AIMS: To examine the associations between antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. We examined these associations using the entire Danish population from 1995 through 2010.

METHODS AND RESULTS: Excluding medication used in atrial fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on β-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57 646), and ARB monotherapy (n = 20 158). Likewise, individuals on ARB monotherapy were matched 1:1 with individuals on β-blocker (n = 20 566), diuretic (n = 20 832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All were free of atrial fibrillation and of predisposing diseases like heart failure, ischaemic heart disease, diabetes mellitus, and hyperthyroidism at baseline and none received any other antihypertensive medication. We studied risk of atrial fibrillation, and used risk of stroke, influenced by lowering blood pressure rather than renin-angiotensin system blockade per se, as an indicator of the importance of blood pressure lowering per se. Hazard ratios of atrial fibrillation for ACEi and ARB monotherapy were 0.12 (95% CI: 0.10-0.15) and 0.10 (0.07-0.14) compared with β-blocker, 0.51 (0.44-0.59) and 0.43 (0.32-0.58) compared with diuretic, and 0.97 (0.81-1.16) and 0.78 (0.56-1.08) compared with calcium-antagonist monotherapy. Risk of stroke did not differ among the five antihypertensive medications.

CONCLUSION: Use of ACEis and ARBs compared with β-blockers and diuretics associates with a reduced risk of atrial fibrillation, but not stroke, within the limitations of a retrospective study reporting associations. This suggests that controlling activation of the renin-angiotensin system in addition to controlling blood pressure is associated with a reduced risk of atrial fibrillation.