May 30, 2018 Read Original Release

Janssen’s claim that Xarelto benefits frail patients better than warfarin built on frail research

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Rating

New Real-World Study Finds Long-Term XARELTO® (rivaroxaban) Use Resulted in Fewer Strokes and Systemic Emboli Compared to Warfarin in Frail Patients with Non-Valvular Atrial Fibrillation

Our Review Summary

This release summarizes a study comparing how three newer anticoagulants performed in preventing stroke and systemic embolism among frail patients compared to warfarin. Systemic embolism refers to a blood clot that causes blockage of blood flow. The 2,600-plus patients analyzed in the study all had non-valvular atrial fibrillation (NVAF). NVAF refers to irregular heart rhythm that is not caused by valvular heart disease.

The 2-year study looked at insurance claims data to analyze patient outcomes from different drugs. According to researchers, the study showed that the patients experienced fewer strokes and systemic embolism when treated with rivaroxaban (brand name Xarelto, manufactured by Janssen) compared to those taking warfarin or other anticoagulants (apixaban and dabigatran). The news release neglected to mention potential biases in this type of research, such as the lack of randomization among compared medications. Importantly, the scientific paper this release is based on compared three of the newer anti-coagulants to warfarin but did not compare them to each other, thus making it hard to determine if one truly was “better” than the others.

Why This Matters

Ideally, research can help determine which, among several therapies, can reduce stroke or systematic embolism in frail patients with non-valvular atrial fibrillation. This type of research using matched cohorts of patients sounds very promising but also has many potential biases, mainly the lack of randomization. Appropriate caveats need to be considered about whether such a study can definitively determine the comparative value of these drugs.

Criteria

Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

No costs were mentioned and it is a significant factor, seeing as warfarin is very inexpensive and produces an anticoagulant effect that is reversible, a characteristic not available with the other anticoagulants.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

The release relies solely on relative numbers in describing the benefits: “long-term XARELTO^® use reduced the risk of stroke and systemic embolism by 32 percent and ischemic stroke alone by 31 percent compared to warfarin, with no significant increase in major bleeding.”

It’s a major omission in the release to not report the absolute numbers. According to Table 3 in the published study, out of 2,635 total patients, 39 of those on rivaroxaban suffered a stroke or systemic embolism compared to 49 patients on warfarin. This makes the absolute differences in these combined events to be 1.48% (for rivaroxaban) and 1.86% (for warfarin). The difference of 0.43% means that the number needed to treat to show a benefit is 233. In other words: If you switch 233 patients from warfarin to rivaroxaban, then at 1 year you would prevent one stroke whereas the other 232 patients would remain stroke-free regardless. At 2 years, the absolute risk reduction was a bit higher at 0.98%.

Does the news release adequately explain/quantify the harms of the intervention?

Satisfactory

The main risk with these anti-coagulants is bleeding and the release mentions bleeding as a main complication. It also comments on the data of major bleeds which was the main safety endpoint of the paper.

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

The published study provides many appropriate cautions about the limitations of this research but unfortunately those details didn’t make it into the news release.

For example: “As a retrospective analysis of claims data, this study has limitations worthy of discussion. First, both misclassification (measurement error) and selection bias (selection of patients in a nonrandomized fashion) are always important limitations in claims database studies and may impact a study’s internal validity.”

Also: “propensity score matching can generate cohorts that are comparable in key characteristics, [yet] only those variables measured in MarketScan databases could be used for matching in this analysis. Therefore, regardless of the sophistication of the methodology and the number of variables used in developing propensity scores, residual confounding cannot be excluded.”

Also there were helpful notes about possibly underpowering the study due to the small sample size of the patient groups. All of these factors should urge a cautious interpretation of results.

Does the news release commit disease-mongering?

Satisfactory

There is no disease mongering here. The release provides appropriate context on the numbers of Americans affected by non-valvular atrial fibrillation.

Does the news release identify funding sources & disclose conflicts of interest?

Not Applicable

It’s assumed that this is a Janssen-sponsored drug trial since the company issued the release but it is not expressly stated.

Does the news release compare the new approach with existing alternatives?

Satisfactory

The study was all about using different drug therapy alternatives in trying to reduce the risk of strokes in certain frail patients. While the release didn’t provide the preferred absolute numbers (see Benefits criteria) it did cite some comparisons with some different drugs.

Does the news release establish the availability of the treatment/test/product/procedure?

Satisfactory

Many people would know these drugs are available in the US but that point isn’t made explicitly in the news release. However, it does state that the patient data came from a company that sells insurance claims data so a savvy reader would know that the drugs are all FDA approved and on the market.

Does the news release establish the true novelty of the approach?

Not Satisfactory

The release doesn’t make any specific claim about novelty, nor does it acknowledge that there are many other studies, even some randomized trials, comparing these newer anticoagulant agents agents to warfarin.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?

Not Satisfactory

It was unjustified use of language to use the term “significant” when it’s not clear that the results of the study proved the performance of Xarelto compared to other anticoagulants was “statistically significant.”

Total Score: 4 of 9 Satisfactory

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