Author + information
- Received November 18, 2013
- Revision received December 18, 2013
- Accepted December 19, 2013
- Published online June 1, 2014.
- Jennifer K. Rogers, PhD∗,
- Pardeep S. Jhund, MBChB, PhD†,
- Ana-Cristina Perez, MD†,
- Michael Böhm, MD, PhD‡,
- John G. Cleland, MD§,
- Lars Gullestad, MD, PhD‖,
- John Kjekshus, MD, PhD‖,
- Dirk J. van Veldhuisen, MD, PhD¶,
- John Wikstrand, MD, PhD#,
- Hans Wedel, PhD∗∗,
- John J.V. McMurray, MD†∗ ( and )
- Stuart J. Pocock, PhD∗
- ∗London School of Hygiene and Tropical Medicine, London, United Kingdom
- †Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom
- ‡Universitätsklinikum des Saarlandes, Homburg/Saar Germany
- §Hull York Medical School, Kingston-Upon-Hull, United Kingdom
- ‖Oslo University Hospital, Rikshospitalet, Oslo, Norway
- ¶University Medical Centre, Groningen, the Netherlands
- #Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
- ∗∗Nordic School of Public Health, Gothenburg, Sweden
- ↵∗Reprint request and correspondence:
Prof. John J. V. McMurray, Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, United Kingdom.
Objectives This study sought to examine the effect of statin therapy hospitalizations for heart failure (HFH) in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) trial.
Background HFH is an important, frequently recurrent event. Conventional time-to-first event analyses do not take account repeat events. We used a number of statistical approaches to examine the effect of treatment on first and repeat HFH in the CORONA trial.
Methods In the CORONA trial, 5,011 patients ≥60 years of age with chronic New York Heart Association functional classes II to IV systolic heart failure resulting from ischemia were randomized to receive rosuvastatin or placebo. Poisson, Andersen-Gill, and negative binomial methods (NB) were used to analyze the effect of rosuvastatin on HFH, and the NB and a parametric joint frailty model (JF) were used to examine this effect while accounting for the competing risk of cardiovascular (CV) death. Rosuvastatin/placebo rate ratios were calculated, both unadjusted and adjusted.
Results A total of 1,291 patients had 1 or more HFH (750 of these had a single HFH only), and there were a total of 2,408 HFHs. The hazard ratio for the conventional time-to-first event analysis for HFH was 0.91 (95% confidence interval [CI]: 0.82 to 1.02, p = 0.105). In contrast, the NB on repeat hospitalizations gave an unadjusted RR (RR) for HFH of 0.86 (95% CI: 0.75 to 0.99, p = 0.030), adjusted 0.82 (95% CI: 0.72 to 0.92, p = 0.001), and after including CV death as the last event, adjusted RR of 0.85 (95% CI: 0.77 to 0.94, p = 0.001). The JF gave an adjusted RR of 0.82 (95% CI: 0.73 to 0.92, p = 0.001). Similar results were found in analyses of all CV hospitalizations and all-cause hospitalizations.
Conclusions When repeat events were included, rosuvastatin was shown to reduce the risk of HFH by approximately 15% to 20%, equating to approximately 76 fewer admissions per 1,000 patients treated over a median 33 months of follow-up. Including repeat events could increase the ability to detect treatment effects in heart failure trials.
Dr. Böhm is a member of the advisory boards of AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, Sanofi-Aventis, and Servier; and a member of the speakers' bureaus of Astra Zeneca, AWD Dresden, Bayer, Boehringer-Ingelheim, Berlin-Chemie, Daiichi-Sankyo, MSD, Novartis, Pfizer, Sanofi-Aventis, Servier, and Medtronic. Dr. Wikstrand is a former advisor with AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Rogers and Jhund contributed equally to this paper.
- Received November 18, 2013.
- Revision received December 18, 2013.
- Accepted December 19, 2013.
- American College of Cardiology Foundation