Exploring the Relationship between Atrial Fibrillation, Hypertension, and Stroke

A sub-analysis of a major drug trial has found that poor blood pressure control was associated with a substantially higher risk of stroke or systemic embolism among people with atrial fibrillation (AF).

“High blood pressure is a risk factor for stroke in patients with atrial fibrillation. In this analysis, poorly controlled blood pressure at any time during the trial increased the risk of stroke by approximately 50%,” said the study’s lead author, Meena Rao, MD, MPH.

“These data highlight the critical importance of blood pressure control in addition to anticoagulation in helping to lower the risk of stroke in patients with atrial fibrillation.”

Some 15,916 (87.5%) of the patients in the ARISTOTLE trial that compared apixaban (Eliquis) to wafarin had a history of hypertension requiring treatment.

Even during the course of the study, half of all patients had — at one or more measurements — poorly controlled hypertension, which study authors defined as systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg.

Such patients faced a 53% increase in the risk of stroke or systemic embolism over the course of the study.

The main results of the ARISTOTLE trial, first announced in August 2011, showed that patients taking apixaban were significantly less likely than those taking wafarin to suffer stroke, systolic embolism, bleeding, or death.

The ARISTOTLE trial randomly assigned 18,201 AF patients to apixaban (5 mg orally twice daily) or warfarin (target INR of 2.0 to 3.0). After following patients for a median of 1.8 years, apixaban was associated with a 21% reduction in the risk of stroke or systemic embolism, a 31% reduction in bleeding, and an 11% reduction in all-cause mortality.

The new sub-analysis found that uncontrolled hypertension increased the risk of stroke or systemic embolism by about the same percentage for patients on either medication. Overall, however, apixaban out-performed wafarin among patients with uncontrolled hypertension to about the same degree that it did among all patients.

The relationship between hypertension, AF, and stroke is a complex one.

Chronic hypertension is the most common etiological factor associated with AF and, thus, both the probable cause and a frequent co-morbidity with many cases of AF.

Studies that have tried to analyze the independent contribution to stroke risk from each have generally placed greater weight on AF. The Framingham Study, for example, has found that hypertension increases stroke risk threefold, while AF increases it fivefold. Other studies have found similar numbers.

Studies that try to measure the combined risk, on the other hand, have reached different conclusions. Indeed, in an analysis of five studies published in the Archives of Internal Medicine in 1994, one study found that stroke risk tripled when AF patients had hypertension as well, while another found the same stroke risk in people with high blood pressure, whether or not they had AF.