Combined pharmacotherapy in atrial fibrillation patients and their risk of stroke, dementia, and cardiovascular deaths

Abstract

Abstract Background Even though there have been many advances in oral anticoagulation (OAC) for stroke prevention among atrial fibrillation (AF) patients, the incidence of adverse outcomes in these patients remain high. Optimal management of underlying cardiovascular (CV) conditions have been proposed to provide additional benefit to the prognosis of AF, including major CV and cognitive outcomes. However, concrete epidemiological evidence is still lacking. Purposes To investigate the effect of combinations of CV pharmacotherapies on the risk of stroke, dementia, and CV deaths among AF patients. Methods Using the Swedish Total Population Register and National Patient Register, we identified all individuals born between 1907-1950, who have been living in Sweden since 1987 and were diagnosed with first-ever AF between January 1st 2006-December 31st 2010. Persons with a history of stroke and dementia at the time of AF diagnoses were excluded. Included AF patients were followed for stroke, dementia, and cardiovascular deaths until December 31st, 2020. Use of CV drugs (i.e., OAC, antihypertensives, antiplatelets, and lipid-lowering drugs (LLD)) was defined as prescription within 1 year since AF diagnosis, ascertained via the Prescribed Drug Register. Results A total of 135896 AF patients were followed for a mean follow-up of 6.8 years (SD 4.8), and 17259 (12.7%) incident stroke, 18092 (13.3%) dementia, and 75514 (55.6%) CV deaths were observed. OAC were prescribed to 41.53% of the AF patients within 1 year since AF diagnosis, and antihypertensives to 80.6%, LLD to 30.8%, and antiplatelets to 45.4%. only 2.8% of the AF patients were using OAC only, and 38.7% were using both OAC and antihypertensives. 10.9% were using both OAC and antiplatelets, and 16.8% both OAC and LLD. After propensity score matching, combination of OAC and antihypertensives was statistically significantly associated with a lower risk of stroke (multi-adjusted hazard ratio [HR]=0.80, 95% confidence interval [CI]: 0.93-0.88) and CV deaths (0.84, 0.80-0.88), although insignificant for dementia (0.93, 0.85-1.02), compared to using only OAC. OAC combined with antiplatelets, and OAC with LLD, were however associated with an increased risk of stroke and dementia (HR ranging from 1.08-1.23), but a decreased risk of CV deaths (HR=0.96, 95% CI: 0.93-0.98; HR=0.82, 95% CI: 0.80-0.85), compared to using only OAC. Using neither drug in the combinations was associated with the highest risk for all three outcomes. Conclusions This observational study indicates that older AF patients may benefit from combined therapy of OAC and antihypertensives in terms of stroke, CV deaths, and dementia. Further evidence from clinical trials is needed to confirm this finding.