Nonstatins- Evolving Role in ASCVD Prevention

Overview

Extensive data from randomized trials have shown that statins reduce atherosclerotic cardiovascular disease (ASCVD) risk in proportion to the magnitude of low-density lipoprotein cholesterol (LDL-C) lowering with a good margin of safety. Based on this evidence, the 2018 multi-society cholesterol guideline recommends statins as the mainstay of drug therapy to reduce ASCVD risk. Moreover, all statin are now available as generics, further strengthening the strong emphasis on their use in patients likely to experience a net ASCVD risk reduction benefit.

Compared to the wealth of cardiovascular (CV) outcomes trial data for statins, relatively few trials have evaluated nonstatins for ASCVD event reduction. Ezetimibe and the PSCK9 inhibitors evolocumab and alirocumab have demonstrated ASCVD risk reduction in combination with statin therapy in the IMPROVE-IT, FOURIER, and ODYSSEY OUTCOMES trials, respectively. Older drug trials that have failed to demonstrate a clear reduction in ASCVD risk when a nonstatin was added to background statin therapy include ACCORD (fenofibrate), AIM-HIGH (niacin) and DAL-OUTCOMES (dalcetrapib, a CETP inhibitor). Some studies have reported an excess of adverse events compared to statin monotherapy (HPS-2 THRIVE: niacin/laropiprant, ILLUMINATE: torcetrapib, a CETP inhibitor). Some older nonstatins did reduce ASCVD events when used as monotherapy in selected patient populations (CDP: niacin, LRC-CPPT: cholestyramine, HHS: gemfibrozil, VA-HIT: gemfibrozil, FIELD primary prevention: fenofibrate).

The 2018 multi-society cholesterol guideline recognizes the fundamental role of LDL-C in the pathogenesis of atherosclerosis. However, clinical trial experience has demonstrated that not all drugs that lowered LDL-C also reduced ASCVD events with a good margin of safety. It was also recognized that the net benefit of additional nonstatin therapy would differ based on the patient’s absolute risk and the magnitude of LDL-C lowering. In general, the 2018 multi-society cholesterol guideline recommends consideration of nonstatin therapy only in selected patients receiving maximally tolerated statin therapy who might benefit from additional LDL-C lowering. Those selected patients should receive a nonstatin shown to reduce ASCVD events in ASCVD outcomes trials. In 2022, the ACC released its Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk (2022 ACC Nonstatin ECDP). The primary goal of this document is to serve as a practical guide to healthcare providers and patients in situations not covered by the 2018 multi-society cholesterol guideline. This applies primarily, but not exclusively, to the use of nonstatin agents approved after 2018, for example inclisiran and bempedoic acid. Note that the 2022 American College of Cardiology Expert Consensus Decision Pathway (ACC ECDP) did not include formal systematic reviews or grading of evidence.

The IMPROVE-IT trial was completed in 2014, demonstrating for the first time that additional LDL-C lowering with a nonstatin drug can reduce ASCVD events in statin-treated patients.

Tables comparing the lipid-lowering efficacy, ASCVD event reduction and safety of statins and nonstatins are included in this module.

Determining Who Might Benefit From Additional LDL-C Lowering

The 2018 multi-society guideline framework of the potential for a net ASCVD benefit from statin therapy can also be used to help determine whether a patient might benefit from the addition of a nonstatin to maximal statin and lifestyle therapy. Clinical decision making might be based on the number-needed-to-treat (NNT) and number-needed-to-harm (NNH) for the added therapy, as reviewed below. Since validated clinical tools are not yet available to estimate NNT or NNH in statin-treated patients, a reasonable interim approach might be to use LDL-C treatment thresholds for different patient risk groups.

Reasons for using an LDL-C threshold approach rather than a titration-to-goal approach include:

• There appears to be no lower LDL-C limit to CV event reduction (i.e., why arbitrarily limit therapy if there is the potential for an additional ASCVD risk reduction benefit).
• A treatment threshold facilitates NNT estimation based on the magnitude of LDL-C lowering expected from the addition of the nonstatin LDL-C lowering therapy.

In contrast, LDL-C treatment goals are blind to the potential for benefit and harm from an added therapy. However, LDL-C level thresholds remain a useful concept to help guide decisions on when to add a nonstatin to an existing statin regimen; see the Nonstatin Therapy Guided by LDL-C Treatment Thresholds section below.

Clinical Highlight I

• Maximize statin therapy.
• Emphasize adherence to lifestyle and statin therapy before considering adding a nonstatin.
• Add a nonstatin only if there is the potential for a net ASCVD risk reduction benefit for that patient.
• The 2018 multi-society cholesterol guideline and the 2022 ACC nonstatin ECDP provides guidance on adding nonstatins for patients unable to tolerate a high-intensity statin or who have a <50% LDL-C reduction (and whose LDL-C levels remain above a treatment group-specific threshold) on maximally tolerated statin. Other patients may also benefit.
• Risk categories and LDL-C thresholds may provide guidance in the absence of guideline recommendations

Nonstatins Within the Context of the 2018 Multi-Society Cholesterol Guideline and the 2022 ACC Nonstatin ECDP

The 2018 multi-society cholesterol guideline recommends considering adding a nonstatin for selected groups of patients on maximal statin therapy or those who cannot tolerate any statin therapy and who might benefit from additional LDL-C lowering. More detailed information is provided in the individual drug sections.

Patient groups in which a statin can be considered include:

• Clinical very high-risk ASCVD: Consider (Class of Recommendation [COR] IIa) ezetimibe and (as second-line therapy, after ezetimibe) a PCSK9 monoclonal antibody (mAb) if LDL-C reduction is <50% and LDL-C level is ≥70 mg/dL on maximally tolerated statin therapy
• Clinical non-very high-risk ASCVD: May consider (COR IIb) ezetimibe if LDL-C reduction is <50% and LDL-C level is ≥70 mg/dL on maximally tolerated statin therapy
• Primary hypercholesterolemia (untreated LDL-C ≥190 mg/dL) in patients 20-75 years of age: Consider (COR IIa) ezetimibe if LDL-C reduction is <50% and LDL-C level is ≥100 mg/dL on maximally-tolerated statin therapy; if LDL-C reduction is <50% after addition of ezetimibe, may consider (COR IIb) a bile acid sequestrant (in patients with triglyceride levels of ≤300 mg/dL); if LDL-C level is ≥100 mg/dL (patients 30-75 years of age with heterozygous familial hypercholesterolemia) or ≥100 mg/dL (patients 40-75 years with baseline LDL-C level of ≥220 mg/dL), a PCSK9 inhibitor may be considered (COR IIb)
• Diabetes in patients 40-75 years of age: May consider (COR IIb) ezetimibe if estimated 10-year ASCVD risk is ≥20% to reduce LDL-C levels by ≥50%
• Primary prevention in adult patients without diabetes and LDL-C levels of 70-189 mg/dL: May consider (COR IIb) adding ezetimibe or a bile acid sequestrant to moderate-intensity statin therapy if estimated 10-year ASCVD risk is ≥7.5% to <20% and if high-intensity statin therapy is not tolerated or advisable.

The 2022 ACC ECDP generally agrees with the 2018 multi-society cholesterol guideline; however, considering the lack of a demonstrated limit to the benefit of LDL-C lowering (see below), it suggests less stringent nonstatin addition criteria and addresses appropriate uses of more novel nonstatins:

• Clinical very high-risk ASCVD: Consider ezetimibe and/or a PCSK9 mAb as first-line nonstatins, and inclisiran or bempedoic acid as second-line nonstatins, if LDL-C reduction is <50% and LDL-C level is ≥55 mg/dL on maximally-tolerated statin therapy
• Clinical non-very high-risk ASCVD: Consider ezetimibe as the first line nonstatin, PCSK9 mAb as second-line nonstatins (after ezetimibe or a bile acid sequestrant, if ezetimibe intolerant), and inclisiran or bempedoic acid as third-line nonstatins, if LDL-C reduction is <50% and LDL-C level is ≥70 mg/dL on maximally-tolerated statin therapy
• Primary hypercholesterolemia (untreated LDL-C ≥190 mg/dL) in patients 20-75 years of age: Consider ezetimibe and/or a PCSK9 mAb as first-line nonstatins, and inclisiran or bempedoic acid as second-line nonstatins, if LDL-C reduction is <50% and LDL-C level is ≥100 mg/dL on maximally-tolerated statin therapy
• Diabetes in patients 40-75 years of age: May consider ezetimibe if LDL-C reduction is <50% and LDL-C level is ≥70 mg/dL on maximally-tolerated statin therapy
• Primary prevention in adult patients without diabetes and LDL-C levels of 70-189 mg/dL: May consider ezetimibe if LDL-C reduction is <50% and LDL-C level is ≥70 mg/dL on maximally-tolerated statin therapy and estimated 10-year ASCVD risk is ≥20%.

As a general rule, nonstatins shown to reduce ASCVD events are preferred, including ezetimibe (also preferred because of a favorable cost-benefit ratio) and the PCSK9 monoclonal antibodies (mAbs) evolocumab and alirocumab.

For patients unable to tolerate ≥2 statin therapies (with at least one attempt at the lowest FDA approved dose and a trial of alternative dosing regimens), the 2022 ACC ECDP suggests the following nonstatins as LDL-C-lowering alternatives:

• Clinical ASCVD (secondary prevention): Ezetimibe and/or PCSK9 mAb (first line), bempedoic acid or inclisiran (second line)
• Baseline LDL-C ≥190 mg/dL (primary prevention): Ezetimibe and/or PCSK9 mAb (first line), bempedoic acid or inclisiran (second line)
• Diabetes (primary prevention): Ezetimibe (first line), bile acid sequestrant (second line), bempedoic acid (third line)
• Baseline LDL-C 70-189 mg/dL (primary prevention): Ezetimibe (first line), bile acid sequestrant (second line), bempedoic acid (third line).

Who Might Benefit From Additional LDL-C Lowering

Patients with intolerance to all statins should receive nonstatin therapy to reduce ASCVD risk (see the guideline section above).

Additional LDL-C lowering might be desirable in patients who are unable to tolerate a high-intensity statin or who achieved a <50% reduction in LDL-C (and whose LDL-C levels are above a treatment group-specific threshold; see the guideline section above) on maximally tolerated statin and lifestyle therapy. About half of patients on a high-intensity statin and almost all patients on a moderate- or low-intensity statin do not achieve 50% of greater reduction in LDL-C level (Figure 20-1).

If patients in high-risk groups are unable to tolerate a high-intensity statin, alternative treatment strategies based on CV outcomes trials of moderate-intensity statins used with nonstatins can be considered. IMPROVE-IT, FOURIER and ODYSSEY OUTCOMES are the only trials to date that demonstrated that a nonstatin agent (ezetimibe, evolocumab and alirocumab respectively) reduced ASCVD events when added to background statin therapy. Ezetimibe and PCSK9 mAbs are the preferred nonstatins for additional LDL-C lowering to reduce ASCVD risk after statin therapy has been maximized.

In patients with elevated triglycerides or low HDL-C, high-intensity statins are the first-line therapy for ASCVD risk reduction. To date, there is no evidence that additional therapy directed specifically at lowering triglycerides or raising HDL-C reduces ASCVD risk. Subgroup analysis of other CV outcomes trials suggest fenofibrate or niacin may reduce risk in selected subsets of patients receiving moderate-intensity statin therapy. These trials are discussed in more detail in the next section.

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Nonstatin Therapy Guided by LDL-C Treatment Thresholds

How Low to Go?

There appears to be no lower threshold to LDL-C reduction for reducing ASCVD risk. Therefore, once statin therapy has been maximized, the decision to add one or more nonstatin therapies should depend on the potential for a net ASCVD risk reduction benefit. Routine application of therapies to achieve an LDL-C goal may result in over- or undertreatment of patients, depending on their level of ASCVD risk and starting LDL-C level. In other words, an LDL-C goal may be too high for a high-risk patient, or too low for a low-risk patient, who has less to gain from therapy added to achieve a specific LDL-C goal.

Precision Therapy on the Horizon but Not Here Yet; LDL-C Thresholds a Stop-gap Measure Until Then

More personalized or “precision” therapy will depend on risk estimation equations for statin-treated patients, akin to the Pooled Cohort Equations for primary prevention patients not receiving a statin. Such equations have not yet been developed. Until these tools become available, it seems reasonable to fall back on LDL-C treatment threshold and patient level of risk to aid in the decision to add a nonstatin such as ezetimibe, bile acid sequestrants, PCSK9 inhibitors, or bempedoic acid to maximal statin therapy (or another nonstatin to statin-ezetimibe therapy). Interim use of previously utilized LDL-C levels as treatment thresholds is more for convenience of recall based on historical use than precision.

Specific Treatment Consideration Threshold in High-Risk Patients

Several sources of evidence support adding a nonstatin when LDL-C is ≥100 mg/dL, with the caveat that the potential for a net ASCVD risk reduction will be greatest in the highest-risk patients or when LDL-C levels are well above 100 mg/dL.

• High-intensity statin trials. Since the randomized trials reviewed used fixed-dose treatment strategies, the 2013 ACC/AHA and 2018 multi-society cholesterol guidelines moved away from the titration to goal approach. However, patients receiving a high-intensity statin in the TNT, IDEAL and PROVE-IT trials achieved an LDL C<100 mg/dL and greater ASCVD reduction occurred with high-intensity compared to moderate-intensity statin. Patients with genetic hypercholesterolemia (eg, untreated LDL-C ≥190 mg/dL) were largely excluded from the high-intensity statin trials, providing further support for adding nonstatin LDL-C lowering drugs in order to achieve an LDL-C closer to 100 mg/dL in such patients.
• Epidemiologic evidence. Epidemiologic evidence suggests little atherosclerotic progression occurs with lifetime non–HDL-C levels <125 mg/dL (corresponding to an LDL-C of about 95 mg/dL in normotriglyceridemic individuals). This could provide some support for long-term maintenance of LDL-C <100 mg/dL to prevent new plaque formation. However, lower LDL-C levels may be needed to induce widespread plaque stabilization or regression in patients with a large burden of atherosclerosis.
• Net benefit approach. The net benefit from the addition of a nonstatin to maximal statin therapy can be estimated by considering the absolute ASCVD risk of the patient benefit, the relative reduction in ASCVD events and the potential for adverse events. This approach is discussed in detail below, where NNT and NNH can be considered when determining when to add an additional LDL-C lowering therapy. The relative reduction in ASCVD risk has to date been closely correlated with the magnitude of reduction in LDL-C level from statins or ezetimibe therapy. Since the percent reduction in LDL-C remained fixed for a given drug and dose, the relative reduction in ASCVD risk will be greater when LDL-C levels are high.

As in the statin trials, evidence from nonstatin RCTs and observational trials suggests there is no limit to the ASCVD benefit of absolute LDL-C reduction. Therefore, the 2018 multi-society cholesterol guideline and the 2022 ACC ECDP suggest even lower thresholds for consideration of nonstatin therapy for some patient groups, particularly patients with very high-risk (Table 8-2) clinical ASCVD (see the guideline section above).

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Ezetimibe

Based on the calculations below, a 20% reduction in LDL-C with ezetimibe will variably reduce the relative risk of ASCVD events depending on the starting LDL-C level, which may range from about a 10% relative risk reduction (RRR) lowering LDL-C from 70 to 54 mg/dL as in IMPROVE-IT, to a 15% RRR when lowering LDL-C from 125 to 100 mg/dL (see below for further discussion). Ezetimibe had no significant adverse effects in the 7-year IMPROVE-IT trial so the NNT does not need to be discounted by NNH when estimating the potential for net benefit.

As shown in Table 20-2, in a very high-risk patient with a 15% 5-year (or a 30% 10-year ASCVD risk), similar to patients with an acute coronary syndrome (ACS) in IMPROVE-IT or patients with coronary artery disease (CAD) and diabetes and an LDL-C = 70 mg/dL, on maximal statin therapy would have a 5-year NNT = 67 and a 10-year NNT = 33 for the addition of ezetimibe. While this is not a compellingly large treatment benefit over 5 years, it may be worth considering in the setting of shared decision-making with a very high-risk patient.

In contrast, in a non-diabetic patient with chronic coronary artery disease (CAD) on maximal statin therapy, with a 10% 5-year or 20% 10-year ASCVD risk (such as in TNT) and an LDL-C = 70 mg/dL, the 5-year NNT = 100 and the 10-year NNT = 50 for adding ezetimibe (10% RRR). The NNTs are reduced if this patient’s LDL-C = 125 mg (and therefore a 15% RRR with the addition of ezetimibe), with a 5-year NNT = 67 and a 10-year NNT = 33.

PCSK9 Inhibitors

The PCSK9 inhibitor drug class currently includes two PCSK9 mAbs, evolocumab and alirocumab and the PCSK9 small interfering RNA (siRNA) inclisiran. These drugs lower LDL-C very effectively (45% to 65%). The PCSK9 mAbs have demonstrated ASCVD risk reduction in the FOURIER (evolocumab) and ODYSSEY OUTCOMES (alirocumab) trial, while a CV outcomes trial is underway for inclisiran. Because of their high cost at mid-2018 prices and lack of CV outcome data at the time, the 2018 multi-society guideline recommended PCSK9 inhibitors for consideration in patient groups at highest risk, and after ezetimibe has been tried; in light of substantially reduced prices and new CV outcome data, the 2022 ACC ECDP recommends PCSK9 mAbs for use in the highest risk groups and inclisiran if ezetimibe and/or PSCK9 mAbs have failed or are not tolerated.

Bempedoic Acid

Bempedoic acid is one of the newest nonstatin agents; it acts to inhibit an important step before HMG-CoA reductase in the cholesterol synthesis pathway. When added to maximally-tolerated statin therapy, bempedoic acid has a placebo-relative LDL-C reduction efficacy of 12-18% in combination with ezetimibe, the placebo-relative LDL-C efficacy is 38%. A CV outcomes trial is ongoing. The 2022 ACC ECDP recommends bempedoic acid for consideration in selected patients who require further LDL-C lowering after nonstatins with proven ASCVD risk reduction benefit (ezetimibe and/or PCSK9 mAbs) have been tried first.

Niacin and Bile Acid Sequestrants

Niacin and bile acid sequestrants have significant adverse event rates and/or drug interactions, so the potential net benefit may be less for these drugs. These two drugs have similar LDL-C lowering efficacy as ezetimibe (see below), so the relative risk reduction (RRR) would be expected to be similar as well. However, if the patient experiences adverse effects, the margin of net benefit is reduced. Whether a patient will experience an adverse event cannot be predicted, and some of the adverse events may be serious and irreversible. In order to enhance the potential for a net ASCVD risk reduction benefit, it may well be prudent to reserve niacin and bile acid sequestrants for high-risk patients with LDL-C ≥130 mg/dL despite maximally tolerated statin and ezetimibe therapy. Niacin increases the risk of diabetes and worsens diabetes control so it would be reasonable to avoid its use in patients with diabetes or diabetes risk factors (HPS2-THRIVE). Colesevelam has been shown to modestly reduce HbA1c levels, but is contraindicated if triglycerides are >300 mg/dL.

Discontinue the Nonstatin if <15% LDL-C Reduction or Significant Adverse Events

LDL-C reductions of <15% were observed in older nonstatin CV outcomes trials that failed to find a reduction in cardiovascular events (SEARCH and A to Z, HPS2-THRIVE, AIM-HIGH, ACCORD). SEARCH and A to Z compared lower doses of simvastatin to simvastatin 80 mg. The net benefit will be reduced when the NNH is subtracted to the NNT for the patient who experiences adverse effects.

Cardiovascular Outcomes Trials

The 2018 multi-society cholesterol guideline and the 2022 ACC ECDP preferentially recommend nonstatins shown to reduce ASCVD events in clinical trials. A number of trials of older nonstatins have shown an ASCVD event reduction benefit in the absence of statins (Table 20-3). To date, ezetimibe, evolocumab and alirocumab are the only nonstatins that clearly reduced ASCVD events when added to background statin therapy in the IMPROVE-IT, FOURIER and ODYSSEY OUTCOMES trials, respectively (Table 20-4). In brief, ezetimibe reduced the incidence of a composite of CV death, nonfatal myocardial infarction (MI), unstable angina requiring rehospitalization, coronary revascularization ≥30 days after randomization, or nonfatal stroke by 6.4%; evolocumab reduced the incidence of a composite of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization by 15%; and alirocumab reduced the risk of a composite of death from CAD, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) by 15%.

A number of lipid-modifying and other drugs added to statin therapy have failed to reduce CV events in the trial overall, although there are hints that there may be benefits in some subgroups of patients. Drugs that have not clearly been shown to reduce ASCVD events when added to background statin therapy include fenofibrate (ACCORD), extended-release niacin/laropiprant (HPS2-THRIVE), two cholesteryl ester transfer protein (CETP) inhibitors torcetrapib (ILLUMINATE) and dalcetrapib (DAL-OUTCOMES), the lipoprotein-associated phospholipase A2 inhibitor darapladib (STABILITY), estrogen-progestin, the secretory phospholipase A2 inhibitor varespladib (VISTA-16), and the dual peroxisome proliferator-activated receptor alpha and gamma agonist aleglitazar (AleCardio). Nor have omega-3 fatty acid supplements been shown to reduce ASCVD events in trials performed in Western populations in the statin era.

Prespecified subgroup analyses of some of the older nonstatin trials suggest benefit in some patient groups. However, there may be evidence of harm in other subgroups, further complicating clear treatment recommendations regarding these drugs for obtaining a net ASCVD risk reduction benefit.

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Choice of Therapy in High-Risk Patient Groups

Choices for cholesterol drug therapy to reduce ASCVD risk are summarized in Table 20-5. Patient case examples for NNT in clinical decision-making are shown in Table 20-6. High-intensity statins have the strongest evidence for ASCVD risk reduction. For patients in LDL-C lowering benefit groups who are unable to tolerate a high-intensity statin or who might benefit from additional LDL-C lowering, nonstatins with proven ASCVD risk reduction benefit (see the above section), including ezetimibe and PCSK9 mAbs, are the next best pharmacological option. Newer nonstatins with good LDL-C-lowering efficacy, including inclisiran and bempedoic acid, are potential second-line options. Older nonstatins – bile acid sequestrants, niacin, fibrates and omega-3 fatty acids – remain situationally useful.

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NNT-Guided Decision-Making

The 2018 multi-society cholesterol guideline used the concept of net benefit to determine patient groups most likely to benefit from statin therapy. For primary prevention with LDL-C <190 mg/dL, the NNT to prevent one ASCVD event was compared with the NNH (based on rates of serious myopathy, hemorrhagic stroke and excess diabetes) to determine whether patients had the potential for a net benefit from moderate- and high-intensity statin therapy. This same principle can be applied to determining whether a patient as the potential for a net benefit from the addition of a nonstatin to further reduce ASCVD risk. Table 20-5 shows how the magnitude of LDL-C reduction from a baseline level (in the absence of significant adverse events to drive NNH) can be used in clinical decision-making. This information could also be used in the setting of shared decision making in a clinician-patient discussion that considers the potential for an ASCVD risk reduction benefit, the potential for adverse events and drug-drug interactions, cost, impact on adherence and patient preferences.

Unfortunately, validated risk prediction equations are not available for patients treated with statin therapy. However, event rates in the statin-treated high-risk patients in clinical trials can be used as a rough rule of thumb:

• Acute coronary syndrome and diabetes: very high risk – 20% 5-year ASCVD risk
• Acute coronary syndrome and no diabetes: very high risk – 15% 5-year ASCVD risk
• Chronic CAD and diabetes: very high risk – 15% 5-year ASCVD risk
• Chronic CAD and no diabetes: high risk – 10% 5-year ASCVD risk
• Familial hypercholesterolemia (FH)—do not estimate risk; lifetime ASCVD risk is very high. Consider FH patients without clinical ASCVD as high risk with ≥10% 5-year ASCVD risk; FH patients with clinical ASCVD should be considered very high risk with ≥15% 5-year ASCVD risk.

PCSK9 inhibitors are particularly efficacious in patients with familial (or genetic) hypercholesterolemia and have been shown to reduce ASCVD outcomes. They were well tolerated in ASCVD outcomes trials. These drugs can lower LDL-C 45% to 65% when added to background lipid-lowering therapy in patients with heterozygous FH.

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Comparative Efficacy and Safety: Statins and Nonstatins

Data on the effects of statin and nonstatin therapy on lipids, cardiovascular event reduction and safety that were reported in randomized trials (many of which were summarized in the 2013 ACC/AHA cholesterol guideline report and online full report) reviews, and manufacturers’ package insert are summarized in the three tables below.

Comparative Lipid-Lowering Efficacy

Comparative lipid-lowering efficacy of statins and nonstatins is provided in Table 20-7.

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Cardiovascular Event Reduction Nonstatin Trials

Brief summaries of the CV outcomes trials of nonstatins are listed in Table 20-8.

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Comparative Safety

Table 20-9 compares the adverse effect profile of statins and nonstatins. See individual drug class sections for drug-drug interactions.

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