Circulation: Heart Failure. 2008;1:81-83
doi: 10.1161/CIRCHEARTFAILURE.108.774323
Challenges for the Basis of Practice |
Challenges for the Basis of Practice in Heart Failure
Lynne Warner Stevenson, MD
From the Advanced Heart Disease Section, Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass.
Correspondence to Lynne Warner Stevenson, MD, Brigham and Women’s Hospital, Division of Cardiology, 75 Francis St, Boston, MA 02115.
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Abstract
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Although evidence from clinical trials has significantly informed
the management of patients with heart failure, many patients
and many clinical situations encountered on a daily basis do
not fit neatly into the narrow definitions of trials. In subsequent
issues,
Circulation: Heart Failure will feature a new series
entitled "Challenges for the Basis of Practice," in which readers
may submit challenging cases that call for management considerations
and decisions that extend well beyond the evidence. An expert
consultant will be invited to comment, and readers can also
submit responses to these challenging situations so that numerous
viewpoints can be explored.
Key Words: heart failure • trials • heart disease
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Introduction
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The science of cardiology has helped propel us into the era
of evidence-based medicine. For heart failure, the traditional
remedy of digoxin was challenged, with subsequent redefinition
of benefits and risks. Rational drug development culminated
in many clinical trials of new therapies such as neurohormonal
antagonists, for which the scope of benefits far exceeds initial
anticipation, and inotropic agents, for which the promise has
never been fulfilled. Level I and level II recommendations have
become the gold and silver currency of the realm. The call to
"Get With The Guidelines" resounds with unprecedented unison
from the American Heart Association, the American College of
Cardiology, and the Heart Failure Society of America.
1,2 Outcomes
with heart failure have dramatically improved as these guidelines
have been incorporated into effective heart failure management.
The disease concept has stretched to encompass the oxymoronic
asymptomatic heart failure, because it is during this time that
treatment may be most effective to improve long-term survival,
as suggested by 12-year follow-up of the Studies Of Left Ventricular
Dysfunction (SOLVD) prevention arm,
3 in which mortality benefit
was not evident during the formal trial.
4 Twenty-five years
ago, patients with heart failure were usually referred only
for research studies or cardiac transplantation, often dying
within 2 years without transplantation. Now, cardiac transplantation
is epidemiologically trivial in heart failure management, with
which many patients survive beyond 10 years with their own hearts.
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Limited Evidence for Practice
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The expanded basis of evidence from clinical trials remains
limited in application to practice. Although the term practice
in relation to medicine has often been invoked as "the repetition
of an action in order to become proficient," this is the last
of the definitions of practice.
5 The first is "the actual application
of a plan or method, as opposed to the theories relating to
it," derived from the Greek praktikos, meaning "concerned with
action," from which also comes the adjective practical. Practical
decisions must be made every day in the care of individual patients.
What are the gaps between trial-based evidence and practice?
Even for successful trials, the fallacy of the mean renders it unlikely that an individual patient will enjoy the average benefit,6 as has been emphasized by Jay Cohn, the founder of the Heart Failure Society of America. This ambiguity of trial results is amplified when beneficial therapies are stacked. While taking 1 proven drug, the trial population that benefits from a new drug may include patients who would derive benefit from both drugs, but it also may combine responders who benefit from one or the other but not both. There is also no reason to believe that the individual is optimally treated with the target dose in the trial, which demonstrates only that aggregate benefit exceeded aggregate toxicity. These uncertainties apply even for the subjects in the trial. Do trial results encompass the larger populations who would have been excluded for comorbidities, many of which increase with age? The Acute Decompensated Heart Failure National Registry (ADHERE), which with more than 100 000 patients hospitalized with heart failure eclipses all trials together,4 has an average patient age of almost 75 years, even in the group with low ejection fraction heart failure; the mean age of patients in heart failure trials is less than 65 years. Fewer than 25% of hospitalized patients would meet heart failure trial criteria,7 yet hospitalization brings most patients to clinical attention. Even if patients and trial subjects were similar, how would trial participants respond in the usual practice settings outside the reimbursed rigor of research organizations? The community experiences with spironolactone demonstrate how a basis of evidence may be altered in translation to practice.8 The relative priority for implantation of devices may be reexamined in a rural indigent setting where patients were not reimbursed for medications.9 Patients differ from the bases of evidence not only in demographics and practice setting, but also for the changing "natural history" of their disease. Since the landmark trials, earlier treatment with angiotensin-converting enzyme inhibitors, β-blockers, and implantable cardioverter-defibrillators has extended the journey and changed the traveler both before and after progression to symptoms that limit daily life.
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Daily Practice: What to Do?
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Despite the inevitable limitations, the trials have established
the key elements from which to design the effective regimen
for an individual patient. Armed with the guidelines, the refractory
questions most commonly remaining on a daily basis are not which
drug to try but when and how to try it.
10 What is target? What
is tolerability? For individual patients, it is often necessary
to compare absolute benefits and risks rather than the relative
benefits and absolute risks as often advertised. What should
be added when first-line therapies are poorly tolerated or ineffective?
Will we ever find surrogate end points for heart failure therapies
as convenient as blood pressure for hypertension and hemoglobin
A1c for diabetes? When does symptomatic relief trump other goals
of therapy? Optimal therapy often requires understanding of
the nature and timing of activities most important to each individual,
and the patient preference for quality versus length of life
remaining.
11
How should the available data be applied to the individual patient? As emphasized during coronary care unit rounds at the University of California Los Angeles by Jan Tillisch, an early proponent of tailored therapy, any fool can make a good decision with good data. If all the relevant data existed, medical care could be relegated to telephone consultants with algorithms. The challenge is to make a good decision with flawed data, which include unbiased trials with limited relevance and relevant experience with unlimited bias. As a keen observer and a clinical trial pioneer, Jay Cohn urges us not to rely exclusively on left brain activity, which converts guidelines to governance and demands new trials to enlighten each uncertainty. Trials can never be performed quickly and cheaply enough to answer even a fraction of the current questions and those raised by each new trial.6,12 The right brain seeks to extrapolate and integrate pieces of information into whole biological and social organisms. Both the left and right brains need to function in daily practice.
The story of β-blocker use provides examples of translation between trials and practice. Reanalyses of the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) demonstrated when and why uptitration of β-blockers was halted before target doses and how benefit on outcomes was equivalent when titration was limited by bradycardia.12 Crucial to defining realistic expectations outside of trials is the prospective analysis of specific strategies, such as the Cleveland Clinic report demonstrating the 70% success of β-blocker initiation, with only half of those patients reaching recommended target doses when diligently pursued in an unselected heart failure clinic population.13 The benefit of β-blockers in patients who did not meet trial criteria was confirmed in a large prospective registry.14 Rather than introducing another new therapy, the Cardiac Insufficiency Bisoprolol Study (CIBIS) III helpfully addressed the common clinical dilemma of which neurohormonal antagonist to start first.15 Such data reinforce the guidelines by positioning them credibly within actual practice.
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Send the Challenge to Practice
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Most questions that we face daily with our patients are unanswered
by guidelines or their practical translations. It is the purpose
of this new section to identify and address challenges that
arise commonly in the practice of heart failure medicine. We
invite clinicians whose practice includes heart failure patients
to summarize in less than 200 words a difficult clinical situation
that requires a decision regarding therapy. As it is anticipated
that this situation will have arisen multiple times, the presentation
should not describe an individual patient, but rather be as
general as possible. A Challenge to Practice article may be
submitted together by up to 5 clinicians, who can include physicians
and/or nurses and will be cited as authors. After selection
and initial publication of the article, an expert consultant
will be invited to review the relevant literature and his or
her own practical approach to the situation. Readers will be
invited to submit brief responses, from which representative
views will be published. We hope that this new feature will
help to guide those who face the challenges, both scientific
and humanistic, of caring for patients with heart failure. Even
when a challenge cannot be satisfactorily addressed by current
experience, the coalescence of efforts should reassure us that
we do not practice alone, but within a dedicated common community.
Finally, we hope that this feature of
Circulation: Heart Failure will not only identify difficult challenges but also inspire
the prospective collection of practical experience from which
those challenges can in the future be better answered.
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Acknowledgments
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Disclosures
None.
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References
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- Jost A, Rauch B, Hochadel M, Winkler R, Schneider S, Jacobs M, Kilkowski C, Kilkowski A, Lorenz H, Muth K, Zugck C, Remppis A, Haass M, Senges J, for the HELUMA study group. Beta-blocker treatment of chronic systolic heart failure improves prognosis even in patients meeting one or more exclusion criteria of the MERIT-HF study. Eur Heart J. 2005; 26: 2689–2697.[Abstract/Free Full Text]
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Abstract
Introduction