Baylor University Medical Center Proceedings October 2017 - 413

Invited Commentary
Turning guidelines into outcomes
Compliance with guideline-based treatment of acute
coronary syndromes improves long-term patient outcomes,
including survival (1). The most recent American College of
Cardiology/American Heart Association (ACC/AHA) guidelines for non-ST-elevation acute coronary syndromes were published in 2014 (2), with additional recommendations published
in 2015 (3) and 2016 (4). These guidelines are comprehensive,
comprising 150 pages and 363 referenced citations. Changes to
the ACC/AHA guidelines are not uncommon, and as many as
20% of all class I recommendations are downgraded or omitted
in subsequent versions. Downgrades, reversals, and omissions
are most common among recommendations not supported by
multiple randomized clinical trials (RCTs) (5).
In this issue of Baylor University Medical Center Proceedings,
Gill and colleagues report on their center's compliance with
recommended medical therapy following acute coronary syndromes/acute myocardial infarction (6). They assessed whether,
at discharge, patients received the ﬁve drug classes recommended
by current ACC/AHA guidelines: 1) aspirin, 2) thienopyridine
inhibitors, 3) beta-blockers, 4) angiotensin-converting enzyme
inhibitors/angiotensin receptor blocking agents (ACEIs/ARBs),
and 5) high-intensity HMG-CoA reductase inhibitors (statins).
All drug classes carry class I indications, meaning that they are
recommended and should be administered. The level of evidence
for aspirin, thienopyridine inhibitors, and high statin therapy is
strong, with level of evidence A, meaning that there is evidence
from multiple RCTs that use improves patient outcomes. Gill
and colleagues found that >90% of patients left the hospital
with prescriptions for aspirin, thienopyridine inhibitors, betablockers, and statins.
Of interest, only 69% of patients were prescribed highintensity statins. This is disappointing given that high-intensity
therapy is safe and is associated with better patient outcomes
than low- or moderate-intensity therapy (2). Both physicians
and patients appear to remain cautious and may worry about
perceived side eﬀects, especially myalgias. My hope is that future
guidelines will refocus on reduction of low-density lipoprotein (LDL). The use of additional agents such as ezetimibe and
PCSK-9 inhibitors to achieve the lowest possible serum LDL
oﬀers an opportunity to improve patient outcomes beyond what
can be achieved with statin therapy alone.
Gill and colleagues report lower compliance for ACEIs/ARBs
at 67%. However, there is debate as to whether or not routine
ACEI/ARB use improves patient outcomes. There is good evidence (level A) that use in patients with heart failure or reduced
ejection fractions (<0.40) improves outcomes but little evidence
of beneﬁt in patients with preserved ejection fractions (level C). If
Proc (Bayl Univ Med Cent) 2017;30(4):413-414

these agents had no side eﬀects, this might be a purely academic
point, but their use exposes patients to side eﬀects including
hypotension, hyperkalemia, and rare cases of angioedema.
The good news is that while there is some room for improvement, the majority of patients evaluated by Gill et al are
being discharged on the agents they investigated. The relatively
lower rate of ACEI/ARB prescribing may be appropriate based
on current guidelines, and that rate combined with use of lowand moderate-, as opposed to high-intensity, statin therapy is
largely responsible for reducing the compliance rate for all ﬁve
agents to 50%, making overall compliance appear worse than it
is. Of interest, the investigators chose to omit analysis of other
agents with class I recommendations. There is proven beneﬁt
for aldosterone antagonists in select patients with reduced ejection fraction but preserved renal function and normal serum
potassium following myocardial infarction. Use carries a class I
indication in current guidelines and comes with strong evidence
that therapy improves outcomes (level A).
It may surprise some that a prescription for sublingual or
nitroglycerine spray also has a class I recommendation, though
this is based on weak evidence (level C). Class I recommendations also exist for prescribing nondihydropyridine calcium
antagonists for patients with ischemic symptoms, either in
addition to or in place of beta-blockers. Again, there is little
evidence for improved patient outcomes (level C). There is
even a guideline-directed class I indication to use proton pump
inhibitors in patients with a history of gastrointestinal bleeding who require triple antithrombotic therapy (level C). This
recommendation may be revisited in future guidelines given
growing evidence that long-term proton pump inhibitor use
can negatively impact patient outcomes (7).
Left out of the study by Gill and colleagues is an analysis of
agents thought to either oﬀer no beneﬁt or cause harm (class III
recommendations). These include vitamins E, C, B6, and B12,
beta-carotene, and folic acid. High-quality data from RCTs has
shown no beneﬁt (level A). Of greater concern, it appears that
both hormone therapy and nonsteroidal antiinﬂammatory drugs
can worsen outcomes. It is a class III recommendation that hormone therapy should not be initiated and chronic use stopped
if feasible (level A). Nonsteroidal antiinﬂammatory drugs also
appear to cause harm, though the supporting evidence is less
strong (level B).
Current ACC/AHA guidelines seek to be both thorough
and comprehensive. This is an admirable goal but one that
may undermine their purpose, which is to improve patient outcomes. How many physicians will read a 150-page guideline?
One option would be for future guidelines to only include
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