Background LDL cholesterol (LDLC) lowering has been revolutionized by PCSK9 inhibitors, which have approved indications as an adjunct to diet-maximally tolerated cholesterol lowering therapy in heterozygous (HeFH) or homozygous (HoFH) familial hypercholesterolemia, and/or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient despite maximal tolerated therapy. Injection site reactions occur in approximately 7.2% of patients (alirocumab) vs. 5.1% (placebo) and allergic reactions are 8.6% (alirocumab) vs. 7.8% (placebo). There is no drug to drug interaction data or warnings when using alirocumab or evolocumab in conjunction with anti-coagulants and/or anti-platelet therapy.
Methods Patient was 70 year old Caucasian male with history of coronary artery disease, transient ischemic attack, amaurosis fugax associated with the G20210A prothrombin gene mutation, and normal carotid artery imaging, atrial fibrillation and mixed hyperlipidemia. Because of daily recurrent amaurosis fugax, he was given rivaroxaban (3 years) and subsequently added clopidogrel after a TIA. Despite rosuvastatin 40 mg and ezetimibe 10 mg, LDL cholesterol (LDLC) was 144 mg/dL (above target goal <70 mg/dL). Alirocumab 150 mg/mL was started subcutaneously every two weeks to achieve a LDLC target <70 mg/dL.
Results After three doses of alirocumab, he presented with a diffuse ecchymotic-hemorrhagic bruising-rash on bilateral arms (see image) which started with an area of central clearing followed by blood spreading out in a circular fashion. Blood oozed out from ecchymotic rash sites at times, but there was no pain or tenderness. Platelet count was 175, hemoglobin 14.7, and hematocrit 44.7 which were all normal and there was no evidence of systemic bleeding. Previous to development of the ecchymotic-brusing, and four weeks after starting alirocumab, total cholesterol had fallen from 211 to 87 mg/dL, and LDLC from 144 to <4 mg/dL. All other labs including complete blood count with differential and comprehensive metabolic panel were normal at four weeks. At week seven, after three doses of alirocumab and appearance of ecchymotic rash, we discontinued clopidogrel, rivaroxaban, and alirocumab and the ecchymosis-bruising faded and receded. Because symptoms of amaurosis fugax accelerated off anticoagulants, clopidogrel and rivaroxaban were uneventfully restarted, without worsening of the skin.
Conclusion We speculate that the reduction of LDLC from 144 to <4 mg/dL on alirocumab may have affected platelet membrane cholesterol, and platelet aggregation, especially in the concurrent presence of clopidogrel and rivaroxaban. In patients with cardiovascular disease and LDLC >70 (target) despite aggressive conventional cholesterol lowering drugs, alirocumab and evolocumab have revolutionary power in lowering LDLC with trivial side effects. For patients with cardiovascular disease and suboptimal LDLC lowering despite maximal tolerated conventional therapy, requiring concurrent anti-platelet and Xa inhibition, further studies need to be done to determine whether extraordinary LDLC lowering mediated by PCSK9 therapy may affect platelet function, leading to bruising-bleeding into the skin⇓.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.