precise-2-logo

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- http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Trial
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

Scores:

(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