Long-term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR

Clin J Am Soc Nephrol. 2012 Jun;7(6):989-1002. doi: 10.2215/CJN.07800811. Epub 2012 Apr 5.

Abstract

Background and objectives: CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone.

Design, setting, participants, & measurements: This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4-8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m(2)) as follows: normal/increased (≥90; n=8027), mild reduction (60-89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD.

Results: After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD.

Conclusions: CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Trial registration: ClinicalTrials.gov NCT00000542.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amlodipine / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • Canada
  • Chlorthalidone / therapeutic use*
  • Chronic Disease
  • Coronary Disease / etiology
  • Coronary Disease / mortality
  • Coronary Disease / prevention & control
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate*
  • Heart Failure / etiology
  • Heart Failure / mortality
  • Heart Failure / prevention & control
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Hypertension / physiopathology
  • Hypolipidemic Agents / therapeutic use*
  • Incidence
  • Kaplan-Meier Estimate
  • Kidney / physiopathology*
  • Kidney Diseases / complications
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / mortality
  • Kidney Diseases / physiopathology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / prevention & control
  • Lisinopril / therapeutic use*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Proportional Hazards Models
  • Puerto Rico
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Stroke / etiology
  • Stroke / mortality
  • Stroke / prevention & control
  • Time Factors
  • Treatment Outcome
  • United States
  • United States Virgin Islands

Substances

  • Antihypertensive Agents
  • Hypolipidemic Agents
  • Amlodipine
  • Lisinopril
  • Chlorthalidone

Associated data

  • ClinicalTrials.gov/NCT00000542