Extended VTE anticoagulation reduces major adverse cardiovascular event risk
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Patients with venous thromboembolism treated with anticoagulants for more than 3 months had a lower risk for major adverse cardiovascular events, according to a study published in CHEST.
Further, VTE treatment with direct oral anticoagulants (DOACs) showed a greater decreased risk for major adverse cardiovascular events (MACE) and cardiovascular death than vitamin K antagonists (VKAs), according to researchers.
“We found that the risk of MACE that occurred following VTE was significantly reduced in patients treated for a long duration,” Steve Raoul Noumegni, MD, PhD, of the internal medicine, vascular medicine and pneumology department at Brest Teaching Hospital in France, and colleagues wrote. “We also found a significant relationship between the type of anticoagulant treatment and the risk of MACE, with a reduced risk in patients treated with DOACs compared with those treated with VKAs.”
In a prospective observational cohort study, Noumegni and colleagues analyzed 3,790 adults (mean age, 60.48 years; 47.2% men) treated with an anticoagulant for symptomatic VTE to determine whether this treatment impacts the risk for MACE, given that data show patients with VTE are at higher risk for cardiovascular events.
From the total study population, 2,788 patients received a VKA, 441 received a DOAC and 561 received low-molecular-weight heparin.
Researchers then divided the total cohort into three groups according to how long they were on their therapy: 1,228 patients (32.4%) received treatment for 0 to 3 months, 1,271 (33.5%) for 3 to 12 months and 1,291 (34.1%) for more than 12 months.
MACE, which included nonfatal acute coronary syndrome, nonfatal stroke and all-cause death, served as the study’s primary endpoint. MACE-2, which included cardiovascular death, nonfatal acute coronary syndrome and nonfatal stroke, was a secondary outcome.
In order to observe the association and risk between anticoagulant therapy and MACE/MACE-2, researchers used Cox proportional and Fine-Gray models.
Median follow-up was 68 months. In that time, 1,520 patients (40.1%) experienced MACE, equating to an annual incidence of 6.3 per 100 patient-years (95% CI, 6-6.62).
Of the defined causes, researchers found that all-cause death was the most common occurrence in 84.3% of patients with MACE, and nonfatal stroke followed after in 10.8%. Overall, the mortality rate was 5.59 per 100 patient-years (95% CI, 5.31-5.89).
Researchers found a significant decreased risk for MACE among patients receiving anticoagulation for 3 to 12 months (adjusted HR = 0.64; 95% CI, 0.54-0.76) or more than 12 months (aHR = 0.47, 95% CI, 0.39-0.56) compared with those treated for less than 3 months after adjusting for confounders in multivariable analysis.
Of 3,201 patients, 539 patients (16.8%) experienced MACE-2, for an annual incidence of 2.24 per 100 patient-years (95% CI, 2.04-2.44). Cardiovascular death was the most common occurrence of MACE-2 at 55.7%, with 324 of the 1,398 patients who died (23.2%) during the study dying of cardiovascular death.
Assessing the risk for MACE-2, researchers found comparable findings to their previous analysis, with patients treated for 3 to 12 months (adjusted sub-HR = 0.61; 95% CI, 0.47-0.79) and more than 12 months (adjusted sub-HR = 0.52; 95% CI, 0.39-0.68) demonstrating a lower risk than patients treated for 3 months or less.
When comparing types of anticoagulation, researchers observed that DOACs significantly reduced the risk for MACE (aHR = 0.53; 95% CI, 0.39-0.71) and MACE-2 (adjusted sub-HR = 0.48; 95% CI, 0.29-0.77) compared with VKAs in both univariable and multivariable analysis.
Notably, low-molecular-weight heparin treatment significantly raised the risk for MACE by 46% (aHR = 1.46: 95% CI, 1.23-1.75) compared with VKAs in adjusted models.
“These findings may influence the choice of type and duration of anticoagulant treatment for VTE; however, they need confirmation by randomized controlled clinical trials,” Noumegni and colleagues wrote.
This study by Noumegni and colleagues adds to the literature indicating that DOACs may provide a “feasible and simple” strategy for the extended secondary prevention of VTE while also preventing MACE, according to an accompanying editorial by Cecilia Becattini, MD, and Maria Cristina Vedovati, MD, of the internal vascular and emergency medicine stroke unit at the University of Perugia.
“In conclusion, extended prevention of recurrent VTE with DOACs may offer the possibility to reduce both recurrent VTE and arterial cardiovascular events,” Becattini and Vedovati wrote. “If confirmed in further studies, these data may change the paradigm for secondary prevention of VTE.”