ORLANDO –The higher a patient’s baseline high-sensitivity C-reactive protein level in the landmark JUPITER study, the greater the incidence of new-onset atrial fibrillation during follow-up, and randomization to rosuvastatin significantly reduced this risk.
Among the 17,120 apparently healthy participants in JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) with no baseline history of atrial fibrillation or other arrhythmia, those in the highest baseline tertile for C-reactive protein (CRP) – that is, more than 5.8 mg/L – had an adjusted 1.96-fold greater incidence of new-onset atrial fibrillation during follow-up, compared with those in the lowest tertile for the inflammatory biomarker, with a CRP of less than 3.2 mg/L, Dr. Jessica M. Peña reported at the annual scientific sessions of the American Heart Association.
Dr. Jessica Pena
Those in the middle tertile had a 1.7-fold increased risk of developing atrial fibrillation after adjustment for age, gender, race, exercise, alcohol intake, current smoking, metabolic syndrome, hypertension, body mass index, and glycosylated hemoglobin.
The incidence of atrial fibrillation was 0.83 cases per 100 person-years in subjects in the top tertile for baseline CRP, 0.75 per 100 person-years for those in the middle tertile, and 0.43 per 100 person-years among patients in the lowest tertile, according to Dr. Peña of Brigham and Women’s Hospital, Boston.
Rosuvastatin (Crestor) proved to have a significant impact upon this risk. The crude incidence was 1.6% with placebo, compared to 1.2% with the statin, which worked out to an adjusted 27% reduction in relative risk in the rosuvastatin group.
The presumed mechanism of benefit lies in the mounting evidence suggesting that inflammation plays a role in both the initiation and maintenance of atrial fibrillation. Statins have anti-inflammatory properties that could be helpful in preventing the arrhythmia, she observed.
It’s important to note that this was a post hoc analysis. Atrial fibrillation was not a prespecified study end point, Dr. Peña stressed. She and her coinvestigators undertook this exploratory analysis because other studies have yielded mixed results regarding statins and atrial fibrillation. The JUPITER analysis provided an opportunity to focus on a population with an underlying proinflammatory state as manifest by the requirement that participants had to have a baseline CRP of at least 2 mg/L.
She and her JUPITER colleagues are now analyzing the data on the relationship between change over time in CRP level and incident atrial fibrillation.
A recently published meta-analysis by University of Oxford (England) researchers looked at published and unpublished data from randomized clinical trials addressing the relationship between statin therapy and atrial fibrillation. The investigators concluded that the available evidence doesn’t support the notion that statins reduce the risk of atrial fibrillation (BMJ 2011 March 16 [doi: 10.1136/bmj.d1250]).
How can this be reconciled with the new JUPITER findings? Dr. Peña surmised that the different study conclusions were probably due to the fact that the various trials involved very different populations and methods of detecting atrial fibrillation.
"Unfortunately, none of these trials, including JUPITER, had atrial fibrillation as a prespecified end point. In the future that will change, but I think until we have better data we can’t definitively answer the question of whether statins protect against atrial fibrillation," Dr. Peña said.
The primary composite end point in JUPITER was myocardial infarction, stroke, cardiovascular death, arterial revascularization, or hospitalization for unstable angina. The rosuvastatin group had a 44% risk reduction compared to controls (N. Engl. J. Med. 2008;359: 2195-207).
JUPITER was funded by AstraZeneca. Dr. Peña reported having no relevant conflicts of interest.