Lower a-fib risk with ACE inhibitors, ARBs vs beta-blockers: study

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - People taking angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) for hypertension are less likely to develop atrial fibrillation than those on beta-blockers or diuretics, according to a new retrospective study from Denmark.

Hypertensive patients who were not otherwise predisposed to atrial fibrillation (AF) had a similar risk of stroke regardless of medication class, researchers wrote December 17 online in the European Heart Journal.

The findings suggest controlling activation of the renin-angiotensin system not only controls blood pressure but is associated with a reduced risk of AF, they added.

"We were surprised that, among people in the general population on antihypertensive monotherapy and without predisposing factors for atrial fibrillation, we found a much lower risk of atrial fibrillation in those treated with ACEis or ARBs versus those treated with beta-blockers," said senior author Dr. Børge G. Nordestgaard, clinical professor in the Department of Clinical Medicine of the University of Copenhagen in Herlev, Denmark, in an email to Reuters Health.

"The safest antihypertensive drugs regarding the risk of atrial fibrillation are ACEis and ARBs," he said.

Dr. Nordestgaard and his research team analyzed data from Danish registries covering 6.7 million people from 1995 through 2010.

Excluding medication used in atrial fibrillation, they matched patients on ACEi monotherapy 1:1 with patients on beta-blockers (n=48,658), diuretics (n=69,630), calcium-antagonists (n=57,646), and ARB monotherapy (n=20,158).

They also matched patients on ARB monotherapy 1:1 with patients on beta-blockers (n=20,566), diuretics (n=20,832), and calcium-antagonist monotherapy (n=20,232). All patients were free of AF, heart failure, ischemic heart disease, diabetes mellitus, and hyperthyroidism at baseline and none of them received any other antihypertensive medication.

People in each group started taking antihypertensive drugs at age 56 to 59, on average. Between 42% and 46% of all users were women.

Hazard ratios of AF for ACEis and ARBs were 0.12 (95% CI, 0.10-0.15) and 0.10 (0.07-0.14) compared with beta-blockers, 0.51 (0.44-0.59) and 0.43 (0.32-0.58) compared with diuretics, and 0.97 (0.81-1.16) and 0.78 (0.56-1.08) compared with calcium-antagonists.

The risk of stroke, used as an indicator of the importance of lowering blood pressure, was similar among the five antihypertensive medications.

"The strengths of the study are the very large size and that, by showing that stroke rates were the same between different classes, this infers that blood pressure control was similar," Dr. Brian Rayner, professor and head of the Division of Nephrology and Hypertension in the Department of Medicine of the University of Cape Town, South Africa, said in an email.

"However, there are several major limitations to this study," said Dr. Rayner, who was not involved in the research. "In particular, certain drugs like beta blockers may have been prescribed because patients were considered at very high risk for atrial fibrillation. Thus, guideline committees are unlikely to make a class 1 recommendation for the use of RAS inhibitors in prevention of atrial fibrillation in hypertensive patients."

"It is unlikely that antihypertensive drugs predispose to atrial fibrillation, and controlling blood pressure is the most important factor in preventing cardiovascular and renal complications. Most patients require two to three drugs to control blood pressure and it is essential to use multiple drugs in combination. Using RAS inhibitors may have additional benefits and should be part of the combination," he said.

"This study is truly remarkable - all 6.7 million people living in Denmark from 1995 to 2010 were screened for this study," said Dr. James Ker, from the Department of Genetics of the University of Pretoria, South Africa, in an email.

"However, the Danish population is ethnically homogeneous, and functional genetic variants of the angiotensin converting enzyme (ACE) gene may influence the susceptibility to atrial fibrillation in patients with hypertensive heart disease. More importantly, when 9,235 individuals from the Danish general population were genotyped, it was shown that genetic variations in the renin-angiotensin system may influence the effect of renin-angiotensin blockers on atrial fibrillation," added Dr. Ker, who was also not involved in the study.

"More specifically, there seems to be a significant association between angiotensin converting enzyme insertion/deletion (ACE I/D) genetic polymorphism and atrial fibrillation in patients with hypertension. Even more fascinating, significant differences exist in the ACE genotype as one moves from Northern to Southern Europe," he said.

"This study proves that, for the Danish population, and maybe for Northern Europe, if you have hypertension and want the greatest risk reduction for atrial fibrillation, use a drug that antagonizes the renin-angiotensin system," he said.

SOURCE: http://bit.ly/1gBR4IQ

Eur Heart J 2013.

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