NOACs safe, effective in octogenarians
Low rates of cardiovascular (CV) or major bleeding complications were observed among octogenarians who were receiving active NOAC* therapy, suggesting that long-term anticoagulation with NOACs may result in a good risk-benefit ratio in this patient subgroup, according to data presented at ASH 2018.
To evaluate the potential of NOACs among elderly patients, researchers evaluated participants from the DRESDEN NOAC registry who were aged ≥80 years (n=935, mean age 84.2 years, 43.4 percent male) and receiving NOAC therapy (rivaroxaban [52.1 percent], apixaban [21.2 percent], edoxaban [17.6 percent], and dabigatran [9.1 percent]). Atrial fibrillation (AF) was the primary indication for anticoagulant therapy (80.4 percent) followed by venous thromboembolism (VTE, 19.1 percent). [ASH 2018, abstract 422]
After a mean follow-up of 2.5 years, an event rate of 1.0/100 patient-years (PY) was observed for the composite endpoint of stroke, transient ischaemic attack (TIA), systemic embolism, or VTE in the intention-to-treat cohort.
In patients with AF, the rate for stroke, TIA, and systemic embolism was 1.0/100 PY. For those with VTE, the rate for recurrent deep venous thrombosis or pulmonary embolism was 0.4/100 PY.
On-treatment analysis revealed event rates of 0.7/100 PY for the composite endpoint, 0.7/100 PY for stroke, TIA, and systemic embolism in AF patients, and 0.1/100 PY for recurrent VTE in VTE patients.
In terms of safety, the overall rate of ISTH** major bleeding was 1.0/100 PY (p<0.0001), while for clinically relevant non-major bleeding, the rate was 6.0/100 PY (p=0.0002).
Nearly 27 percent of patients discontinued their NOAC regimen. Although bleeding was the primary reason (28 percent), the other reasons for NOAC discontinuation should also be considered, pointed out study author Dr Jan Beyer-Westendorf from King’s College London in London, UK. “There [was no] single driver of discontinuation … Bleeding [was only one reason],” he said, noting other factors such as inconvenience in taking medications, scheduled end of treatment, nonbleeding side effects, worsening of renal function, and physicians’ decision to discontinue therapy. Other infrequent reasons were vascular events, contraindication to anticoagulation, and frequent falls.
A total of 255 deaths (27.3 percent) were reported, with almost half (n=120) occurring within 3 days after the last NOAC intake. The leading cause of death was fatal cardiovascular event (n=86, ie, non-thromboembolic causes, acute coronary syndrome, ischaemic stroke/systemic embolism, VTE), which occurred mostly after anticoagulant discontinuation. Other causes of death were age-related mortality (n=79), sepsis/infection (n=40), terminal malignant disease (n=26), and fatal bleeding (n=11).
According to Beyer-Westendorf, the mortality rate was unsurprising in this population as the deaths were primarily due to ‘natural causes’ and not major thromboembolism or bleeding.
“[Among those who died within 3 days of last NOAC intake,] only 21 fatalities occurred which were not prevented or, in the case of bleeding, might have been caused, by NOAC therapy,” highlighted Beyer-Westendorf. “From a clinician’s point of view … [these are] acceptably low rates of CV or major bleeding events … [As] these patients are at high risk of bleeding [given] their comedication, comorbidities, and renal impairment, it is impressive that … overall, we only had a total of eleven fatal bleeding events.”
Taken together, the results address the challenges associated with this patient subgroup given their high thromboembolic and bleeding risks, noted Beyer-Westendorf. The findings may help streamline treatment decisions for very old patients who require anticoagulant therapy, he added. “[Moreover,] the use of warfarin in elderly patients is quite rare … NOACs might be [a favourable] alternative.”