From 87th EAS: High Lipoprotein(a) Levels not Linked to Increased Prothrombotic Effects

MAASTRICHT, The Netherlands - Elevated levels of plasma lipoprotein(a) (Lp[(a]) have been linked to risk for cardiovascular (CV) disease. Although it has historically been thought that this elevated risk is related to both the atherogenic and prothrombotic effects of Lp(a), a recent study found that antiplatelet and antithrombin therapies to reduce Lp(a) levels are not associated with any significant impact on CV outcomes, including heart attack and stroke. Results of the large-scale European study were presented May 27th at the 87th Annual Congress of the European Atherosclerosis Society (EAS). 

The proposed prothrombic and atherogenic effects of Lp(a) have been difficult to separate. Thus, the current study sought to determine whether Lp(a) actually has significant prothrombic effects. “Antiplatelet and antithrombin therapies are part of the routine evidence-based management of patients at high and very high risk of cardiovascular events,” explained Brian Ference, MD, a cardiologist and genetic epidemiologist and Executive Director of the Centre for Naturally Randomised Trials at Cambridge University, who presented the latest data. “Given current understanding of the biology of lipoprotein(a), a key question is whether these treatments are likely to influence cardiovascular risk associated with high lipoprotein(a) levels,” he said.

Using a pool of 480,000 people of European descent from the UK Biobank database, 375,000 of whom were identified as having high Lp(a) levels using a single assay, the study showed that high Lp(A) levels were not associated with increased risk of thrombotic outcomes such as deep vein thrombosis or pulmonary embolism. This trend persisted in the cohort regardless of whether they carried gene variants for platelet activation, or for Factor II and Factor V genes for prothrombin disorders. Taken together the results seem to argue against a clinically significant prothrombotic effect for Lp(a) “Based on the results of our analysis, in which lipoprotein(a) levels were measured with the same sensitive assay, concomitant antiplatelet therapy should not have any effect on the amount that lipoprotein(a) must be reduced to achieve clinically meaningful benefit in a short-term trial,” Dr. Ference reported.

These findings are likely to have a significant impact on clinical trial design for hyperlipidemia by altering the current practice of enrolling patients with cardiovascular disease who are already taking antiplatelet therapy, he concluded.

Reference: Katzmann J, Laufs U, Ference BA. Mendelian randomization analysis of lipoprotein(a) lowering and cardiovascular risk stratified by LDL cholesterol, gender, and antiplatelet therapy: implications for clinical outcome trials. Paper presented at 87th EAS Congress: May 26-29, 2019; Maastricht, The Netherlands; Abstract  EAS19-0777.