RECENT RECOMMENDATIONS FOR PATIENTS WITH HEART DISEASE
From Topics and Advances in Internal Medicine, sponsored by University of California, San Diego, School of
Medicine
| NEW GUIDELINES FOR MANAGING HEART FAILURE —Barry H. Greenberg, MD, Professor of Medicine and
Director, Advanced Heart Failure Treatment Program, University of California, San Diego, School of Medicine
|
| Source of guidelines: American College of Cardiology (ACC) and American Heart Association (AHA) issued
new guidelines within past 12 mo
|
| About heart failure (HF): prevalence increasing; ≈90% of cases due to hypertension, diabetes, or coronary disease,
either alone or in combination; injury to heart initiates structural remodeling, leading to progressive deterioration
in cardiac function; management targets neurohormonal activation that drives remodeling; many effective
therapies not used adequately
|
| Advances in therapy: prevention through managing diseases that cause HF; shift from digitalis and diuretics to
blockade of neurohormonal activation through renin-angiotensin and sympathetic nervous systems, including use of
angiotensin-receptor blockers (ARBs); selection of specific β-blockers, rather than β-blockers as class; integration of
device therapy; new strategies to improve utilization of existing therapies
|
| Components of guidelines: derived from evidence from clinical trials combined with expert opinion into framework
physicians can use in daily management of patients
|
 | Class of recommendation: class I—benefit far outweighs risk; therapy should be used; class II—conflicting evidence
and/or divergent opinion over usefulness/efficacy; class IIa—weight of evidence/opinion favors usefulness/efficacy;
class IIb—usefulness/efficacy less well established by evidence/opinion; class III—risk-benefit
ratio not favorable; therapy should not be used
|
| Level of evidence: evaluates data behind recommendation; level A—multiple randomized clinical trials; level B—
single randomized clinical trial; level C—reflects opinion of experts in field
|
| Stages of HF: focus attention on preventing progression; stage A—at high risk for HF but without structural heart disease
or HF symptoms; stage B—structural heart disease but without signs and symptoms of HF; stage C—structural
heart disease with prior or current HF symptoms; stage D—refractory HF requiring specialized interventions
|
| Primary prevention: identify and treat risk factors, eg, hypertension, diabetes, hyperlipidemia, physical inactivity,
obesity, smoking, excessive alcohol intake; early use of neurohormonal blocking agents to prevent progression to overt
HF
|
| Stage A HF: benefits of angiotensin-converting enzyme (ACE)–inhibitor therapy—reduced risk of myocardial infarction
(MI) 20%, risk of stroke 31%, risk of HF 23%; significantly reduced risk of cardiovascular death and total
mortality; benefits of β-blocker therapy—in addition to reducing blood pressure (BP), reduced risk of stroke ≈30%,
coronary heart disease 7%, and risk of HF 42%
|
| Stage B HF: evidence based on post-MI patients with left ventricular (LV) dysfunction; benefits of ACE inhibitor—
reduced all-cause mortality ≈20%; reduced all other cardiovascular end points of study; benefits of ARB therapy—
ARB as effective as ACE inhibitor in reducing mortality; combining ACE inhibitor and ARB produced no added
benefit; benefits of β-blocker therapy—long-term use produced reduction of 23% to 30% in all-cause mortality,
sudden death, and nonfatal reinfarction; however, only ≈33% of post-MI population receive β-blocker therapy, and
patients with LV dysfunction least likely to receive therapy; adding β-blocker to patients on ACE-inhibitor
therapy—adding carvedilol reduced all-cause and cardiovascular mortality
|
| Stage C HF: ACE-inhibitor therapy—class I recommendation; level of evidence A; based on data compiled over
many years establishing benefits, eg, reduced hospitalization and mortality, improved exercise capacity; new
recommendations—use ACE inhibitors in all patients with recent or remote MI, regardless of left ventricular
ejection fraction (LVEF) or presence of HF; use in patients with reduced ejection fraction (EF) and no symptoms
of HF, even if they have not had MI (eg, dilated cardiomyopathy)
|
| ARB therapy: recommended for patients intolerant of ACE-inhibitors; in study of >2000 ACE inhibitor-intolerant patients
with low EF, reduced morbidity and mortality 23% (similar to ACE-inhibitor benefits); new
recommendations—class I; use in patients with current or prior symptoms of HF and low EF who are intolerant of
ACE inhibitors; use in post-MI patients without HF who are ACE-inhibitor intolerant and have low EF; reasonable
alternative to ACE inhibitor as first-line therapy for patients with mild-to-moderate HF and reduced EF (especially
if already on ARB); additional recommendation—beneficial in ACE inhibitor-intolerant patients with low EF and
no symptoms of HF; level of evidence C; recommendation class IIa (based on clinical judgment of experts)
|
| β-blocker therapy: benefits of combining with ACE inhibitor established “beyond a doubt” in 4 large clinical trials
(using carvedilol, metoprolol, or bisoprolol; found significant reductions in all-cause mortality); not all β-blockers
effective (eg, study found bucindolol ineffective); recommendation class I (level of evidence A) limited to
bisoprolol, carvedilol, sustained-release metoprolol succinate (no recommendation for metoprolol tartrate,
atenolol, or propranolol); additional recommendations—indicated in all patients with history of MI, regardless
of EF or presence of HF (recommendation class I; level of evidence C); probably useful in asymptomatic LV
dysfunction (use of β-blocker justified by risk of HF from underlying coronary disease or hypertension); overcoming
impediments to β-blocker therapy—eg, diabetes, peripheral vascular disease, chronic obstructive airway
disease; clinical experience shows most patients able to tolerate effective dose; initiate therapy during
hospitalization—study found post-MI patients discharged on β-blocker much more likely to be maintained on
therapy
|
| Adding third drug to ACE inhibitor– β-blocker combination
|
| Adding ARB: consider in persistently symptomatic patients with low EF; produced additional reduction of 15%
in combined mortality and morbidity
|
| Adding aldosterone antagonist: benefit shown in study that added spironolactone to regimen (mortality risk reduced
by ≈30%); addition reasonable in selected patients with more severe HF and low EF (monitor renal
function and serum potassium levels; if not possible, risk of hyperkalemia may exceed benefit)
|
| Adding isosorbide-hydralazine combination: reduced risk for all-cause mortality 43% in study involving black
patients (with suspected deficiency in nitric oxide production); consider therapy in patients with low EF and
persistent symptoms (recommendation not limited to blacks); also consider therapy in patients intolerant to
ACE-inhibitor or ARB
|
| Selecting add-on therapy: consider in patients who remain symptomatic; base on underlying renal function, serum
potassium level, BP, volume status, and race
|
| Implantable devices: cardiac resynchronization therapy (CRT)—ventricular dyssynchrony present in 15% to
30% of HF patients; biventricular (BiV) pacing improved exercise capacity, relieved symptoms, and reduced morbidity
and mortality; CRT recommended in symptomatic patients already on optimal medical therapy with low EF,
New York Heart Association class III HF, or ambulatory class IV HF with wide QRS (recommendation does not
include atrial fibrillation and underlying right bundle branch block; not used for rescue therapy); implantable cardioverter
defibrillator (ICD)—improved survival, compared to optimal medical therapy, including addition of
amiodarone (etiology ischemic disease in half of patients in study, dilated cardiomyopathy in other half)
|
| Questions and answers: depression and HF—present in 20% to 40% of patients; treated with adequate HF therapy,
education, and antidepressants; β-blocker recommendations—choose between carvedilol and metoprolol succinate;
diastolic HF—termed HF with preserved systolic function; same risk factors and similar outcomes as systolic
HF; medical therapy similar; ARB selection—candesartan and valsartan; for symptomatic HF; losartan reduces risk
of HF in patients with hypertension; exercise tolerance—improved by ACE inhibitors; no short-term benefit from β-
blockers
|
| UPDATE ON SCREENING FOR CORONARY ARTERY DISEASE (CAD)—Daniel M. Blanchard, MD, Professor
of Clinical Medicine, University of California, San Diego, School of Medicine, and Chief of Clinical Cardiology,
UCSD Thornton Hospital, San Diego
|
| Screening based on key assumptions
|
| Asymptomatic people with coronary artery disease (CAD) do worse than asymptomatic people without CAD:
comment—abnormal exercise tolerance test (ETT) predicts increased risk of cardiac event in next 10 yr
|
| Abnormal screening test accurately predicts future adverse events: comment—while abnormal ETT predicts higher
risk of cardiac event in next 5 yr, most common event new-onset angina; abnormal results associated with angina
but not MI (plaque often ruptures in area of limited narrowing not detected on ETT)
|
| Early detection of CAD leads to treatment that improves quantity and quality of life: comment—evidence from
primary prevention studies demonstrate benefit of early treatment of asymptomatic patients with mild CAD (eg,
reduction in risk of MI 35% and reduction in risk of stroke over 3.5 yr ≈30%)
|
| Screening tests provide information not obtainable by other means: comment—not always true; simple risk factor
analysis may provide same information; consider cost; expensive tests may not provide useful information
|
| Continuum of screening tests
|
| Simple tests: blood pressure; lipid panel; C-reactive protein (CRP); ankle-brachial index; blood pressure—huge impact
on CAD mortality, HF, and stroke; tell patients that if BP treated effectively, resulting risk similar to person without
hypertension (shown in 25-yr study); cholesterol—for men 40 yr of age, total cholesterol >240 mg/dL confers 60%
chance of developing coronary disease, compared to ≈30% risk with cholesterol <200 mg/dL
|
| Stress tests: ETT; exercise echocardiography; dobutamine echocardiography; technetium-99m hexakis 2-methoxyisobutylisonitrile
(MIBI) study (nuclear perfusion imaging)
|
| Direct vascular imaging: cardiac catheterization (angiography gold standard); electron beam computed tomography
(EBCT); MRI; multi-slice computed tomography (MSCT)
|
| EBCT: low-radiation imaging of chest for coronary calcification (proof of atherosclerosis); may detect much calcification
when stenosis insignificant; absence of calcification in patients >35 yr of age indicates excellent
prognosis
|
| MSCT: received much attention in media; noninvasive form of angiography; accuracy high when disease absent
but low when present; radiation dose too high; not recommended for screening
|
| Recommendations for screening
|
| Low risk: eg, typical asymptomatic 30- to 40-yr-old patient; BP; lipid panel (total, high-, and low-density lipoprotein
[HDL and LDL] cholesterol; triglycerides); obtain glucose and serum creatinine levels (CRP testing may be
considered)
|
| Intermediate risk: eg, 45-yr-old woman with well-controlled hypertension, family history of CAD, HDL 39 mg/dL,
and LDL 125 mg/dL; same tests as for low-risk patient (add CRP; consider Lp(a) lipoprotein or homocysteine);
consider direct vascular imaging (best applied in this group to detect presence of disease, which would then indicate
need for treatment and for stress testing to determine extent of stenosis)
|
| High risk: eg, patients with diabetes, peripheral vascular disease, previous silent MI, and long-term smokers (all indications
for aggressive treatment); go directly to stress testing to determine risk for coronary events; study data
show abnormal stress testing associated with higher mortality; ACC recommends coronary angiography for
these patients, even if asymptomatic; however, value of revascularization for improving outcome not established
in asymptomatic patients, ie, percutaneous coronary intervention has not been shown conclusively to lower risk
of MI in asymptomatic patients
|
| Questions and answers: noncalcific causes of stenosis—calcification sign of “old plaque” (usually nonstenotic
on angiography); plaque at highest risk relatively new, uncalcified, and highest in lipids; absence of plaque does
not rule out CAD in younger patient; erectile dysfunction—indication of vascular disease and need for screening;
value of CRP testing—currently helpful in treatment decisions in patients at intermediate risk
|
Educational Objectives
| The goal of this program is to educate the listener about new guidelines for managing heart failure and screening for
coronary artery disease (CAD). After hearing and assimilating this program, the clinician will be better able to:
|
| Employ new guidelines from the American College of Cardiology and the American Heart Association in managing
patients with heart failure.
|
| Select therapy for each stage of heart failure based on evidence of benefit from clinical trials.
|
| Identify potential candidates for implantable devices to relieve symptoms of heart failure.
|
| Explain the role of the continuum of screening tests for CAD, including simple tests, stress tests, and direct vascular
imaging.
|
| Choose screening tests for CAD in asymptomatic patients based on their level of risk for CAD.
|
Discussed on This Program
Amiodarone HCl [Cordarone, Pacerone]
Atenolol [Tenormin]
Bisoprolol fumarate [Zebeta]
Bucindolol (investigational)
Candesartan cilexetil [Atacand]
Carvedilol [Coreg]
Isosorbide dinitrate and hydralazine hydrochloride [BiDil]
Losartan potassium [Cozaar]
Metoprolol succinate [Lopressor, Metoprolol Tartrate, Toprol XL]
Propranolol HCl [Inderal, Inderal LA, InnoPran XL]
Spironolactone [Aldactone]
Valsartan [Diovan]
Suggested Reading
Benetos A et al: Why cardiovascular mortality higher in treated hypertensives versus subjects of the same age, in the
general population. J Hypertens 21:1635, 2003; Cleland JG et al: The effect of cardiac resynchronization on morbidity
and mortality in heart failure. N Engl J Med 352:1539, 2005;. Davies RF et al: Asymptomatic Cardiac Ischemia
Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical
therapy versus revascularization. Circulation 95:2037, 1997; Gottlieb SS et al: Effect of beta-blockade on mortality
among high-risk and low-risk patients after myocardial infarction. N Engl J Med 339:489, 1998; Hachamovitch R
et al: Comparison of the short-term survival benefit associated with revascularization compared with medical therapy
in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed
tomography. Circulation 107:2900, 2003; Hunt SA et al: ACC/AHA 2005 Guideline Update for the Diagnosis
and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation
and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians
and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation
112:e154, 2005; Hunt SA et al: ACC/AHA guidelines for the evaluation and management of chronic heart failure in
the adult: executive summary. J Heart Lung Transplant 21:189, 2002; O'Keefe JH Jr et al: Optimal low-density lipoprotein
is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol 43:2142, 2004; Psaty BM
et al: Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and
meta-analysis. JAMA 277:739, 1997; Sever PS et al: Prevention of coronary and stroke events with atorvastatin in
hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian
Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet
361:1149, 2003; Smith SC Jr et al: ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention:
a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
(ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). Circulation
113:e166, 2006; Smith SC Jr et al: ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention-Summary
Article A Report of the American College of Cardiology/American Heart Association Task Force
on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary
Intervention). J Am Coll Cardiol 47:216, 2006; Yusuf S et al: Effects of an angiotensin-converting-enzyme inhibitor,
ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study
Investigators. N Engl J Med 342:145, 2000.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has
been disclosed: Dr. Greenberg—Aventis (research grant); GlaxoSmithKline (speakers bureau, consultant); Pfizer
(speakers bureau, consultant); Merck (speakers bureau); CNP Solutions (consultant); Dr. Blanchard—Novartis (grant
support); Pfizer (speakers bureau); Plough (speakers bureau).
Drs. Greenberg and Blanchard were recorded at Topics and Advances in Internal Medicine, sponsored by the University
of California, San Diego, School of Medicine and held in San Diego, March 2-8, 2006. The Audio-Digest Foundation
thanks the speakers and the sponsor for their cooperation in the production of this program.
|
