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Statin desensitisation
Abstracts / Atherosclerosis Supplements 28 (2017) e1ee18
18/ An audit of the effectiveness of PCSK9 inhibition in reducing cholesterol in patients attending lipid clinics M. Kohli 1, Z. McMahon 1, R. Ramachandran 1, M.A. Crook 1, T.M. Reynolds 2, A.S. Wierzbicki 1 1
Dept Metabolic Medicine, Guy’s & St Thomas’ Hospitals, London, UK 2 Dept Chemical Pathology, Queen’s Hospital, Burton-on-Trent, UK Introduction: Evolocumab and alirocumab are monoclonal antibodies that inhibit PCSK-9 and reduce LDl-C. This audit assessed the effectiveness of PCSK9 inhibitor administration in patients attending lipid clinics at regional and local centres. Methods: Data from patients in treated in accord with NICE Technology Appraisals TA394 and TA396 was obtained from the lipid clinics at Guy’s & St. Thomas’ Hospitals and Queen’s Hospital, Burton-on-Trent. All patients had undergone a cardiovascular assessment and lipid measurements. Results: The 75 patients were aged 61.112.1 (averageSD) years and 33% were female. The indications for prescription were Familial Hypercholesterolaemia (75%); intolerance to >3 statins (67%), coronary heart disease with LDL-C>4 mmol/L (33%); multivascular disease and LDL-C>3.50 mmol/L (26%) and other (9%). Scripts were issued for Evolocumab (140mg; n¼52) and Alirocumab (n¼17; 12 receiving 150 mg and 5 75 mg respectively). Data was available for 43 patients who had completed more than 3 months treatment. Pre-treatment total cholesterol (TC) was 7.942.37 mmol/L, LDL-cholesterol (LDLC) 5.441.90 mmol/L, triglycerides (TG) median 1.89 (range 0.5-34.8) mmol/l and HDL-C 1.390.38 mmol/L. Post-treatment levels were TC 5.912.45 mmol/l, LDL-C 3.301.63 mmol/L, TG 1.67 (0.63-27.8) mmol/l and HDLC 1.420.4 mmol/L. The average reductions in lipids were a median 41 (range 90 to -35) %; (2.071.17 mmol/L) for LDL-C, and 27 (range 52 to -19)% (2.101.48 mmol/L) for TC respectively. Discontinuations were reported in 7 patients and 3 reported adverse effects (myalgia). A <25% LDL-C response was seen in 19% of patients. Conclusion: Treatment with PCSK9 inhibitor therapy is associated with a 41% reduction in LDL-C in qualifying patients who tolerate the medication but 19% fail to respond. http://dx.doi.org/10.1016/j.atherosclerosissup.2017.08.019 19/ Statin desensitisation A. Pottle, M. Barbir Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, London, UK
e11
Background: Statin therapy is the cornerstone for the prevention and treatment of cardiovascular disease (CVD) and is generally well tolerated. However statins do cause side effects such as muscle pain and rarely myositis and allergic reactions. A 46 year old male, hypertensive smoker was referred to the lipid clinic in 2002 following an NSTEMI and PCI to the RCA. His cholesterol was 9.0 mmol/L. He was initially treated with Atorvastatin 40 mg. He required further stenting to the RCA in 2007. In 2009 he developed a rash which was thought to be due to the statin. Simvastatin, Pravastatin and Rosuvastatin were tried but all resulted in a rash at low doses. He was subsequently treated with a fibrate and bile acid sequestrant but neither achieved target cholesterol levels. Lipoprotein apheresis was commended in 2009 which achieved a greater than 50% reduction in the cholesterol levels however he developed an allergic reaction to a whole blood treatment after 17 sessions and anaphylaxis on double filtration after 38 treatments. Apheresis was therefore stopped and the patient was referred to an allergy clinic in 2013. He was diagnosed with diabetes in 2011 and stopped smoking in 2014. Method: Skin testing for allergy to ACD-A, the anticoagulant used in some apheresis machines, was performed which resulted in flushing and chest pain. A diagnosis of idiopathic urticarial and angioedema was made. Statin desensitisation was recommended and subsequently carried out over a 2 week period in November 2014. Work up for this included an exercise stress test and cessation of beta blocker therapy. The patient attended the allergy clinic on a daily basis for two weeks and was treated with increasing doses of Rosuvastatin. Results: Desensitisation treatment was tolerated with only minor reactions e itchy palms and feet and slight swelling of the tongue. The patient was able to tolerated 0.3 mg Rosuvastatin at the end of the first week. At the end of the process the dose had been increased to 10 mg Rosuvastatin which has been maintained since. Total cholesterol (TC) in January 2015 was 6.6 mmol/L, TG 6.3 mmol/L; in July 2015 TC was 4.2 mmol/L, LDL 2.14 mmol/L and in June 2016 TC was 3.6 mmol/L, LDL 1.78 mmol/L. He developed atypical chest pain at the end of 2016 and repeat angiography was arranged. In October 2016 the TC was 5.2 mmol/L in the pre-admission clinic. He has recently undergone single coronary bypass grafting e LIMA to the LAD. Conclusion: Intolerance to statins is a frequent problem in clinical practice. The incidence of true statin allergy is unknown. This case study demonstrates not only the importance of treating raised cholesterol levels but also raises the possibility of desensitisation to statins. This will not be an option for all patients but is worth considering in selected cases. It may be necessary to consider the addition of a PCSK9 inhibitor in this patient in view of the progression of his disease and the sub-optimal lipid levels. http://dx.doi.org/10.1016/j.atherosclerosissup.2017.08.020
18/ An audit of the effectiveness of PCSK9 inhibition in reducing cholesterol in patients attending lipid clinics M. Kohli 1, Z. McMahon 1, R. Ramachandran 1, M.A. Crook 1, T.M. Reynolds 2, A.S. Wierzbicki 1 1
Dept Metabolic Medicine, Guy’s & St Thomas’ Hospitals, London, UK 2 Dept Chemical Pathology, Queen’s Hospital, Burton-on-Trent, UK Introduction: Evolocumab and alirocumab are monoclonal antibodies that inhibit PCSK-9 and reduce LDl-C. This audit assessed the effectiveness of PCSK9 inhibitor administration in patients attending lipid clinics at regional and local centres. Methods: Data from patients in treated in accord with NICE Technology Appraisals TA394 and TA396 was obtained from the lipid clinics at Guy’s & St. Thomas’ Hospitals and Queen’s Hospital, Burton-on-Trent. All patients had undergone a cardiovascular assessment and lipid measurements. Results: The 75 patients were aged 61.112.1 (averageSD) years and 33% were female. The indications for prescription were Familial Hypercholesterolaemia (75%); intolerance to >3 statins (67%), coronary heart disease with LDL-C>4 mmol/L (33%); multivascular disease and LDL-C>3.50 mmol/L (26%) and other (9%). Scripts were issued for Evolocumab (140mg; n¼52) and Alirocumab (n¼17; 12 receiving 150 mg and 5 75 mg respectively). Data was available for 43 patients who had completed more than 3 months treatment. Pre-treatment total cholesterol (TC) was 7.942.37 mmol/L, LDL-cholesterol (LDLC) 5.441.90 mmol/L, triglycerides (TG) median 1.89 (range 0.5-34.8) mmol/l and HDL-C 1.390.38 mmol/L. Post-treatment levels were TC 5.912.45 mmol/l, LDL-C 3.301.63 mmol/L, TG 1.67 (0.63-27.8) mmol/l and HDLC 1.420.4 mmol/L. The average reductions in lipids were a median 41 (range 90 to -35) %; (2.071.17 mmol/L) for LDL-C, and 27 (range 52 to -19)% (2.101.48 mmol/L) for TC respectively. Discontinuations were reported in 7 patients and 3 reported adverse effects (myalgia). A <25% LDL-C response was seen in 19% of patients. Conclusion: Treatment with PCSK9 inhibitor therapy is associated with a 41% reduction in LDL-C in qualifying patients who tolerate the medication but 19% fail to respond. http://dx.doi.org/10.1016/j.atherosclerosissup.2017.08.019 19/ Statin desensitisation A. Pottle, M. Barbir Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, London, UK
e11
Background: Statin therapy is the cornerstone for the prevention and treatment of cardiovascular disease (CVD) and is generally well tolerated. However statins do cause side effects such as muscle pain and rarely myositis and allergic reactions. A 46 year old male, hypertensive smoker was referred to the lipid clinic in 2002 following an NSTEMI and PCI to the RCA. His cholesterol was 9.0 mmol/L. He was initially treated with Atorvastatin 40 mg. He required further stenting to the RCA in 2007. In 2009 he developed a rash which was thought to be due to the statin. Simvastatin, Pravastatin and Rosuvastatin were tried but all resulted in a rash at low doses. He was subsequently treated with a fibrate and bile acid sequestrant but neither achieved target cholesterol levels. Lipoprotein apheresis was commended in 2009 which achieved a greater than 50% reduction in the cholesterol levels however he developed an allergic reaction to a whole blood treatment after 17 sessions and anaphylaxis on double filtration after 38 treatments. Apheresis was therefore stopped and the patient was referred to an allergy clinic in 2013. He was diagnosed with diabetes in 2011 and stopped smoking in 2014. Method: Skin testing for allergy to ACD-A, the anticoagulant used in some apheresis machines, was performed which resulted in flushing and chest pain. A diagnosis of idiopathic urticarial and angioedema was made. Statin desensitisation was recommended and subsequently carried out over a 2 week period in November 2014. Work up for this included an exercise stress test and cessation of beta blocker therapy. The patient attended the allergy clinic on a daily basis for two weeks and was treated with increasing doses of Rosuvastatin. Results: Desensitisation treatment was tolerated with only minor reactions e itchy palms and feet and slight swelling of the tongue. The patient was able to tolerated 0.3 mg Rosuvastatin at the end of the first week. At the end of the process the dose had been increased to 10 mg Rosuvastatin which has been maintained since. Total cholesterol (TC) in January 2015 was 6.6 mmol/L, TG 6.3 mmol/L; in July 2015 TC was 4.2 mmol/L, LDL 2.14 mmol/L and in June 2016 TC was 3.6 mmol/L, LDL 1.78 mmol/L. He developed atypical chest pain at the end of 2016 and repeat angiography was arranged. In October 2016 the TC was 5.2 mmol/L in the pre-admission clinic. He has recently undergone single coronary bypass grafting e LIMA to the LAD. Conclusion: Intolerance to statins is a frequent problem in clinical practice. The incidence of true statin allergy is unknown. This case study demonstrates not only the importance of treating raised cholesterol levels but also raises the possibility of desensitisation to statins. This will not be an option for all patients but is worth considering in selected cases. It may be necessary to consider the addition of a PCSK9 inhibitor in this patient in view of the progression of his disease and the sub-optimal lipid levels. http://dx.doi.org/10.1016/j.atherosclerosissup.2017.08.020