scholarly journals PCSK9 Inhibitors in a Statin-Intolerant Transgender Man With Heterozygous Familial Hypercholesterolemia: A Case Report

2019 ◽  
Vol 3 (8) ◽  
pp. 1461-1464 ◽  
Author(s):  
Carlo Pirazzi ◽  
Federica Tavaglione ◽  
Åsa Tivesten ◽  
Stefano Romeo
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Genetic Diagnosis ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Lipoprotein Cholesterol ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Lipid Clinic ◽  
High Doses

Abstract In female-to-male transgender individuals, testosterone is used to induce masculinization. Sex steroid therapy may increase circulating triglyceride and low-density lipoprotein cholesterol (LDL-C) levels and may decrease high-density lipoprotein cholesterol (HDL-C) levels, resulting in a more atherogenic lipid profile. These potentially adverse effects of androgen therapy may be exacerbated by the presence of familial hypercholesterolemia (FH). We describe the case of a transgender man with genetically diagnosed FH who was intolerant to statins and was started on a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to control his lipoproteins more effectively. The 35-year-old female-to-male transgender individual was referred to our center with a history of elevated LDL-C levels. Despite treatment with high doses of high-potency statins and ezetimibe, he had never achieved a sustained reduction in LDL-C; his levels of LDL-C were fluctuating between 170 and 344 mg/dL (4.4 and 8.9 mmol/L). Moreover, he developed side effects to statins in the form of myalgia and discontinued statin treatment. At the Sahlgrenska Lipid Clinic, a genetic diagnosis of heterozygous FH was established, and PCSK9 inhibitor therapy was started. The patient’s LDL-C level has been reduced by approximately 40% for 23 months, and no adverse events have been reported.

scholarly journals Improving Familial Hypercholesterolemia Index Case Detection: Sequential Active Screening from Centralized Analytical Data

2021 ◽  
Vol 10 (4) ◽  
pp. 749
Author(s):  
Fernando Sabatel-Pérez ◽  
Joaquín Sánchez-Prieto ◽  
Víctor Manuel Becerra-Muñoz ◽  
Juan Horacio Alonso-Briales ◽  
Pedro Mata ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Diagnostic Yield ◽  
Low Density Lipoprotein ◽  
Analytical Data ◽  
Genetic Diagnosis ◽  
Density Lipoprotein ◽  
Screening Strategy ◽  
Cascade Screening ◽  
Active Screening ◽  
Lipid Clinic

The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on centralized analytical data. From 2016 to 2019, a clinical screening of FH was performed on 469 subjects with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥220 mg/dL), applying the Dutch Lipid Clinic Network (DLCN) criteria. All patients with a DLCN ≥ 6 were genetically tested, as were 10 patients with a DLCN of 3–5 points to compare the diagnostic yield between the two groups. FH was genetically confirmed in 57 of the 84 patients with DLCN ≥ 6, with a genetic diagnosis rate of 67.9% and an overall prevalence of 12.2% (95% confidence interval: 9.3% to 15.5%). Before inclusion in the study, only 36.8% (n = 21) of the patients with the FH mutation had been clinically diagnosed with FH; after genetic screening, FH detection increased 2.3-fold (p < 0.001). The sequential, active screening strategy for FH-IC increases the diagnostic yield for FH with a rational use of the available resources, which may facilitate the implementation of FH universal and family-based cascade screening strategies.

scholarly journals Real-world use of PCSK9 inhibitors: A single-center experience

2018 ◽  
Vol 47 (1) ◽  
pp. 265-270 ◽  
Author(s):  
Sinan Sarsam ◽  
Abeer Berry ◽  
George Degheim ◽  
Robby Singh ◽  
Marcel Zughaib
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Profile ◽  
Real World ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
The Impact

Objective Hyperlipidemia is an important risk factor for atherosclerotic cardiovascular disease. Many patients are intolerant to or have limited benefit from statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved for treating hyperlipidemia in these patients. We sought to investigate the impact of these medications in a real-world cardiology practice. Methods This was a retrospective study of 17 patients with either heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) levels above the treatment target despite maximally tolerated statins. Baseline lipid profile was compared with a repeat lipid profile obtained 4 to 6 weeks after initiating treatment with a PCSK9 inhibitor. Results The average duration of PCSK9 inhibitor treatment was 10.7 months. Lipid profile comparison showed that total cholesterol decreased from 243 ± 72 to 148 ± 39 (mg/dL) (39% reduction), triglycerides decreased from 185 ± 86 to 149 ± 62 (mg/dL) (19.5% reduction), high-density lipoprotein cholesterol increased from 56 ± 20 to 62 ± 26 (mg/dL) (10.7% increase), and LDL-C decreased from 154 ± 30 to 57 ± 32 (mg/dL) (63% reduction) from baseline. Conclusions PCSK9 inhibitors as add-on therapy to maximally tolerated statins resulted in an approximately 63% reduction in LDL-C.

scholarly journals The Prevalence of Heterozygous Familial Hypercholesterolemia in Selected Regions of the Russian Federation: The FH-ESSE-RF Study

2021 ◽  
Vol 11 (6) ◽  
pp. 464
Author(s):  
Alexey N. Meshkov ◽  
Alexandra I. Ershova ◽  
Anna V. Kiseleva ◽  
Svetlana A. Shalnova ◽  
Oxana M. Drapkina ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Russian Federation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
Pcsk9 Inhibitor ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Lipid Clinic ◽  
The Russian Federation ◽  
Artery Disease

Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic conditions but remains substantially underdiagnosed. The aim of our study was to investigate the prevalence of HeFH in the population of 11 different regions of Russia. Individuals were selected from the Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study. All participants who had low-density lipoprotein cholesterol (LDL-C) higher than 4.9 mmol/L, or LDL-C lower than 4.9 mmol/L, but had statin therapy, were additionally examined by FH experts. FH was diagnosed using the Dutch Lipid Clinic Network criteria, incorporating genetic testing. HeFH prevalence was assessed for 18,142 participants. The prevalence of patients with definite or probable HeFH combined was 0.58% (1 in 173). A total of 16.1% of patients with definite or probable HeFH had tendon xanthomas; 36.2% had mutations in one of the three genes; 45.6% of FH patients had coronary artery disease; 63% of HeFH patients received statins; one patient received an additional PCSK9 inhibitor; no patients received ezetimibe. Only 3% of patients reached the LDL-C goal based on 2019 ESC/EAS guidelines. Underdiagnosis and undertreatment of FH in Russia underline the need for the intensification of FH detection with early and aggressive cholesterol-lowering treatment.

scholarly journals Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies

2020 ◽  
pp. 204748732091580 ◽  
Author(s):  
Tahir Mahmood ◽  
Jessica Minnier ◽  
Matthew K Ito ◽  
Qian H Li ◽  
Andrew Koren ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Pooled Analysis ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Phase 3 ◽  
Pcsk9 Inhibitor

Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors consistently reduce low-density lipoprotein cholesterol (LDL-C) by 50–60% and lipoprotein(a) (Lp(a)) by 20–30%, but the mechanism of Lp(a) lowering remains unclear. If Lp(a) is cleared by the LDL receptor, similar to LDL-C, then one would expect PCSK9 inhibition to induce a concordant LDL-C/Lp(a) response in an approximately 2:1 ratio. We aim to determine the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab. Methods This is a post hoc, pooled analysis of 10 randomized controlled trials from the ODYSSEY Phase 3 clinical trial program for alirocumab. Patients enrolled in the trials were high cardiovascular risk and/or with heterozygous familial hypercholesterolemia. The primary end point was prevalence of discordant LDL-C/Lp(a) response to alirocumab at 24 weeks. Discordant response was defined as LDL-C reduction >35% and Lp(a) reduction ≤10%, or LDL-C reduction ≤35% and Lp(a) reduction >10%. Results Of the 1709 patients in the pooled study cohort, 62.4% were male, and the mean age was 59.2 (SD: 11.0) years. Baseline mean LDL-C was 126.5 (SD: 46.3) mg/dL and baseline median Lp(a) was 46.9 (interquartile range: 21.8-89.0) mg/dL. Total prevalence of discordant LDL-C/Lp(a) response was 21.5% (12.6% with LDL-C >35% reduction and Lp(a) ≤10% reduction; 8.9% with LDL-C ≤35% reduction and Lp(a) >10% reduction). Baseline Lp(a) and familial hypercholesterolemia status did not affect discordance. Conclusion A high prevalence of discordant LDL-C/Lp(a) response was observed with alirocumab, further suggesting that PCSK9 inhibitor therapy with alirocumab reduces plasma Lp(a) through alternative pathways to LDL receptor clearance.

scholarly journals Risk of Recurrent Coronary Events in Patients With Familial Hypercholesterolemia; A 10-Years Prospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Kjell-Erik Arnesen ◽  
Ann Vinh Phung ◽  
Karoline Randsborg ◽  
Irene Mork ◽  
Marlene Thorvall ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Term Treatment ◽  
Lipid Lowering ◽  
Treat To Target ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Long Term Treatment

Background and Aim: Real world evidence on long term treatment of patients with familial hypercholesterolemia (FH) is important. We studied the effects of intensive lipid lowering medication (LLM) and optimized lifestyle in the study TTTFH–Treat To Target FH.Materials and Methods: Adults with a first known total cholesterol of mean (95% CI) 9.8 mmol/L (9.5, 10.1) were included consecutively in their routine consultation during 2006. Of the patients 86.4% had a pathogenic FH-mutation and the remaining were clinically diagnosed. We included 357 patients and 279 met for follow-up after median 10.0 (min 8.1, max 12.8) years.Results: Mean (95% CI) low density lipoprotein (LDL-C) was reduced from 3.9 (3.8, 4.1) to 3.0 (2.9, 3.2). More men than women used high intensity statin treatment, 85.2 and 60.8%, respectively. Women (n = 129) had higher LDL-C; 3.3 mmol/L (3.0, 3.5), than men; (n = 144) 2.8 mmol/L (2.6, 3.0), p = 0.004. Add-on PCSK9 inhibitors (n = 25) reduced mean LDL-C to 2.0 (1.4, 2.6) mmol/L. At enrollment 57 patients (20.4%) had established atherosclerotic cardiovascular disease (ASCVD), and 46 (80.4%) of them experienced a new event during the study period. Similarly, 222 (79.6%) patients had no detectable ASCVD at enrollment, and 29 of them (13.1%) experienced a first-time event during the study period.Conclusion: A mean LDL-C of 3.0 mmol/L was achievable in FH, treated intensively at a specialized clinic with few users of PCSK9 inhibitors. LDL-C was higher (0.5 mmol/L) in women than in men. In patients with ASCVD at enrollment, most (80.7%) experienced a new ASCVD event in the study period. The FH patients in primary prevention had more moderate CV risk, 13% in ten years.

scholarly journals Use of PCSK9 Inhibitor in a Mexican Boy with Compound Heterozygous Familial Hypercholesterolemia: A Case Report

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
José Juan Ceballos-Macías ◽  
Ramón Madriz-Prado ◽  
Norma Alejandra Vázquez Cárdenas ◽  
Carlos Aguilar-Salinas ◽  
Maria Teresa Tusié-Luna ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Compound Heterozygous ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Functional Studies ◽  
Dietary Plan

Abstract We report on the case of an 8-year-old Mexican male, with a 3-year-old clinical diagnosis of familial hypercholesterolemia, and the difficulties encountered in his treatment while in our care. His treatment started with a regimen consisting of ezetimibe/simvastatin, cholestyramine, and a dietary plan of 1600 calories, with a limited intake of 200 mg of cholesterol per day. Problems arose when the patient’s low-density lipoprotein cholesterol (LDL) levels did not meet ideal targets, which prompted the use of LDL cholesterol apheresis (not available in Mexico) for 6 months. As a last resort, PCSK9 inhibitors were administered but the LDL levels remained in the 600 mg/dL range. AmbryGenetics conducted a genetic test employing the Sanger method. The results suggested that there were 2 different mutations for each allele of the same LDL receptor gene (c.249delTinsGG and p.(Cys109Arg)), located in exons 3 and 4, respectively. We identified compound heterozygous mutations in our index case, with him having both the p.C109R mutation (from the maternal lineage), as well as a c.249delTinsGG mutation (from the paternal lineage). The p.C109R mutation has been previously reported, not only in Mexico, but in European regions (Germany, Czech Republic, Ireland, Italy) as well. Functional studies indicated a residual enzymatic activity of 15% to 30% for heterozygotes. To date, the variant c.249delTinsGG has not been reported. This case study illustrates the fact that in Mexico there are limited options available for treatment in such a scenario. As medical professionals, we are limited by the tools at our disposal.

scholarly journals Adoption of PCSK9 Inhibitors Among Patients With Atherosclerotic Disease

2021 ◽  
Author(s):  
Elias J. Dayoub ◽  
Lauren A. Eberly ◽  
Ashwin S. Nathan ◽  
Sameed Ahmed M. Khatana ◽  
Srinath Adusumalli ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Number Of Patients

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors represent a promising class of lipid‐lowering therapy, although their use has been limited by cost concerns. Methods and Results A retrospective cohort study was conducted using a nationwide commercial claims database comprising patients with atherosclerotic cardiovascular disease (ASCVD), aged 18 to 64 years. We identified the number of patients with ASCVD started on a PCSK9 inhibitor from the dates of US Food and Drug Administration approval in quarter 3 2015 through quarter 2 2019. Secondary objectives identified the proportions of patients started on a PCSK9 inhibitor in various ASCVD risk groups based on statin use and baseline low‐density lipoprotein cholesterol. We identified 126 419 patients with ASCVD on either PCSK9 inhibitor or statin therapy. Among these patients, 1168 (0.9%) filled a prescription for a PCSK9 inhibitor. The number of patients initiating a PCSK9 inhibitor increased from 2 patients in quarter 3 2015 to 119 patients in quarter 2 2019, corresponding to an increase from 0.05% to 2.5% of patients with ASCVD already on statins who started PCSK9 inhibitor therapy. Of patients with ASCVD with high adherence to a high‐intensity statin, 13 643 had low‐density lipoprotein cholesterol ≥70 mg/dL, and in this subgroup, 119 (0.9%) patients initiated a PCSK9 inhibitor. Conclusions Few patients started PCSK9 inhibitors from 2015 through mid‐2019, despite increasing trial evidence of efficacy, guidelines recommending PCSK9 inhibitors in high‐risk patients with ASCVD, and price reductions during this period. The magnitude of price reductions may not yet be sufficient to influence use management strategies aimed to limit PCSK9 inhibitor use.

Role of PCSK9 Inhibitors in High Risk Patients with Dyslipidemia: Focus on Familial Hypercholesterolemia

2019 ◽  
Vol 24 (31) ◽  
pp. 3647-3653 ◽  
Author(s):  
Vasilios Papademetriou ◽  
Konstantinos Stavropoulos ◽  
Christodoulos Papadopoulos ◽  
Konstantinos Koutsampasopoulos ◽  
Kiriakos Dimitriadis ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Population Characteristics ◽  
Lipid Lowering ◽  
Pcsk9 Inhibitors ◽  
Autosomal Dominant Disorder ◽  
Pcsk9 Inhibitor ◽  
Cv Disease ◽  
The Impact

Background: Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that is characterized by substantially increased Low-Density Lipoprotein Cholesterol (LDL-C) levels. Patients with FH have a significantly higher risk for Cardiovascular (CV) events, and the timely reduction of LDL-C is of paramount importance to ameliorate the risk for CV disease. Among the available lipid-lowering therapies, the novel Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors have emerged as a very promising class of drugs for the management of such patients. Objective: The purpose of this review is to present available data on the efficacy and safety of the two available PCSK9 inhibitors in patients with FH, and importantly to discuss potential differences between the two drugs. Methods: A comprehensive literature search was performed to identify available data from clinical studies evaluating the impact of evolocumab or alirocumab on lipid and CV parameters in patients with FH. Results: Several studies have assessed the lipid-lowering profile of PCSK9 inhibitors in patients with FH. Both evolocumab and alirocumab were found to significantly reduce LDL-C by more than 50-60% in FH patients. Furthermore, data also support a lower rate of lipid apheresis in FH patients receiving a PCSK9 inhibitor. In terms of CV outcomes, both drugs were found to possess CV-ameliorating effects of the same extent in patients with CV disease. However, alirocumab reduced all-cause mortality, as well, a finding not observed with evolocumab. Several differences in the study population characteristics might explain this and other mild differences observed in the CV trials of these drugs. Conclusion: Available evidence suggests similar potency of alirocumab and evolocumab in reducing lipids and CV events.

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