Long-term follow-up of participants with heart failure in the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT)

BACKGROUND: In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/d) and lisinopril (10-40 mg/d) arms compared with the chlorthalidone (12.5-25 mg/d) arm. Similar to other studies, mortality rates following new-onset HF were very high (>=50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases. METHODS AND RESULTS: With the use of national databases, posttrial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups, with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%), with no significant differences by randomized treatment arm. CONCLUSIONS: Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with the development of HF is to be addressed. Clinical Trial Registration- Unique identifier: NCT00000542.

Journal Ref. Piller LB, Baraniuk S, Simpson LM, Cushman WC, Massie BM, Einhorn PT, Oparil S, Ford CE, Graumlich JF, Dart RA, et al: Circulation 2011, 124:1811-1818.
Intervention Drug - amlodipine (2.5-10 mg/d), lisinopril (10-40mg/d), and chlorthalidone 12.5-25mg/d)
Number of sites 600
Countries involved U.S.A., Puerto Rico, the Virgin Islands, and in Canada.
Sample size 42418
Type of statistical analyses Intention-to-treat
Risk of bias Overall: Low Risk details
Participant characteristics Age: Mean 66.7 (7.6)
Condition: heart failure
Baseline severity: high risk anti-hypertensive patients
Duration of trial 8 years: February 23, 1994 to March 31, 2002
Primary outcome Fatal CHD
Effect Measures
Events Intervention Total Events Control Total Risk Diff.
555 15002 364 8904 -0.39%
Non-fatal HF was also outcome investigated in follow up. AND data for amlodipine HF showed 429 total dead out of 8898 participants
Show Score Ranges


(shows median if more than one score was entered)

Elig. Recr. Setting Org. Int. Flex. Del. Flex. Adherence Follow-Up Prim. Out. Prim. An.
2 1 4 2 4 3 5 5 5