Effect of High-Dose Atorvastatin on Hospitalizations for Heart Failure: Subgroup Analysis of the Treating to New Targets (TNT) Study
Open accessAbstract
Background— Statins reduce the rate of major cardiovascular events in high-risk patients, but their potential benefit as treatment for heart failure (HF) is less clear. Methods and Results— Patients (n=10 001) with stable coronary disease were randomized to treatment with atorvastatin 80 or 10 mg/d and followed up for a median of 4.9 years. A history of HF was present in 7.8% of patients. A known ejection fraction <30% and advanced HF were exclusion criteria for the study. A predefined secondary end point of the study was hospitalization for HF. The incidence of hospitalization for HF was 2.4% in the 80-mg arm and 3.3% in the 10-mg arm (hazard ratio, 0.74; 95% confidence interval, 0.59 to 0.94; P =0.0116). The treatment effect of the higher dose was more marked in patients with a history of HF: 17.3% versus 10.6% in the 10- and 80-mg arms, respectively (hazard ratio, 0.59; 95% confidence interval, 0.4 to 0.88; P =0.009). Among patients without a history of HF, the rates of hospitalization for HF were much lower: 1.8% in the 80-mg group and 2.0% in the 10-mg group (hazard ratio, 0.87; 95% confidence interval, 0.64 to 1.16; P =0.34). Only one third of patients hospitalized for HF had evidence of preceding angina or myocardial infarction during the study period. Blood pressure was almost identical during follow-up in the treatment groups. Conclusions— Compared with a lower dose, intensive treatment with atorvastatin in patients with stable coronary disease significantly reduces hospitalizations for HF. In a post hoc analysis, this benefit was observed only in patients with a history of HF. The mechanism accounting for this benefit is unlikely to be due primarily to a reduction in interim coronary events or differences in blood pressure.
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The clinical benefit of adding ezetimibe was consistent across patient subgroups and led to reductions in total cardiovascular events, stroke, and rehospitalizations.
“The clinical benefit of adding ezetimibe was consistent across patient subgroups [299,444] and also led to a reduction of total CV events [445], stroke [446], and rehospitalizations [447].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [444]
Four key prospective RCTs found that a more intensive drug regimen reduced hospitalization due to HF by an average of 27% in patients with acute and stable CAD without previous HF.
“The more intense approach reduced the incidence of hospitalization due to HF by an average of 27% in patients with acute and stable CAD without previous HF. 358,370-372”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [372]
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- Authors
- Khush, K. K., Waters, D. D., Bittner, V., Deedwania, P. C., Kastelein, J. J. P., Lewis, S. J., & Wenger, N. K.
- Affiliations
- Emory University (US)
- ORCID
- Venue
- Circulation
- Published
- 2007-02-06
- Volume
- 115
- Issue
- 5
- Pages
- 576-583
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2103918731
- Cited by
- 172
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 10 · 2013: 10 · 2012: 7
- FWCI
- 30.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Keywords
- atorvastatin, high-intensity statin therapy, heart failure hospitalization, stable coronary artery disease, statin dose comparison, secondary prevention, cardiovascular risk reduction
- MeSH terms
- Atorvastatin, Aged, Female, Follow-Up Studies, Heart Failure, Heptanoic Acids, Hospitalization, Humans, Male, Middle Aged, Pyrroles, Drug Delivery Systems
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