Thromboembolic stroke is the most serious and debilitating of all AF complications, explains Laurence M. Epstein, MD, chief of cardiac arrhythmia service at Brigham and Women’s Hospital in Boston. “To ratchet down the costs associated with AF, we must first ensure that our patients are properly treated for stroke prevention, which is one of the biggest expenses.” The annual cost of stroke in Medicare patients with AF is estimated at $8 billion annually (Am J Managed Care 2004:10[14]S451-S461).

Anticoagulation therapy with warfarin is widely considered the standard of care for stroke prophylaxis in AF patients who are at high risk of stroke. Yet, Reynolds and Essebag reported that 30 to 50 percent of eligible AF patients receive no preventive anticoagulation with warfarin, and among those who do, measures of anticoagulant activity are outside the optimal international normalized ratio (INR) range 52 percent of the time (Am J Pharm Benefits 2012;4[2]:58-65). They estimated that the use of well-controlled warfarin therapy in just half of these patients could prevent 19,000 strokes and save more than $1.1 billion in direct costs annually.

However, managing patients with warfarin is notoriously complicated. “Warfarin takes clinicians’ time and expertise to manage, since patients must be counseled on how to take it and when to return for INR testing. Also, adherence is important since its most serious adverse events—bleeding or thrombosis—can be life-threatening,” says Laura T. Pizzi, PharmD, MPH, of the Jefferson School of Pharmacy in Philadelphia. “Frankly, it is an old-fashioned medication, for which the industry has been looking for a replacement for a while. But there haven’t been many alternatives until the past two years when the newer anticoagulants began entering the market.”

Despite newer options, the gold standard remains warfarin for stroke prevention in AF patients. To gain insight into the current costs of inpatient and transitional anticoagulation care, using anticoagulants, oral warfarin and low-molecular-weight heparins (LMWHs), Pizzi et al sought to examine inpatient cost drivers in the inpatient and transitional anticoagulation care settings through the use of real-world data from the Thomas Jefferson University Hospital’s Consult Anticoagulation Service.

Of the 816 patients included in the analysis, approximately 80 had a primary diagnosis of AF, and the additional patients had a secondary diagnosis of AF. Published as a 2011 Hospital Quality Foundation white paper, Pizzi and her colleagues found that the average cost per year for managing each Consult Anticoagulation Service patient was $418, and anticoagulation discharge counseling cost approximately $26 for a typical uncomplicated patient. The mean length of stay (LOS) for these patients was 3.5 days, and the mean costs to the hospital were $25,467.

Hospitals will be under increasing pressure to reduce LOS for these admissions, says Pizzi. “Healthcare reform includes provisions related to hospital payment which, if implemented, will require hospitals to become more efficient. Furthermore, the law will allow more Americans to have insurance coverage, which could lead to increased demand for services,” she says. “These factors will challenge hospitals to treat more patients while containing costs—which, for AF patients, would entail minimizing LOS while confirming patient linkages to outpatient follow-up at discharge.”

Pizzi et al learned that most of the hospital resources were consumed at the point of discharge. “At discharge, the patient needs to be counseled on a number of things—how to take warfarin, dietary issues, potential adverse events, the importance of adherence and the time of their next INR test. In addition, a subset of patients will need further discharge training on how to administer subcutaneous heparin or LMWH bridging therapy to ensure adequate anticoagulation before warfarin takes effect.”  

In cases where a pharmacist performs warfarin discharge counseling, approximately 30 minutes was required for each newly started anticoagulation patient. Discharge counseling for established patients typically took 15 minutes. Counseling time increased by approximately 15 minutes if the patient required instruction on subcutaneous bridging therapy.

Meanwhile, the newer anticoagulants may shift much of the costs from the hospitals to the patients, as these medications do not require INR monitoring or intense counseling, but some analyses suggest they may be cost effective. After much anticipation, the FDA approved dabigatran (Pradaxa, Boehringer Ingelheim) for the prevention of stroke and systemic embolism in AF patients in October 2010. An analysis of RELY, including patients 65 years or older with AF who were at increased risk of stroke, estimated a cost of $45,372 per quality-adjusted life year gained with high-dose dabigatran (150 mg twice daily) compared with warfarin, using an assumed daily cost for dabigatran above its actual U.S. price (Ann Intern Med 2011;154[1]:1-11). In November 2011, the FDA approved rivaroxaban (Xarelto, Janssen Pharmaceuticals/Bayer HealthCare) to reduce the risk of stroke in patients with non-valvular AF, and at least one model study showed it is a cost-effective alternative to warfarin (Am J Cardiol 2012;110[6]:845-851).

“The novel anticoagulants appear to provide better anticoagulation with the increased price of the drug offset by less INR tests, less clinic visits for the warfarin management, as well as fewer strokes downstream,” says Kim, who notes that the uptake in the U.S. has been fairly slow. 

“Some prescribers will remain reticent until the medical community as a whole has more experience with using these drugs in practice,” says Pizzi.

Drugs vs. ablation

While studies have not settled the argument about whether rate vs. rhythm control is better to manage AF patient outcomes, rate control has been found to be less costly (Pharmacotherapy 2011;31[6]:552-565). 

One way to lower costs, says Kim, is to reduce elective admissions for antiarrhythmic drug initiations. “They are very costly, with a mean length of stay of three days. It cost thousands of dollars to initiate some of these drugs, and the respective guidelines simply don’t factor in cost.”

Kim and his colleagues conducted one of the few analyses examining costs associated with the initiation of rhythm-control therapies for AF. Among 7,290 adults with a primary diagnosis of AF in the Premier Perspective Database who were hospitalized between January 2002 and September 2007, they found that the mean inpatient costs per patient were $3,278 in the sotalol group and $3,610 in the dofetilide group (Ann Pharmacother 2009;43[5]:840-848). The greatest costs were for room/board ($1,874 sotalol, $1,985 dofetilide) and electrocardiograms ($394 sotalol, $443 dofetilide). Pharmacy costs were $230 and $201 per patient in the sotalol and dofetilide groups, respectively.

However, some inpatient expenses may be recouped in fewer rehospitalizations. The ATHENA trial enrolled 4,628 patients with AF at 551 centers to assess the efficacy of dronedarone 400 mg bid for the prevention of CV hospitalization or all-cause mortality in patients with AF or atrial flutter. Over the median 22 months of follow-up, this primary outcome event occurred in 31.9 percent of patients randomized to dronedarone and in 39.4 percent of those randomized to placebo.

In a retrospective analysis, Naccarelli et al analyzed the incidence and direct costs of ATHENA-type outcomes in 15,552 patients with AF who were covered by employer-sponsored Medicare supplemental insurance from 2004 to 2007 (Clin Cardiol 2010;33[5]:270-279). During the first year after initial hospitalization for AF, 54 percent were rehospitalized for CV causes. The 10,547 rehospitalizations cost an average of $11,085 each, resulting in total costs of $117 million. Another 3.4 percent of patients died from CV causes, at a mean cost of $17,486 each, resulting in a total of $9.4 million. Given the 24 percent relative reduction in hospitalizations demonstrated in the ATHENA trial, dronedarone has the potential to reduce the costs associated with the use of these resources in patients with AF.

In certain AF patients, particularly those with paroxysmal AF, in whom drug therapy has not been very effective, catheter radiofrequency ablation may present an alternative. “The higher upfront expenses may reduce long-term costs of readmission or additional treatments,” says Epstein, who points to the improved outcomes and cost-effective benefits of ablation in patients with supraventricular tachycardia.

Catheter ablation successfully treats paroxysmal AF in 41 to 94 percent of patients, with recent success rates of greater than 80 percent (Eur Heart J 2010;31[9]:1046-1054). There is great disparity in technique for AF ablation, including the use of various catheters, electroanatomical mapping tools and imaging tools, making it hard to pinpoint an exact cost. One Canadian registry, CARAF, estimated the cost of catheter ablation ranged from $14,000 to $18,000 in U.S. dollars.

Assessing total costs, one U.S. decision-analytic model of AF ablation vs. rate control or antiarrhythmic drugs found that life costs ranged from $43,036 to $59,380 for ablation, compared with ranges of $24,540 to $50,509 for rate control (with combination of digoxin and atenolol) and $38,425 to $55,795 for amiodarone (2004 U.S. dollars) (J Am Coll Cardiol 2006;47[12]:2513-2520). The authors largely based their analysis on the potential for AF ablation to reduce the risk of stroke.

These cost reductions may be less certain in patients with chronic or persistent AF, who often require multiple procedures, says Epstein. “It will be interesting to see if a cost-benefit persists in this population.”

Admittance & readmissions

If these more expensive procedures aren’t a factor, then the largest upfront costs to the hospital focus on admission to the hospital and discharge from the hospital.

“There are a percentage of patients who present to the clinic or to the ER with AF who probably do not need to be admitted,” says Kim, “and there are algorithms that can estimate which patients with new onset AF should be admitted to the hospital from the ER. Virtually no ERs follow that algorithm, and they likely admit more people than they need to.”

This type of “appropriate admissions process” is one way to lower expenses at the outset, he adds. Another option is treating some cases in observation units as opposed to admitting them for an overnight stay, Pizzi adds. 

An exception to this algorithm is patients who get hospitalized for pneumonia or heart failure, for example, who later present with AF. “I have learned that AF impacts across cardiovascular and non-cardiovascular lines. This is just a population that appears to be sicker and is clearly costing our society more dollars,” Kim adds.

Readmission of these patients is another chart-topper for expenses. A 2010 Avalere Health study of 14,174 Medicare beneficiaries with AF found that medical costs for treating these patients during 15 months of follow-up were an average of $24,000 per patient—with 63 percent of these costs related to readmission. Sixty-one percent of the patients visited the ED at least once during follow-up. On average, these patients went to the ED three times during this period.

A “pill-in-pocket” approach is one low-cost option, Epstein says, that may be effective in reducing readmissions in some AF patients. “We send a patient home with either a particular medication or a cocktail of medicines that can be self-administered when he or she goes into AF, according to physician instructions,” he says. “This patient can often avoid going to the hospital because he or she can convert him or herself.”

Epstein also makes a clear distinction between heart failure patients and AF patients. “AF patients tend to be so symptomatic that they are much more proactive about becoming engaged with their care process,” he says. “Also, the lifestyle modifications with heart failure are far more multifaceted, whereas changes with AF patients are far more straightforward, allowing for a greater ability to self-manage.”

Whether providers have to be more proactive about their admission or discharge process, switch anticoagulants or get patients engaged their care, experts agree about the need to slow the unsustainable pace of costs associated with AF.