COLORADO SPRINGS — The stroke risk without warfarin therapy in atrial fibrillation patients aged 85 years and older who have no other stroke risk factors is more than double that of patients aged 75–84 years, according to new data from the ATRIA study.
Moreover, the absolute reduction in stroke risk achieved with warfarin in the 85-plus age group appears to be substantially greater than in younger atrial fibrillation (AF) patients, study investigator Dr. Daniel E. Singer reported at a conference sponsored by the American Heart Association.
These findings from the National Institutes of Health-sponsored Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study indicate a need to revisit current national guidelines, which allow aspirin rather than warfarin for AF patients aged 75 years and up with no stroke risk factors other than their advanced age.
“These data suggest that looking at old people with just a single age cutoff at 75 misses the fact that those who are age 85 and older are at considerably heightened risk. The risk in the rapidly growing oldest old population shouldn't be confused with that of the younger old population age 75–84. Those 85 and up should be considered strong candidates for warfarin,” said Dr. Singer, professor of medicine and epidemiology at Harvard Medical School and chief of the clinical epidemiology unit at Massachusetts General Hospital, both in Boston.
Dr. Singer also is the principal investigator in ATRIA, a study to assess the impact of warfarin in usual care that has enrolled 13,559 northern California patients with nonvalvular AF. In effect, ATRIA is a real-world postmarketing study of a 60-year-old drug.
The 4,330 ATRIA participants who had no additional stroke risk factors at baseline have accumulated 16,000 person-years of follow-up. During that period, those aged 75–84 years who were not on warfarin had a 1.41% annual stroke rate, compared with a 3.31% annual rate among the patients aged 85 and up with no other stroke risk factors who were not on warfarin.
Those aged 75–84 years who were on warfarin had a 0.53% annual stroke rate, while those aged 85 years and older had a 0.86% event rate on warfarin, indicating a substantially greater absolute benefit for warfarin in the oldest group. The caveat, he stressed in an interview, is that ATRIA was not a randomized trial, so the main focus should be on the core stroke risk off warfarin—impressively greater in patients aged 85 and older.
As for the dark side of warfarin therapy, the intracranial hemorrhage rate in patients aged 85 years and older with no stroke risk factors other than age was 0.60%/year on warfarin and 0.58%/year in those not taking the anticoagulant.
“When you get into these older age groups, the intracranial hemorrhage rate is quite substantial. But the fact is, it's high on or off warfarin,” he observed.
The widely used CHADS2 stroke risk scoring system for AF patients awards one point each for congestive heart failure, hypertension, age over 75 years, and diabetes, and two points for a history of stroke. The ATRIA findings suggest that age 85 years or greater ought to receive more weight—perhaps two points—although this has to be viewed as a tentative conclusion, because ATRIA is the first study to show a substantially greater stroke risk in the oldest old, Dr. Singer stressed.
Surveys indicate roughly 60% of AF patients in North America received warfarin; the rate drops off sharply at age 85 years.
The landmark randomized, placebo-controlled clinical trials have established that warfarin reduces stroke risk in AF by 68% across the board. That's based on intention-to-treat analysis. In reality, many patients who had strokes in the trials had stopped taking the drug or were clearly underanticoagulated.
“The relative risk reduction on treatment probably approaches 80%, which is very much what you'd expect to find if you were reversing the entire effect of atrial fibrillation,” Dr. Singer said.
There was considerable hope in the 1990s for aspirin as a safer alternative, but its impact proved to be quite small. And aspirin turned out to be particularly poor at preventing severe or fatal strokes, he said.
'Those who are age 85 and older are at considerably heightened risk.' DR. SINGER