RE-LY Registry: Wide Global Variation in AF Management, Mortality

September 06, 2012

September 5, 2012 (Munich, Germany) — About one in 10 people who present to the emergency department with atrial fibrillation (AF) around the world are dead within a year, but mortality varies widely from region to region, suggests a study based on a large registry [1]. The mortality is twice as high in some parts of the world.

The analysis also suggested that global variation in such mortality rates, as well as in stroke rates, is less pronounced once they are adjusted for cardiovascular risk and differences in anticoagulation management.

The prospective RE-LY AF Registry study, which included 15 408 patients from 47 countries spanning the Americas, Western and Eastern Europe, Australia, Africa, India, China, and Southeast Asia, was presented here last week at the European Society of Cardiology (ESC) 2012 Congress by Dr Jeff S Healey (McMaster University, Hamilton, ON). It was conducted separately from the randomized RE-LY trial of dabigatran etexilate (Pradaxa, Boehringer Ingelheim) vs placebo for thromboembolic protection in nonvalvular AF.

The patients presented to emergency departments with AF from 2008 to 2011 and were followed for one year for mortality, stroke, embolism, heart failure, major bleeding, and hospitalization. Presentation led to a primary diagnosis of AF in 44% of cases.

Worldwide, the proportion of patients presenting with AF who were dead within a year, Healey noted, "was quite high and somewhat higher than expected, at 11%." Absolute rates by world region, however, showed wide differences. "The most striking of these is the rate in Africa, where 20% died within one year of presentation with AF." Other numbers around the world were 18% for South America, about 7.5% for Western Europe, 8% for Eastern Europe, and about 9% for India.

"This may represent not only differences in patient characteristics but unmonitored biases in the types of patients recruited and in the way that they are managed between countries," Healey said. Indeed, most of the differences between one-year mortality were attenuated after adjustment for heart failure, coronary disease, hypertension, diabetes, and rheumatic heart disease, "although there are still some outliers such as India, where the mortality rates remained lower than the rest of the world," at about 7%.

Also in the registry, the global rate of stroke at one year was just over 4%, and "globally, CHADS2 score had a greater influence on stroke risk than the presence or absence of rheumatic heart disease," he said.

"Across the board, the rate of stroke in the West--Western Europe and North America--is quite low, between 2% and 3%. However, we see three regions where stroke rates are much higher: Africa, China, and Southeast Asia, where the rates are twofold higher, in excess of 7% and 8%, for the outcome of stroke."

Dr Gregory YH Lip (University of Birmingham, UK), Healey's assigned discussant, pointed out how absolute stroke rates across world regions were consistently attenuated after adjustment for age, history of stroke or transient ischemic attack, heart failure, hypertension, geographic region, and use of vitamin-K antagonists.

The differences between crude rate and adjusted rate were particularly dramatic in Africa (going from about 8.4% to 3.9% after adjustment), China (from about 7.2% to 5.0%), and Southeast Asia (6.7% to about 4.9%), according to Healey's presentation.

"That raises the question, therefore, of whether it is the uptake or mechanism of looking after anticoagulation therapy that is proven to reduce stroke in this setting," Lip said. "Countries do vary by availability of structured anticoagulation services and cardiovascular prevention strategies."

The CHADS2 score, an index based on a composite of stroke risk factors, predicted stroke better than rheumatic heart disease in the RE-LY registry. In India, which had both the lowest crude and adjusted rates of stroke, the mean CHADS2 score was only 1, compared to a mean of 2 in North and South America and about 2.3 in Eastern Europe.

And at least one-third of the patients in India had documented rheumatic heart disease, often perceived to be a predictor of high stroke risk. But in the registry, those with rheumatic disease had a lower stroke risk; they were older but had less coronary disease and hypertension. They were more likely to get oral anticoagulation.

Features of rheumatic heart disease (n=1788 in the RE-LY AF Registry)

End point No rheumatic heart disease (n=13 507) Rheumatic heart disease (n=1788)
Stroke (%) 4 3
Age (y) 66.2 49.5
Female (%) 45.4 64.9
Hypertension (%) 60.3 19.6
Coronary disease (%) 34.3 5.5
Heart failure (%) 33 34.7
Warfarin use (%) 32 68.7

 

And, Healey noted, "When one adjusts for differences in cardiovascular risk factors, age, even warfarin use, the difference does not appear to go away."

Concluding, Lip affirmed that "there is clear unmet need for improving stroke prevention in atrial-fibrillation patients. Anticoagulation therapy not only reduces stroke but also has a significant impact on reducing mortality. There's a necessity to validate and implement stroke and bleeding risk assessment, and perhaps to extend how stroke and bleeding risk assessment performs in some of these diverse ethnic groups and patient populations."

Healey discloses receiving grants or research support from Boston Scientific, St Jude Medical, Boehringer Ingelheim, and AstraZeneca and serving on an advisory board for Sanofi and Boehringer Ingelheim. Lip discloses consulting for Bayer, Astellas, Merck, Sanofi, Bristol-Myer Squibb, Daiichi-Sankyo, Biotronik, Portola, and Boehringer Ingelheim and serving on a speakers' bureau for Bayer, Bristol-Myer Squibb/Pfizer, Boehringer Ingelheim, and Sanofi.

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