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PCSK9i (protein convertase subtilisin/kexin type 9 inhibitors) are set to revolutionize the treatment of hypercholesterolemia in the management of atherosclerotic risk, but numerous reports have detailed unprecedented barriers to access for these drugs. To overcome these challenges, our group created a model to facilitate provision of this new therapy for patients who qualify according to Food and Drug Administration criteria. This report details the real-world follow-up experience of PCSK9i use in a large patient cohort structured to ensure rigor in data collection, analysis, and interpretation. The 271 patients approved and actively followed in our PCSK9i clinic between July 2015 and August 2018 represent a 97% approval rate from insurance, with 28% of prescriptions requiring at least one appeal. Over 50% of patients were statin intolerant. On average, there was a median lapse of 15 days between initial visit and insurance approval. PCSK9i therapy was affordable for most patients, with an average monthly out-of-pocket expense of $58.05 (median $0). Only 2.3% of patients were unable to initiate or continue therapy because of cost. Reductions from baseline in LDL (low-density lipoprotein) cholesterol and Lp(a) (lipoprotein [a])were comparable to published reports with median reductions of 60% and 23% at 1 year, respectively. PCSK9i therapy was well-tolerated overall, though 9% of patients reported adverse events, and 5% of patients discontinued due mostly to musculoskeletal and flu-like symptoms. Our practice model demonstrates that PCSK9i therapy can be accessed easily and affordably for the majority of eligible patients, resulting in dramatic improvement in lipid profile results. Moreover, our registry data suggest that results from the prospective clinical trials of PCSK9i on LDL and Lp(a) reduction and on tolerability are applicable to a real-world cohort.

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) are an innovative treatment option for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require further lowering of low-density lipoprotein cholesterol. However, the high costs of these agents have spurred payers to implement utilization management policies to ensure appropriate use. We examined prior authorization (PA) requirements for PCSK9is across private and public US payers., Methods and Results: We conducted an analysis of 2016 formulary coverage and PA data from a large, proprietary database with information on policies governing >95% of Americans with prescription drug coverage (275.3 million lives) within 3872 plans across the 4 major insurance segments (commercial, health insurance exchange, Medicare, and Medicaid). The key measures included administrative PA criteria (prescriber specialty, number of criteria in PA policy or number of fields on PA form, requirements for medical record submission, reauthorization requirements) and clinical/diagnostic PA criteria (approved conditions, required laboratories or other tests, required concomitant therapy, step therapy requirements, continuation criteria) for each of 2 Food and Drug Administration-approved PCSK9is. Select measures (eg, number of PA criteria/fields, medical record submission requirements) were obtained for 2 comparator cardiometabolic drugs (ezetimibe and liraglutide). Between 82% and 97% of individuals were enrolled in plans implementing PA for PCSK9is (depending on insurance segment), and one third to two thirds of these enrollees faced PAs restricting PCSK9i prescribing to a specialist. For patients with familial hypercholesterolemia, diagnostic confirmation via genetic testing or meeting minimum clinical scores/criteria was also required. PA requirements were more extensive for PCSK9is as compared with the other cardiometabolic drugs (ie, contained 3×-11× the number of PA criteria or fields on PA forms and more frequently involved the submission of medical records as supporting documentation)., Conclusions: PA requirements for PCSK9is are greater than for selected other drugs within the cardiometabolic disease area, raising concerns about whether payer policies to discourage inappropriate use may also be restricting access to these drugs in patients who need them., (© 2018 American Heart Association, Inc.)

Background: Prescription drug copayments and cost-sharing have been linked to reductions in prescription drug use and expenditures. However, little is known about their effect on specific health outcomes., Objective: To evaluate the association between prescription drug copayments and uncontrolled hypertension, uncontrolled hypercholesterolemia, and prescription drug utilization among Medicaid beneficiaries with these conditions., Subjects: Select adults aged 20-64 from NHANES 1999-2012 in 18 states., Measures: Uncontrolled hypertension, uncontrolled hypercholesterolemia, and taking medication for each of these conditions., Research Design: A differencing regression model was used to evaluate health outcomes among Medicaid beneficiaries in 4 states that introduced copayments during the study period, relative to 2 comparison groups-Medicaid beneficiaries in 14 states unaffected by shifts in copayment policy, and a within-state counterfactual group of low-income adults not on Medicaid, while controlling for individual demographic factors and unobserved state-level characteristics., Results: Although uncontrolled hypertension and hypercholesterolemia declined among all low-income persons during the study period, the trend was less pronounced in Medicaid beneficiaries affected by copayments. After netting out concurrent trends in health outcomes of low-income persons unaffected by Medicaid copayment changes, we estimated that introduction of drug copayments in Medicaid was associated with an average rise in uncontrolled hypertension and uncontrolled hypercholesterolemia of 7.7 and 13.2 percentage points, respectively, and with reduced drug utilization for hypercholesterolemia., Conclusions: As Medicaid programs change in the years following the Affordable Care Act, prescription drug copayments may play a role as a lever for controlling hypertension and hypercholesterolemia at the population level.

Background: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused primarily by mutations in the low-density lipoprotein receptor gene. Familial hypercholesterolemia is characterized by exceedingly high levels of low-density lipoprotein cholesterol (LDL-C) and subsequent premature coronary heart disease. Homozygous FH (HoFH) is less prevalent, but more severe, than heterozygous FH. Current treatment options include dietary therapy, lipid-lowering agents (eg, statins), and/or LDL-C apheresis., Purpose: Despite the available treatment options, patients with FH rarely attain treatment goals. This review will focus on 2 novel agents, lomitapide and mipomersen, with recently approved US Food and Drug Administration (FDA) labeling for use in patients with HoFH., Conclusions: Lomitapide and mipomersen are 2 agents with novel mechanisms of action and the ability to significantly lower LDL-C, apolipoprotein B, and non-high-density lipoprotein cholesterol levels. A black box warning exists for lomitapide and mipomersen regarding the risk for transaminase elevations and hepatic steatosis. Furthermore, these agents are currently restricted for use only in patients with HoFH and have been required by the FDA to participate in a Risk Evaluation and Mitigation Strategy., Clinical Implications: These new agents offer additional treatment options for clinicians managing patients with HoFH, but it remains uncertain whether lomitapide and mipomersen will gain FDA approval for use in patients with heterozygous FH or in the general population. Cost and concern for the risk for hepatotoxicity will remain limiting factors to these agents being more widely used.

Background: The coronary artery calcium (CAC) score predicts future coronary heart disease (CHD) events and could be used to guide primary prevention interventions, but CAC measurement has costs and exposes patients to low-dose radiation., Methods and Results: We estimated the cost-effectiveness of measuring CAC and prescribing statin therapy based on the resulting score under a range of assumptions using an established model enhanced with CAC distribution and risk estimates from the Multi-Ethnic Study of Atherosclerosis. Ten years of statin treatment for 10,000 55-year-old women with high cholesterol (10-year CHD risk, 7.5%) was projected to prevent 32 myocardial infarctions, cause 70 cases of statin-induced myopathy, and add 1108 years to total life expectancy. Measuring CAC and targeting statin treatment to the 2500 women with CAC>0 would provide 45% of the benefit (+501 life-years), but CAC measurement would cost $2.25 million and cause 9 radiation-induced cancers. Treat all was preferable to CAC screening in this scenario and across a broad range of other scenarios (CHD risk, 2.5%-15%) when statin assumptions were favorable ($0.13 per pill and no quality of life penalty). When statin assumptions were less favorable ($1.00 per pill and disutility=0.00384), CAC screening with statin treatment for persons with CAC>0 was cost-effective (<$50 000 per quality-adjusted life-year) in this scenario, in 55-year-old men with CHD risk 7.5%, and in other intermediate risk scenarios (CHD risk, 5%-10%). Our results were critically sensitive to statin cost and disutility and relatively robust to other assumptions. Alternate CAC treatment thresholds (>100 or >300) were generally not cost-effective., Conclusions: CAC testing in intermediate risk patients can be cost-effective but only if statins are costly or significantly affect quality of life.

Purpose of Review: Lowering LDL cholesterol (LDL-C) reduces vascular risk. Current guidelines recommend initiating statin therapy in patients with a yearly coronary heart disease risk of around 1.5-2%, and most clinicians prescribe standard statin regimens (e.g. 40 mg simvastatin daily). However, there is some uncertainty about whether patients at somewhat lower vascular risk should receive lipid-lowering therapy and also how intensive statin treatment should be., Recent Findings: Lowering LDL-C by around 1 mmol/l reduces vascular mortality and major morbidity by about one-fifth, and more recent randomized trials comparing intensive versus standard statin regimens confirm that a further LDL-C reduction of 0.5 mmol/l results in an additional 15% reduction in the risk of a major vascular event. Furthermore, statin therapy significantly reduces vascular mortality and morbidity in patients with less than 1% annual risk of a major vascular event. In general, statins are safe and well tolerated, but 80 mg simvastatin is associated with an unacceptably high risk of statin-induced myopathy., Summary: Lipid-lowering therapy with statins is cost-effective for a wider range of patients than currently recommended. Intensive statin therapy is associated with larger reductions in vascular risk, and lower LDL-C targets (particularly for higher-risk individuals) should help reduce vascular mortality and major vascular morbidity substantially.

Purpose of Review: Policy decision-making in cardiovascular disease is increasingly informed by the results generated from decision-analytic models (DAMs). The methodological approaches and assumptions used in these DAMs impact on the results generated and can influence a policy decision based on a cost per quality-adjusted life year (QALY) threshold. Decision makers need to be provided with a clear understanding of the key sources of evidence and how they are used in the DAM to make an informed judgement on the quality and appropriateness of the results generated., Recent Findings: Our review identified 12 studies exploring the cost-effectiveness of pharmaceutical lipid-lowering interventions published since January 2010. All studies used Markov models with annual cycles to represent the long-term clinical pathway. Important differences in the model structures and evidence base used within the DAMs were identified. Whereas the reporting standards were reasonably good, there were many instances when reporting of methods could be improved, particularly relating to baseline risk levels, long-term benefit of treatment and health state utility values., Summary: There is a scope for improvement in the reporting of evidence and modelling approaches used within DAMs to provide decision makers with a clearer understanding of the quality and validity of the results generated. This would be assisted by fuller publication of models, perhaps through detailed web appendices.

Background: Despite the importance of secondary prevention, nonadherence rates for patients with myocardial infarction (MI) range from 13% to 60% for prescribed, evidence-based medicines. Although rates and consequences of discontinuance vary for different medications, the existing literature provides little insight into reasons for discontinuance., Objective: To address this gap, we explored clopidogrel and cholesterol-lowering therapy (CLT) discontinuance after an MI to understand patients' reasons for stopping these 2 medications., Methods: In this qualitative descriptive study, 2 groups of patients who stopped a heart medication-either clopidogrel or CLT-were recruited from a prospective MI registry. Patients who discontinued CLT (n = 29) or clopidogrel (n = 11) were interviewed within 18 months of hospitalization. Patients were recruited and interviewed until data saturation was achieved. The Health Belief Model was used as an organizing framework in analyzing and coding the narrative data. The codes were then summarized for each group and compared to identify similarities and differences in reasons for CLT and clopidogrel discontinuance., Results and Conclusions: The most common reason for CLT discontinuance was adverse effects that were painful and interfered with daily life. Less common reasons for discontinuance were prescription confusion, cost, mistrust in medicines/healthcare system, and preference for alternative therapies. Reasons for clopidogrel discontinuance were duration confusion, adverse effects, and cost. Although doctors stopped patients' clopidogrel in preparation for surgery, doctors conceded to discontinuance of CLT for patients who experienced adverse effects after trying 2 to 3 different CLTs. Patients who discontinued CLT were more likely to believe that they did not need the treatment than do patients who discontinued clopidogrel. Clinicians should be aware that reasons may vary across patients and medication class for prematurely stopping therapy; thus, proactive interventions should be targeted to address these differences. Identifying at-risk patients for targeted interventions to prevent premature cardiac medication discontinuation is vital.

The preponderance of evidence confirms the importance of aggressive lipid modification in patients at risk for coronary heart disease (CHD). However, data suggest that this information is underimplemented in the clinical setting, even in patients with existing CHD, in whom the greatest benefit of such treatment has been shown. The fact that many practitioners do not pursue a proven treatment strategy in patients who qualify must be redressed through education and reinforcement of existing recommendations. In the present review, the current clinical and mechanistic understanding of the benefit of aggressive lipid management is summarized, with a focus on the clinical implications of recent findings. These include growing public awareness of cholesterol as a modifiable CHD risk factor, recommendations for earlier and more aggressive intervention in patients with existing disease, and discussion of the cost-effectiveness of lipid-regulating therapy. Despite the secular trend of declining CHD morbidity and mortality rates in recent years, CHD remains the leading cause of death in both men and women in the United States. It is imperative to prevent any reduction in public focus on primary and secondary prevention.

Clinical, angiographic and ultrasonographic data from new trials of the primary and secondary prevention of atherosclerosis and coronary artery disease with lipid-lowering therapy are reviewed. In the West of Scotland Coronary Prevention Study pravastatin significantly decreased cardiovascular events in asymptomatic men with moderate hypercholesterolaemia without increasing noncardiovascular mortality. The favourable effects of pravastatin may also extent to carotid arteries. Preliminary data from the Cholesterol and Recurrent Events Study testify to the value of lowering cholesterol in patients with near normocholesterolaemia and established coronary artery disease. New angiographic and ultrasonographic studies concur with findings of previous trials and indicate that the benefits of statins extend to noncoronary vascular beds. Meta-regression analysis of angiographic trials shows that optimal treatment for regression of coronary artery disease should aim for an LDL-cholesterol of approximately 3.0 mmol/l. The value of regulating high plasma triglyceride and low HDL-cholesterol has been emphasized by a bezafibrate study. Angiographic trials also suggest that aggressive pharmacotherapy may match the beneficial effects of LDL apheresis in heterozygous familial hypercholesterolaemia. Post-hoc analyses from previous angiographic trials have provided new hypotheses for future studies. The implications of the new evidence presented is examined, as well as issues of cholesterol screening and the economics of treatment.

Background: A broad, scientific consensus supports the role of cholesterol as a risk factor for coronary heart disease and agrees that lowering cholesterol levels will reduce coronary heart disease incidence. Cost-effectiveness analysis is a potentially powerful method for measuring the benefits to be achieved by expenditures of health care dollars., Methods and Results: The literature related to the effectiveness and cost-effectiveness of cholesterol lowering was reviewed. Application of cost-effectiveness methodology to the question of cholesterol reduction generally supports the use of population-wide educational programs and the aggressive use of cholesterol-lowering therapy for the secondary prevention of subsequent coronary events in persons with preexisting coronary heart disease. For primary prevention, however, therapy with medication has a favorable cost-effectiveness ratio only in identifiable high-risk persons, and the different costs of the various available medications should be taken into account. Therapy with medications, especially for primary prevention, would be more appealing if the price of the available medications were lower., Conclusions: High priority should be given to research that could validate these cost-effectiveness projections as well as to further studies of the elderly and women, in whom direct data on the precise costs, risks, and benefits of interventions to lower cholesterol remain sparse.