Cardiovascular critical event pathways for the progression of heart failure: A report from the ATLAS study

John G F Cleland, K. Thygesen, B. F. Uretsky, P. Armstrong, J. D. Horowitz, B. Massie, M. Packer, P. A. Poole-Wilson, L. Rydén

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Aims: To determine the sequence of critical cardiovascular events in the progression of heart failure, and whether aetiology or high-dose vs low-dose lisinopril affected these pathways. Methods and Results: This was a post-hoc investigation of the ATLAS database, which comprised 3164 patients with chronic heart failure, randomized to low- (2.5-5.0 mg. day-1) or high-dose (32.5-35.0 mg. day-1) lisinopril, followed up for a median of 46 months. Two-thirds (64.3%) of patients had heart failure attributed to ischaemic heart disease. During the study, most patients (61.1%) had at least one cardiovascular hospitalization and 42.5% of all patients died: most deaths (88.2%) were cardiovascular. Nearly half (49.7%) of the cardiovascular deaths were considered sudden and 45.2% of cardiovascular deaths occurred as the first cardiovascular event. A third (30.2%) of deaths resulted from heart failure and were generally preceded by hospitalization, either for heart failure (85.5%), myocardial ischaemic events (21.7%) or arrhythmias (18.0%). Compared with low-dose, high-dose lisinopril was associated with a lower risk of death or hospitalization for any reason (P=0.002) and death or hospitalization with worsening heart failure (P<0.001). High-dose lisinopril delayed the time to all-cause mortality and hospitalization for chronic heart failure by 7.1 months. Conclusions: Vascular and arrhythmic events may not only be important precipitants of sudden death, but were also seen to contribute to the progression of heart failure. A reduction in vascular events, as well as benefits on ventricular remodelling, could account for the decrease in death or hospitalization with high-dose lisinopril.

Original languageEnglish (US)
Pages (from-to)1601-1612
Number of pages12
JournalEuropean heart journal
Issue number17
StatePublished - 2001


  • Arrhythymia
  • Critical events pathways
  • Heart failure
  • Ischaemia
  • Lisinopril
  • Progression

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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