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/day) and lisinopril (10-40 mg/day) arms compared with the chlorthalidone (12.5-25 mg/day) 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 Using national databases, post-trial 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 development of HF is to be addressed.

Longitudinal Changes in Left Ventricular Stiffness

“…14 Uninterrupted progressive stiffening of the ventricle may partly explain why afterload-targeting therapies have failed to improve outcomes in HFpEF trials, 38 and why blood pressure reduction with lisinopril or amlodipine has not been associated with reductions in incident HFpEF in ancillary analyses from the ALLHAT trial. 39 Because ventricular stiffening is a key process driving progression to HFpEF, 3 and because 10 year outcomes after diagnosis are abysmal, 40 future research should identify the mechanisms underlying load-independent, age-related ventricular stiffening to better treat and prevent HFpEF.…”

Heart failure in young adults: 20-year trends in hospitalization, aetiology, and case fatality in Sweden

“…7,8 Studies indicate that HF incidence and mortality in Sweden, Scotland, and Australia have been decreasing since the early 1990s. 6,9–12 Whether this change occurs in younger age groups has to our knowledge not been examined.…”

Team-Based Care for Managing Cardiac Comorbidities in Heart Failure

“…47 This tasks the primary care physician or affiliate provider with recommending appropriate antihypertensive therapies that follow guidelines and provide mortality benefit wherever possible. Interestingly, however, higher baseline blood pressures have more favorable prognoses compared with normotensive patients.…”