Elevated cholesterol is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD), acute cardiovascular events, and premature death (Pignone, 2021). Achieving cholesterol targets is paramount in preventing cardiovascular conditions and events. Backed by expert groups like the ACC and AHA and recommended specifically by the USPSTF, statin therapy has emerged as the mainstay treatment of ASCVD showing great efficacy in preventing acute cardiovascular events and reducing overall cardiovascular mortality (Pignone, 2021). Despite this, questions continue to surround statin prescribing. This uncertainty is perpetuated by biased risk versus benefit considerations and a misinterpretation of research.
The Lower, The Better
Hyperlipidemia is diagnosed at a serum total cholesterol level greater than 200mg/dL and an LDL-C level greater than 100mg/dL.While a serum total cholesterol of ~150 mg/dL may optimize a low ASCVD risk level, a specific LDL-C cholesterol target is more elusive after the achievement of sub-100mg/dL levels (Grundy et al., 2018). The landmark study, “JUPITER”, supports the understanding that there is no specific low threshold that conveys negative effects as the study was halted early given LDL-C level as low as 55 mg/dL demonstrated great cardiovascular benefit (Pignone, 2021). In short, “the lower, the better” (Grundy et al., 2018).
Statin Therapy
The 2018 ACC/AHA Blood Cholesterol Guidelines outline screening for lipid disorders, how to calculate ASCVD risk scores, and score utilization in statin initiation and selection. Focus, in treatment decisions, is placed on intensity of response rather than specific lipid value (Karr, 2017).
Statins are the first line pharmaceuticals given their superior ability to reduce cholesterol more than any other lipid lowering drugs, proven to lower LDL-C by more than 50% depending on dosage (Grundy et al., 2018). There is an overwhelming amount of evidence regarding statin efficacy in reducing risk of ASCVD, acute cardiovascular and thrombotic events, and even all cause mortality (Pignone, 2021).
Statin Use: Hesitations
Statin muscle-related injury and myalgias are perhaps the most common worries among patients and can create significant barriers to care. Karr (2017) reported approximately 1 out of 10 people document some muscle-related symptoms, like myalgias, weakness, or inflammation, with statin use (Karr, 2017). However, the USPSTF found no statistical difference in control versus interventional cohorts when specifically assessing muscle pain related to statin use (USPSTF, 2016). Clinicians should reassure patients that myalgias are often temporary and mild, do not cause long term exercise intolerance, and can be addressed with certain interventions if they do occur.
Gastrointestinal distress, weakness, and headache are other common side effects that contribute to patient noncompliance and treatment plan failure (Karr, 2017). Other more concerning adverse events include elevated LFTs and rhabdomyolysis, but are very rare and easily managed with proper monitoring and patient education. Decreased cognitive function was documented in a few case reports but disproven in 3 large RCTs, so clear association seems very limited and unlikely. (Grundy et al., 2018). Further, increased cancer prevalence, renal dysfunction, low testosterone, and hemorrhagic stroke lack the research to support correlation claims (Rosenson, 2021).
Statins and Diabetes Mellitus
Some research suggests statins influence glucose metabolism in a way that causes an increase in blood glucose levels (Rosenson, 2021). Logically, this could confer an increased risk for developing diabetes, but the details of this are not fully understood. Several observational and meta-analysis studies produce no clear answer, but many RCT’s did not show a statistical significance in diabetes prevalence with and without statin use (USPSTF, 2016). The JUPITER study did report a statistically significant increase in diabetes mellitus with statin use, but this study uniquely involved high intensity statins (Karr, 2017). Consistent duplication of these results has not been achieved, potentially pulling weight from its significance. The ACC/AHA do acknowledge a possible increased risk of diabetes mellitus with statin use, but the increase is small and is likely affected by other factors rather than pure statin use, like using a high intensity dose and other diabetes risk factors (ie: obesity, metabolic syndrome, etc) (Grundy et al., 2018).
Ultimately, the research is unclear with different expert groups drawing different conclusions.
Decision Time
Overall, clinicians must weigh risk versus benefit for each patient, engaging in shared decision-making regarding statin use. Clinicians should consider and explain a statin’s known ability to make a concrete impact in the risk of heart attacks and strokes with the possible, unclear risks of diabetes mellitus and potential side effects. This discussion should include education about potential side effects and the “red flag” signs for rhabdomyolysis and other serious adverse events. Slow dose titration and careful statin selection – as some statins may produce more muscle pain and weakness – can help reduce side effects and improve tolerance. As all pharmaceuticals can produce side effects, clinicians and patients must decide if a statin is more dangerous than other lipid lowering drugs.
Other Therapies
Adjunct to pharmaceutical therapies, lifestyle interventions create a holistic approach that addresses both inherent factors, like age and family history, as well as modifiable risk factors, like physical inactivity, a diet high in saturated and trans fats, obesity, and smoking (USPSTF, 2016).
Other medications that lower LDL-C levels include ezetimibe, bile acid sequestrants, and PCSK9 inhibitors (Karr, 2017). Niacin and fibric acid derivatives target the reduction of triglycerides with only a small LDL-C lowering effect, but can be helpful in some cases (Grundy et al., 2018). These medications are used in conjunction with statins when the LDL continues to stay elevated or ASCVD risk is high. Solo use has not been proven to provide the adequate reduction of risk or improve outcomes.
Grundy, S. M.,, Stone, N. J., Bailey, A. L.,, … Al., E. (2018, November 10). 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000625.
US Preventive Services Task Force. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(19):1997–2007. doi:10.1001/jama.2016.15450
Hyperlipidemia and Statin Therapy
By: Devin Pinaroc, MSN, FNP-C
Elevated cholesterol is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD), acute cardiovascular events, and premature death (Pignone, 2021). Achieving cholesterol targets is paramount in preventing cardiovascular conditions and events. Backed by expert groups like the ACC and AHA and recommended specifically by the USPSTF, statin therapy has emerged as the mainstay treatment of ASCVD showing great efficacy in preventing acute cardiovascular events and reducing overall cardiovascular mortality (Pignone, 2021). Despite this, questions continue to surround statin prescribing. This uncertainty is perpetuated by biased risk versus benefit considerations and a misinterpretation of research.
The Lower, The Better
Hyperlipidemia is diagnosed at a serum total cholesterol level greater than 200mg/dL and an LDL-C level greater than 100mg/dL. While a serum total cholesterol of ~150 mg/dL may optimize a low ASCVD risk level, a specific LDL-C cholesterol target is more elusive after the achievement of sub-100mg/dL levels (Grundy et al., 2018). The landmark study, “JUPITER”, supports the understanding that there is no specific low threshold that conveys negative effects as the study was halted early given LDL-C level as low as 55 mg/dL demonstrated great cardiovascular benefit (Pignone, 2021). In short, “the lower, the better” (Grundy et al., 2018).
Statin Therapy
The 2018 ACC/AHA Blood Cholesterol Guidelines outline screening for lipid disorders, how to calculate ASCVD risk scores, and score utilization in statin initiation and selection. Focus, in treatment decisions, is placed on intensity of response rather than specific lipid value (Karr, 2017).
Statins are the first line pharmaceuticals given their superior ability to reduce cholesterol more than any other lipid lowering drugs, proven to lower LDL-C by more than 50% depending on dosage (Grundy et al., 2018). There is an overwhelming amount of evidence regarding statin efficacy in reducing risk of ASCVD, acute cardiovascular and thrombotic events, and even all cause mortality (Pignone, 2021).
Statin Use: Hesitations
Statin muscle-related injury and myalgias are perhaps the most common worries among patients and can create significant barriers to care. Karr (2017) reported approximately 1 out of 10 people document some muscle-related symptoms, like myalgias, weakness, or inflammation, with statin use (Karr, 2017). However, the USPSTF found no statistical difference in control versus interventional cohorts when specifically assessing muscle pain related to statin use (USPSTF, 2016). Clinicians should reassure patients that myalgias are often temporary and mild, do not cause long term exercise intolerance, and can be addressed with certain interventions if they do occur.
Gastrointestinal distress, weakness, and headache are other common side effects that contribute to patient noncompliance and treatment plan failure (Karr, 2017). Other more concerning adverse events include elevated LFTs and rhabdomyolysis, but are very rare and easily managed with proper monitoring and patient education. Decreased cognitive function was documented in a few case reports but disproven in 3 large RCTs, so clear association seems very limited and unlikely. (Grundy et al., 2018). Further, increased cancer prevalence, renal dysfunction, low testosterone, and hemorrhagic stroke lack the research to support correlation claims (Rosenson, 2021).
Statins and Diabetes Mellitus
Some research suggests statins influence glucose metabolism in a way that causes an increase in blood glucose levels (Rosenson, 2021). Logically, this could confer an increased risk for developing diabetes, but the details of this are not fully understood. Several observational and meta-analysis studies produce no clear answer, but many RCT’s did not show a statistical significance in diabetes prevalence with and without statin use (USPSTF, 2016). The JUPITER study did report a statistically significant increase in diabetes mellitus with statin use, but this study uniquely involved high intensity statins (Karr, 2017). Consistent duplication of these results has not been achieved, potentially pulling weight from its significance. The ACC/AHA do acknowledge a possible increased risk of diabetes mellitus with statin use, but the increase is small and is likely affected by other factors rather than pure statin use, like using a high intensity dose and other diabetes risk factors (ie: obesity, metabolic syndrome, etc) (Grundy et al., 2018).
Ultimately, the research is unclear with different expert groups drawing different conclusions.
Decision Time
Overall, clinicians must weigh risk versus benefit for each patient, engaging in shared decision-making regarding statin use. Clinicians should consider and explain a statin’s known ability to make a concrete impact in the risk of heart attacks and strokes with the possible, unclear risks of diabetes mellitus and potential side effects. This discussion should include education about potential side effects and the “red flag” signs for rhabdomyolysis and other serious adverse events. Slow dose titration and careful statin selection – as some statins may produce more muscle pain and weakness – can help reduce side effects and improve tolerance. As all pharmaceuticals can produce side effects, clinicians and patients must decide if a statin is more dangerous than other lipid lowering drugs.
Other Therapies
Adjunct to pharmaceutical therapies, lifestyle interventions create a holistic approach that addresses both inherent factors, like age and family history, as well as modifiable risk factors, like physical inactivity, a diet high in saturated and trans fats, obesity, and smoking (USPSTF, 2016).
Other medications that lower LDL-C levels include ezetimibe, bile acid sequestrants, and PCSK9 inhibitors (Karr, 2017). Niacin and fibric acid derivatives target the reduction of triglycerides with only a small LDL-C lowering effect, but can be helpful in some cases (Grundy et al., 2018). These medications are used in conjunction with statins when the LDL continues to stay elevated or ASCVD risk is high. Solo use has not been proven to provide the adequate reduction of risk or improve outcomes.
Want to learn more..
Learn more about dyslipidemia at our June 9-11 Virtual Conference from expert Gary Graf, MSN, ARPN-C!
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial
Optimizing Dyslipidemia Management for the Prevention of Cardiovascular Disease: a Focus on Risk Assessment and Therapeutic Options
References
Grundy, S. M.,, Stone, N. J., Bailey, A. L.,, … Al., E. (2018, November 10). 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000625.
Karr, S. (2017). Epidemiology and management of hyperlipidemia. The American journal of managed care, 23 (9 Suppl), S139–S148. https://www.ajmc.com/view/epidemiology-and-management-of-hyperlipidemia-article
Pignone, M. (2021, January 15). Management of elevated low density lipoprotein-cholesterol (LDL-C) in primary prevention of cardiovascular disease. UpToDate. https://www.uptodate.com/contents/management-of-elevated-low-density-lipoprotein-cholesterol-ldl-c-in-primary-prevention-of-cardiovascular-disease?search=Dislipidemia&topicRef=7573&source=see_link#H3715821088.
Rosenson, R. (2021, February 21). Statins: Actions, side effects, and administration UpToDate. https://www.uptodate.com/contents/statins-actions-side-effects-and-administration?search=statin&source=search_result&selectedTitle=2~133&usage_type=default&display_rank=1#H17
US Preventive Services Task Force. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(19):1997–2007. doi:10.1001/jama.2016.15450
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