Are DOACs better than warfarin in patients undergoing bariatric surgery?

A recent meta-analysis has shown a clinically higher pooled incidence of thromboembolism and mortality in patients on direct oral anticoagulants (DOACs) and that of bleeding in those on warfarin after bariatric surgery. However, the P values comparing the two groups are nonsignificant statistically.

“Our results do not support the change in the current recommendation from warfarin to DOAC following bariatric surgery but provide a rationale for future randomized controlled trials or comparative observational designs,” the researchers said.

Using the databases of PubMed, Embase, Cochrane and clinicaltrial.gov, the researchers performed a systematic literature search on 10 November 2019 for studies with adult patients who were on either warfarin or DOACs following bariatric surgery and reported the incidence of thromboembolism, bleeding, or mortality.

Eleven studies involving a total of 805 patients were included in the meta-analysis. A random-effects model was used to calculate the pooled incidence of the prespecified outcomes and its 95 percent confidence interval (CI) for each drug separately, along with a nonadjusted P value comparing the two subgroups.

Pooled incidence comparing DOACs to warfarin were as follows: mortality (DOACs: 3.0 percent, 95 percent CI, 0.4–18.6 vs warfarin: 1.5 percent, 95 percent CI, 0.8–2.9; p=0.38), thromboembolism (DOACs: 4.9 percent, 95 percent CI, 1–21.1 vs warfarin: 1.5 percent, 95 percent CI, 0.8–2.9; p=0.18), and bleeding (DOACs: 3.9 percent, 95 percent CI, 0.7–18.2 vs warfarin: 11.3 percent, 95 percent CI, 5.7–21.4; p=0.23). [Am J Med 2021;134:1403-1412.E2]

“The clinical relevance of this systematic review is driven predominantly by the significant anatomical and physiological changes that occur following bariatric surgery, which can affect the pharmacokinetic and pharmacodynamics of any drugs, especially anticoagulation drugs,” the researchers said. [J Laparoendosc Adv Surg Tech A 2018;28:930-937; J Gastrointest Surg 2011;15:219-228; Surg Obes Relat Dis 2019;15:1861-1871; Am J Health Syst Pharm 2006;63:1852-1857]

“Another contributor to the changes observed in the pharmacological effect of drugs in this patient population is the volume of distribution, which is defined as the apparent volume in which the drug is distributed,” they added. [Clin Pharmacokinet 2015;54:573-579]

Of note, DOACs are substrates for P-glycoprotein efflux transporters, which pump substances into the lumen and thus decrease their absorption. These transporters are greater in number in the distal than proximal regions of the small intestine. As a result, resection of the proximal intestine may alter the bioavailability of the drug in malabsorptive procedures. [Pharm Res 2003;20:1595-1599]

“This altered pharmacokinetics, coupled with the absence of an effective monitoring tool for anticoagulation with DOACs, may have resulted in a higher incidence of thromboembolic adverse events observed with DOACs,” the researchers said.

Warfarin, on the other hand, is primarily absorbed in the jejunum and ileum. By decreasing the surface area of the stomach following surgery, a potential reduction in the dissolution of the drug could occur. [Br J Anaesth 1984;56:59-67]

“After bariatric surgery, there is an alteration in the size and pH of the stomach and the small intestines, altering the dissolution and absorption of this drug,” the researchers said. [Am J Health Syst Pharm 2011;68:2241-2247]

Due to the lack of high-quality randomized controlled trials and comparative studies in this meta-analysis, further research is warranted to compare anticoagulation therapy using warfarin vs DOACs in patients undergoing bariatric surgery.