Lipid-lowering therapies in peripheral artery disease: A review

2020 ◽  
pp. 1358863X2095709
Author(s):  
Nedaa Skeik ◽  
Meagan E Nowariak ◽  
Jenna E Smith ◽  
Jason Q Alexander ◽  
Jesse M Manunga ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Lipid Lowering ◽  
Extensive Literature ◽  
Lipid Lowering Therapy ◽  
Current Guideline ◽  
Peripheral Artery ◽  
Pcsk9 Inhibitors ◽  
Risk Factor Modification ◽  
The Us ◽  
Artery Disease

Peripheral artery disease (PAD) is estimated to affect approximately 8.5 million individuals in the US above the age of 40, and is associated with significant morbidity, mortality, and impairment. Despite the significant adverse limb and cardiovascular (CV) outcomes seen in patients with PAD, there is typically less attention paid to risk factor modification relative to other atherosclerotic diseases such as coronary artery disease (CAD) or stroke. In the current literature, statins have been shown to reduce mortality, major adverse CV events, major adverse limb events, and improve symptomatic outcomes in patients with PAD. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are emerging as an additional lipid-lowering therapy for patients with PAD. However, despite current guideline recommendations based on growing evidence, PAD patients are consistently undertreated with lipid-lowering therapies. We provide an extensive literature review and evidence-based recommendations for the use of statins and PCSK9 inhibitors in patients with PAD.

P938Extensive formation of atherosclerotic cardiovascular disease in subjects with severe familial hypercholesterolemia defined by the international atherosclerosis society criteria

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Funabashi ◽  
Y Kataoka ◽  
M Harada-Shiba ◽  
M Hori ◽  
T Doi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Peripheral Artery Disease ◽  
Cardiac Death ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Lowering Therapy ◽  
Artery Disease

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia (FH)” as a FH phenotype with the highest cardiovascular risk. Coronary artery disease (CAD) represents a major atherosclerotic change in FH patients. Given their higher LDL-C level and atherogenic clinical features, more extensive formation of atherosclerosis cardiovascular disease including not only CAD but stroke/peripheral artery disease (PAD) may more frequently occur in severe FH. Methods 481 clinically-diagnosed heterozygous FH subjects were analyzed. Severe FH was defined as untreated LDL-C>10.3 mmol/l, LDL-C>8.0 mmol/l+ 1 high-risk feature, LDL-C>4.9 mmol/l + 2 high-risk features or presence of clinical ASCVD according to IAS proposed statement. Cardiac (cardiac death and ACS) and non-cardiac (stroke and peripheral artery disease) events were compared in severe and non-severe FH subjects. Results Severe FH was identified in 50.1% of study subjects. They exhibit increased levels of LDL-C and Lipoprotein (a) with a higher frequency of LDLR mutation. Furthermore, a proportion of %LDL-C reduction>50% was greater in severe FH under more lipid-lowering therapy (Table). However, during the observational period (median=6.3 years), severe FH was associated with a 5.9-fold (95% CI, 2.05–25.2; p=0.004) and 5.8-fold (95% CI, 2.02–24.7; p=0.004) greater likelihood of experiencing cardiac-death/ACS and stroke/PAD, respectively (picture). Multivariate analysis demonstrated severe FH as an independent predictor of both cardiac-death/ACS (hazard ratio=3.39, 95% CI=1.12–14.7, p=0.02) and stroke/PAD (hazard ratio=3.38, 95% CI=1.16–14.3, p=0.02) events. Clinical characteristics of severe FH Non-severe FH Severe FH P-value Baseline LDL-C (mmol/l) 5.3±1.5 6.6±2.0 <0.0001 Lp(a) (mg/dl) 15 [8–28] 21 [10–49] <0.0001 LDLR mutation (%) 49.6% 58.9% 0.00398 On-treatment LDL-C (mmol) 133 [106–165] 135 [103–169] 0.9856 %LDL-C reduction>50% 21.3% 49.8% <0.0001 High-intensity statin (%) 13.3% 42.3% <0.0001 PCSK9 inhibitor (%) 6.3% 21.2% <0.0001 Clinical outcome Conclusions Severe FH subjects exhibit substantial atherosclerotic risks for coronary, carotid and peripheral arteries despite lipid lowering therapy. Our finding underscore the screening of systemic arteries and the adoption of further stringent lipid management in severe FH patients.

scholarly journals Efficacy and Safety of Vorapaxar by Intensity of Background Lipid‐Lowering Therapy in Patients With Peripheral Artery Disease: Insights From the TRA2P‐TIMI 50 Trial

2021 ◽  
Author(s):  
Ian C. Gilchrist ◽  
David A. Morrow ◽  
Mark A. Creager ◽  
Jeffrey W. Olin ◽  
Benjamin M. Scirica ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Peripheral Artery Disease ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Artery Disease ◽  
Ischemic Events ◽  
Statin Use

Background Patients with peripheral artery disease are at increased risk of both major adverse cardiovascular events (MACEs) and limb events. The pathobiology of limb events is likely multifactorial. Observational studies suggest a benefit of statin therapy for reducing the risk of limb ischemic events while randomized trials demonstrate a benefit with more potent antithrombotic therapies, particularly those targeting thrombin. Whether the effects of these therapeutic pathways are independent and complementary is not known. Methods and Results The TRA 2°P‐TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50) trial demonstrated that vorapaxar significantly reduced MACEs and limb events. The purpose of the current analysis was to evaluate the association of statin use and intensity and the occurrence of MACEs and limb events in 5845 patients with symptomatic peripheral artery disease randomized in TRA 2°P‐TIMI 50 and then to understand whether statin use modified the benefits of vorapaxar for MACEs or limb ischemic events. We found that statin therapy was associated with significantly lower risk of MACEs (hazard ratio [HR], 0.77; 95% CI, 0.66–0.89; P <0.001) and limb ischemic events (HR, 0.73; 95% CI, 0.60–0.89; P =0.002). The benefit of vorapaxar for reducing MACEs and limb events was consistent regardless of background statin ( P ‐interaction=0.715 and 0.073, respectively). Event rates were lowest in patients receiving the combination of statin therapy and vorapaxar. Conclusions In conclusion, statin use and intensity is associated with significantly lower rates of MACEs and limb ischemic events. Thrombin inhibition with vorapaxar is effective regardless of background statin therapy. These results suggest that targeting both lipid and thrombotic risk in peripheral artery disease is necessary in order to optimize outcomes.

A systematic review and meta-analysis of the role of statins and their intensity in peripheral artery disease

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Sagris ◽  
J Katsaros ◽  
S Giannopoulos ◽  
DG Kokkinidis
Keyword(s):  
Systematic Review ◽  
Peripheral Artery Disease ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Free Survival ◽  
Low Intensity ◽  
All Cause Mortality ◽  
Artery Disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Peripheral artery disease (PAD) affects more than eight million Americans. However, several studies have shown that those patients are often undertreated, and that statin utilization is suboptimal.  American Heart Association guidelines highlight statins as the first-line lipid-lowering therapy to treat patients with PAD. Our objective with this meta-analysis was to further explore the impact of statins on PAD outcomes and examine whether the actual statin (high vs low intensity) dose impacts outcomes. Methods We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented a comparison of statins vs no statins for PAD patients or compared high vs low intensity statins and provided outcomes with hazard ratio was considered as potentially eligible. The Medline (PubMed) database was searched up to August 30, 2020. A random effects meta-analysis was performed. Results In total, 38 studies and 275,670 patients were included in this meta-analysis. In total, 136,025 (49.34%) were on statins vs 139,645 (50.66%) who were not on statins. Statins had an association with a reduction in all cause-mortality by 42% (HR:0.58, 95% CI: 0.49-0.67, I2= 96.26%) and cardiovascular death by 43% (HR:0.57, 95% CI: 0.40-0.74, I2= 80.39%). Statins use was associated with an increase in amputation-free survival by 56% (HR:0.44, 95% CI: 0.30-0.58, I2 = 15%). The risk of amputation and loss of patency was reduced by 35% (HR:0.65, 95% CI:0.41-0.89, I2 = 86.91%), 46% (HR:0.54, 95% CI: 0.34-0.74, Ι2 = 0%), respectively. Statins use was also associated with a reduction in the risk of major adverse cardiovascular events (MACE) by 35% (HR:0.65, 95% CI: 0.51-0.80, I2= 93.22%) and the incidence of myocardial infarction (MI) by 41% (HR:0.59, 95% CI: 0.33-0.86, I2 = 76.78%). Among patients treated with statins, high-intensity treatment group was associated with a reduction in all cause-mortality by 36% (HR:0.64, 95% CI: 0.54-0.74, I2 = 96.49%) compared to patients treated with low intensity statins. Conclusion Statin treatment among patients with PAD was associated with a statistically significant reduction in all-cause mortality, cardiovascular mortality, MI, MACE, risk for amputation or loss of patency. Statins were also associated with a higher amputation free survival.

Improved lipid target level attainment in patients with peripheral artery disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Jörn F. Dopheide ◽  
Luise Adam ◽  
Sebastian Wiedmer ◽  
Mathias Kaspar ◽  
Günther Silbernagel ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Prospective Observational Study ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Target Level ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Very High ◽  
Vascular Region

Background: Patients with peripheral artery disease (PAD) fall under the category of a very high cardiovascular risk. Although, consequent lipid lowering therapy (LLT) is advised, only sparse data on attained target level in PAD exists. Objectives: We aimed to analyse contemporary guideline recommendations for LLT in symptomatic PAD patients. Methods: monocentric, prospective, observational study involving 200 symptomatic PAD patients. Guideline target level attainment and LLT were analysed between 2017 and 2019. Results: Overall 78.5% of the patients were on statin therapy, mainly of high intensity with atorvastatin in 50% and rosuvastatin in 33% of the cases. Average statin dosage adjusted for simvastatin was 55 mg/d. Low density lipoproteincholesterol (LDL-C) was <1.8 mmol/L in 53% and <1.4 mmol/L in 34% of the cases. Mean LDL-C levels were at 1.85 ± 0.88 mmol/L. We observed no difference in the treatment and the target level attainment of patients with a stable PAD (intermittent claudication) or chronic critical PAD. However, patients with ≥1 vascular region affected (i.e. coronary and/or cerebrovascular) were treated more intensively and had lower LDL-C levels than patients with PAD alone. Conclusion: It appears that there is more awareness and improvement of previously documented undertreatment of LDL-C levels in symptomatic PAD patients. Although statin treatment is initiated in the majority of patients, our findings call for a continuously intensified LLT in symptomatic PAD patients.

Lipid-lowering treatment in peripheral artery disease

2018 ◽  
Vol 39 ◽  
pp. 19-26 ◽  
Author(s):  
Niki Katsiki ◽  
Athanasios D Giannoukas ◽  
Vasilios G Athyros ◽  
Dimitri P Mikhailidis
Keyword(s):  
Peripheral Artery Disease ◽  
Lipid Lowering ◽  
Peripheral Artery ◽  
Artery Disease

scholarly journals Association of sleep apnea with outcomes in peripheral artery disease: Insights from the PORTRAIT study

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256933
Author(s):  
Qurat-ul-ain Jelani ◽  
Carlos Mena-Hurtado ◽  
Kensey Gosch ◽  
Moghniuddin Mohammed ◽  
Clementine Labrosciano ◽  
...  
Keyword(s):  
Health Status ◽  
Sleep Apnea ◽  
Peripheral Artery Disease ◽  
Rank Test ◽  
Peripheral Artery ◽  
Clinical Trial Registration ◽  
The Us ◽  
History Of ◽  
Artery Disease

Background Sleep apnea is a predictor of adverse cardiovascular outcome in many cardiovascular diseases but whether it is associated with worse health status outcomes or mortality in peripheral artery disease (PAD) is unknown. Methods PORTRAIT is an international (US, Netherlands, Australia) prospective PAD registry that consecutively enrolled patients who presented with new-onset or recent exacerbations of PAD symptoms to any of 16 vascular specialty clinics. Health status was assessed upon presentation and at 12 months with the disease-specific Peripheral Artery Questionnaire (PAQ). Higher PAQ scores indicate better health status. A sequentially-adjusted hierarchical linear regression model examined the association between sleep apnea and 1-year PAQ symptoms, quality of life, and summary scores. Five-year survival curves by comorbid sleep apnea status for US patients were compared using the log-rank test. Results The mean age of the 1204 PORTRAIT participants was 67.6 ± 9.4 years with 37.5% women and 8.3% (n = 100) having sleep apnea. Patients with sleep apnea were more likely to be from the US, more sedentary, and to have diabetes, obesity, coronary disease, more depressive symptoms and a history of prior peripheral interventions. Paradoxically, they also had higher ankle-brachial indices, but lower PAQ Summary scores at presentation and 12 months (41.2 ± 22.0 vs. 49. 9± 21.6 and 58.6 ± 27.9 vs. 71.3 ± 24.9, respectively, p = <0.05). The association between sleep apnea and 1-year health status persisted after multivariable adjustment, but there were no differences in all-cause mortality over 5 years (28.0% vs. 23.4%, p = 0.76). Conclusion In patients presenting with PAD, comorbid sleep apnea is independently associated with worse health status over time. Future studies should test whether better treatment of sleep apnea can improve the health status of patients with PAD. Clinical trial registration NCT01419080

scholarly journals The impact of the revised ESC Dyslipidaemia Guidelines on lipid-lowering therapy: simulating the need for PCSK9 inhibition in a contemporary ASCVD cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Blaum ◽  
F.J Brunner ◽  
F Kroeger ◽  
J Braetz ◽  
B Bay ◽  
...  
Keyword(s):  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Treatment Target ◽  
Pcsk9 Inhibitor ◽  
Lowering Therapy ◽  
Artery Disease ◽  
Pcsk9 Inhibition ◽  
The Impact

Abstract Introduction The recently updated ESC guidelines on the management of dyslipidaemias recommend a more intense LDL-cholesterol (LDL-C) reduction. For patients with atherosclerotic cardiovascular disease (ASCVD) the LDL-C goal has been revised to ≤55 mg/dl with a concomitant class IA upgrade for cost intensive PCSK9 inhibitors. Purpose We aim to quantify the need for PCSK9 inhibitors to achieve the revised LDL-C target compared to former ESC recommendations in ASCVD patients Methods We included all patients with ASCVD (angiographically documented coronary artery disease, history of peripheral artery disease or stroke) from an observational cohort study ongoing since 2015. A simulation treatment algorithm adding sequentially a high intensity statin, ezetimibe and a PCSK9 inhibitor in case of a missed treatment target was applied with consideration of both partial and total statin intolerance. The need for PCSK9 inhibitors was calculated for 3 recommendations: 1. LDL-C treatment target ≤55 mg/dl (ESC 2019 Guidelines), 2. LDL-C treatment target ≤70 mg/dl (ESC 2016 Guidelines) and 3. risk-based use of PCSK9 inhibitors restricted to patients with a residual LDL-C &gt;140 mg/dl or &gt;100 mg/dl with clinical/angiographic risk factors (ESC consensus update 2017). Results We included 1936 patients (mean age 69 years, 74% male). Median LDL-C at inclusion was 86 mg/dl, with 60% of patients taking lipid lowering medication (55% statin only, 4% statin + ezetimibe, 1% ezetimibe only). Table 1 shows the distribution of medications required to meet recommendations 1–3. After simulated stepwise intensification of lipid lowering therapy 99% of patients achieved the revised LDL-C target of ≤55 mg/dl, with a need of 23.5% for a PCSK9 inhibitor. For the former LDL-C target of ≤70 mg/dl the need for PCSK9 inhibitors was 10.5%. Restricting the use of PCSK9 inhibitors to the highest risk patients according to the ESC 2017 consensus statement reduced the need for PCSK9 inhibition to only 1.4% with slightly fewer patients achieving their LDL-C target (78% for ≤55 mg/dl and 91% for ≤70 mg/dl respectively). Conclusion The revised LDL-C treatment goals substantially increase the projected need for PCSK9 inhibitors with an unclear health economic impact. Identification of ASCVD patients with a reasonable benefit/cost-ratio of PCSK9 inhibition remains to be investigated urgently. Funding Acknowledgement Type of funding source: None

Abstract 177: Heterogeneity in Blood Pressure Management in Patients With Peripheral Artery Disease; Insights From the PORTRAIT Registry

2018 ◽  
Vol 11 (suppl_1) ◽  
Author(s):  
Poghni A Peri-Okonny ◽  
Krishna Patel ◽  
Jingyan Wang ◽  
Nancy Stone ◽  
Kim Smolderen
Keyword(s):  
Blood Pressure ◽  
Peripheral Artery Disease ◽  
Beta Blockers ◽  
Performance Measure ◽  
Prior History ◽  
Significant Heterogeneity ◽  
Peripheral Artery ◽  
The Us ◽  
Artery Disease ◽  
New Guidelines

Introduction: Patients with peripheral artery disease (PAD) are known to have the highest cardiovascular risk across the spectrum of patients with atherothrombotic disease. Hypertension (HTN) management is currently not a key performance measure for PAD despite being a common risk factor in patients with PAD. As there is lack of data on the management of blood pressure (BP) in PAD, we prospectively studied BP management among patients with new or worsening symptomatic PAD. Methods: In PORTRAIT, patients were evaluated for new or worsening PAD symptoms in 16 PAD clinics across the US, Netherlands and Australia. BP was measured in clinic and at time of enrollment. HTN was defined as prior history of HTN, use of antihypertensives or [SBP ≥140 or DBP ≥90 mmHg per old guidelines; or SBP≥130 or DBP≥80 per new ACC/AHA guidelines]. Untreated HTN was defined as patients with HTN who were not on antihypertensive therapy. HTN with BP <140/90 (old) or <130/80 (new guidelines) was defined as controlled HTN. We estimated country differences in BP and untreated HTN rates. Median odds ratio (MOR) and 95% confidence intervals was derived from hierarchical logistic regression modelling to estimate variability in achieving controlled HTN. Results: Among 1006 participants with documented BP, the prevalence of HTN increased from 96% to 98% based on old and new definitions respectively. BP control decreased from 51% (old) to 31% (new definition). Beta blockers (66.1%) were the most commonly used antihypertensive drug class (Table 1). Overall, 6.5% and 8.3% of HTN patients were untreated based on the old and new definitions respectively. Mean BP was lowest in the US compared to Netherlands and Australia (135/73 ± 21/11 mmHg, 146/76 ± 22/12, 151/80 ± 19/10, p <0.001) respectively. The MOR across sites was 1.7 (1.3 -2.5) for BP <140/90 (p <0.001), and 1.4 (1.0 -2.1) for BP<130/80 (p = 0.045) after adjusting for country. Conclusion: The prevalence of HTN among PAD patients with new or worsening symptoms was high independent of BP cut off. Based on new HTN definition, only 1 in 3 HTN patients in this cohort have controlled BP. There was significant heterogeneity in BP control and rates of untreated hypertension differed by country independent of HTN definition. This suggests an opportunity to improve BP control in PAD patients.

scholarly journals Statin Intolerance: Diagnosis and Management

2017 ◽  
Vol 02 (03) ◽  
pp. 014-020
Author(s):  
Roopali Khanna ◽  
Dandu Himanshu
Keyword(s):  
Adverse Effects ◽  
Clinical Symptoms ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Statin Intolerance ◽  
Artery Disease ◽  
Statin Dose

AbstractStatins are the main cornerstone in the treatment of coronary artery disease. Statins not only reduce the cardiovascular events but also significantly reduce the all-cause mortality. Due to adverse effects of statins, 20 to 30% of patients discontinue statins without consulting the physician. Most common adverse effects reported are muscle symptoms. Studies have shown that the majority of these patients can tolerate statin upon rechallenge. Alternative statin dosing, alternate-day statin, or twice-weekly statin dosing are different strategies to be given before changing to nonstatin lipid-lowering therapy. The newer nonstatin lipid-lowering drugs (ezetimibe, PCSK9 inhibitors) can be added if the low-density lipoprotein (LDL) target level can be achieved despite the maximally tolerated statin dose. This article reviews the etiology, clinical symptoms, and management of statin intolerance.

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