Farmakis IT, Christodoulou KC, Hobohm L, et al. Lipid lowering for prevention of venous thromboembolism: a network meta-analysis. Eur Heart J. 2024 Jun 14:ehae361. doi: 10.1093/eurheartj/ehae361. (Systematic review)

BACKGROUND AND AIMS: Studies have suggested that statins may be associated with reduced risk of venous thromboembolism (VTE). The aim of the current study was to assess the evidence regarding the comparative effect of all lipid-lowering therapies (LLT) in primary VTE prevention.

METHODS: After a systematic search of PubMed, CENTRAL, and Web of Science up until 2 November 2022, randomized controlled trials (RCT) of statins (high- or low-/moderate-intensity), ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were selected. An additive component network meta-analysis to compare VTE risk during long-term follow-up across different combinations of LLT was performed.

RESULTS: Forty-five RCTs (n = 254 933 patients) were identified, reporting a total of 2084 VTE events. Compared with placebo, the combination of PCSK9i with high-intensity statin was associated with the largest reduction in VTE risk (risk ratio [RR] 0.59; 95% confidence interval [CI] 0.43-0.80), while there was a trend towards reduction for high-intensity (0.84; 0.70-1.02) and low-/moderate-intensity (0.89; 0.79-1.00) statin monotherapy. Ezetimibe monotherapy did not affect the VTE risk (1.04; 0.83-1.30). There was a gradual increase in the summary effect of VTE reduction with increasing intensity of the LLT. When compared with low-/moderate-intensity statin monotherapy, the combination of PCSK9i and high-intensity statin was significantly more likely to reduce VTE risk (0.66; 0.49-0.89).

CONCLUSIONS: The present meta-analysis of RCTs suggests that LLT may have a potential for VTE prevention, particularly in high-intensity dosing and in combination therapy.

Discipline Area Score
Cardiology 6 / 7
Hemostasis and Thrombosis 6 / 7
Internal Medicine 6 / 7
Family Medicine (FM)/General Practice (GP) 5 / 7
General Internal Medicine-Primary Care(US) 5 / 7
Comments from MORE raters

Cardiology rater

This study confirms that the more intense the lipid-lowering therapy (LLT), the lower the risk for a first spontaneous venous thromboembolism (VTE). However, the generalizability of these data remain to be ascertained as LLT is not typically used in clinical practice for the primary prevention of VTE. Thus, these results should be interpreted as an ancillary positive effect of LLT.

Hemostasis and Thrombosis rater

LLT treatment might be considered for VTE prevention with the combination of a PCSK9 inhibitor, with a high-intensity statin being the most promising regimen. This is a very new message.

Internal Medicine rater

As a hospitalist, I do not generally think about initiating lipid lowering except in the cases of new cerebrovascular and cardiovascular disease, and I do not usually think about these medications as preventing venous thrombotic disease. In this very nicely performed network meta-analysis, it looks like the best effects were for the drug regimens that lowered cholesterol the most, with the combination of PCSK9 and HMG Co A having the greatest effect while ezetimibe had the least. I will consider this in my very thrombotic patients as a potential treatment option.
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