The quality of evidence is downgraded by study limitations (unclear allocation concealment and incomplete outcome data), and by potential publication bias (asymmetrical funnel plot).
A Cochrane review [Abstract]1 included 27 studies with a total of 122 601 adult subjects who had never experienced venous thromboembolism (VTE). They were healthy, had various medical conditions (e.g. hypercholesterolemia), or were at risk for cardiovascular disease. The statins used in the studies were atorvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, and simvastatin. The median follow-up durations ranged from 90 days to 6.1 years. Only one study used VTE as a primary endpoint.
The median incidence of VTE in the statins group was 0.72% and in the control group 0.89%. Statins slightly reduced the overall incidence of VTE (OR 0.86, 95% CI 0.76 to 0.98; 27 studies, n=122 601). The was no difference between groups in the incidence of deep vein thrombosis, DVT (OR 0.70, 95% CI 0.41 to 1.18; 6 studies, n=40 305), pulmonary embolism, PE (OR 0.83, 95% CI 0.46 to 1.52; 5 studies, n=28 427), or myopathy (OR 1.10, 95% CI 0.83 to 1.45; 10 studies, n=75 551). Statin use slightly decreased the incidence of any serious adverse event (OR 0.95, 95% CI 0.91 to 0.99; 13 studies, n=67 020) and all-cause mortality (OR 0.90, 95% CI 0.86 to 0.95; 24 studies, n=116 761), compared to control.
Subgroup analysis showed that the effect of statins on VTE incidence varies by type (p=0.05). Rosuvastatin reduced VTE incidence compared to the control group (OR 0.64, 95% CI 0.50 to 0.82; 9 studies, n=44 892). No significant difference in VTE incidence was found for atorvastatin, fluvastatin, lovastatin, simvastatin, and pravastatin compared to controls.
Another Cochrane review [Abstract] 2 included 1 study (17 citations) with a total of 17 802 subjects. The purpose of this study (JUPITER trial) was to determine the safety and efficacy of long-term therapy with rosuvastatin 20 mg in the prevention of cardiovascular events among participants aged 50 years or more (men) or 60 years or more (women) with no history of cardiovascular disease, low level of LDL cholesterol (less than 3.4 mmol/l), and elevated level of high-sensitivity-CRP (2.0 mg/l or more). Metabolic syndrome was present in 41.7% of the participants. Venous thromboembolic events (VTE) were secondary outcome measures.
Rosuvastatin reduced the incidence of all cases of VTE (rosuvastatin 34/8901, placebo 60/8901; OR 0.57, 95% CI 0.37 to 0.86), provoked VTE that occurred in the presence of cancer, recent trauma, hospitalisation, or surgery (rosuvastatin 15/8901, placebo 29/8901; OR 0.52, 95% CI 0.28 to 0.96), and deep vein thrombosis (DVT) only (rosuvastatin 17/8901, placebo 38/8901; OR 0.45, 95% CI 0.25 to 0.79) but did not reduce the incidence of unprovoked VTE (rosuvastatin 19/8901, placebo 31/8901; OR 0.61, 95% CI 0.35 to 1.08), and pulmonary embolism (PE) (rosuvastatin 17/8901, placebo 22/8901; OR 0.77, 95% CI 0.41 to 1.46).
Rosuvastatin reduced the incidence of all VTE in men (OR 0.50, 95% CI 0.30 to 0.84) and patients aged 50 to 69 years (OR 0.55, 95% CI 0.31 to 0.96) but it did not reduce the incidence of all VTE in women (OR 0.74, 95% CI 0.35 to 1.56) and patients aged 70 to 97 years (OR 0.59, 95% CI 0.31 to 1.11).
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