Special Clinical Populations
Introduction
Patient populations with serious comorbidities have also been largely excluded from the statin cardiovascular outcomes trials, with the exception of two trials in patients with heart failure and two trials in patients with end-stage renal disease (ESRD) or undergoing maintenance hemodialysis. Notably, the four trials in heart failure and chronic kidney disease (CKD)/hemodialysis populations found no atherosclerotic cardiovascular disease (ASCVD) risk reduction benefit from statin therapy despite being at risk for ASCVD and death. Nor did another cardiovascular (CV) outcomes trial with simvastatin and ezetimibe find a significant reduction in ASCVD events in the subgroup with ESRD.7 Death from competing causes of mortality appear to be the explanation, at least in part.
The lack of demonstrated benefit in the high-risk patient populations with heart failure or ESRD/hemodialysis is of further concern for other populations at high ASCVD risk, such as those with chronic…
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Introduction
Patient populations with serious comorbidities have also been largely excluded from the statin cardiovascular outcomes trials, with the exception of two trials in patients with heart failure and two trials in patients with end-stage renal disease (ESRD) or undergoing maintenance hemodialysis. Notably, the four trials in heart failure and chronic kidney disease (CKD)/hemodialysis populations found no atherosclerotic cardiovascular disease (ASCVD) risk reduction benefit from statin therapy despite being at risk for ASCVD and death. Nor did another cardiovascular (CV) outcomes trial with simvastatin and ezetimibe find a significant reduction in ASCVD events in the subgroup with ESRD.7 Death from competing causes of mortality appear to be the explanation, at least in part.
The lack of demonstrated benefit in the high-risk patient populations with heart failure or ESRD/hemodialysis is of further concern for other populations at high ASCVD risk, such as those with chronic inflammatory, immunosuppressed, or infectious conditions, who also are at increased risk of competing causes of mortality. The limited availability of evidence from randomized trials for an ASCVD risk reduction benefit, coupled with the potential for serious drug-drug interactions, makes it difficult to determine whether there is the potential for net benefit from statin or other lipid-lowering therapy in these individuals.
Cholesterol, inflammation and thrombosis are the major contributors to the risk of ASCVD events, placing patients with chronic inflammatory, immunosuppressed, or infectious conditions at a higher ASCVD risk than might be expected from their risk factor levels. Many of these patients experience secondary hyperlipidemia from their underlying condition or the drugs used to treat it. Glucocorticoids and other drugs may also increase weight gain, insulin resistance and diabetes.
Heart Failure
The 2018 multi-society (including the American College of Cardiology (ACC) and the American Heart Association (AHA) cholesterol guideline made no recommendation regarding the initiation or continuation of statins in individuals with advanced heart failure.
Two randomized trials have evaluated statins in heart failure patients. CORONA enrolled individuals ≥60 years of age with NYHA class II-IV ischemic systolic heart failure. GISSI-HF enrolled individuals with a clinical diagnosis of NYHA class II-IV heart failure of any type. There were no lipid entry criteria for either trial.
Initiation of a moderate-intensity statin (rosuvastatin 10 mg) did not reduce ASCVD events or death in either placebo-controlled heart failure trial. There were no ASCVD risk reduction benefits in any pre- specified subgroups, including age, ischemic etiology, ejection fraction, presence of diabetes and low-density lipoprotein cholesterol (LDL-C) level. A prespecified analysis in CORONA did find fewer CV hospitalizations in the rosuvastatin group. There was no indication of an excess of adverse events in the statin groups.
A subsequent pooled analysis of the two trials suggests there was a 19% decreased risk of MI patients with ischemic heart failure who were not already on a statin. The 2018 multi-society guidelines state that moderate-intensity statins may be taken into consideration (Class of Recommendation [COR] IIb) to reduce the occurrence of ASCVD events in individuals with heart failure with reduced ejection fraction due to ischemic heart disease who have a reasonable life expectancy (3-5 years). A post hoc analysis of CORONA suggested patients with milder heart failure, as evidenced by an NT-Pro BNP level <103 pmol/L (868 pg/mL) may benefit from rosuvastatin.
Clinical Highlight I
- Patients with ischemic cardiomyopathy, fewer comorbidities and mild heart failure (Class I or II) may benefit from initiating or continuing a moderate-intensity statin.
- Patients with familial hypercholesterolemia and ischemic cardiomyopathy may benefit from initiating or continuing a statin along with nonstatin therapy if needed.
- Patients with nonischemic heart failure are unlikely to benefit from initiating a statin. Consider discontinuing statin therapy in those with significant comorbidities or moderate to severe heart failure to simplify their drug regimen.
Renal Disease
Chronic Kidney Disease (CKD)
According to the 2018 multi-society cholesterol guideline, individuals with CKD who do not have ESRD or are not undergoing hemodialysis can be managed based on their membership in a statin-benefit group (clinical ASCVD, LDL-C ≥190 mg/dL, diabetes, or 10-year ASCVD risk). With respect to the treatment algorithm for secondary prevention, CKD is considered a high-risk condition (Table 8-2). With respect to primary prevention, CKD is considered a risk enhancer which may inform the decision to initiate statin therapy in patients with intermediate (or occasionally borderline) estimated 10-year risk of ASCVD (Figure 8-3).
Other guidelines have identified those with CKD as a coronary artery disease (CAD) risk equivalent and universally recommend statin therapy. The 2013 ACC/AHA Risk Assessment Guideline did not find sufficient evidence to determine whether renal disease (creatinine, glomerular filtration rate (GFR), albuminuria) added sufficient incremental information to improve risk prediction. However, since the prevalence of CKD increases with age, long-standing hypertension and diabetes, most individuals will have a ≥7.5% 10-year ASCVD risk and be clear candidates for statin therapy on that basis. Statin therapy is reasonable for CKD patients with 5-<7.5% 10-year ASCVD risk. In CKD patients with <5% 10-year ASCVD risk, consideration of other characteristics, including LDL-C ≥160 mg/dL, lifetime ASCVD risk, hs-CRP, CAC and family history of premature ASCVD may be helpful.
Since the safety of some statins may differ according to the GFR (see Statins) or other patient characteristics, for primary prevention patients it is recommended to engage in a clinician-patient discussion to determine the potential for a net ASCVD risk reduction benefit, potential for adverse events and drug-drug interactions and patient preferences when initiating statin therapy.
Patients with stage III-IV CKD were excluded from the high-intensity statin trials so there are insufficient data to support the initiation of high-intensity statin therapy in secondary or primary prevention in this patient group. However, patients who received high-intensity statin therapy during the trials experienced improved renal outcomes.
In the SHARP trial, CKD patients without ESRD/ hemodialysis did have a reduction in ASCVD events with simvastatin 20 mg/ezetimibe 10 mg combination therapy compared to placebo. The addition of ezetimibe may therefore be a reasonable option to achieve a 50% reduction in LDL-C in CKD patients.
ESRD/Hemodialysis
The 2018 multi-society cholesterol guideline states that continuing statin therapy in patients with advanced kidney disease who require dialysis treatment may be reasonable (COR IIb). Starting a statin is not advised (COR III: No Benefit) for patients with severe kidney disease who require dialysis.
These recommendations are based on the lack of demonstrated benefit in this patient population. Two randomized trials have evaluated statins in hemodialysis patients, and one trial has evaluated simvastatin-ezetimibe combination in ESRD/hemodialysis patients. AURORA enrolled individuals receiving maintenance hemodialysis aged 50-80 years, 40% of whom had a history of ASCVD. GDDS enrolled individuals receiving maintenance hemodialysis aged 18-80 years with diabetes and LDL-C 80-190 mg/dL, 25% of whom had a history of CAD and 18% had a history of stroke. SHARP enrolled individuals with CKD, ESRD and receiving hemodialysis without a history of ASCVD.
Rosuvastatin 10 mg, atorvastatin 20 mg and simvastatin 20 mg/ezetimibe 10 mg did not reduce ASCVD events or death, overall or in subgroups of ESRD/hemodialysis patients.
There is little to no data available at present on the efficacy of PCSK9 inhibitors and bempedoic acid in patients with ESRD and receiving dialysis.
Renal Transplant
The 2018 multi-society cholesterol guideline contains no specific recommendations on LDL-C lowering therapy in individuals with a renal transplant.1 The 2013 KDIGO lipid guideline recommends initiation or continuation of statin therapy in renal transplant patients (Class 2 recommendation).
Renal transplant patients have a >20% 10-year risk of CAD, a risk similar to those with clinical ASCVD. In the ALERT trial, the moderate-intensity statin fluvastatin 40-80 mg was shown to reduce the risk of nonfatal MI and coronary death by 35%, a benefit that extended over an additional 7 years of follow-up. Cyclosporine in combination with glucocorticoids, azathioprine and mycophenolate mofetil were the main immunosuppressant drugs used at the time this trial. Refer to the Organ Transplant section below for other statin interactions with immunosuppressant drugs.
There is no data available on PCSK9 inhibitor or bempedoic acid efficacy in patients with a renal transplant.
Clinical Highlight II
- Chronic CKD (but not ESRD):
- Initiate or continue moderate-intensity statin therapy according to the recommendations for clinical ASCVD and primary prevention.
- Continue moderate- or high-intensity statin if tolerated.
- High-intensity statin therapy is reasonable for high-risk patients if GFR ≥60 mg/dL and no other safety concerns. Or, consider adding ezetimibe to achieve a ≥50% LDL-C reduction.
- ESRD/hemodialysis:
- To date, there has not been a subgroup of hemodialysis/ESRD patients that seems to benefit from initiation of statin therapy.
- Continuation of statin therapy might be reasonable in stable patients, especially those with clinical ASCVD or who have an untreated LDL-C ≥190 mg/dL.
- Potential for adverse effects should be considered. Patient preferences should play a large role.
- Renal transplant:
- It is reasonable to initiate or continue a moderate-intensity statin chosen to minimize interactions with the immunosuppressant drug regimen. Fluvastatin 40 mg is a reasonable initial selection.
Human Immunodeficiency Virus (HIV)
ASCVD Risk Reduction
According the 2018 multi-society cholesterol guideline, patients with HIV should be managed based on their membership in a statin-benefit group (clinical ASCVD, LDL-C ≥190 mg/dL, diabetes, or 10-year ASCVD risk). Shared decision-making in a clinician-patient discussion is important for all patients with HIV. HIV infection is considered a risk enhancer in patients at risk of ASCVD (Figure 8-3). The potential for an ASCVD risk reduction benefit, adverse effects and drug-drug interaction and patient preferences all need to be considered in the decision to initiate statin therapy.
Patients with HIV are at increased ASCVD risk, which may be accelerated due to their high active antiretroviral therapy (HAART) regimen. Individuals with HIV have a higher prevalence of dyslipidemia, earlier incidence of atherosclerosis progression and up to a 2-fold higher risk of ASCVD. On the other hand, long-term viral suppression may ameliorate this excess risk.
The decision to initiate statin therapy for primary prevention in patients with HIV may be approached in at least two ways. One, it may be reasonable to increase the 10-year ASCVD risk estimated by the Pooled Cohort Equations (PCE) by 50% to 60%. Or, it may be reasonable to consider adults ≥30-35 years of age with HIV to be at high risk of ASCVD and initiate statin therapy along with lifestyle changes for ASCVD prevention. In addition, in primary prevention, consideration should be given to initiating statin therapy when LDL-C levels are ≥160 mg/dL, itself an important risk enhancer. Like all other patients, HIV-positive patients with clinical ASCVD, untreated LDL-C ≥190 mg/dL, or diabetes aged 40-75 years should receive a statin, with dosing considerations given to safety.
Statins
Because of the potential for drug-drug interactions between statins and antiretroviral therapy (which may vary widely), careful consideration must be given to the choice and dosage of statin therapy. Lovastatin and simvastatin should be avoided due to highest potential for antiretroviral drug interactions due to CYP3A4 inhibition. Table 17-1 lists manufacturer’s package insert as of January 2, 2023; consult the most recent package insert and pharmacy databases before prescribing a statin. Atorvastatin and fluvastatin at sub-maximal doses are relatively safe if monitored. Pitavastatin, pravastatin and rosuvastatin seem to have the least potential for drug-drug interactions. A primary prevention cardiovascular (CV) outcomes trial with pitavastatin in HIV-positive patients is underway (REPRIEVE).
Ezetimibe
Ezetimibe is also an option for additional LDL-C lowering, especially in high risk patients with HIV in whom a ≥50% reduction in LDL-C is desirable. Ezetimibe has no reported interactions with antiretroviral drugs.
PCSK9 Inhibitors
There is a theoretical concern that PCSK9 inhibitors could increase uptake of HIV-1 by increasing the availability of the LDL-receptor on the cell surface. In vitro studies have found that HIV-1 can be taken into the cell via the LDL receptor-related protein; this finding has not yet been reported in humans. Evolocumab was shown to be safe and effective in a trial in patients with HIV on maximally tolerated statin therapy.
For the most updated list of lipid-lowering drug-antiretroviral interactions, use the online tool: https://www.hiv-druginteractions.org/checker.
Bempedoic acid
No data is yet available on the effect of bempedoic acid on patients with HIV.
Management of Secondary Hyperlipidemia in Patients with HIV
HIV infection itself may increase triglyceride levels due to impaired lipolysis and increased hepatic lipogenesis. Hypertriglyceridemia commonly occurs in patients receiving HAART for HIV suppression and hypercholesterolemia somewhat less commonly. Redistribution of adipose tissue and ectopic fat deposition occurs in about half of patients receiving long-term HAART. Lipodystrophy can manifest as both lipoatrophy and hypertrophy (eg, the buffalo hump). Lipohypertrophy and visceral fat deposits are commonly associated with hypertriglyceridemia, reduced insulin sensitivity and diabetes.
The extent of lipid changes varies among antiretroviral regimens (Table 17-2). First-generation protease inhibitors (e.g., indinavir, lopinavir) are more likely to cause greater increases in total cholesterol, LDL-C and triglycerides than second-generation protease inhibitors (e.g., atazanavir and darunavir). Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz) increase total cholesterol and LDL-C more than second generation protease inhibitors. Improvements in triglyceride and LDL-C levels are observed when switching from lopinavir/ritonavir or atazanavir (refer to most recent HIV management guidelines for updates).
Triglycerides ≥500 mg/dL
If lifestyle changes (including a very low-fat diet and avoidance of alcohol and refined carbohydrates) and maximally tolerated intensity of statin are not effective in reducing triglycerides to <500 mg/dL, fibrates and omega-3 fatty acids represent additional drug options. Gemfibrozil has more drug interactions than fenofibrate or fenofibric acid and should be avoided. Omega 3 fatty acids (3-3.5 g/d DHA +EPA) have no potential for drug interaction but may have lower adherence at the effective dose.
For an up-to-date list of lipid-lowering drug-antiretroviral interactions, access https://www.hiv-druginteractions.org/checker.
Clinical Highlight III
- Patients with HIV and clinical ASCVD, diabetes, LDL-C ≥160 mg/dL, or ≥5% 10-year ASCVD risk using PCE (ACC/AHA risk calculator):
- Initiate statin therapy with lowest likelihood of adverse effects and drug-drug interactions. Carefully counsel patient on potential for myopathy. Consider adding ezetimibe to achieve a ≥50% LDL-C reduction. May also consider other characteristics that could increase ASCVD risk.
- Strongly encourage lifestyle adherence, smoking avoidance and control blood pressure.
- Engage in shared decision-making.
Hepatitis C
ASCVD Risk Reduction
The 2018 multi-society cholesterol guideline did not address patients with hepatitis C infection. Individuals with chronic active hepatitis C appear to be at increased ASCVD risk. It is not known if this risk returns to the level expected based on ASCVD risk factors alone after antiviral treatment. It is reasonable to assume that patients with a history of hepatitis C, either untreated or treated, have at least the risk expected from their membership in a statin-benefit group (clinical ASCVD, LDL-C ≥190 mg/dL, diabetes, or 10-year ASCVD risk as estimated by PCE). Shared decision-making in a clinician-patient discussion is important for all patients with hepatitis C. The potential for an ASCVD risk reduction benefit, adverse effects and drug-drug interactions and patient preferences all need to be considered in the decision to initiate statin therapy.
Like all other patients, patients with hepatitis C and with clinical ASCVD, untreated LDL-C ≥190 mg/dL, or diabetes age 40-75 years should receive a statin, with dosing consideration given to safety. In primary prevention, consideration should be given to initiating statin therapy in patients with hepatitis C and with borderline or intermediate 10-year ASCVD risk or with LDL-C levels ≥160 mg/dL, since these conditions are considered ASCVD risk enhancers.1
The hepatitis C antiviral drugs boceprevir and telaprevir are potent CYP3A4 inhibitors, and the use of statins metabolized by this pathway should be avoided or the dose reduced (Table 17-3).
Clinical Highlight IV
- Clinical ASCVD, diabetes, or LDL-C ≥160 mg/dL or ≥5% 10-year ASCVD risk using Pooled Cohort Equations (ACC/AHA risk calculator):
- Initiate statin therapy with lowest likelihood of adverse effects and drug-drug interactions. Carefully counsel patient on potential for myopathy. Consider adding ezetimibe to achieve a ≥50% LDL-C reduction. May also consider other characteristics that could increase ASCVD risk.
- Strongly encourage lifestyle adherence, smoking avoidance, and control blood pressure.
- Engage in shared decision-making.
Post Organ Transplant
Increased ASCVD Risk
The 2018 multi-society cholesterol guideline did not make recommendations for patients with a solid organ transplant.
It would be reasonable to consider all of these patients at high ASCVD risk. Advances in immunosuppressive therapy have led to long-term survival expectations for these patients. Statin therapy has been shown to increase long-term survival in patients who have undergone renal or cardiac transplantation and may improve graft survival. As for most other groups of patients at risk of ASCVD, shared decision-making in a clinician-patient discussion is essential for determining whether to initiate or continue statin therapy.
LDL-C lowering to reduce ASCVD risk can be achieved with lifestyle changes, a carefully selected statin regimen, and ezetimibe. Niacin, PCSK9 inhibitors and bempedoic acid have not been evaluated in this population. Bile acid sequestrants should not be used due to potential for adversely affecting immunosuppressant drug levels.
Statins and Immunosuppressant Drugs
Statins have significant interactions with a number of immunosuppressive agents, including cyclosporine and tacrolimus (Table 17-4).
In comparison to cyclosporine, only a few controlled drug interaction studies have been carried out for other immunosuppressive agents. Cyclosporine and tacrolimus are CYP3A4 substrates and inhibitors, although cyclosporine appears to be much more potent in this regard and additionally interferes with other drug metabolic pathways. Only low doses of fluvastatin (20 mg), pravastatin (20 mg) and rosuvastatin (5 mg) should be used with cyclosporine per the manufacturer’s package insert (Table 17-4). The other statins are contraindicated for use with cyclosporine.
A reasonable approach is to start with a low dose of a statin (starting with generic pravastatin) and increase dose as tolerated. Generic fluvastatin is a good second choice, although usually more expensive than generic pravastatin, followed by rosuvastatin and pitavastatin (if not on cyclosporine). Atorvastatin 10 mg to 20 mg has also been used in some patients receiving immunosuppressants other than cyclosporine with good tolerability. Higher doses and other statins should be tried with caution and careful monitoring for muscle symptoms. Patients must be carefully counseled on the potential for myopathy and to immediately discontinue the statin and notify the healthcare provider if muscle symptoms develop.
Statins and Other Drugs Commonly Used in Transplant Patients
Many azole antifungals inhibit CYP3A4 and concomitant use with statins should be avoided. Notably, fluconazole interacts with fluvastatin. Voriconazole inhibits CYP3A4 (atorvastatin, lovastatin, simvastatin), CYP2C9 (fluvastatin) and CYP2C19; alternative statins for concomitant use are low doses of rosuvastatin, pitavastatin, or pravastatin.
Ezetimibe
Ezetimibe appeared to be well-tolerated in >1500 renal transplant patients at a single center. The only immunosuppressive drug interaction appears to be with cyclosporine.
Management of Secondary Hyperlipidemia in Organ Transplant Patients
Following organ transplantation, most patients develop moderate-severe hypertriglyceridemia and occasionally hypercholesterolemia. Hyperlipidemia also occurs in patients with autoimmune diseases. Immunosuppressant drugs are the leading cause of hyperlipidemia in these patients, with contributions from genetics, diabetes and renal disease. Calcineurin inhibitors (cyclosporine, tacrolimus), mammalian target of rapamycin (mTOR) inhibitors (sirolimus, everolimus, temsirolimus) and glucocorticoids are the most common immunosuppressive drugs causing hyperlipidemia.
The risk of complications from severe hypertriglyceridemia needs to be carefully weighed against the potential loss of immunosuppression from altering the immunosuppressant drug regimen. Triglycerides ≥500 mg/dL should be managed with lifestyle changes (avoidance of alcohol and refined sugars, adopting a very low-fat diet) and omega-3 fatty acids 3-3.5 g/d (if tolerated). Omega-3 fatty acids are preferable to fenofibrate, or gemfibrozil, which may significantly increase the risk of myopathy when used in combination with statins and cyclosporine.
Hyperlipidemia refractory to lipid drugs may respond to changes in immunosuppression. Changes in immunosuppression should only be undertaken by a transplant specialist. Strategies may include 1) conversion of cyclosporine to tacrolimus; 2) calcineurin reduction (e.g., add mycophenolate mofetil); and 3) discontinuation of sirolimus.
Clinical Highlight V
- Consider patients at high ASCVD risk following organ transplantation:
- Initiate a statin therapy with lowest likelihood of adverse effects and drug-drug interactions for that patient. Carefully counsel patients on potential for myopathy. Consider adding ezetimibe to achieve a ≥50% LDL-C reduction.
- Strongly encourage lifestyle adherence, smoking avoidance and control blood pressure.
- Engage in shared decision-making.
Autoimmune and Inflammatory Disorders
The 2018 multi-society cholesterol guideline observed that patients with autoimmune or inflammatory disorders are likely at increased ASCVD risk. Rheumatologic diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systematic vasculitis, other inflammatory arthritis), chronic skin diseases (psoriasis, bullous skin diseases, lichen planus) and inflammatory bowel diseases (ulcerative colitis, Crohn’s disease) are all associated with increased ASCVD risk. These conditions and their treatment can increase risk factor levels, but these patients appear to be at higher-than-expected ASCVD risk due to chronic inflammation and what appears to be accelerated atherosclerosis.70 Observed ASCVD rates in patients with rheumatologic and inflammatory disorders are between 25% and 2-fold higher than predicted using 10-year risk prediction equations. According to the 2018 multi-society cholesterol guidelines, chronic inflammatory disorders are risk enhancing factors that should prominently feature in the shared decision making on statin therapy initiation for primary prevention in patients with borderline and intermediate 10-year ASCVD risk (Figure 8-3). Patients with these conditions and clinical ASCVD, diabetes, or untreated LDL-C ≥190 mg/dL should be treated according to the 2018 multi-society cholesterol guideline recommendations for patients without an autoimmune or inflammatory condition. The PCE can be used to as the starting point for estimating 10-year ASCVD risk and upward adjustment of risk by 1.5 to 2-fold may be reasonable.
Periodontal disease is associated with increased ASCVD risk, but the risk appears mediated via conventional risk factors. Treatment of periodontitis does not appear to influence ASCVD risk.
In general, patients with chronic immune or inflammatory conditions have lower LDL-C levels than the general population. Many patients can develop secondary hypertriglyceridemia and diabetes from chronic glucocorticoid therapy.
Observational studies suggest long-term anti- inflammatory treatment to modify the disease can decrease ASCVD risk in these patients. However, many of these patients have undertreated risk factor levels and are likely to benefit from more aggressive risk factor control.
A post-hoc analysis of the TNT and IDEAL trials found that high-intensity statin therapy reduced LDL-C and ASCVD risk similarly in patients with and without rheumatologic diseases and showed similar rates of adverse events in the two patient groups. Statins have been shown to reduce hs-CRP levels, but whether they have the same effect or modulate disease course in patients with inflammatory disorders is unclear.
To date, statins and ezetimibe have not been reported to have interactions with glucocorticoids, methotrexate, hydroxychloroquine, biologic immune modulating agents, sulfasalazine, or aminosalicylates. However, the manufacturer’s package insert should always be reviewed prior to prescribing a new medication.
Muscle Symptoms or Fatigue
Many patients with autoimmune and inflammatory disorders will have muscle symptoms or fatigue prior to initiating statin therapy or develop muscle symptoms afterward. Prior to initiating a statin or increasing the dose, patients should be counseled on the potential for muscle symptoms to develop or worsen (aching, tenderness, fatigue). New symptoms or worsening of symptoms more than twice the baseline intensity should result statin discontinuation, followed by rechallenge with the same or different statin once symptoms return to baseline. This should occur within 1 to 2 months if due to statin. Statin-associated autoimmune myopathy (muscle weakness, substantial and prolonged CK elevation, presence of HMG CoA reductase [HMGCR] antibodies, necrotizing myopathy and absence of or incomplete resolution on statin withdrawal) is an uncommon disorder that requires statin discontinuation as well as additional therapy directed against the autoimmune process. It may be beneficial for patients with statin-related autoimmune myopathy to visit a neurologist with expertise in neuromuscular diseases.
In CV outcome trials of PCSK9 monoclonal antibodies (mAbs), muscle symptoms occurred at similar rates in the PCSK9 mAb and placebo groups, and in randomized, double-blind studies conducted in statin-intolerant patients, the symptoms occurred less frequently in people receiving PCSK9 inhibitors than in those taking ezetimibe or atorvastatin (Figure 23-13).
Since its target enzyme is not expressed in the muscle, bempedoic acid is thought to have minimal to no risk of muscle-related adverse effects.
Clinical Highlight VI
- Clinical ASCVD, diabetes, or LDL-C ≥190 mg/dL, or intermediate (and in some cases borderline) 10-y ASCVD risk estimated using PCE (ACC/AHA risk calculator):
- Initiate moderate- or high-intensity statin (as appropriate in each individual case) unless there are safety concerns or potential for drug-drug interaction.
Carefully counsel the patient on potential for myopathy, and differentiate it from usual musculoskeletal symptoms. Consider adding ezetimibe to achieve a ≥50% LDL-C reduction. May also consider other characteristics that could increase ASCVD risk.
- Initiate moderate- or high-intensity statin (as appropriate in each individual case) unless there are safety concerns or potential for drug-drug interaction.
- Strongly encourage lifestyle adherence, smoking avoidance, and control blood pressure.
- Engage in shared decision-making.
Cancer Survivors
Cancer survivors may be at increased risk of ASCVD, as well as heart failure or valvular heart disease, over and above that expected from their risk factor levels, depending on the type of cancer therapy used. With advances in therapy, long-term survival has increased dramatically for many types of cancer, making it reasonable to engage in ASCVD prevention efforts in most cancer survivors.
Mantle radiation to treat breast cancer and non- Hodgkin’s lymphoma is associated with increased ASCVD risk within 5 years of cancer treatment. The 2018 multi-society cholesterol guideline made no specific recommendations regarding treatment of cholesterol in this patient group, which was generally excluded from participation in clinical trials.
Clinical Highlight VII
- Use the 2018 ACC/AHA cholesterol guideline recommendations in patients with a history of cancer and anticipated long-term survival.
- In primary prevention, consider 10-y ASCVD risk to be 2- to 3-fold higher than estimated using the PCE.
- Strongly encourage lifestyle adherence, smoking avoidance and control blood pressure.
- Engage in shared decision making.
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