Novel oral anticoagulants introduced since October 2010 have been adopted into clinical practice rapidly, and within 2.5 years were prescribed for more than 60% of patients with newly diagnosed atrial fibrillation, according to a report published online in the American Journal of Medicine.
Further, the new drugs are being prescribed for a different patient population from that indicated by the clinical trials on which Food and Drug Administration (FDA) approval was based. Specifically, dabigatran, rivaroxaban, and apixaban are selectively prescribed for younger, healthier men who have high incomes and reside in wealthier communities, reported Dr. Nihar R. Desai of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates.
In what they described as the first study to evaluate real-world use of all novel anticoagulants, researchers found that the rapid uptake of the drugs as first-line therapy for atrial fibrillation (AF) was accompanied by a marked decline in the use of warfarin. The difference in total costs between the generic warfarin and the proprietary dabigatran, rivaroxaban, or apixaban totaled $900 per patient during the first 6 months alone, which "translates into billions of dollars at the national level."
This has important economic implications for patients, payers, and the health care system. The impending FDA approval of new factor Xa inhibitors such as edoxaban and betrixaban will likely further complicate the picture, the researchers said.
The researchers analyzed nationwide medical and prescription claims data for 6,893 adults covered by Aetna who had newly diagnosed nonvalvular AF and were prescribed an oral anticoagulant between October 2010 and June 2013. The direct thrombin inhibitor dabigatran was approved in October 2010, and the factor Xa inhibitors rivaroxaban and apixaban were approved in November 2011 and December 2012.
During the study period, these patients filled 45,472 prescriptions for oral anticoagulants: 57.7% for warfarin, 32.8% for dabigatran, 9.3% for rivaroxaban, and 0.1% for apixaban. However, these figures don’t reflect the trend over time in which prescriptions for the newer agents rapidly displaced those for warfarin. Within 1 year of appearing on the market, dabigatran was equally likely to be prescribed as warfarin was for new AF patients. Its use as a first-line therapy dropped considerably a year later, after reports of excess rates of myocardial infarction and serious and fatal bleeding events in patients taking dabigatran. But at that point rivaroxaban had been introduced, and it soon overtook both dabigatran and warfarin as first-line therapy for AF. (Apixaban accounted for 2% of new anticoagulant prescriptions as of 6 months after it was approved, which is the most recent date for which such statistics were available.)
Simultaneously, the costs of oral anticoagulants rose dramatically, with the new agents accounting for 98% of that escalation. It is estimated that insurers spend $5.82 million every month for all agents combined, and that warfarin accounts for only $0.43 million of that. Similarly, patient out-of-pocket spending for all oral anticoagulants combined was estimated to be $1.3 million per month, with warfarin accounting for $3,844 of that total.
Viewed from another perspective, the average combined patient and insurer spending for anticoagulants during the first 6 months of therapy for warfarin was $122, dabigatran $1,053, and rivaroxaban $1,084. "This represents a difference of more than $900 per patient," said Dr. Desai, who is also at the Center for Outcomes Research and Evaluation, Yale-New Haven Health Services, and his associates.
The greatest benefit from novel anticoagulants is among patients at the highest risk for stroke or systemic embolization, as measured by higher scores on CHADS (Congestive Heart Failure, Hypertension, Age of 75 years or more, Diabetes Mellitus, and Stroke) and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol) assessments. This is also the patient population targeted in the clinical trials that formed the basis for FDA approval.
But in this study, 46% of patients with low CHADS and HAS-BLED scores were initially prescribed the novel anticoagulants, compared with 26% of those with high scores. "For every 1-point increase in CHADS, patients were 20% less likely to receive a novel anticoagulant. Similarly, for every 1-point increase in HAS-BLED, patients were 18% less likely to receive a novel anticoagulant.
"In addition, women were 24% less likely to be initiated on a novel oral anticoagulant as compared with men. [And] there was a significant, stepwise increase in the likelihood of receiving a novel agent with progressively increasing neighborhood household income, compared with a median household income of $50,000 or less," the investigators said (Amer. J. Med. 2014 May 20 [doi: 10.1016/j.amjmed.2014.05.013]).