STRAIGHT TALK
CARL “CHIP” LAVIE, MD, FACC
New Cardiac Medications:
Great Opportunities
and Tough Challenges
A
lthough 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
44 CardioSource WorldNews
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 subspecialty 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