Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.
In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.
The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote.is in Annals of Internal Medicine.
Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).
Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.
The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.
“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
Head-to-head trial needed to change practice
Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”
Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.
“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”
Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.
The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.
Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.
“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.
On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.
More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.
This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.