TORONTO – The use of statins showed no benefit in reducing the risk of recurrent venous thromboembolism in patients enrolled in phase III trials comparing direct oral anticoagulants with vitamin K antagonists, a large meta-analysis demonstrated.
Recurrence after an unprovoked VTE is 10%-15% in the first 6-12 months, and recurrence risk in the first 6 months is reduced by 80%-90% with anticoagulants, Dr. Mandy N. Lauw said at the International Society on Thrombosis and Haemostasis congress.
“However, the use of anticoagulants has the risk of bleeding, and therefore the long-term risk-benefit ratio is unclear,” said Dr. Lauw of the department of vascular medicine at Academic Medical Center, Amsterdam. “Therefore it’s interesting to look at modalities outside the coagulation cascade to treat patients for longer term and to prevent recurrent thrombosis. One of these modalities has been the use of statins, which are known to reduce arterial vascular events by lowering cholesterol levels. However, recent studies have also indicated that they may have an effect on VTE events.”
In an effort to evaluate the effects of statins on recurrent VTE, Dr. Lauw and her associates conducted a meta-analysis of statins in three randomized, phase III trials comparing non–vitamin K oral anticoagulant (NOAC) with vitamin K antagonist (VKA) therapy in patients with acute symptomatic VTE.
The trials included 5,153 patients enrolled in RE-COVER I and II (an analysis of dabigatran vs. standard therapy for acute VTE), 8,281 enrolled in the EINSTEIN clinical trials for DVT and pulmonary embolism (an analysis of rivaroxaban vs. standard therapy for symptomatic VTE), and 8,292 enrolled in a trial conducted by the Hokusai-DVT investigators (an analysis of edoxaban vs. standard therapy for symptomatic VTE). The researchers examined the effect of statin use on recurrent VTE or VTE-related death, recurrent DVT or PE, and major bleeding. To do this they conducted a pooled meta-analysis and an analysis per study, adjusted for age, gender, diabetes mellitus, creatinine clearance of less than 50 mL/min, hypertension, prior VTE, and use of aspirin.
Dr. Lauw reported results from 21,587 patients included in the analysis. Among all three studies, 2,754 patients (12.8%) used statins and 18,833 (87.2%) did not. In an unadjusted pooled analysis, the use of statins at baseline did not have an influence on the risk of recurrent VTE or VTE-related death, with an odds ratio of 0.91. There was also no effect of statins on the risk of recurrent PE or DVT (ORs of 0.84 and 1.05, respectively), while major bleeding seemed to be increased with the use of statins (OR, 1.65). A subanalysis in patients getting NOAC or VKA separately showed a non–statistically significant benefit of statins with NOACs, compared with VKAs on the risk of recurrent VTE or VTE-related death (ORs of 0.60 vs. OR 1.24, respectively). The results were similar for NOACs, compared with VKA, on the risk of recurrent DVT (ORs of 0.47 vs. OR 1.67) and the risk of recurrent PE (ORs of 0.73 vs. 1.02).
On adjusted analysis, the risk of recurrent VTE or VTE-related death between all three studies was similar and nonsignificant (hazard ratio of 0.99 in RE-COVER I and II, HR of 0.78 in the EINSTEIN clinical trials for DVT & PE, and HR of 0.99 in the trial conducted by the Hokusai-DVT Investigators). There also were no significant differences between the study groups in recurrent PE, recurrent DVT, or major bleeding. “So statins have no beneficial effect, but also no harmful effect,” Dr. Lauw said.
She acknowledged certain limitations of the study, including the fact that it was an on-treatment analysis, “so it could be that we had inadequate follow-up duration,” she said. “Also, we don’t have any assessment of statin effects without anticoagulation in these patients. Perhaps it would be interesting to use the extension trials to explore these results as well.”
For now, “there is no evidence that statins reduce the recurrence of VTE,” she concluded. “The only way to explore this is to do a randomized controlled trial properly designed and powered to estimate this effect prospectively.”
Dr. Lauw reported having no financial disclosures.