Fuller J, Stevens LK, Chaturvedi N, Holloway JF. Anti-hypertensive therapy in diabetes mellitus. (WITHDRAWN from Cochrane Library in 2002) Cochrane Database of Systematic Reviews. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 1355 diabetic patients in two primary prevention trials and 3922 diabetic patients in seven long-term and five short-term secondary prevention trials)
ii. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study (UKPDS) Group. British Medical Journal 1998;317:703-13
(Type II evidence - randomised controlled trial of 1148 hypertensive patients with type 2 diabetes (mean age 56, mean entry BP 160/94) comparing the effect of intensive blood pressure control with moderate control, median follow-up 8.4 years)
1.6 Physical activity
1.6a. Physical activity is independently associated with a two-fold reduction in the relative risk of CHDi,ii and strokeiii, with a protective effect similar to not smoking, not being hypertensive or not being hypercholesterolaemic.
(Health gain notation - 1 "beneficial")
i. Berlin JA, Colditz GA. A meta-analysis of physical activity in the prevention of coronary heart disease. American Journal of Epidemiology 1990;132:612-28
(Type IV evidence - systematic review and meta-analysis of 27 prospective cohort studies)
ii. Shaper AG, Wannamethee G. Physical activity and ischaemic heart disease in middle-aged British men. British Heart Journal 1991;66:384-94
(Type IV evidence - prospective cohort study of 7735 men aged 40-59 years with eight year follow-up)
iii. Wannamethee G, Shaper AG. Physical activity and stroke in British middle aged men. British Medical Journal 1992;304:597-601
(Type IV evidence - prospective cohort study of 7735 men aged 40-59 years with nine year follow-up)
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1.7 Obesity
1.7a. Obesity (body mass index (BMI) >25) is associated with an increase in cardiac and stroke mortality, particularly at follow-up of ten years or morei-iii.
(Health gain notation - 6 "harmful")
i. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26 year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968-77
(Type IV evidence - prospective cohort study of 5209 males and females aged 28-62 years with 26 year follow-up)
ii. Jarrett RJ, Shipley MJ, Rose G. Weight and mortality in the Whitehall study. British Medical Journal 1982;285:535-37
(Type IV evidence - prospective cohort study of 18,393 males aged 40 to 64 at ten year follow-up)
iii. Imeson JD, Haines AP, Meade TW. Skinfold thickness, body mass index and ischaemic heart disease. Journal of Epidemiology and Community Health 1989;43:223-27
(Type IV evidence - prospective occupational cohort study of 1511 males aged 40-64 years with six year follow-up)
1.7b. Patients with central obesity are at higher risk of MI, angina or stroke death than those of similar BMI with peripheral fat distributioni-iii.
(Health gain notation - 6 "harmful")

 

i. Ducimetiere P, Richard J, Cambien F. The pattern of subcutaneous fat distribution in middle aged men and the risk of coronary heart disease: the Paris Prospective Study. International Journal of Obesity 1986;10:229-40
(Type IV evidence - prospective cohort study of 6718 men aged 42 to 53 with six year follow-up)
ii. Lapidus L, Benbgtsson C, Larsson B, Pennert K, Rybo E, Sjostrom L. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12-year follow-up of participants in the population study of women in Gothenburg, Sweden. British Medical Journal 1984;289:1257-61
(Type IV evidence - prospective cohort study of 1462 women aged 38 to 60 years with 12 year follow-up)
iii. Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bjorntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow-up of participants in the study of men born in 1913. British Medical Journal 1984;288:1401-4
(Type IV evidence - well designed prospective cohort study of 792 men aged 54 years with 13 year follow-up)

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1.7c. Weight loss has beneficial effects on cardiovascular risk factors - blood pressure, plasma lipids and insulin resistancei,ii.
(Health gain notation - 1 "beneficial")
i. Noppa H. Body weight change in relation to incidence of ischaemic heart disease and change in risk factors for ischaemic heart disease. American Journal of Epidemiology 1980;111:693-704
(Type IV evidence - prospective cohort study of 1302 women aged 38-60 years with six year follow-up)
ii. Hubert HB, Eaker ED, Garrison RJ, Castelli WP. Life-style correlates of risk factor change in young adults: an eight-year study of coronary heart disease risk factors in the Framingham offspring. American Journal of Epidemiology 1987;125:812-31
(Type IV evidence - prospective cohort study of 794 persons aged 20-29 years with eight year follow-up)
1.8 Alcohol consumption
1.8a. Observational studies in both men and women consistently show a strong J-shaped dose-effect relationship between alcohol consumption and incidence of CHDi-iv and ischaemic strokev; consumption of one or two drinks per day is associated with a risk reduction of 30% - 50%, compared to abstinence. (Number needed to treat (NNT) to prevent one ischaemic heart disease event in six years = 24; 95% CI: 13, 169)iv,vi.
(Health gain notation - 3 "trade-off between beneficial and adverse effects").

 

 

 

 

 

 

 

 

 

i Rimm EB, Giovannucci EL, Willett WC, et al. Prospective study of alcohol consumption of coronary disease in men. Lancet 1991;338:464-68
(Type IV evidence - prospective cohort study of 44,000 men aged 40-75 with two year follow-up)
ii. Klatsky AL, Armstrong MA, Friedman GD. Alcohol and Mortality. Annals of Internal Medicine 1992;117:646-54
(Type IV evidence - well designed prospective cohort study of 128,934 adults with seven year follow-up)
iii. Fuchs CS, Stampfer MJ, Colditz GA, et al. Alcohol consumption and mortality among women. New England Journal of Medicine 1995;332:1245-50
(Type IV evidence - prospective cohort study of 85,709 women aged 34-59 years with 12 year follow-up
iv. Hein HO, Suadicani P, Gyntelberg F. Alcohol consumption, serum low density lipoprotein cholesterol concentration, and risk of ischaemic heart disease: six year follow up in the Copenhagen male study. British Medical Journal 1996;312:736-41
(Type IV evidence - prospective cohort study of 2826 men aged 53-74 years with six year follow-up)
v. Camargo CA. Moderate alcohol consumption and stroke: the epidemiologic evidence. Stroke 1989;20:1611-26
(Type IV evidence - narrative review of 62 observational studies)
vi. Evidence-based drinking. Bandolier 1996, Number 27. Volume 3 Issue 5
http://www.jr2.ox.ac.uk/bandolier/band27/b27-9.html
(Type IV evidence - NNT calculations using data from reference (iv) - prospective cohort study of 2826 men aged 53-74 years with six year follow-up)

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1.8b. Both acute and chronic heavy alcohol consumption of over four drinks per day is associated with increased blood pressurei and an increased risk of stroke, especially cerebral haemorrhageii. Heavy consumption of alcohol is associated with cardiomyopathyiii.
(Health gain notation - 6 "harmful")
i. Klatsky AL. Blood pressure and alcohol consumption. In: Bulpitt CJ, ed. Epidemiology of hypertension. Amsterdam: Elsevier, 1985: 159-74. (Birkenhager WH, Reid JL, eds. Handbook of hypertension, Vol 6)
(Type IV evidence - summary of observational evidence)
ii. Camargo CA. Moderate alcohol consumption and stroke: the epidemiologic evidence. Stroke 1989;20:1611-26
(Type IV evidence - narrative review of 62 observational studies)
iii. Urbano-Marquez A, Estruch R, Navarro-Lopez F, Grau JM, Mont L, Rubin E. The effects of alcoholism on skeletal and cardiac muscle. New England Journal of Medicine 1989;320:409-15
(Type III evidence - non-randomised cross-sectional comparison of 50 alcoholic men, mean age 38.5 years, with healthy controls)
1.8c. The balance of risk and benefit is against a population strategy of increased alcohol consumption to reduce the risk of coronary heart diseasei.
(Health gain notation - 5 "unlikely to be beneficial")
i. Marmot M, Brunner E. Alcohol and cardiovascular disease: the status of the U-shaped curve. British Medical Journal 1991;303:565-68
(Type IV evidence - review of observational studies)
1.9 Antiplatelet therapy
1.9a. Antiplatelet therapy in low risk "primary prevention" patients for five years is associated with a small but significant reduction in non-fatal MI of 5 (SD 2) per 1000 patients treated (% odds reduction 29%, SD 8%; p<0.0005, NNT=200) and a non-significant reduction in MI, stroke or vascular death. A small, non-significant increase was found for non-fatal stroke, and a marginally significant excess of haemorrhagic fatal or non-fatal strokei.
(Health gain notation - 3 "trade-off between beneficial and adverse effects")
i. Antiplatelet Trialist's Collaboration. Collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. British Medical Journal 1994; 308: 81-106.
http://www.bmj.com/cgi/content/full/308/6921/81
In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 28,000 low risk patients in five trials of antiplatelet therapy)

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1.10 Atrial fibrillation
1.10a. Atrial fibrillation is a major risk factor for stroke, associated with a five-fold excess in age-adjusted incidencei. Anticoagulation in patients with non-rheumatic atrial fibrillation is effective in the primary prevention of ischaemic stroke - relative risk reduction 68% (NNT 31/1000, p<0.001) with a significant increase in the risk of major haemorrhage of 3/1000ii. Patients with atrial fibrillation aged under 65 years were at very low risk of stroke even when not treatedii.
(Health gain notation - 1 "beneficial")

Caveat: Primary prevention trials included six percent of patients with a previous TIA or stroke. Generalisability of the results is limited by entry into the trials of a small proportion of eligible patients and only 20% of patients were aged over 75 years.

i. Wolf PA, Abbott R, Kannel W. Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke 1991;22:983-88
(Type IV evidence - prospective cohort study of 5070 participants with 34 year follow-up)
ii. Atrial Fibrillation Investigators. Risk factors for stroke and efficiency of antithrombotic therapy in atrial fibrillation analysis of pooled data from five randomised controlled trials. Archives of Internal Medicine 1994;154:1449-57
(Type I evidence - meta-analysis of 1889 patient-years receiving warfarin and 1802 control)

 

1.10b. There is evidence that aspirin alone in patients with non-rheumatic atrial fibrillation is effective in the primary prevention of stroke. Two trials have shown a reduction of 15-20 strokes per 1000 patients treated per yeari,ii. One study found a non-significant 16% relative risk reduction with 75mg aspirini and the second study found a significant 42% (95% CI: 9%, 63%; p=0.02) reduction with 325mg aspirin dailyii. An overview of these primary prevention trials found a non-significant risk reduction of 31% (95% CI: -12%, 58%)iii.

An extended overview which included a third secondary prevention trial found a borderline significant risk reduction of 21%; 95% CI: 0%, 38%; p=0.05iv,v for aspirin alone and a significant risk reduction of 49%, p<0.001iv,v, associated with a greater risk of major haemorrhage (2.8% vs. 0.9% per year) for anticoagulation with warfarin compared to aspirin. Further trials comparing warfarin, low-dose warfarin, warfarin plus aspirin and aspirin alone are in progress.
(Health gain notation - 1 "beneficial")

i. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study. Lancet 1989;i:175-79
(Type II evidence - randomised controlled trial of 1007 patients aged >18 years (median age 74 years) with chronic atrial fibrillation, two year follow-up)
ii. Stroke Prevention in Atrial Fibrillation Investigators. Stroke prevention in atrial fibrillation study: final results. Circulation 1991;84:527-39
(Type II evidence - randomised controlled trial of 1330 patients with constant or intermittent atrial fibrillation with one year follow-up)
iii. Antiplatelet Trialist's Collaboration. Collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. British Medical Journal 1994;308:81-106.
http://www.bmj.com/cgi/content/full/308/6921/81
In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 1792 patients with non-rheumatic atrial fibrillation in two primary prevention trials of aspirin vs. placebo)
iv. Atrial Fibrillation Investigators. The efficacy of aspirin in patients with atrial fibrillation: analysis of pooled data from three randomised trials. Archives of Internal Medicine 1997;157:1237-40
(Type I evidence - meta-analysis of 3852 patient-years, mean age 70 years)
v. Albers GW. Atrial fibrillation and stroke. Three new studies, three remaining questions. Archives of Internal Medicine 1994;154:1443-48
(Type II evidence - review of randomised controlled trials)

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1.10c. Evidence-based guidelines for the management of patients with atrial fibrillation are availablei.
(Health gain notation - 1 " beneficial")

 

i. Prystowsky EN, Benson WD Jr, Fuster V et al. Management of patients with atrial fibrillation: a statement for healthcare professionals from the subcommittee on electrocardiography and electrophysiology, American Heart Association. Circulation 1996;93:1262-77
http://216.185.112.5/presenter.jhtml?identifier=1507
(Type V evidence - expert opinion)
1.10d. Evidence-based guidelines for the investigation and management of valvular heart disease are availablei.
(Health gain notation - 1 "beneficial")

 

i. Prendergast BD, Banning AP, Hall RJC. Valvular heart disease: recommendations for investigation and management. Guidelines produced by a working group of the British Cardiac Society and the research unit of the Royal College of Physicians. London: Royal College of Physicians, 1996
http://www.cardiac.org.uk/
(Type V evidence - expert opinion)
1.11 Multifactorial clinical guidelines
1.11a. UK multi-factorial evidence-based guidelines for the prevention of coronary heart disease are due for publication in 1998i. Updated Joint European guidelines are now availableii.
(Health gain notation - 1 "beneficial")

 

i. British Cardiac Society, British Hypertension Society, British Hyperlipidaemia Association
http://www.cardiac.org.uk
(Type V evidence - expert opinion)

ii. Wood D, De Backer G, le Faergeman O, Graham I, Mancia G, Pyorala K. Prevention of coronary heart disease in clinical practice. Recommendations of the Second Joint Task Force of European and other Societies on coronary prevention. European Heart Journal 1998;19:1434-1503
http://www.escardio.org/scinfo/Guidelines/98prevention.pdf
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(Type V evidence - expert opinion)

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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk