The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT study overview Double-blind, randomized trial to determine whether.

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Presentation transcript:

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT study overview Double-blind, randomized trial to determine whether the occurrence of fatal CHD or nonfatal MI is lower for high-risk hypertensive patients treated with newer agents (amlodipine, lisinopril, or doxazosin) compared with a diuretic (chlorthalidone) Cohort 42,418 patients (55 years old) from 623 sites in North America –Stage 1 or 2 hypertension –1 additional risk factor for CHD Comparisons between chlorthalidone and amlodipine and chlorthalidone and lisinopril have been reported together, excluding the doxazosin arm (n=9,062), which was terminated early ALLHAT Research Group. JAMA. 2002;288: CHD=coronary heart disease; MI=myocardial infarction

ALLHAT Study Design n=13,854 2,235 (16.1%) stopped drug Chlorthalidone n=15,255 Amlodipinen=9,048 Randomized n=42,418 n=15, (2.2%) lost to follow-up 80 (0.5%) refused follow-upn=9, (2.2%) lost to follow-up 58 (0.6%) refused follow-up n=6,210 n=6,210 1,873 (30.2%) stopped drug n=9, (2.4%) lost to follow-up 58 (0.6%) refused follow-up n=8,215 1,357 (16.5%) stopped drug n=3,769 n=3,769 1,052 (27.9%) stopped drug YEAR 1 n=8,158 1,842 (22.6%) stopped drug n=3,605 1,399 (38.8%) stopped drug Lisinopriln=9,054 YEAR 5 ALLHAT Research Group. JAMA. 2002;288: Intent-to- Treat Analysis Doxazosin n=9,062 Discontinued early at 3.3 yrs

ALLHAT Endpoints Primary endpoint Composite of fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI) Other predefined endpoints –all-cause mortality –stroke –combined CHD – nonfatal MI, CHD death, coronary revascularization, hospitalized angina –combined cardiovascular disease – combined CHD, stroke, lower extremity revascularization, treated angina, fatal/ hospitalized/treated congestive heart failure, hospitalized or outpatient peripheral arterial disease –other – renal ALLHAT Research Group. JAMA. 2002;288:

Chlorthalidone n=15,255 Amlodipine n=9,048 Lisinopril n=9,054 systolicdiastolicsystolicdiastolicsystolicdiastolic Mean BP (mmHg) Treated (90%) Untreated (10%) Mean age (yrs)67 Black (%)3536 Women (%)47 46 Current smoking (%)22 History of CHD (%) Type 2 diabetes (%) ALLHAT Baseline Characteristics ALLHAT Research Group. JAMA. 2002;288: BP=blood pressure CHD=coronary heart disease

ALLHAT Mean Systolic and Diastolic Blood Pressure During Follow-up Systolic BP (mmHg) Follow-up, yrs Diastolic BP (mmHg) Chlorthalidone Amlodipine Lisinopril Chlorthalidone Amlodipine Lisinopril ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association. SBP=systolic blood pressure DBP=diastolic blood pressure Compared to chlorthalidone: DBP significantly lower in amlodipine group (~1 mmHg). Compared to chlorthalidone: SBP significantly higher in amlodipine (~1 mmHg) and lisinopril (~2 mmHg) groups.

ALLHAT BP Controlled to <140/90 mmHg LisinoprilAmlodipineChlorthalidone † ALLHAT Research Group. JAMA. 2002;288: % Patients with BP <140/90 mmHg *P<0.001 for amlodipine vs chlorthalidone †P<0.001 for lisinopril vs chlorthalidone † † *†

ALLHAT Treatment and Blood Pressure Control 6 mos1 yr3 yr5 yr 1 Drug2 Drugs 3 Drugs Patients (%) Cushman WC, et al. J Clin Hypertens. 2002;4: Average # of drugs Blood pressure controlled <140/90 mmHg 49.8%55.2%62.3%65.6%

ALLHAT Primary Outcome by Treatment Group Cumulative Fatal CHD and Nonfatal MI event rate (%) Time to event, yrs No. at Risk Chlorthalidone Amlodipine Lisinopril Chlorthalidone Amlodipine Lisinopril ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association.

Relative Risk (95% CI) Relative Risk (95% CI) TOTAL 0.98 ( ) 0.99 ( ) Age < ( ) 0.95 ( ) Age  ( ) 1.01 ( ) Men 0.98 ( ) 0.94 ( ) Women 0.99 ( ) 1.06 ( ) Black 1.01 ( ) 1.10 ( ) Nonblack 0.97 ( ) 0.94 ( ) Diabetic 0.99 ( ) 1.00 ( ) Nondiabetic 0.97 ( ) 0.99 ( ) ALLHAT CHD Death and Nonfatal MI Favors lisinopril Favors chlorthalidone Favors amlodipine Favors chlorthalidone ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association.

Relative Risk (95% CI) Relative Risk (95% CI) TOTAL 0.96 ( ) 1.00 ( ) Age < ( ) 0.93 ( ) Age  ( ) 1.03 ( ) Men 0.95 ( ) 0.99 ( ) Women 0.96 ( ) 1.02 ( ) Black 0.97 ( ) 1.06 ( ) Nonblack 0.94 ( ) 0.97 ( ) Diabetic 0.96 ( ) 1.02 ( ) Nondiabetic 0.95 ( ) 1.00 ( ) ALLHAT All-Cause Mortality Favors lisinopril Favors chlorthalidone Favors amlodipine Favors chlorthalidone 1 ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association.

Relative Risk (95% CI) Relative Risk (95% CI) TOTAL 1.04 ( ) 1.10 ( ) Age < ( ) 1.05 ( ) Age  ( ) 1.13 ( ) Men 1.04 ( ) 1.08 ( ) Women 1.04 ( ) 1.12 ( ) Black 1.06 ( ) 1.19 ( ) Nonblack 1.04 ( ) 1.06 ( ) Diabetic 1.06 ( ) 1.08 ( ) Nondiabetic 1.02 ( ) 1.12 ( ) ALLHAT Combined CV Disease Favors amlodipine Favors chlorthalidone Favors lisinopril Favors chlorthalidone 11 ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association.

ALLHAT Stroke by Treatment Group No. at Risk Chlorthalidone Amlodipine Lisinopril Cumulative event rate (%) Chlorthalidone Amlodipine Lisinopril Time to event, yrs ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association.

Relative Risk (95% CI) Relative Risk (95% CI) TOTAL 0.93 ( ) 1.15 ( ) Age < ( ) 1.21 ( ) Age  ( ) 1.13 ( ) Men 1.00 ( ) 1.10 ( ) Women 0.84 ( ) 1.22 ( ) Black 0.93 ( ) 1.40 ( ) Nonblack 0.93 ( ) 1.00 ( ) Diabetic 0.90 ( ) 1.07 ( ) Nondiabetic 0.96 ( ) 1.23 ( ) ALLHAT Stroke Favors amlodipine Favors chlorthalidone Favors lisinopril Favors chlorthalidone 1 ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association.

ALLHAT Heart Failure by Treatment Group No. at Risk Chlorthalidone Amlodipine Lisinopril Cumulative event rate (%) Chlorthalidone Amlodipine Lisinopril Time to event, yrs P<0.001 for chlorthalidone vs amlodipine and chlorthalidone vs lisinopril ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association.

Relative Risk (95% CI) Relative Risk (95% CI) TOTAL 1.38 ( ) 1.20 ( ) Age < ( ) 1.23 ( ) Age  ( ) 1.20 ( ) Men 1.41 ( ) 1.19 ( ) Women 1.33 ( ) 1.23 ( ) Black 1.47 ( ) 1.32 ( ) Nonblack 1.33 ( ) 1.15 ( ) Diabetic 1.42 ( ) 1.22 ( ) Nondiabetic 1.33 ( ) 1.20 ( ) ALLHAT Heart Failure Favors amlodipine Favors chlorthalidone Favors lisinopril Favors chlorthalidone 11 ALLHAT Research Group. JAMA. 2002;288: Copyright ©2002, American Medical Association.

ALLHAT Conclusions Better control of systolic BP was achieved with chlorthalidone than with amlodipine or lisinopril There were no differences in risk for CHD death/nonfatal MI between chlorthalidone and amlodipine or lisinopril In secondary endpoints, chlorthalidone was associated with lower risk for –stroke, combined CVD, and HF compared with lisinopril –HF compared with amlodipine MI=myocardial infarction CHD=coronary heart disease HF=heart failure ALLHAT Research Group. JAMA. 2002;288:

ALLHAT Implications Unless contraindicated, or unless specific indications are present that would favor use of another drug class, diuretics should be the initial drug of choice in antihypertensive regimens Only 30 percent of patients achieve both systolic BP <140 mmHg and diastolic BP <90 mmHg on monotherapy Many high-risk hypertensive patients will require 2 or more drugs for BP control ALLHAT Research Group. JAMA. 2002;288: