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Trial suggests diuretic based antihypertensive treatment is more effective than newer alpha blocker based treatments for preventing cardiovascular disease
ARTICLE IN PRESS Evidence-based Cardiovascular Medicine (2004) 8, 12–13
Evidence-based
CARDIOVASCULAR MEDICINE www.elsevier.com/locate/ebcm
HYPERTENSION
Trial suggests diuretic based antihypertensive treatment is more effective than newer alpha blocker based treatments for preventing cardiovascular disease$ Abstracted from: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group. Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension 2003;42(3):239–46 Background Alpha blockers have favourable effects on surrogate cardiovascular markers, including cholesterol and glucose. The benefits of these newer antihypertensive agents compared with diuretics remains uncertain.
Trial (ALLHAT) used an intention to treat analysis. The study was discontinued in February 2000 and incomplete outcome data were reported. This article presents the final results, including follow up to March 2002.
Setting Objective This study assessed the effects of the alpha blocker doxazosin compared with the diuretic chlothalidone in hypertensive people at high risk of coronary heart disease. The primary endpoint was a composite of fatal coronary heart disease and non-fatal myocardial infarction. Secondary endpoints included all cause mortality, stroke, combined coronary heart disease (fatal coronary heart disease, non-fatal myocardial infarction, hospitalised angina and coronary revascularisation), and combined cardiovascular disease (coronary heart disease, stroke, angina treated outside hospital, heart failure, or peripheral arterial disease).
Method The randomised double blind Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack $
doi of associated commentary: 10.1016/j.ebcm.2003.12.014
doi:10.1016/j.ebcm.2003.12.015
623 centres in the United States, Canada, Puerto Rico and the Virgin Islands enrolled participants between February 1994 and January 1998.
Participants 24,316 people aged 55 years and older participated (mean age 67 years, 47% women, 47% white). All had hypertension and at least one other coronary heart disease factor. Hypertension was defined as systolic blood pressure of at least 140 mmHg, diastolic blood pressure of at least 90 mmHg, or consumption of antihypertensive medication(s). Other coronary heart disease risk factors included previous myocardial infarction or stroke, left ventricular hypertrophy, type 2 diabetes, current smoking, and low HDL cholesterol level. 90% of participants had received antihypertensive medication prior to randomisation. Exclusion criteria were heart failure and low ejection fraction.
ARTICLE IN PRESS Hypertension
Table 1
13
Cardiovascular outcomes at 4 years for people with hypertension receiving doxazosin or chlorthalidone.
Fatal CHD or non-fatal myocardial infarction All cause mortality Stroke Combined cardiovascular disease Combined coronary heart disease
Doxazosin (%) (n ¼ 9061)
Chlorthalidone (%) (n ¼ 15; 255)
Relative risk
95% CI
7.9
7.8
1.02
0.92 to 1.15
10.5 5.5 28.6 16.0
11.0 4.1 25.1 14.9
1.03 1.26 1.20 1.07
0.94 1.10 1.13 0.99
Intervention Participants were randomly assigned to doxazosin or chlorthalidone. Target blood pressure was less than 140/90 mmHg. The dose of doxazosin was 2, 4, or 8 mg per day. The dose of chlorthalidone was 12.5, 12.5 (sham titration), or 25 mg per day. 1 mg doxazosin and 12.5 mg chlorthalidone were given during the first week to minimise postural hypotension associated with doxazosin. Participants meeting the blood pressure target at maximal tolerated doses of these agents could receive open label drugs, including atenolol, reserpine, clonidine, and hydralazine. The investigators prohibited open label medications from one of the intervention drugs unless systolic blood pressure was greater than 160 mmHg, diastolic blood pressure was greater than 100 mmHg, or both. After 4 years, 78% of the chlorthalidone group and 71% of the doxazosin group remained on their assigned treatment. Mean follow-up was 3.2 years. About 5% of participants were lost to follow-up.
People receiving doxazosin had a 26% higher risk of stroke and a 20% higher risk of combined cardiovascular disease compared with those receiving chlorthalidone (see Table 1). About half of the increased risk of combined cardiovascular disease was due to an increased risk of heart failure (80% higher in the doxozosin group). There was no
1.13 1.46 1.27 1.16
difference between groups in all cause mortality or the composite primary endpoint of fatal coronary heart disease and non-fatal myocardial infarction.
Authors’ conclusions The authors suggest that diuretic based antihypertensive treatment is just as effective, if not moreso, than newer alpha blocker-based treatments for preventing cardiovascular disease.
Overall quality topic importance method quality practical use Poor
Main results
to to to to
Fair
Good
Excellent
Source of funding: US National Heart, Lung and Blood Institute and Pfizer Inc Enquiries to: MH Alderman, Albert Einstein College of Medicine, Department of Epidemiology and Population Health, 1300 Morris Park Ave, Bronx, NY 10461, US. Email: [email protected] Abstracted by Debbie Singh.
Evidence-based
CARDIOVASCULAR MEDICINE www.elsevier.com/locate/ebcm
HYPERTENSION
Trial suggests diuretic based antihypertensive treatment is more effective than newer alpha blocker based treatments for preventing cardiovascular disease$ Abstracted from: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group. Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension 2003;42(3):239–46 Background Alpha blockers have favourable effects on surrogate cardiovascular markers, including cholesterol and glucose. The benefits of these newer antihypertensive agents compared with diuretics remains uncertain.
Trial (ALLHAT) used an intention to treat analysis. The study was discontinued in February 2000 and incomplete outcome data were reported. This article presents the final results, including follow up to March 2002.
Setting Objective This study assessed the effects of the alpha blocker doxazosin compared with the diuretic chlothalidone in hypertensive people at high risk of coronary heart disease. The primary endpoint was a composite of fatal coronary heart disease and non-fatal myocardial infarction. Secondary endpoints included all cause mortality, stroke, combined coronary heart disease (fatal coronary heart disease, non-fatal myocardial infarction, hospitalised angina and coronary revascularisation), and combined cardiovascular disease (coronary heart disease, stroke, angina treated outside hospital, heart failure, or peripheral arterial disease).
Method The randomised double blind Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack $
doi of associated commentary: 10.1016/j.ebcm.2003.12.014
doi:10.1016/j.ebcm.2003.12.015
623 centres in the United States, Canada, Puerto Rico and the Virgin Islands enrolled participants between February 1994 and January 1998.
Participants 24,316 people aged 55 years and older participated (mean age 67 years, 47% women, 47% white). All had hypertension and at least one other coronary heart disease factor. Hypertension was defined as systolic blood pressure of at least 140 mmHg, diastolic blood pressure of at least 90 mmHg, or consumption of antihypertensive medication(s). Other coronary heart disease risk factors included previous myocardial infarction or stroke, left ventricular hypertrophy, type 2 diabetes, current smoking, and low HDL cholesterol level. 90% of participants had received antihypertensive medication prior to randomisation. Exclusion criteria were heart failure and low ejection fraction.
ARTICLE IN PRESS Hypertension
Table 1
13
Cardiovascular outcomes at 4 years for people with hypertension receiving doxazosin or chlorthalidone.
Fatal CHD or non-fatal myocardial infarction All cause mortality Stroke Combined cardiovascular disease Combined coronary heart disease
Doxazosin (%) (n ¼ 9061)
Chlorthalidone (%) (n ¼ 15; 255)
Relative risk
95% CI
7.9
7.8
1.02
0.92 to 1.15
10.5 5.5 28.6 16.0
11.0 4.1 25.1 14.9
1.03 1.26 1.20 1.07
0.94 1.10 1.13 0.99
Intervention Participants were randomly assigned to doxazosin or chlorthalidone. Target blood pressure was less than 140/90 mmHg. The dose of doxazosin was 2, 4, or 8 mg per day. The dose of chlorthalidone was 12.5, 12.5 (sham titration), or 25 mg per day. 1 mg doxazosin and 12.5 mg chlorthalidone were given during the first week to minimise postural hypotension associated with doxazosin. Participants meeting the blood pressure target at maximal tolerated doses of these agents could receive open label drugs, including atenolol, reserpine, clonidine, and hydralazine. The investigators prohibited open label medications from one of the intervention drugs unless systolic blood pressure was greater than 160 mmHg, diastolic blood pressure was greater than 100 mmHg, or both. After 4 years, 78% of the chlorthalidone group and 71% of the doxazosin group remained on their assigned treatment. Mean follow-up was 3.2 years. About 5% of participants were lost to follow-up.
People receiving doxazosin had a 26% higher risk of stroke and a 20% higher risk of combined cardiovascular disease compared with those receiving chlorthalidone (see Table 1). About half of the increased risk of combined cardiovascular disease was due to an increased risk of heart failure (80% higher in the doxozosin group). There was no
1.13 1.46 1.27 1.16
difference between groups in all cause mortality or the composite primary endpoint of fatal coronary heart disease and non-fatal myocardial infarction.
Authors’ conclusions The authors suggest that diuretic based antihypertensive treatment is just as effective, if not moreso, than newer alpha blocker-based treatments for preventing cardiovascular disease.
Overall quality topic importance method quality practical use Poor
Main results
to to to to
Fair
Good
Excellent
Source of funding: US National Heart, Lung and Blood Institute and Pfizer Inc Enquiries to: MH Alderman, Albert Einstein College of Medicine, Department of Epidemiology and Population Health, 1300 Morris Park Ave, Bronx, NY 10461, US. Email: [email protected] Abstracted by Debbie Singh.