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

Abstract

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.

Figure 1. Consort diagram for heart failure extension

*Wilcoxon test for equality of survival function p values are: A vs C: P=.12; L vs. C: P<.001 †Separate from/does not include incident HF deaths ‡Among In-Trial (Limited Access Data Set; LADS) Hospitalized HF Cases

Figure 2. Adjusted KM curves by treatment group for all-cause mortality of participants with hospitalized heart failure*

*Adjusted for baseline characteristics of age, race, gender, smoking, education, treatment of hypertension, SBP, DBP, pulse, type II diabetes, LVH by ECG, history of CHD, BMI, eGFR, and time to HF. Approximately 92% of participants with hospitalized (including hospitalized fatal) heart failure events during ALLHAT were part of the Heart Failure Validation Study (HFVS). This figure reflects only those participants with events meeting ALLHAT HF definition in the Validation Study^, and eligible for Extension. HF=heart failure