Statin use decreases coagulation in users of vitamin K antagonists

Abstract

PurposeThe purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs).MethodsWe selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test.ResultsFour hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower.ConclusionsInitiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.

Statins do not Increase the Rate of Bleeding Among Warfarin Users

“…In healthy volunteers, rosuvastatin 40 mg/day for one week did not alter the effects of warfarin on laboratory markers of blood clotting [12]. A recent Dutch study concluded that initiation of statins had a minor, although statistically significant, decreasing effect on phenprocoumon and acenocoumarol doses [10].…”

“…However, the results of systematic studies on potential vitamin K antagonist-statin interaction are inconsistent. Anticoagulant activity has been found to be increased [9,10] or unchanged [11,12] during their concomitant use. A parallel-group study in patients on warfarin showed lower daily warfarin dose requirements in patients on concomitant simvastatin compared to those on warfarin alone; the presence of a pharmacokinetic interaction was claimed [9].…”

Differential effect of statin use on coagulation markers: an active comparative analysis in the NEO study

“…Similarly, rosuvastatin but not pitavastatin was shown to increase international normalized ratio (INR) in healthy volunteers on steady-state warfarin [26]. A Dutch study that assessed the immediate and long-term effects of new statin use on the dosage of vitamin K antagonist (VKA) showed that statin users needed lower doses of VKA to achieve the target INR, with the most substantial effect seen with simvastatin and rosuvastatin [27]. Pravastatin was also noted to potentiate the anticoagulant effects of dalteparin [28].…”

The Prescription of Vitamin K Antagonists in a Very Old Population: A Cross-Sectional Study of 8696 Ambulatory Subjects Aged Over 85 Years

“…This result can be explained by the fact that cardiovascular diseases were more frequent in the VKAG [ 7 , 29 , 30 , 31 ]. A study showed a risk of overdose for phenprocoumon and acenocoumarol in cases of concomitant statins use [ 32 ]. These drug interactions raise questions regarding the role of statins in very elderly people treated with VKA.…”