Aims: Cardiovascular (CV)-related hospitalization has been used as a surrogate endpoint for mortality in recent treatment studies on atrial fibrillation (AF), but our understanding of the relationship between CV-related hospitalization and death is incomplete. We aimed to investigate whether CV-related hospitalization is an independent risk factor and suitable as a surrogate endpoint for death in clinical studies of patients with AF.
Method and results: All 2912 patients with a diagnosis of AF in 2002 at one of Sweden's largest hospitals were studied for 6.5 years using information about medication from the local medical records. In a sub-study of the last 2.5 years of the study period, we used detailed information about medication from the new National Prescription Register. Information about diagnoses, hospitalizations, and deaths was obtained from national registries. Patients who were re-admitted to hospital with a CV diagnosis within the first 3 months had higher mortality than those who were not (15.6 vs. 9.3 deaths per 100 patient-years at risk, P < 0.0001). Those who spent >2% of their time-at-risk in hospital with a CV diagnosis had higher mortality than those who had spent less time in hospital (36.0 vs. 8.2 deaths per 100 patient years, P < 0.0001). After adjustment for co-factors, mortality was still higher for patients who had been re-hospitalized for CV disease within 3 months than for those who had not [hazard ratio (HR) = 1.36; 95% confidence interval (CI) = 1.18-1.57]. When analyses were performed on patients who had survived for 3 years since inclusion, and with the use of detailed information about the exposure to medication, the association between CV-related hospitalization and death was highly significant (HR 2.69, CI 1.96-3.68). These results were virtually unchanged after propensity score matching, which was done in order to adjust further for residual unidentified confounding.
Conclusion: CV-related hospitalization is a marker for patients who are at increased risk of death, and may be used as a valid surrogate endpoint in studies of AF.