DOACs, VKAs show similar efficacy, safety for VTE in octogenarians

In an international multi-database cohort study, direct oral anticoagulants (DOACs) demonstrated comparable efficacy and safety with vitamin K antagonists (VKAs) for octogenarians with venous thromboembolism (VTE).

“[Our findings showed that] in octogenarians with VTE, DOACs were associated with a similar risk of recurrent VTE, [major bleeding, and death] compared with VKAs,” said the researchers.

The crude incidence rates (CIRs) in the DOAC vs the VKA arm were 1.6 vs 2.7/100 person-years [PY] for recurrent VTE, 8.8 vs 10.2/100 PY for major bleeding, and 17.8 vs 12.7/100 PY for all-cause mortality. The corresponding weighted hazard ratios for the respective outcomes were 0.80, 0.96, and 1.04. [Am J Med 2023;136:79-87.e7]

Using administrative healthcare databases from Quebec, Canada, and Germany, two population-based cohorts of octogenarians with incident VTE initiated on DOACs or VKAs were brought together. The overall cohort comprised 6,737 participants (62 percent from the Germany database) who were taking DOACs (n=3,778) or VKAs (n=2,959; warfarin or phenprocoumon). The most common DOAC used was rivaroxaban (60 percent), followed by apixaban (31 percent).

There were 80 events of recurrent VTE (CIR, 2.0/100 PY), 364 major bleedings (CIR, 9.3/100 PY), and 645 all-cause deaths (CIR, 15.9/100 PY) during follow up. The median duration of follow up was between 5.3 and 5.9 months depending on the database and the outcome.

Contrasts previous data?

Current guidelines suggest DOACs over VKAs as first-line treatment for VTE. [Chest 2016;149:315-352; Blood Adv 2020;4:4693-4738] However, guideline recommendations are not age-specific and are usually based on studies with limited generalizability.

“Indeed, only 10–17 percent of patients included in randomized controlled trials (RCTs) were ≥75 years,” said the researchers. Moreover, conditions that were excluded from these studies are highly prevalent in older adults (ie, severe renal disease, liver disease, concomitant use of drugs that have potential interactions with DOACs). [Circulation 2014;129:764-772; N Engl J Med 2012;366:1287-1297; N Engl J Med 2013;369:1406-1415; N Engl J Med 2013;369:799-808] This further compromises the external validity  of these studies, they added.

“[Also,] meta-analyses of these RCTs showed that compared with VKAs, DOACs were more efficacious in preventing recurrent VTE (rate ratio [RR], 0.56) and possibly safer as reflected in a numerically decreased risk of major and clinically relevant nonmajor bleeding (RR, 0.77),” the researchers pointed out.

Nonetheless, the contrasting results may have been driven by the differences in patient characteristics between previous data and the current study, the researchers. “[Moreover,] the relatively low number of recurrent VTE events in our study may have masked a moderate decrease in the risk with DOACs.”

It is also important to note that the reduction in bleeding risk in the meta-analyses was driven by apixaban. In the current analysis, rivaroxaban was the most common DOAC used, they added.

The findings substantiate those seen in an observational study showing comparable risks of major bleeding and death with DOAC and VKA use in individuals aged ≥75 years. [BMJ 2017;359:j4323] The current study expands on these by adding more evidence to support the use of DOACs for the treatment of VTE in a high-risk patient group, the researchers said.