Rivaroxaban May Help Dissolve Left Atrial Thrombus in Patients With A-fib
Providing validation to what many physicians are already doing, a new study suggests that non-vitamin K antagonist oral anticoagulants (NOACs)—rivaroxaban, in particular—are effective alternatives to warfarin for resolving thrombi in the left atria or left atrial appendages of patients with A-fib or atrial flutter.
In the single-arm, open-label study, the adjudicated thrombus resolution rate following about 6 weeks of treatment was 41.5%, with resolution or reduction seen in 60.4%, Gregory Lip, MD (University of Birmingham, England), and colleagues report online ahead of print in the American Heart Journal.
Moreover, there were no stroke or thromboembolic events during treatment and follow-up and no safety concerns emerged, they say.
Commenting on the study for TCTMD, John Day, MD (Intermountain Heart Institute, Murray, UT), noted that current A-fib guidelines call for 3 to 4 weeks of anticoagulation when left atrial/left atrial appendage (LA/LAA) thrombi are identified on transesophageal echocardiography (TEE) but do not specify what medication should be used.
Warfarin or one of the NOACs are options, said Day, immediate past president of the Heart Rhythm Society. Although no large studies have evaluated using NOACs in these types of patients, he said, “it’s already being done in clinical practice and has been done in clinical practice since these drugs became approved.”
A Challenging Clinical Problem
Using TEE—typically ordered to rule out thrombus ahead of cardioversion or catheter ablation—LA/LAA thrombi are found in about 10% of patients with A-fib. Reported resolution rates using vitamin K antagonists (VKAs) range widely from 50% to 90%, but there is little information on the effectiveness of the NOACs.
To help fill the gap, the investigators examined data from two studies. X-TRA, conducted at 17 centers in seven countries between August 2013 and December 2014, was a prospective study of 60 patients with A-fib or atrial flutter and TEE-confirmed LA/LAA thrombus who were not treated or had previously been suboptimally treated with VKA therapy. Patients received rivaroxaban (Xarelto; Janssen Pharmaceuticals) once daily at a dose of 20 mg (or 15 mg in those with moderate-to-severe renal impairment) for 6 weeks.
Information on outcomes with standard-of-care treatment—predominantly with VKAs—came from the retrospective CLOT-AF registry, which recruited 156 patients with A-fib or atrial flutter who had LA/LAA thrombus recorded in their medical records between January 2010 and February 2013.
Centrally adjudicated complete thrombus resolution was seen in about four out of every 10 patients who had TEE measurements both at baseline and after treatment in the X-TRA cohort.
In CLOT-AF, the reported thrombus resolution rate—which was not centrally adjudicated—was 62.5%. That tended to be higher in Western versus Eastern European countries (68.0% vs 56.5%).
As for safety, there were no reports of major bleeding or stroke or non-central nervous system systemic embolism during treatment or 30-day follow-up in X-TRA. Treatment-emergent adverse events were observed in 36.7%, although only three events—ear hemorrhage, gingival bleeding, and petechia—were considered related to treatment. There was one serious adverse event deemed related to treatment and one patient death.
The rate of adverse events and bleeding “was in the expected range observed in other phase III/IV studies of rivaroxaban, and the drug-related treatment-emergent [serious adverse event] rate was also low (1.7%),” the authors say.
In CLOT-AF, stroke/transient ischemic attack or non-central nervous system systemic embolism was seen in four patients (2.6%), with one major bleed.
Lip and colleagues note that the results of X-TRA and CLOT-AF cannot be directly compared because of differences in study design, patient demographics, disease severity, and data quality. “Thus, our results report descriptive observations, and no causality is implied,” they say.
Nevertheless, useful information can be gleaned from the findings, they suggest.
“Data from prospective studies of the other NOACs in this setting are currently lacking, although one prospective study with dabigatran is ongoing,” they say. “In this context, the X-TRA study provides important insights into a challenging clinical problem and the potential of NOACs for this subgroup of [A-fib] patients.”
Day said that the decision about whether to choose warfarin or one of the NOACs is often physician-specific. He said he prefers a NOAC whenever possible because of the more predictable response and the avoidance of the routine blood testing needed with warfarin. Using NOACs also facilitates a healthier diet, he said, pointing to the high levels of vitamin K—which make it hard to maintain a therapeutic dose of warfarin—in green leafy vegetables.
But some patients are unable to take a NOAC, and Day says the primary reason is cost.
Also commenting for TCTMD, David Callans, MD (Hospital of the University of Pennsylvania, Philadelphia), said the study represents “another valuable experience in expanding what we know we can trust these drugs to do. . . . It’s nice to have the validation..”
He added that he starts most of his patients with A-fib on a NOAC. “And I probably wouldn’t have thought twice about it [in this setting] . . . but now I’m sleeping a little bit easier to know that this is potentially the right thing to do,” he said, adding that the lack of strokes on rivaroxaban treatment is reassuring.
Lip GYH, Hammerstingl C, Marin F, et al. Left atrial thrombus resolution in atrial fibrillation or flutter: results of a prospective study with rivaroxaban (X-TRA) and a retrospective observational registry providing baseline data (CLOT-AF). Am Heart J. 2016;Epub ahead of print.
- The studies were funded by Bayer Pharma AG.
- Lip reports serving as a member of various guideline and position statement committees and steering committees for various phase II, phase III, and health economics and outcomes research studies; as an investigator in various clinical trials in cardiovascular disease, including those on antithrombotic therapies in A-fib, ACS, and lipids; as a consultant for Bayer/Janssen, Astellas, Merck, Sanofi, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic, Portola, Boehringer Ingelheim, Microlife, and Daiichi Sankyo; and as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche, and Daiichi Sankyo.
- Callans and Day report no relevant conflicts of interest.