Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000542
Status:
COMPLETED
Last Update Posted:
2016-07-29
First Post:
1999-10-27
Brief Title:
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2009-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine if the combined incidence of nonfatal myocardial infarction and coronary heart disease death differs between diuretic-based and each of three alternative antihypertensive pharmacological treatments Also to determine in a subset of this population if lowering serum cholesterol with a HMG CoA reductase inhibitor in older adults reduces all-cause mortality compared to a control group receiving usual care Conducted in conjunction with the Department of Veterans Affairs
Detailed Description:
BACKGROUND
An estimated 58 million people in the United States have elevated blood pressure systolic blood pressure SBP of 140 mmHg or greater andor diastolic blood pressure DBP of 90 mmHg or greater on initial examination or are taking antihypertensive medication Perhaps one-half to two-thirds of these have sustained hypertension
Despite the known etiologic relationship of hypertension to coronary heart disease large-scale randomized clinical trials in mild to moderate hypertension have failed to demonstrate conclusively that antihypertensive drug treatment largely based on thiazide-like diuretics reduces the occurrence of coronary heart disease death or non-fatal myocardial infarction The pooled results of nine such trials using primarily thiazide-like diuretics and involving over 43000 subjects suggest a 9 percent benefit with 95 percent confidence limits consistent with a 19 percent benefit or 1 percent adverse outcome This observed treatment effect compares with a maximum predicted effect on coronary heart disease of approximately 23 percent for an equivalent blood pressure difference as derived from epidemiologic data In contrast the observed beneficial effect on stroke in these trials 36 percent is almost exactly that which would be predicted from epidemiologic data A more recent overview of 14 trials in participants with all levels of hypertension estimated a somewhat larger benefit of 14 percent While this may be an over-estimate of benefit these overviews do not include the strongly positive results of the Systolic Hypertension in the Elderly Program SHEP in which diuretic-based treatment reduced stroke incidence by 36 percent and major coronary heart disease events by 27 percent
In the early 1980s two new classes of antihypertensive agents the calcium antagonists and ACE inhibitors were developed and licensed for use in chronic antihypertensive therapy These agents cost more than older agents such as diuretics and beta-blockers and evidence was limited that might justify their use despite the increased cost The 1988 Joint National Committee on Detection Evaluation and Treatment of High Blood Pressure recommended beta-blockers calcium antagonists ACE-inhibitors and diuretics as equally acceptable first-line therapy All four classes of drugs have been found to control diastolic blood pressure as single agents in 50 percent or more of patients with mild hypertension
Of these drug classes only beta-blockers have been compared directly to diuretics in large-scale long-term clinical trials in hypertension Three such trials completed in Europe in 1985-1986 showed approximate equivalence of effects on morbidity and mortality in diuretic- and beta-blocker-based regimens Pooled analysis of these trials yields a 6 percent lower coronary heart disease mortality from beta-blockers These data are in contrast to the recent Medical Research Council MRC Trial in the Elderly in which patients treated with a thiazide diuretic had significantly lower rates of coronary heart disease compared to beta-blocker treatment or placebo both by about 45 percent
Circulating levels of cholesterol specifically cholesterol associated with the low-density lipoprotein LDL fraction have been established as a major etiologic factor in coronary heart disease in observational epidemiologic studies in metabolic pathologic and genetic studies in humans and selected animal models and in randomized clinical trials The clinical trials that have demonstrated a reduction in coronary heart disease incidence from lowering LDL-cholesterol levels have been conducted primarily in middle-aged men with hypercholesterolemia or established coronary heart disease Experimental evidence for the efficacy of cholesterol lowering in older men is confined to the analysis of small subgroups of clinical trials and is lacking for women of any age The paucity of clinical trial data led the National Cholesterol Education Programs Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults in their 1987 Guidelines to allow for considerable physician judgement regarding the elderly
DESIGN NARRATIVE
Patients were recruited through office-based practices and hypertension clinics which were reimbursed by the Clinical Trials Center on a per-patient basis Six hundred patients were entered into the vanguard or feasibility phase and a total of 42448 were entered into the full-scale trial The primary hypothesis of the antihypertensive trial was that the combined incidence of fatal coronary heart disease and nonfatal myocardial infarction would be lower in hypertensive patients randomized to amlodipine a calcium antagonist lisinopril an angiotensin-converting enzyme ACE inhibitor or doxazosin an alpha adrenergic blocker as compared to those randomized to chlorthalidone a thiazide-like diuretic Secondary endpoints were total cardiovascular mortality major morbidity all-cause mortality and health-related quality of life
The primary hypothesis of the cholesterol-lowering trial was that mortality from all causes would be lower in the subset of hypertensive patients with LDL cholesterol levels between 120 and 189 mgdl between 100 and 159 mgdl for those with known coronary heart disease who were randomized to receive pravastatin a HMG CoA reductase inhibitor plus the National Cholesterol Education Program Step I cholesterol-lowering diet than those randomized to receive usual care plus diet Secondary endpoints were the combined incidence of nonfatal myocardial infarction and coronary heart disease death major non-cardiovascular heart disease morbidity and mortality and health-related quality of life
Recruitment for the feasibility phase began in February 1994 The clinical phase of the feasibility study ended in September 1994 Recruitment for the full-scale trial began in October 1994 and ended in January 1998 The mean follow-up was 49 years There were over 600 clinics in 47 states Puerto Rico Virgin Islands and Canada
An estimated 58 million people in the United States have elevated blood pressure systolic blood pressure SBP of 140 mmHg or greater andor diastolic blood pressure DBP of 90 mmHg or greater on initial examination or are taking antihypertensive medication Perhaps one-half to two-thirds of these have sustained hypertension
Despite the known etiologic relationship of hypertension to coronary heart disease large-scale randomized clinical trials in mild to moderate hypertension have failed to demonstrate conclusively that antihypertensive drug treatment largely based on thiazide-like diuretics reduces the occurrence of coronary heart disease death or non-fatal myocardial infarction The pooled results of nine such trials using primarily thiazide-like diuretics and involving over 43000 subjects suggest a 9 percent benefit with 95 percent confidence limits consistent with a 19 percent benefit or 1 percent adverse outcome This observed treatment effect compares with a maximum predicted effect on coronary heart disease of approximately 23 percent for an equivalent blood pressure difference as derived from epidemiologic data In contrast the observed beneficial effect on stroke in these trials 36 percent is almost exactly that which would be predicted from epidemiologic data A more recent overview of 14 trials in participants with all levels of hypertension estimated a somewhat larger benefit of 14 percent While this may be an over-estimate of benefit these overviews do not include the strongly positive results of the Systolic Hypertension in the Elderly Program SHEP in which diuretic-based treatment reduced stroke incidence by 36 percent and major coronary heart disease events by 27 percent
In the early 1980s two new classes of antihypertensive agents the calcium antagonists and ACE inhibitors were developed and licensed for use in chronic antihypertensive therapy These agents cost more than older agents such as diuretics and beta-blockers and evidence was limited that might justify their use despite the increased cost The 1988 Joint National Committee on Detection Evaluation and Treatment of High Blood Pressure recommended beta-blockers calcium antagonists ACE-inhibitors and diuretics as equally acceptable first-line therapy All four classes of drugs have been found to control diastolic blood pressure as single agents in 50 percent or more of patients with mild hypertension
Of these drug classes only beta-blockers have been compared directly to diuretics in large-scale long-term clinical trials in hypertension Three such trials completed in Europe in 1985-1986 showed approximate equivalence of effects on morbidity and mortality in diuretic- and beta-blocker-based regimens Pooled analysis of these trials yields a 6 percent lower coronary heart disease mortality from beta-blockers These data are in contrast to the recent Medical Research Council MRC Trial in the Elderly in which patients treated with a thiazide diuretic had significantly lower rates of coronary heart disease compared to beta-blocker treatment or placebo both by about 45 percent
Circulating levels of cholesterol specifically cholesterol associated with the low-density lipoprotein LDL fraction have been established as a major etiologic factor in coronary heart disease in observational epidemiologic studies in metabolic pathologic and genetic studies in humans and selected animal models and in randomized clinical trials The clinical trials that have demonstrated a reduction in coronary heart disease incidence from lowering LDL-cholesterol levels have been conducted primarily in middle-aged men with hypercholesterolemia or established coronary heart disease Experimental evidence for the efficacy of cholesterol lowering in older men is confined to the analysis of small subgroups of clinical trials and is lacking for women of any age The paucity of clinical trial data led the National Cholesterol Education Programs Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults in their 1987 Guidelines to allow for considerable physician judgement regarding the elderly
DESIGN NARRATIVE
Patients were recruited through office-based practices and hypertension clinics which were reimbursed by the Clinical Trials Center on a per-patient basis Six hundred patients were entered into the vanguard or feasibility phase and a total of 42448 were entered into the full-scale trial The primary hypothesis of the antihypertensive trial was that the combined incidence of fatal coronary heart disease and nonfatal myocardial infarction would be lower in hypertensive patients randomized to amlodipine a calcium antagonist lisinopril an angiotensin-converting enzyme ACE inhibitor or doxazosin an alpha adrenergic blocker as compared to those randomized to chlorthalidone a thiazide-like diuretic Secondary endpoints were total cardiovascular mortality major morbidity all-cause mortality and health-related quality of life
The primary hypothesis of the cholesterol-lowering trial was that mortality from all causes would be lower in the subset of hypertensive patients with LDL cholesterol levels between 120 and 189 mgdl between 100 and 159 mgdl for those with known coronary heart disease who were randomized to receive pravastatin a HMG CoA reductase inhibitor plus the National Cholesterol Education Program Step I cholesterol-lowering diet than those randomized to receive usual care plus diet Secondary endpoints were the combined incidence of nonfatal myocardial infarction and coronary heart disease death major non-cardiovascular heart disease morbidity and mortality and health-related quality of life
Recruitment for the feasibility phase began in February 1994 The clinical phase of the feasibility study ended in September 1994 Recruitment for the full-scale trial began in October 1994 and ended in January 1998 The mean follow-up was 49 years There were over 600 clinics in 47 states Puerto Rico Virgin Islands and Canada
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P20RR011104 | NIH | None | httpsreporternihgovquickSearchP20RR011104 |