Straight Talk | Although numerous advances are constantly being made in the prevention and treatment of cardiovascular diseases (CVD), still, in 2015, CVD remains the leading cause of morbidity and mortality in the United States (U.S.) and most of Westernized civilization. Several new medications have recently been approved by the FDA for the treatment of heart failure (HF) and dyslipidemia that show tremendous promise for the prevention and treatment of CVD.

Many months ago, ivabradine (Corlanor^®) from Amgen was approved for patients with stable chronic HF and left ventricular ejection fraction ≤ 35% who are in normal sinus rhythm but who continue with a resting heart rate ≥ 70 bpm despite maximally tolerated beta-blockers. In approximately 6,500 systolic HF patients in the SHIFT trial, this agent produced 26% reductions in hospitalizations and death due to HF.

More recently on July 7, 2015, the FDA approved Novartis’ Entresto® (sacubitril/valsartan) to treat chronic HF based on the results of the Paradigm-HF study, where the combined angiotensin receptor blocker (ARB) valsartan and the neprilysin inhibitor sacubitril produced a 20% reduction in major CVD events compared with the angiotensin converting enzyme inhibitor (ACEI) enalapril. Therefore, this agent can be taken with other HF therapies but replacing other ACEI/ARBs for systolic HF. At a cost of nearly $400 per month, this agent will have to compete with very inexpensive generic medications that cost less than a dollar per day. Conceivably, a patient with systolic HF who could not take beta-blockers or who had persistent heart rate ≥ 70 bpm on maximally tolerated beta-blockers could take both of these new HF drugs (Corlanor^® and Entresto^®) at an expensive price tag.

Perhaps more exciting is the recently anticipated FDA approval of two new injectable monoclonal antibodies that inactivate a protein in the liver called proprotein convertase subtilisin/kexin type 9 (PCSK9), and these agents are being marketed by Amgen for evolocumab (Repatha^®) and Regeneron and Sanofi for Alirocumab (Praluent^®). These agents typically produce 60% reductions in low-density lipoprotein cholesterol (LDL-C), and so far in two major New England Journal of Medicine papers in March 2015, showed approximately 50% CVD event reductions at 52-78 weeks of follow-up. Although the potential indications for these agents is huge, the major studies so far have been in high-risk patients with persistently high LDL values despite statins (e.g. LDL values despite statins of approximately 120 mg/dL), those who cannot tolerate statins, and patients with very severe dyslipidemia (e.g. familial hypercholesterolemia/FH). Likely, these agents initially will only be indicated for such patients who continue with very high risk dyslipidemia despite maximally tolerated statins and likely statins and ezetimibe in combination, those who have well-documented statin intolerance, or very high risk patients with FH and severe dyslipidemia. Certainly, there will be considerable potential to expand these initial indications for other groups of patients as the long-term efficacy and safety of these potent agents become available.

However, there will be several major obstacles for the use of these potent, injectable PCSK9 agents. Will all clinicians be able to prescribe these agents or will their use be limited to those with certain sub-specialty interest and training? Will patients with dyslipidemia be routinely receptive to using injectable agents, which has become standard for years for the treatment of diabetes mellitus? Will patients who are intolerant of statins (or who believe that this is the case) be able to tolerate these potent injectable monoclonal antibodies, as they have in relatively small clinical trials? Probably most importantly, what will be the initial price tag on these agents (currently thought to be in the $5,000-$10,000 per year range) and will insurance companies be willing to cover these agents, and what will be required to gain approval for their use and at what co-pay? All of these are legitimate questions that will have to be tackled by patients, insurers, and many groups of clinicians—especially CVD specialists. There is no question that these agents offer great opportunities, but they also pose many tough challenges.

As these four new medications (two for HF and two for severe dyslipidemia) enter our CVD practices, it is worth considering what can be accomplished by greater efforts directed at a healthy lifestyle (HL). I have recently had the opportunity, along with Ross Arena, MD, of the American Heart Association (AHA), and Marco Guazzi, MD, FACC, of the European Society of Cardiology (ESC) and European Association of Cardiovascular Prevention and Rehabilitation (EACPR), and many others, to co-author a policy statement from the AHA, ESC, EACPR, and the American College of Preventive Medicine on healthy lifestyle interventions¹, which was dually published in July 2015, by a leading internal medicine journal, the Mayo Clinic Proceedings² (with a readership of nearly 130,000 physicians, third highest of the world’s medical journals), and by the prestigious European Heart Journal^3,4, which potentially will reach large numbers of primary care clinicians and CVD Specialists. Hopefully, this policy statement encourages an integrated action by all stakeholders to create a much-needed paradigm shift to achieve broad adoption of healthy lifestyle behaviors on a global scale that could potentially reduce the need for some of these other expensive pharmaceuticals and interventional procedures routinely used in the prevention and treatment of CVD.

References

1. Joseph L, Robinson JG. Prog Cardiovasc Dis. 2015;58:19-31.
2. Arena R et al. Mayo Clin Proc. 2015;doi:10.1016/j.mayocp.2015.05.001.
3. Arena R, et al. Eur Heart J. 2015;doi:10.1093/eurheartj/ehv207.
4. Arena R, Lavie CJ, Guazzi M. Eur Heart J. August 2015; in press.

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Carl J. Lavie, MD, is medical director of cardiac rehabilitation and director of exercise laboratories at the John Ochsner Heart and Valvular Institute at the University of Queensland School of Medicine in New Orleans. Dr. Lavie also works in the department of preventive medicine at the Pennington Biomedical Research Laboratory in Baton Rouge.

Keywords: CardioSource WorldNews, Cardiovascular Diseases, Heart Failure, Dyslipidemias

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