Antihypertensive & Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) study

Introduction

Study characteristics:

• double-blind, randomized trial
• 33,357* people > 54 years of age
• hypertension with at least 1 other coronary risk factor
• mean blood pressure (baseline) = 146/84 mm Hg (from graphs of data)
• nearly 1/2 women, > 1/3 with diabetes mellitus
• average follow-up of 5 years

* 10,000 also studied for statin therapy

• LDL cholesterol 120-189 mg/dL, 100-120 gm/dL (if documented CAD)

Patients received either:

• • chlorthalidone (thiazide diuretic)
  • amlodipine (Ca+2 channel blocker)
  • lisinopril (ACE inhibitor)
  • doxazosin (alpha-blocker)

* pravastatin 40 mg QD

Patients who need additional blood pressure control received either atenolol, reserpine or clonidine (not blinded)

* The doxazosin arm was terminated early (2000) because of a high incidence of congestive heart failure

Primary outcome: mycardial infarction (MI)

Secondary outcomes:

• all-cause mortality
• CHD: combined MI, PCI, acute coronary syndrome
• CVD: combined CHD, stroke, angina without hospitalization, heart failure, peripheral arterial disease

Conclusions:

• NO differences in mortality or myocardial infarction in the 3 groups
• thiazide (chlorthalidone) AS effective as ACE inhibitor (lisinopril) or calcium channel blocker (amlodipine) in preventing myocardial infarction or mortality resulting from coronary artery disease
• thiazide MORE effective than ACE inhibitor or calcium channel blocker for preventing heart failure or stroke
  • amlodipine associated with 38% higher risk of heart failure than chlorthalidone (13.2% vs 7.7%)
  • lisinopril vs chlorthalidone
    • 15% higher risk of stroke (6.3% vs 5.6%)
    • 19% higher risk of heart failure (8.7% vs 7.7%)
      • relative risk 2.08 year 1
      • no difference beyond year 1
    • 11% higher risk of angina (13.6% vs 12.1%)
• no difference in myocardial infarction or in all cause mortality at 5 years in statin arm of trial
• creatinine-based measures of renal function were more favorable in the amlodipine &/or lisinopril groups; however, rates of end-stage renal disease (ESRD) & rate of decline of glomerular filtration rate (GFR) to 50% of its initial value were not significantly in the 3 groups
• mean blood pressure after 6 years 134/74 mm Hg
  • 5-year systolic blood pressures significantly higher in amlodipine (0.8 mm Hg) & lisinopril (2 mm Hg) groups compared with chlorthalidone
  • 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg)
  • systolic blood pressure differences among groups greatest in 1st year

Limitations of study:

• looks ONLY at initial treatment
• overlooks observation that incidence of diabetes lower with ACE inhibitor than with thiazide diuretic
• does NOT achieve similar blood pressure reduction in groups
  • systolic blood pressure reduction greatest in thiazide group
• only compares 4 different antihypertensives

Notes

• lisinopril, but not amlodipine seems to protect against cardiac conduction system defects relative to chlorthalidone (RR=0.81)

More general terms

• hypertension clinical trials