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Rosuvastatin 20 mg/day substantially improved the coagulation profile among patients with prior VT. These results suggest that statin therapy might be beneficial in patients at risk of recurrent VT.

Essentials The role of statins in hemostasis and venous thromboembolism (VTE) prophylaxis is not clear.This trial assessed whether rosuvastatin use affects thrombin generation in patients with VTE.Endogenous thrombin potential and peak were decreased by 10% and 5% with rosuvastatin therapy.These results provide basis for trials on the efficacy of statins in reducing recurrent VTE risk. SummaryBackgroundStatin therapy could form an alternative prophylactic treatment for venous thromboembolism (VTE) if statins are proven to downregulate hemostasis and prevent recurrent VTE, without increasing bleeding risk.ObjectivesThe STAtins Reduce Thrombophilia (START) trial investigated whether statin affects coagulation in patients with prior VTE.Patients/methodsAfter anticoagulation withdrawal, patients were randomized to rosuvastatin 20 mg day−1 for 4 weeks or no intervention. Plasma samples taken at baseline and at the end of the study were analyzed employing thrombin generation assay.Results and conclusionsThe study comprised 126 rosuvastatin users and 119 non‐users. Mean age was 58 years, 61% were men, 49% had unprovoked VTE and 75% had cardiovascular (CV) risk factors. Endogenous thrombin potential (ETP) increased from baseline to end of study in non‐statin users (mean 97.22 nm*min; 95% CI, 40.92–153.53) and decreased in rosuvastatin users (mean −24.94 nm*min; 95% CI, −71.81 to 21.93). The mean difference in ETP change between treatments was −120.24 nm*min (95% CI, −192.97 to −47.51), yielding a 10.4% ETP reduction by rosuvastatin. The thrombin peak increased in both non‐statin (mean 20.69 nm; 95% CI, 9.80–31.58) and rosuvastatin users (mean 8.41 nm; 95% CI −0.86 to 17.69). The mean difference in peak change between treatments was −11.88 nm (95% CI, −26.11 to 2.35), yielding a 5% peak reduction by rosuvastatin. Other thrombin generation parameters did not change substantially. The reduction in ETP and peak by rosuvastatin was more pronounced in the subgroups of participants with CV risk factors and with unprovoked VTE. We conclude that rosuvastatin reduces thrombin generation potential in patients who had VTE.

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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 may be causally associated with a decreased risk of venous thrombosis. If so, this could be a substantive breakthrough since statins do not increase the risk of bleeding and could therefore be used as a safer antithrombotic drug. However, scepticism exists on the observed reduction of venous thrombosis by statins, as it may have been confounded by healthy user effects or other biases. Areas covered: The main focus of this review will be the biases that may have arisen in clinical studies that investigated the relationship between statin use and risk of venous thrombosis. We also discuss the suggested causal association from a pathophysiological perspective. Furthermore, we integrate the knowledge from clinical and pathophysiological studies into a proposal for new study designs that are needed to sufficiently answer the question whether we can, and should, prevent recurrent venous thrombosis with statins. Expert commentary: A drug to prevent recurrent venous thrombosis in patients at risk of bleeding that does not induce bleeding and in which the number needed to treat for the prevention of venous thrombosis is sufficiently high, is a remedy that we should continue to look for, and for which statin therapy might be a suitable candidate.

BackgroundDecreased physical function is known to raise mortality risk. Little is known about how different physical function measures compare in predicting mortality risk in older men and women. The objective of this study was to compare four, objective and self-reported, physical function measures in predicting 15-year mortality risk in older men and women.MethodsData were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study in a population-based sample of the older Dutch population, sampled from municipal records. The 1995–96 cycle, including 727 men and 778 women aged 65–88 years, was considered as the baseline. Mortality was followed up through September 1, 2011. Physical function measures were: lower-body performance (chair stands test, walk test and tandem stand); handgrip strength (grip strength dynamometer); lung function (peak expiratory flow rate); functional limitations (self-report of difficulties in performing six activities of daily living). Cox proportional hazard models were used to determine the predictive value of each physical function measure for 15-year mortality risk, adjusted for demographic, lifestyle and health variables as potential confounders.Results1031 participants (68.5%) had died. After adjustments for confounders, in models assessing single functional measures, peak flow was the strongest predictor of all-cause mortality in men (HR 1.76, CI 1.38–2.26, CI) and lower-body performance in women (HR 1.97,CI 1.40–2.76, CI). In a model including all four functional measures only peak flow was statistically significant in predicting mortality in both genders (men HR 1.54,CI 1.18–2.01 and women HR 1.45,CI 1.08–1.94). In women, lower-body performance (HR 1.66, CI 1.15–2.41) followed by grip strength (HR 1.38, CI 1.02–1.89), and in men, functional limitations (HR 1.43, CI 1.14–1.8) were the other significant predictors of all-cause mortality.ConclusionBoth objective and self-reported measures of physical functioning predicted all-cause mortality in a representative sample of the older Dutch population to different extents in men and women. Peak flow contributed important unique predictive value for mortality in both men and women. In women, however, lower-body performance tests had better predictive ability. A second-best predictor in men was self-reported functional limitations. Peak flow, and possibly one of the other measures, may be used in clinical practice for assessment in the context of time constraints.

Patients on vitamin K antagonists (VKA) often undergo invasive dental procedures. International guidelines consider all dental procedures as low-risk procedures, while bleeding risk may differ between standard low-risk (e. g. extraction 1-3 elements) and extensive high-risk (e. g. extraction of >3 elements) procedures. Therefore current guidelines may need refinement. In this cohort study, we identified predictors of oral cavity bleeding (OCB) and evaluated clinical outcome after low-risk and high-risk dental procedures in patients on VKA. Perioperative management strategy, procedure risk, and 30-day outcomes were assessed for each procedure. We identified 1845 patients undergoing 2004 low-risk and 325 high-risk procedures between 2013 and 2015. OCB occurred after 67/2004 (3.3 %) low-risk and 21/325 (6.5 %) high-risk procedures (p=0.006). In low-risk procedures, VKA continuation with tranexamic acid mouthwash was associated with a lower OCB risk compared to continuation without mouthwash [OR=0.41, 95 %CI 0.23-0.73] or interruption with bridging [OR=0.49, 95 %CI 0.24-1.00], and a similar risk as interruption without bridging [OR=1.44, 95 %CI 0.62-3.64]. In high-risk procedures, VKA continuation was associated with an increased OCB risk compared to interruption [OR=3.08, 95 %CI 1.05-9.04]. Multivariate analyses revealed bridging, antiplatelet therapy, and a supratherapeutic or unobjectified INR before the procedure as strongest predictors of OCB. Non-oral cavity bleeding (NOCB) and thromboembolic event (TE) rates were 2.1 % and 0.2 %. Bridging therapy was associated with a two-fold increased risk of NOCB [OR=1.93, 95 %CI 1.03-3.60], but not with lower TE rates. In conclusion, predictors of OCB were mostly related to perioperative management and differed between low-risk and high-risk procedures. Perioperative management should be differentiated accordingly.