Lipid lowering drugs and the risk of recurrent venous thromboembolism

Delluc, Aurélien; Tromeur, Cécile; Moigne, Emmanuelle Le; Nowak, Emmanuel; Mottier, Dominique; Gal, Grégoire Le; Lacut, Karine

doi:10.1016/j.thromres.2012.08.296

Cited by 41 publications

(35 citation statements)

References 31 publications

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“…Previous studies on the association between statin use and risk of venous thrombosis recurrence have reported somewhat diverging results. A French study of 432 patients with a first unprovoked venous thrombosis, followed for a median of 29.5 months, found no association between statin use and risk of recurrence . In contrast, a Dutch register‐based study of 3,093 patients hospitalized for pulmonary embolism followed for a median of 4 years found that statin use was associated with 50% reduction of recurrent pulmonary embolism .…”

Section: Discussionmentioning

confidence: 98%

“…In contrast, Delluc et al. reported no association between statin intake and recurrent venous thrombosis . Several methodological aspects of these studies warrant consideration, such as the selection of comparison groups, low statistical power, lack of information on important confounders, and particularly that the majority of the studies did not distinguish between incident and prevalent statin use which may have introduced “incidence/prevalence bias.”…”

Section: Introductionmentioning

confidence: 99%

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Statin use and risk of recurrent venous thrombosis: results from the MEGA follow‐up study

Brækkan

Caram‐Deelder

Siegerink

et al. 2017

Research and Practice in Thrombosis and Haemostasis

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IntroductionWhether statin use after first venous thrombosis reduces the risk of recurrence is uncertain. Therefore, we aimed to examine the risk of recurrent venous thrombosis in statin users vs non‐users.MethodsPatients with a first venous thrombosis were recruited from the MEGA follow‐up study. Information on statin use was obtained by linkage to the Dutch Foundation for Pharmaceutical Statistics register. Linkage was successful in 54% of all patients (n = 2,547). Cox‐regression models with statin‐exposure as a time‐dependent co‐variate were used to estimate hazard ratios (HR) with 95% confidence intervals (CI 95) for recurrence.ResultsStatin therapy was continued in 153 (6.0%) patients and initiated in 233 (9.1%) patients during a median follow‐up of 5.7 years. There were 367 recurrent venous thrombotic events, of which 32 occurred among statin users. Incident statin use was associated with 22% reduced risk of recurrence after multivariable adjustments (HR 0.78, CI 95: 0.46‐1.31), and 13% reduced risk after propensity score adjustment (HR 0.87, CI 95: 0.52‐1.47). Statin use seemed not to have an effect on recurrence in patients with an unprovoked first event (multivariable HR 1.03, CI 95: 0.54‐1.98), but the statistical power was low due to few events and the results must be interpreted with caution. In general, the risk estimates were slightly attenuated when prevalent users were included in the analyses.ConclusionOur findings suggest that statins may have a modest decreasing effect on the risk of recurrent venous thrombosis. While we took care to minimize bias and confounding, the causality of the association is still unsettled.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Statin use and risk of recurrent venous thrombosis: results from the MEGA follow‐up study

Brækkan

Caram‐Deelder

Siegerink

et al. 2017

Research and Practice in Thrombosis and Haemostasis

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“…Whether previously identified baseline characteristics remain predictors of recurrence after adjusting for treatments and interim exposures is unknown. Interim exposure to lipid-lowering drugs[23] and among women, to oral contraceptives[24] and hormone therapy,[25] have been identified as predictors of VTE recurrence, but no study has comprehensively studied interim exposures; we do not know which exposures are independent predictors of recurrence nor the magnitude of recurrence risk associated with each. These are important issues because the 5-year VTE recurrence rate has changed little over the last 35 years.…”

Section: Discussionmentioning

confidence: 99%

“…Non-statin lipid-lowering therapy was marginally associated with a reduced hazard of recurrence (HR=0.52 [0.23, 1.21; p=0.13]; Table 3). [23] Sixty-six (16%) patients in the sub cohort received lipid-lowering therapy for at least one day during follow-up; 59 received a statin and 26 received a non-statin (20 of these 26 also received a statin). An association of lipid-lowering therapy with a reduced hazard of recurrence may have been missed due to inadequate power.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Venous Thromboembolism Recurrence, Adjusted for Treatments and Interim Exposures: A Population-based Case-cohort Study

Heit

Lahr

Ashrani

et al. 2015

Thrombosis Research

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Background Predictors of venous thromboembolism (VTE) recurrence are uncertain. Objective To identify predictors of VTE recurrence, adjusted for treatments and interim exposures. Materials and Methods Using Rochester Epidemiology Project resources, all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988–2000, who survived ≥1 day were followed for first objectively-diagnosed VTE recurrence. For all patients with recurrence, and a random sample of all surviving incident VTE patients (n=415), we collected demographic and baseline characteristics, treatments and interim exposures. In a case-cohort study design, demographic, baseline, treatment and interim exposure characteristics were tested as potential predictors of VTE recurrence using time-dependent Cox proportional hazards modeling. Results Among 1262 incident VTE patients, 306 developed recurrence over 6,440 person-years. Five-year recurrence rates, overall and for cancer-associated, idiopathic and non-cancer secondary VTE, were 24.5%, 43.4%, 27.3% and 18.1%, respectively. In multivariable analysis, interim hospitalization, active cancer, pregnancy, central venous catheter and respiratory infection were associated with increased hazards of recurrence, and warfarin and aspirin were associated with reduced hazards. Adjusting for treatments and these interim risk factors, male sex, baseline active cancer and failure to achieve a therapeutic aPTT in the first 24 hours were independently associated with increased hazards of VTE recurrence over the entire follow-up period, while the hazards of recurrence for patient age, chronic lung disease, leg paresis, prior superficial vein thrombosis and idiopathic VTE varied over the follow-up period. Conclusions Baseline and interim exposures can stratify VTE recurrence risk and may be useful for directing secondary prophylaxis.

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“…Among the few studies examining statins' effect on VTE recurrence, a cohort study of 432 patients who had discontinued anticoagulant therapy after a first‐time unprovoked VTE found no effect of statin use on recurrent events (HR, 1.02; 95% CI, 0.36–2.91) . However, the small sample size yielded imprecise estimates . Another cohort study followed 3093 patients with a first‐time PE and reported a 50% reduced rate of recurrent PE (HR, 0.50; 95% CI, 0.36–0.70) .…”

Section: Discussionmentioning

confidence: 99%

Statin use and venous thromboembolism recurrence: a combined nationwide cohort and nested case–control study

Schmidt

Cannegieter

Johannesdottir

et al. 2014

Journal of Thrombosis and Haemostasis

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To cite this article: Schmidt M, Cannegieter SC, Johannesdottir SA, Dekkers OM, Horv ath-Puh o E, Sørensen HT. Statin use and venous throm-boembolism recurrence: a combined nationwide cohort and nested case-control study. J Thromb Haemost 2014; 12: 1207-15. See also Rodger M. Is it time to try or to trial statins to prevent recurrent venous thromboembolism?. This issue, pp 1204-6. Summary. Background: Data on statins' effect on venous thromboembolism (VTE) recurrence are conflicting. Objectives: We examined whether statin use was associated with reduced risk of recurrent VTE in a nationwide population-based setting. Patients/Methods: Using the Danish National Patient Registry, we identified first-time and recurrent VTEs between 1 July 2004 and 31 Decem-ber 2012 (n = 27 862). VTE diagnoses were validated by medical record review of a subsample of patients. We ascertained nationwide prescription data and categorized statin use as current (further divided into new and long-term use), former and no use. We identified statin use at baseline (mimicking an intention-to-treat analysis) and in a time-varying manner during follow-up (mimicking per-protocol analysis) and computed hazard ratios (HRs) for recurrent VTE using Cox regression. In a supplementary nested case-control study, we identified statin use at time of VTE recurrence and computed odds ratios as unbiased estimates of the incidence rate ratios (IRRs) using conditional logistic regression. We adjusted for age, sex, year of diagnosis, provoking factors, co-morbidities and co-medications, including time-varying use of aspirin and anticoagulant drugs. Results: The adjusted HR comparing current use with no use was 0.72 (95% confidence interval [CI], 0.59-0.88) for recurrent VTE, with a stronger effect of high (0.40; 95% CI, 0.21-0.78) vs. low potency statins (0.77; 95% CI, 0.63-0.94). Consistently, the recurrence rate was reduced in both the time-varying analysis (HR=0.64; 95% CI, 0.54-0.77) and nested case-control analysis (IRR=0.55; 95% CI, 0.45-0.67). The effect was largest for recurrent deep venous thrombosis. Conclusions: Statin use was associated with reduced VTE recurrence .

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Lipid lowering drugs and the risk of recurrent venous thromboembolism

Cited by 41 publications

References 31 publications

Statin use and risk of recurrent venous thrombosis: results from the MEGA follow‐up study

Statin use and risk of recurrent venous thrombosis: results from the MEGA follow‐up study

Predictors of Venous Thromboembolism Recurrence, Adjusted for Treatments and Interim Exposures: A Population-based Case-cohort Study

Statin use and venous thromboembolism recurrence: a combined nationwide cohort and nested case–control study

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