Page 479 - Read Online

Page 4 of 9 Agdamag et al. Vessel Plus 2020;4:42 I http://dx.doi.org/10.20517/2574-1209.2020.60

PCSK9 INHIBITORS IN PATIENTS WITH HEART FAILURE
The medical management of patients with heart failure has become increasingly more complex over the
past decades with several new drug classes added to the treatment pool. Diuretics are the most commonly
used agents aiming to achieve euvolemia. Medications that reduce sympathetic nervous system activity
or block the renin-angiotensin-aldosterone axis have been shown to improve outcomes significantly and
are recommended by all guidelines [28,29] . In contrast, the routine use of lipid lowering agents remains
controversial in this population. Statins may be indicated for patients with ischemic cardiomyopathy
or with high 10-year ASCVD risk score. However, their use is not established in individuals with non-
ischemic heart failure etiology. In two randomized controlled trials (CORONA and GISSI-HF), moderate
dose rosuvastatin administration was not associated with improved mortality or a decrease in adverse
cardiovascular events in patients with heart failure of any cause, despite significant reduction in LDL-C [30,31] .
The possible benefit of targeting the PCSK9-LDL-R pathway in this population also remains uncertain. In a
recent sub-study of BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure), frozen
serum samples obtained from patients with worsening heart failure were analyzed for circulating levels of
[32]
PCSK9 and LDL-R . Authors described an independent and significant association between the activity
of this axis and adverse clinical outcomes. However, it remains unclear if elevated circulating PCSK9 level
is merely a marker or possibly a contributor to increased mortality. New evidence suggests a possible
additional benefit of PCSK9 inhibitors stemming from their anti-inflammatory properties [11,33] . However, as
of today, no randomized controlled trials have been published assessing the efficacy of PCSK9 inhibitors in
patients with heart failure. Further studies are warranted to establish their benefit in this population.

PCSK9 INHIBITOR USE IN PATIENTS WITH DURABLE MECHANICAL CIRCULATORY
SUPPORT DEVICES
The use of durable mechanical circulatory support (MCS) devices has been steadily rising over the past
decade in patients with advanced heart failure. Despite the technological advancements and dramatic
improvement in clinical outcomes with newer generation devices, neurological complications remain
relatively high in these patients [34,35] . With the newest generation Heart Mate 3 LVAD (Abbott Laboratories,
[36]
Minneapolis, MN), the cumulative rate of stroke remains at around 10% at two years . Many of these
ischemic and hemorrhagic cerebrovascular events are related to hypertension, micro embolization,
infection and changes in cerebral autoregulation, owing to the continuous flow profile. Although many
patients supported with MCS have underlying ischemic cardiomyopathy and diffuse atherosclerotic
vascular disease, there is limited evidence for statin therapy to improve survival in this population. Vieira
and colleagues found that statin use after LVAD implantation is associated with lower rates of ischemic, but
[37]
not hemorrhagic strokes . On further evaluation, it was hypothesized that the pleiotropic effects of statins,
including their anti-inflammatory, immunologic and anti-thrombotic effects, are primarily responsible for
[37]
these clinical benefits . No specific guidelines currently address statin use in patients receiving LVAD, and
providers often rely on risk calculators and consider other indications when prescribing statins. Similarly,
there are no published data or guidelines on PCSK9 inhibitor use in this population. More studies are
needed to evaluate how these novel lipid lowering agents are tolerated in patients supported with an LVAD
and how these may affect long-term clinical outcomes, including stroke.

PCSK9 INHIBITORS IN HEART TRANSPLANT RECIPIENTS
Heart transplantation is the most definitive treatment option for patients with end stage heart failure.
Advances in post-transplant care has led to significant reduction in rejection rates, infections, and the
incidence of malignancies. The improvement in graft and patient survival unmasked cardiac allograft
vasculopathy (CAV) as the leading cause of morbidity and mortality a few years following transplantation.
With the prevalence of CAV rising to 47% at 10 years, effective and early prevention are critically
important [38,39] . The predominant histological feature of CAV is the progressive, diffuse thickening of the