scholarly journals Atherosclerotic Cardiovascular Disease Risk Profile of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Gregory D Huhn ◽  
David J Shamblaw ◽  
Jean-Guy Baril ◽  
Priscilla Y Hsue ◽  
Brittany L Mills ◽  
...  

Abstract Background In human immunodeficiency virus (HIV) treatment, tenofovir alafenamide (TAF) is associated with greater increases in all fasting cholesterol subgroups compared with tenofovir disoproxil fumarate (TDF). Because lipid abnormalities may contribute to cardiovascular morbidity and mortality, cardiovascular risk assessment is integral to routine HIV care. This post hoc study evaluates the impact of lipid changes on predicted atherosclerotic cardiovascular disease (ASCVD) risk and statin eligibility in treatment-naive adults living with HIV treated with TAF or TDF. Methods Participants (N = 1744) were randomized (1:1) to initiate TAF or TDF, each coformulated with elvitegravir/cobicistat/emtricitabine (studies GS-US-292-0104 and GS-US-292-0111). Eligibility for statin therapy and estimated 10-year ASCVD risk among adults aged 40–79 years treated with TAF or TDF for 96 weeks (W96) were analyzed based on American College of Cardiology/American Heart Association Pooled Cohort Equations. Categorical shifts in 10-year ASCVD risk from <7.5% to ≥7.5% by W96 on TAF versus TDF were calculated. Results Participants initiating TAF versus TDF in the overall study population showed small but significant increases in median fasting lipid parameters at W96, including total cholesterol (191 vs 177 mg/dL; P < .001), low-density lipoprotein ([LDL] 119 vs 112 mg/dL; P < .001), and high-density lipoprotein ([HDL] 51 vs 48 mg/dL; P < .001), respectively. At baseline, 18% and 23% on TAF versus TDF had a 10-year ASCVD risk score ≥7.5%, with mean risk scores low overall for TAF versus TDF at baseline (4.9% vs 5.4%; P = .35) and W96 (6.1% vs 6.2%; P = .04). Increases in ASCVD risk from baseline to W96 were driven by both increasing age and changes in total cholesterol (TC) and HDL cholesterol. At W96, TC/HDL ratios (median) were 3.7 for both groups (P = .69). There was no difference between shifts in categorical risk for TAF versus TDF (9% vs 5%; P = .19). Eligibility for high-intensity statin therapy were similar for TAF versus TDF groups (19% vs 21%; P = .47). Conclusions Lipid changes with TAF as part of coformulated regimens do not substantively affect CVD risk profiles compared with TDF.

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Aliza Hussain ◽  
Christie M. Ballantyne

Although numerous trials have convincingly shown benefits of statin therapy in both primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), most showed relative risk reductions of 25–40%, and thus many individuals continue to have ASCVD events despite statin therapy. Substantial progress has been made in developing therapies that address the residual risk for ASCVD despite statin therapy. In this review, we summarize progress of currently available therapies along with therapies under development that further reduce low-density lipoprotein cholesterol and apolipoprotein B–containing lipoproteins, reduce lipoprotein(a), reduce ASCVD events in patients with high triglycerides, and directly target inflammation to reduce ASCVD risk. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S179-S179
Author(s):  
Patrick Mallon ◽  
Laurence Brunet ◽  
Jennifer S Fusco ◽  
Girish Prajapati ◽  
Andrew P Beyer ◽  
...  

Abstract Background People living with HIV (PLWH) have been observed to have twice the risk for atherosclerotic cardiovascular disease (ASCVD) as the general population. Increases in total and low-density lipoprotein cholesterol have been observed in PLWH switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Changes in regimens represent an opportunity for healthcare providers to assess health markers and address clinical concerns. Current guidelines recommend initiating statin therapy in individuals with an elevated ASCVD risk. Failure to initiate statins in PLWH with an ASCVD ≥ 7.5% at switch represents a missed opportunity for statin initiation. We aimed to assess missed opportunities for statin therapy in PLWH switching from TDF to TAF-containing antiretroviral therapy. Methods Adults switching from TDF to TAF with ≥1 lipid measure on TDF ≤6 months prior to switch and ≥1 lipid measure ≥7 days after switch to TAF were identified in the OPERA® cohort (84 clinics in 18 US states/territories). The proportion of PLWH prescribed statins pre- and post-switch was stratified by ASCVD risk (recommended threshold: ASCVD ≥ 7.5%). The ASCVD score was imputed using the limit value for components out of the pre-specified range. Results 6,451 PLWH switched from TDF to TAF (Figure 1); over 90% had ASCVD scores available pre- (n = 5801) and post-switch (n = 5881). High ASCVD risk (≥7.5%) was more likely post-switch (34.1) than pre-switch (32.1%, P = 0.02; Figure 2). Of those with high ASCVD risk, only 31% and 41% were prescribed statins pre- vs. post-switch, respectively (Figure 3), representing a considerable missed opportunity for ASCVD prevention, with 59% of PLWH with an elevated risk of ASCVD not prescribed statins after switch from TDF to TAF. ASCVD scores were imputed for those outside the range of the score (e.g., patients < 40 years of age) to evaluate the entire population. Comparable results were obtained when the analysis was limited to PLWH who did not require ASCVD score imputation. Conclusion Despite a switch from TDF to TAF being associated with higher numbers of PLWH with elevated ASCVD risk, most did not receive a statin, representing considerable missed opportunities to reduce risk of cardiovascular disease in this at-risk population. Disclosures All authors: No reported disclosures.


2021 ◽  
pp. 089719002199979
Author(s):  
Roshni P. Emmons ◽  
Nicholas V. Hastain ◽  
Todd A. Miano ◽  
Jason J. Schafer

Background: Recent studies suggest that statins are underprescribed in patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD), but none have assessed if eligible patients receive the correct statin and intensity compared to uninfected controls. Objectives: The primary objective was to determine whether statin-eligible PLWH are less likely to receive appropriate statin therapy compared to patients without HIV. Methods: This retrospective study evaluated statin eligibility and prescribing among patients in both an HIV and internal medicine clinic at an urban, academic medical center from June-September 2018 using the American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk. Patients were assessed for eligibility and actual treatment with appropriate statin therapy. Characteristics of patients appropriately and not appropriately treated were compared with chi-square testing and predictors for receiving appropriate statin therapy were determined with logistic regression. Results: A total of 221/300 study subjects were statin-eligible. Fewer statin-eligible PLWH were receiving the correct statin intensity for their risk benefit group versus the uninfected control group (30.2% vs 67.0%, p < 0.001). In the multivariable logistic regression analysis, PLWH were significantly less likely to receive appropriate statin therapy, while those with polypharmacy were more likely to receive appropriate statin therapy. Conclusion: Our study reveals that PLWH may be at a disadvantage in receiving appropriate statin therapy for ASCVD risk reduction. This is important given the heightened risk for ASCVD in this population, and strategies that address this gap in care should be explored.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hiroaki Ikezaki ◽  
Elise Lim ◽  
Ching-Ti Liu ◽  
L Adrienne Cupples ◽  
Bela F Asztalos ◽  
...  

Introduction: Elevated plasma low-density lipoprotein cholesterol (LDL-C), small-dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), triglycerides (TG), remnant-lipoprotein cholesterol (RLP-C), triglyceride-rich lipoprotein-C (TRL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein(a) [Lp(a)] levels have been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, these parameters have not been included in risk factors for ASCVD in the pooled cohort equation (PCE). Hypothesis: We assessed the hypothesis that these atherogenic lipoprotein parameters add significant information for ASCVD risk prediction in the Framingham Offspring Study. Methods: We evaluated 3,147 subjects without ASCVD at baseline (mean age 58 years) from participants of Framingham Offspring Study cycle 6, 677 (21.5%) of whom developed inclusive ASCVD over 16 years. Biomarkers of risk were assessed in frozen plasma samples. Total cholesterol, TG, HDL-C, direct LDL-C, sdLDL-C, LDL-TG, Lp(a), RLP-C, and TRL-C were measured by standardized automated analysis. Calculated LDL-C, large buoyant low-density lipoprotein cholesterol (lbLDL-C), VLDL-C, and non-HDL-C values were calculated. Data were analyzed using Cox proportional regression analysis and net reclassification improvement (NRI) analysis to identify parameters significantly associated with the incidence of ASCVD after controlling for standard ASCVD risk factor and applying the PCE model. Results: All specialized lipoprotein parameters were significant ASCVD risk factors on univariate analysis, but only direct LDL-C, sdLDL-C, and Lp(a) were significant on multivariate analysis with standard risk factors in the model. Together these parameters significantly improved the model c statistic (0.716 vs 0.732, P < 0.05) and net risk reclassification (mean NRI 0.104, P < 0.01) for ASCVD risk. Using the ASCVD risk pooled cohort equation, sdLDL-C, TG, LDL-TG, LDL-C, RLP-C, and TRL-C individually added significant information, but no other parameter added significant information with sdLDL-C (hazard ratio 1.30 for 75th vs 25th percentile, P < 0.0001) in the model. Conclusions: In multivariate analysis, sdLDL-C, direct LDL-C, and Lp(a) contributed significantly to ASCVD risk, but only sdLDL-C added significant risk information to the PCE model, indicating that sdLDL-C may be the most atherogenic lipoprotein particle.


2020 ◽  
Vol 26 (10) ◽  
pp. 1196-1224 ◽  
Author(s):  
Yehuda Handelsman ◽  
Paul S. Jellinger ◽  
Chris K. Guerin ◽  
Zachary T. Bloomgarden ◽  
Eliot A. Brinton ◽  
...  

The treatment of lipid disorders begins with lifestyle therapy to improve nutrition, physical activity, weight, and other factors that affect lipids. Secondary causes of lipid disorders should be addressed, and pharmacologic therapy initiated based on a patient’s risk for atherosclerotic cardiovascular disease (ASCVD). Patients at extreme ASCVD risk should be treated with high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol (LDL-C) of <55 mg/dL, and those at very high ASCVD risk should be treated to achieve LDL-C <70 mg/dL. Treatment for moderate and high ASCVD risk patients may begin with a moderate-intensity statin to achieve an LDL-C <100 mg/dL, while the LDL-C goal is <130 mg/dL for those at low risk. In all cases, treatment should be intensified, including the addition of other LDL-C-lowering agents (i.e., proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, colesevelam, or bempedoic acid) as needed to achieve treatment goals. When targeting triglyceride levels, the desirable goal is <150 mg/dL. Statin therapy should be combined with a fibrate, prescription-grade omega-3 fatty acid, and/or niacin to reduce triglycerides in all patients with triglycerides ≥500 mg/dL, and icosapent ethyl should be added to a statin in any patient with established ASCVD or diabetes with ≥2 ASCVD risk factors and triglycerides between 135 and 499 mg/dL to prevent ASCVD events. Management of additional risk factors such as elevated lipoprotein(a) and statin intolerance is also described. Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; ACS = acute coronary syndrome; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BA = bempedoic acid; CAC = coronary artery calcium; CHD = coronary heart disease; CK = creatine kinase; CKD = chronic kidney disease; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FCS = familial chylomicronemia syndrome; FDA = United States Food and Drug Administration; FOURIER = Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; HDL-C = high-density lipoprotein cholesterol; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hyper-cholesterolemia; hsCRP = high-sensitivity C reactive protein; IDL = intermediate-density lipoproteins; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; IPE = icosapent ethyl; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein a; MACE = major adverse cardiovascular events; MI = myocardial infarction; OSA = obstructive sleep apnea; PCSK9 = proprotein convertase subtilisin/kexin type 9; REDUCE-IT = Reduction of Cardiovascular Events with EPA-Intervention Trial; UKPDS = United Kingdom Prospective Diabetes Study; U.S. = United States; VLDL = very-low-density lipoproteins


2018 ◽  
Vol 47 (1) ◽  
pp. 265-270 ◽  
Author(s):  
Sinan Sarsam ◽  
Abeer Berry ◽  
George Degheim ◽  
Robby Singh ◽  
Marcel Zughaib

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.


2018 ◽  
Vol 7 (3) ◽  
pp. e000071
Author(s):  
Smita Bakhai ◽  
Aishwarya Bhardwaj ◽  
Parteet Sandhu ◽  
Jessica L. Reynolds

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines focus on atherosclerotic cardiovascular disease (ASCVD) risk reduction, using a Pooled Cohort Equation to calculate a patient’s 10-year risk score, which is used to guide initiation of statin therapy. We identified a gap of evidence-based treatment for hyperlipidaemia in the Internal Medicine Clinic. Therefore, the aim of this study was to increase calculation of ASCVD risk scores in patients between the ages of 40 and 75 years from a baseline rate of less than 1% to 10%, within 12 months, for primary prevention of ASCVD. Root cause analysis was performed to identify materials/methods, provider and patient-related barriers. Plan-Do-Study-Act cycles included: (1) creation of customised workflow in electronic health records for documentation of calculated ASCVD risk score; (2) physician education regarding guidelines and electronic health record workflow; (3) refresher training for residents and a chart alert and (4) patient education and physician reminders. The outcome measures were ASCVD risk score completion rate and percentage of new prescriptions for statin therapy. Process measures included lipid profile order and completion rates. Increase in patient wait time, and blood test and medications costs were the balanced measures. We used weekly statistical process control charts for data analysis. The average ASCVD risk completion rate was 14.2%. The mean ASCVD risk completion rate was 4.0%. In eligible patients, the average lipid profile completion rate was 18%. ASCVD risk score completion rate was 33% 1-year postproject period. A team-based approach led to a sustainable increase in ASCVD risk score completion rate. Lack of automation in ASCVD risk score calculation and physician prompts in electronic health records were identified as major barriers. Furthermore, the team identified multiple barriers to lipid blood tests and treatment of increased ASCVD risk based on ACC/AHA guidelines.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S179-S180
Author(s):  
Jason J Schafer ◽  
Roshni Patel ◽  
Nicholas V Hastain ◽  
Todd Miano

Abstract Background Patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD) should receive risk reduction interventions recommended in current guidelines. This includes routine ASCVD risk assessments and when eligible, statins selected and dosed to achieve appropriate low-density lipoprotein cholesterol (LDL-C) reduction. Recent studies suggest that statins are underprescribed in PLWH, but none have assessed if eligible patients receive the correct statin intensity compared with uninfected controls. Methods This retrospective study evaluated statin eligibility and prescribing among consecutive patients in an HIV clinic and an internal medicine clinic at an urban, academic medical center from June-September 2018. To determine statin eligibility, the 2013 American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk was used. Patients aged 40–75 that had a lipid panel obtained within the last year were included. All patients were assessed to determine eligibility for and actual treatment with appropriate statin therapy. Characteristics of patients correctly and incorrectly treated with statins were compared with chi-square testing and predictors for receiving correct statin therapy were determined with logistic multivariable regression. Results A total of 221/300 study subjects were statin eligible (Table 1). While many eligible PLWH were receiving a statin (54/106), considerably fewer were on the correct statin intensity for their benefit group (33/106). In the univariate analysis (Table 2), correctly treated patients were less likely to be PLWH or female, and were more likely to have polypharmacy and hypertension. In the multivariable logistic regression analysis (Table 3), PLWH (OR 0.26, CI95 0.12–0.57)) were significantly less likely to receive correct statin therapy, while those with concomitant polypharmacy were significantly more likely to receive correct statin therapy (OR 5.52, CI95 1.94, 15.69). Conclusion This study reveals that PLWH may be at a substantial disadvantage in terms of receiving correct statin therapy for ASCVD risk reduction. This finding may be particularly important given the heightened risk for ASCVD in this patient population. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Jason J Schafer ◽  
Kaitlin N Sassa ◽  
Jaclyn R O’Connor ◽  
Ayako Shimada ◽  
Scott W Keith ◽  
...  

Abstract Background Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) can improve renal function and bone mineral density in people with human immunodeficiency virus (PWH). The switch can also negatively influence cholesterol, but changes in body mass index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk are unknown. Methods This retrospective observational study evaluated BMI and ASCVD risk score changes in virologically suppressed PWH who switched from TDF to TAF without switching other ART regimen components. Adults on TDF for ≥1 year with 2 consecutive HIV ribonucleic acid values &lt;200 copies/mL before a TAF switch were included. Body weight, BMI, cholesterol, and ASCVD risk score were collected for the year before and after the switch. Pre- and postswitch values were compared with the Wilcoxon signed-rank test. Changes in BMI and ASCVD scores were modeled using generalized estimating equations regression. Results One hundred ten patients were included. In unadjusted analyses, there were significant increases in weight, BMI, total cholesterol, LDL, HDL, and ASCVD risk score in the year after switching from TDF to TAF (each P ≤ .01). In regression models, switching from TDF to TAF was associated with a 0.45 kg/m2 increase in BMI (95% confidence interval [CI], 0.14–0.76) and a 13% increase in ASCVD risk score (95% CI, 4%–23%). Conclusions We observed significant BMI and ASCVD score increases in PWH 1 year after switching from TDF to TAF. The mechanism of changes is unclear and requires additional study.


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