Cardiovascular disease prevention in the health economics era: Clinicians need more than just prescription pads.

This inaugural issue of the American Journal of Preventive Cardiology provides a perfect opportunity to shine a light on a veiled cardiovascular risk factor that has emerged over the last few years. The risk is insidious, and it disproportionately impacts the elderly, the handicapped, and those within the lower socio-economic class. I am not referring to obesity, hypertension, dyslipidemia, or any of the other disorders that will be frequent subjects of future articles in this journal. Rather, I am alluding to a phenomenon, the inability of patients to access available and appropriate FDA-approved event-reducing medications prescribed by their healthcare practitioners. Though not a standard sign, symptom, or disease state, this is an affliction and it has been proved to increase cardiovascular event rates among Americans with established cardiovascular disease [1].

This economically driven restriction of drug access is largely a consequence of convoluted relationships that have developed among doctors, patients, pharmaceutical companies, and payers. Who pays for prescriptions, patients or payers? Who pays a doctor’s bill, the insurance company or the patient? Who determines the price of a drug, a pharmaceutical company, pharmacies, payers, or pharmacy benefit managers (PBM)? It is challenging to answer any one of these seemingly simple questions. An important consequence of such murky relationships has been the shift of medical decision making from doctor and patient to payer. The payer now sits in the driver’s seat, wielding the final say over many medical decisions. Though the clinician writes the script, the payer approves or denies the medication. The previously sacrosanct and fully protected patient/doctor relationship has been punctured; payers now unabashedly call the shots. Clinicians and patients have been rendered helpless and frustrated, feeling as though the prospect of effecting change is remote, if not impossible. Doctors and patients can’t impact drug prices, prior authorizations, or insurance company policies. Or can we? Do we have the power to help reshape the system and make medicines accessible to those who need and deserve them? I believe we do, and more importantly we must. Two enduring examples will help illuminate these problems and highlight some solutions.

In 2015, two proprotein convertase subtilisin/kexin inhibitors (PCSK9i) were approved by FDA for the treatment of hypercholesterolemia. Perhaps the greatest advance in lipid lowering therapy in 30 years, these drugs answered the hopes of patients and clinicians by offering a novel mechanism to markedly lower cholesterol among some of the 80% of high-risk patients inadequately controlled [2]. Within months however, preventive cardiologists and others recognized that although effective and safe, PCSK9i were being almost uniformly denied by payers [3]. Prior Authorization (PA) forms up to 17 pages long were just one of the barriers payers forged. Another effective impediment to access was the establishment of untenably high co-pays. Patients, unable to either acquire or afford the drugs prescribed by their clinicians, were rendered more vulnerable to stroke, heart attack, and other cardiovascular events [1].

Responding to this challenge the American Society for Preventive Cardiology (ASPC) led a charge to identify and comprehend the medication access problems and then solve them. We created a Town Hall series inviting all stakeholders: payers, pharmaceutical companies, pharmacists, patients, clinicians of all types, lawmakers, and others. As we understood more, we responded more effectively. One ASPC-driven publication clearly defined “maximally tolerated statins” and “clinical ASCVD” and even created a single-page prior authorization form in order to facilitate proper drug approval [3]. These steps were fairly effective; some payers accepted the PA form and the published clinical definitions gave doctors leverage when they contested drug denials. The improvement in access was insufficient though, so in 2018 the pharmaceutical companies reduced their list prices by 60%. Though most stakeholders expected that patients would instantly benefit from this substantial price reduction, that did not occur. Instead, payers chose to continue their tight control over access to these medications. In 2020 approximately 70% of payers placed PCSK9i on a “non-preferred” tier, pushing patient co-pays up to 50% of the drug’s cost and continuing to make PCSK9i unaffordable and inaccessible to many [4]. It has been demonstrated that higher co-pays yield greater drug abandonment rates, with > $80 per month translating into a 50% abandonment rate and >$350 per month yielding a 75% abandonment rate [4]. Prior to the 2018 price reduction co-pays for PCSK9i were in the $200–400 range for Medicare patients and abandonment rates were correspondingly high. In view of persistently high copays we can anticipate that this year nothing will change. The payers’ decision to sustain inordinately high copays will ensure that PCSK9i will remain unaffordable. Consequently, many Medicare patients will be deprived of their CV benefits [1]. Some of these people will experience what should have been a preventable heart attack, stroke, or even CV death [1]. Regardless of the reason for restricted access, the end result is the same: patients endure more cardiovascular events. Fortunately though, groups like Partnership to Advance Cardiovascular Health, the Familial Hypercholesterolemia Foundation, the National Lipid Association, the National Forum, American Society for Preventive Cardiology, and others continue to monitor and respond to such non-medical threats to appropriate drug access, a fundamental aspect of the patient/doctor relationship.

Recently, another similar struggle has emerged. In late 2019 Icosapent ethyl, a highly purified form of eicosapentaenoic acid (EPA), received FDA approval for reduction of the risk of CV events. In view of its impressive clinical trial findings, this inexpensive and well-tolerated drug is poised to dramatically reduce CV events [5]. Even the economic watchdog ICER (Institute for Clinical and Economic Review) found it to be highly cost effective [6]. In view of the enormous burden of CVD in the US - 92 million Americans have some form of heart disease - and the excellent efficacy and safety characteristics of the drug – a large randomized, controlled trial demonstrated significant reductions in MACE - it seems obvious that all patients who qualify according to FDA indications should have easy access to icosapent ethyl [5]. But, as we continue to see with PCSK9i, payers are pushing back. Placing the drug on a non-preferred status and introducing new PA forms are techniques being employed again as barriers to access. The argument promulgated has been that although the drug is priced low, its “budget impact” will be vast because of the large number of people who will benefit. I encourage the reader to mull over this last sentence, as its faulty logic is stunningly careless. In cardiovascular disease prevention we search for inexpensive medications to decrease risk among large numbers of patients. Icosapent ethyl is a superb example of such drug: natural, safe, accepted by patients, endorsed by providers, supported by data. And yet patients and clinicians will once again find themselves in a battle for access. Clearly, we have more work to do.

Last year ASPC launched a novel educational initiative, Health Economics 101, A Must for the Modern Clinician [7,8]. It is a primer in Health Economics and truly a must for those of us who want to arm ourselves with the knowledge needed to help us succeed in the modern era of economically driven medicine. This year we will introduce its sequel: Health Economics 2.0, The Clinical Ramifications of Pharmaceutical Rationing. The program will build on its predecessor’s base and enable clinicians to more easily navigate the tortuous systems enveloping what should be writing and delivering a simple prescription. In 2020 and 2021 Health Economics 2.0 will be held at major meetings and, along with Health Economics 1.0, it will be available on line at www.aspconline.org as well as on the ASPC mobile app.

In sum, we have identified a novel risk factor for cardiovascular disease: It is the inability of many patients to receive appropriately prescribed, effective, FDA-approved medications proven to reduce CV events, thereby increasing their risk for major adverse cardiovascular events. As with other CV risks our job is to diagnose and treat this when it afflicts our patients. We now have the resources to do so. Additionally, as in the case of other risk factors, coordinated care is required in order to achieve optimal outcomes: Medical doctors, ARNPs, societies and groups such as those mentioned above should support ongoing communication and coordination of efforts. Clinicians armed with a fundamental knowledge of health economics can better navigate the murky waters in which we have all been thrown. Just as we do with other newly identified disorders, we must keep this one on the tips of our diagnostic tongues. By recognizing the problem and using all necessary resources we will certainly prevail and in so doing move one step closer to restoring the sanctity of the patient/doctor relationship.

Relationships with industry

Amgen Consultant/Advisory Board/Speaker, Regeneron Consultant/Advisory Board, Sanofi Consultant/Advisory Board, Akcea Consultant/Advisory Board/Speaker, Boehringer Ingelheim Consultant/Advisory Board, Lily Consultant/Advisory Board, Esperion Consultant/Advisory Board, Amarin Consultant/Advisory Board, Madrigal Consultant.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Amgen Consultant/Advisory Boards/Speaker Sanofi Consultant/Advisory Boards, Regeneron Consultant/Advisory Boards, Amarin Advisory Boards