Treatment with VKAs has long been one of the most effective strategies for preventing ischemic stroke caused by embolic events in AF. More than half a century passed from the introduction of warfarin to the advent of dabigatran in 2010, marking one of the first direct oral anticoagulants. Over the past decade, substantial evidence has emerged for DOACs, warranting their consideration in specific settings, such as rheumatic valvular disease, bioprosthetic valve carriers, and post-valve repair patients. These clinical contexts were typically excluded from early efficacy and safety trials of DOACs.

This study aims to evaluate anticoagulation management in patients with AF and bioprosthetic valve replacement. The review covered literature up to March 2021, examining outcomes such as all-cause mortality, major bleeding, stroke, and systemic embolism.

Four randomized clinical trials (n = 1,007) and six observational studies (n = 5,084) were identified, totaling 6,405 patients. Of these, patients with AF and bioprosthetic valve replacement were selected, with 1,007 patients in the DOAC group and 1,233 in the VKA group. The combined analysis indicated comparable overall mortality rates without statistically significant differences. However, the major bleeding rate was significantly lower in the DOAC group (HR = 0.66; p = .006), with no significant differences in stroke or systemic embolism rates.

The study’s authors concluded that DOACs may reduce the risk of major bleeding without increasing the risk of stroke, systemic embolism, or all-cause mortality in patients with AF carrying a bioprosthetic valve.

COMMENTARY:

The use of DOACs has become more widespread over the past decade. Their advantage lies in the lack of monitoring requirements, diet-independent effect, and fewer drug interactions, which advocates for their replacement of VKAs. Evidence for the safe use of DOACs is accumulating across most oral anticoagulation scenarios, including AF, venous thromboembolism, acute coronary syndrome, peripheral artery disease, and bioprosthetic valves. In fact, European clinical guidelines view DOAC use in patients with AF and bioprosthetic valves as a valid anticoagulant option, provided at least three months have passed since valve surgery. The American guidelines take this a step further, giving DOACs a class IA recommendation based on findings from the RIVER trial (Rivaroxaban for thromboembolism prophylaxis in patients with atrial fibrillation and bioprosthetic mitral valve). This trial provides the most substantial patient contribution to the meta-analysis, highlighting DOACs as a viable option after cardiac surgery. Another study noted a threefold increase in DOAC use for anticoagulation following bioprosthetic valve replacement over the past seven years.

The growing role of DOACs across all facets of anticoagulant therapy also has a commercial dimension. Developing a new drug costs, on average, one billion dollars, a cost pharmaceutical companies recoup within the first six months post-launch. Subsequently, FDA approval grants 14 years of exclusive marketing rights, enabling companies to capitalize on the drug’s profitability. Currently, exclusivity periods for several DOACs are nearing expiration, likely spurring increased use as new clinical trials explore their expanded applications.

Despite the enthusiasm for DOACs, critical evaluation of this meta-analysis’s findings is warranted. First, four different anticoagulation regimens were included without evaluating each one’s separate efficacy and safety. Additionally, all bioprostheses were analyzed together, whether aortic, mitral, or transcatheter, resulting in a varied patient profile in terms of embolic risk and oral anticoagulation strategies. Potential biases from the six observational studies also warrant consideration. Lastly, the follow-up periods were relatively short, given the chronic nature of these treatments.

In conclusion, the use of DOACs represents an unavoidable reality. It is not far-fetched to anticipate that, in the future, they may fully replace VKAs, at least in patients with AF and bioprosthetic valves.

REFERENCE:

Yokoyama Y, Briasoulis A, Ueyama H, Mori M, Iwagami M, Misumida N et al. Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and bioprosthetic valves: A meta-analysis. J Thorac Cardiovasc Surg. 2023 Jun;165(6):2052-2059.e4. doi: 10.1016/j.jtcvs.2021.07.034.