Antihypertensive Treatment and Risk of Atrial Fibrillation
Antihypertensive Treatment and Risk of Atrial Fibrillation
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.
Hypertension is the most prevalent independent and potentially modifiable risk factor for atrial fibrillation, and up to 70% of patients with atrial fibrillation have a history of hypertension. Despite the close link between hypertension and atrial fibrillation, the underlying pathophysiology of atrial fibrillation in patients with hypertension remains unclear. In patients with hypertension, the two major mechanisms thought to lead to the development of atrial fibrillation are: stretch and hemodynamic changes in the atria due to diastolic dysfunction and left atrial enlargement, and activation of the renin-angiotensin system. All classes of antihypertensive medication may potentially reduce the risk of atrial fibrillation, but some studies have suggested that drugs targeting the renin-angiotensin system may be particularly favourable because of their effect on atrial remodelling.
Six randomized hypertension trials investigating the risk of atrial fibrillation in hypertensive patients receiving renin-angiotensin system blockade [angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)] compared with patients receiving other classes of antihypertensive medication or placebo have reported conflicting results. In the six trials, individuals with risk factors for atrial fibrillation were included and they reported either reduced risk of atrial fibrillation or no difference in risk. Exclusion of individuals with such risk factors was, however, done in an atrial fibrillation trial and in an English nationwide, nested case-control hypertension study similar to the present study. In spite of this, results were not similar, as the atrial fibrillation trial reported no difference in risk of atrial fibrillation for hypertensive patients treated with ARB or placebo and the English nationwide study showed a reduced risk of atrial fibrillation for hypertensive patients treated with ACEis, ARBs, or β-blockers compared with hypertensive patients treated with calcium-channel blockers. Thus, first, it remains unclear whether the reduced risk of atrial fibrillation associated with antihypertensive treatment is primarily due to controlling blood pressure and haemodynamic changes or due to the controlling activation of the renin-angiotensin system. Second, if renin-angiotensin system blockade is associated with the reduced risk of atrial fibrillation, it remains unclear whether the effect is present in hypertensive individuals free of other diseases predisposing to atrial fibrillation.
We examined the associations between antihypertensive treatment with ACEis or ARBs, β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. For this purpose, we identified all individuals in the Danish population from 1995 through 2010 treated with only one class of antihypertensive medication, and matched individuals treated with ACEis 1:1 with individuals treated with β-blockers, diuretics, calcium-antagonists, or ARBs. Likewise, individuals treated with ARBs were matched 1:1 with individuals treated with β-blockers, diuretics, calcium-antagonists, or ACEis. We excluded the use of medication within these classes if the specific medication could also be used to treat atrial fibrillation. All individuals 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 than the one examined.
Abstract and Introduction
Abstract
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.
Introduction
Hypertension is the most prevalent independent and potentially modifiable risk factor for atrial fibrillation, and up to 70% of patients with atrial fibrillation have a history of hypertension. Despite the close link between hypertension and atrial fibrillation, the underlying pathophysiology of atrial fibrillation in patients with hypertension remains unclear. In patients with hypertension, the two major mechanisms thought to lead to the development of atrial fibrillation are: stretch and hemodynamic changes in the atria due to diastolic dysfunction and left atrial enlargement, and activation of the renin-angiotensin system. All classes of antihypertensive medication may potentially reduce the risk of atrial fibrillation, but some studies have suggested that drugs targeting the renin-angiotensin system may be particularly favourable because of their effect on atrial remodelling.
Six randomized hypertension trials investigating the risk of atrial fibrillation in hypertensive patients receiving renin-angiotensin system blockade [angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)] compared with patients receiving other classes of antihypertensive medication or placebo have reported conflicting results. In the six trials, individuals with risk factors for atrial fibrillation were included and they reported either reduced risk of atrial fibrillation or no difference in risk. Exclusion of individuals with such risk factors was, however, done in an atrial fibrillation trial and in an English nationwide, nested case-control hypertension study similar to the present study. In spite of this, results were not similar, as the atrial fibrillation trial reported no difference in risk of atrial fibrillation for hypertensive patients treated with ARB or placebo and the English nationwide study showed a reduced risk of atrial fibrillation for hypertensive patients treated with ACEis, ARBs, or β-blockers compared with hypertensive patients treated with calcium-channel blockers. Thus, first, it remains unclear whether the reduced risk of atrial fibrillation associated with antihypertensive treatment is primarily due to controlling blood pressure and haemodynamic changes or due to the controlling activation of the renin-angiotensin system. Second, if renin-angiotensin system blockade is associated with the reduced risk of atrial fibrillation, it remains unclear whether the effect is present in hypertensive individuals free of other diseases predisposing to atrial fibrillation.
We examined the associations between antihypertensive treatment with ACEis or ARBs, β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. For this purpose, we identified all individuals in the Danish population from 1995 through 2010 treated with only one class of antihypertensive medication, and matched individuals treated with ACEis 1:1 with individuals treated with β-blockers, diuretics, calcium-antagonists, or ARBs. Likewise, individuals treated with ARBs were matched 1:1 with individuals treated with β-blockers, diuretics, calcium-antagonists, or ACEis. We excluded the use of medication within these classes if the specific medication could also be used to treat atrial fibrillation. All individuals 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 than the one examined.
