Download CORONARY HEART DISEASE IN END STAGE RENAL DISEASE

CORONARY HEART
DISEASE IN ESRD
PATIENTS
INTRODUCTION
• Cardiovascular disease is the single best
predictor of mortality in patients with
ESRD.
Fig 5. Causes of death among period prevalent patients 1997–1999,
treated with hemodialysis, peritoneal dialysis, or kidney transplantation.
NKF K/DOQI guidelines
RISK FACTORS
• A large percentage of dialysis patients have
traditional risk factors for cardiovascular disease.
• Many dialysis patients have more than one of
these risk factors, resulting in an even higher risk
of adverse outcomes.
• Some risk factors result directly from the loss of
renal function and/or the utilization of measures
aimed at replacing such function.
RISK FACTORS
• CKD alone: Should be considered to be in the
high risk category, equivalent to that of patients
with known CHD. Risk increases with increasing
renal dysfunction and/or severity of proteinuria.
• Increased calcium intake and disorders of
mineral metabolism: may directly enhance
coronary arterial calcification. Vascular
calcification among dialysis patients is also
associated with abnormalities of calcium and
phosphorus, dialysis vintage, hypertension, and
other factors.
RISK FACTORS
• Anemia.
• Uremia and Renal replacement therapy: Result
in an increase of oxidant stress producing
complement fragments and cytokines, increased
adhesion molecules in endothelial cells, and other
proinflammatory factors that may provide the
proper milieu for the development of accelerated
atherosclerosis.
RISK FACTORS
• Increased plasma homocysteine levels: due to
decrease renal removal, low serum levels of
vitamin cofactors required for homocysteine
metabolism.
• Abnormal nitric oxide metabolism: inhibition of
NO synthesis may cause vasoconstriction and
hypertension, thereby resulting in adverse
cardiovascular outcomes.
• Increase fibrinogen levels.
CLINICAL MANIFESTATIONS
• Angina during dialysis: most common
presentation in patients with coronary
disease.
• Exercise-induced Angina, dyspnea,
arrhythmias.
• Silent Myocardial ischemia.
SCREENING AND DIAGNOSIS
Who should be screened?
SCREENING AND DIAGNOSIS
(K/DOQI guidelines)
• All patients upon initiation of renal replacement
therapy, independent of symptoms.
• Kidney transplant wait list patients should be reevaluated at intervals ranging from every year to
every three years.
• Change in symptoms and signs, including
recurrent hypotension, heart failure that is
unresponsive to changes in dry weight, and
hypotension that prevents attaining dry weight.
SCREENING AND DIAGNOSIS
(Modalities)
• Base line ECG and ECHO for all patients.
• Exercise or pharmacologic stress Echo: the
K/DOQI guidelines state that dobutamine Echo
was more sensitive in diagnosing obstructive
coronary artery disease in the dialysis population.
• Angiography: should be considered in dialysis
patients who are candidates for coronary
interventions and have positive stress tests or have
signs and/or symptoms of coronary artery disease.
SCREENING AND DIAGNOSIS
(Angiography)
• Among those with residual renal function,
N-acetylcysteine and iso-osmolar
radiocontrast media should also be
administered to help decrease the risk of
radiocontrast nephropathy.
• Administration of sodium bicarbonate
hydration is not recommended, given the
increased intravascular volume.
SCREENING AND DIAGNOSIS
(Acute MI)
• Diagnosis is based upon the clinical presentation,
the electrocardiogram, and relevant laboratory
tests.
• Serum cardiac enzymes: CK-MB and cTnT
alone are often associated with false positive
results. The most specific marker for myocardial
damage among patients with ESRD appears to be
serial measurements of cTnI.
SERUM CARDIAC ENZYMES
Use in prognosis
• There is an increasing evidence that elevations in
serum troponin levels in stable asymptomatic
patients with ESRD are predictive of worse long
term and short term outcomes.
• Further study is required to determine whether a
more aggressive approach to treatment should be
employed among asymptomatic patients with
ESRD and elevated cTnT and (possibly) Creactive protein levels.
PREVENTION
• Hypertension: The targeting goal should ideally
be set individually based upon the patient's cardiac
and neurologic status, comorbid conditions, age,
and other clinical factors.
• Goal:
– pre-dialysis value <140/90 mmHg on no medications, if
possible.
– BP <135/85 mmHg during the day and <120/80 mmHg
by night, if clinical characteristics permit.
PREVENTION
• Hypertriglyceridemia: treatment with
lifestyle changes and a triglyceridelowering agent should be considered for
those with fasting triglycerides ≥500
mg/dL that cannot be corrected by
removing an underlying cause.
PREVENTION
• Hypercholesterolemia: There are no randomized,
controlled trials testing the hypothesis that
dyslipidemias cause ACVD in patients with CKD.
A number of retrospective, cross-sectional studies
found no relationship, or even paradoxical
correlations between dyslipidemias and ACVD in
hemodialysis patients. However, none of these
studies was a long-term, prospective, cohort study,
and it is likely that illness, inflammation, and poor
nutrition confounded the relationships between
dyslipidemias and ACVD.
PREVENTION
• Hypercholesterolemia
– 4D Trial ( Deutsche Diabetes Dialyse Studie):
randomized, placebo-controlled study in 1,255
type 2 diabetic patients on chronic HD. Out of
those patients, 619 were treated with 20 mg
atorvastatin compared to 636 matched controls
treated with placebo for a median of 4 years.
Wanner, C, Krane, V, Marz, W, et al. Atorvastatin in patients with \Type 2 diabetes mellitus undergoing hemodialysis.
N Engl J Med 2005; 353:238. Copyright © 2005 Massachusetts Medical Society.
Wanner, C, Krane, V, Marz, W, et al. Atorvastatin in patients with \Type 2 diabetes mellitus undergoing
hemodialysis. N Engl J Med 2005; 353:238. Copyright © 2005 Massachusetts Medical Society.
PREVENTION
• Hypercholesterolemia:
– 4D Trial: the study did not exclude the possibility that
statin therapy provides some long-term cardiovascular
benefits in dialysis patients with increased cholesterol
levels. Statin therapy was well tolerated and not
associated with an increased incidence of adverse
effects.
– SHARP and AURORA: Ongoing trials that will test the
efficacy of statins in patients with CKD, including
those with ESRD.
PREVENTION
• Hypercholesterolemia:
– Recommendation: statins should be
administered to dialysis patients with elevated
serum LDL cholesterol. (Weak evidence)
– Goal:
• serum LDL-cholesterol < 100 mg/dL.
• Non-HDL cholesterol concentration < 130 mg/dL
among patients who have a goal LDL cholesterol at
baseline and fasting triglycerides ≥200 mg/dL.
PREVENTION
• Hyperhomocysteinemia: HOST study
compared the effect of folic acid,
pyridoxine, and vitamin B12 versus placebo
on vascular outcomes in 2056 patients with
CKD, including ESRD. At a median followup of 3.2 years, there was no difference
between the groups in terms of total
mortality, myocardial infarction, stroke, and
amputations.
PREVENTION
• Increased calcium phosphorus product:
the K/DOQI guidelines recommend that the
calcium phosphate product be maintained
below 55 mg2/dL2 in dialysis patients.
However, it is unclear whether maintaining
lower calcium/phosphorous levels is
associated with a decreased risk of heart
disease.
PREVENTION
• Increase oxidative stress: some recommend
vitamin E. (Level C)
• Fish oil: Only one randomized study of the effects
of omega-3 fatty acids for secondary prevention
has been performed in dialysis patients. The
ability of this approach to prevent coronary events
in patients with ESRD requires further study,
particularly in larger trials.
TREATMENT
RECOMMENDATIONS
• Anemia: Goal Hemoglobin level 11 to
12g/dl. Higher Hemoglobin levels are NOT
RECOMMENDED. (Level B)
• Hypertension: Should be controlled by
removal of fluid and, if necessary,
antihypertensive medications.
PHARMACOLOGIC THERAPY
OF STABLE ANGINA
• The optimal choice of antianginal agent
varies with the presence or absence of
comorbid conditions, principal route of
elimination and effect upon blood pressure,
particularly in patients prone to hypotension
during dialysis.
• Nitrates and, if necessary, beta-blockers or
calcium channel blocker. (Level C)
PHARMACOLOGIC THERAPY
OF STABLE ANGINA
• Aspirin: Although there is a paucity of data
related to the effectiveness and safety of
ASA in patients with ESRD the K/DOQI
guidelines recommend the administration of
aspirin. (Level C)
PHARMACOLOGICAL THERAPY OF
ACUTE CORONARY SYNDROMES
• All dialysis patients presenting with ACS should
be treated as in the nondialysis population, with
the exception of specific attention to drugs that
have altered clearances in kidney failure. (Level
C)
• The mortality after acute MI in dialysis patients
has been reported to be approximately 75% in 2
years, in part due to inadequate post-MI treatment.
PHARMACOLOGICAL THERAPY OF
ACUTE CORONARY SYNDROMES
• Aspirin, beta-blockers and Nitroglycerin
should be given, if indicated and appropriately
dosed, in dialysis patients. (Level C)
• Thrombolytic agents: should be administered,
when appropriate, to patients with renal failure.
However, PCI is the preferred modality in most
patients, as recommended by K/DOQI guidelines.
(Level C)
PHARMACOLOGICAL THERAPY OF
ACUTE CORONARY SYNDROMES
• Thrombolytic agents: caution with
Hypertension.
• Glycoprotein IIb/IIIa inhibitors: should
be administered when indicated. Abcximab
may be preferred since it does not require
any renal dose adjustment. Tirofiban
requires dose adjustment. Eptifibatide is
contraindicated. (Weak evidence)
PHARMACOLOGICAL THERAPY OF
ACUTE CORONARY SYNDROMES
• Heparin: the mainstay of therapy in
unstable angina and is typically used in
acute myocardial infarction for patients with
or without renal insufficiency.
Administration requires careful attention to
dosing, particularly with low molecular
weight.
INVASIVE MANAGEMENT
• The short-term and long-term mortality after
coronary revascularization procedures in dialysis
patients is considerably higher than those in the
general population.
• Based upon retrospective and observational
studies, the K/DOQI guidelines recommend that
CABG and PCI are appropriate revascularization
techniques. (Level C)
• The indication for these procedures are similar to
the ones for patients without renal failure.
INVASIVE MANAGEMENT
• CABG is the preferred therapy in those with
three vessel and/or left main disease.(Level
C)
• CABG may also be preferred in those who
are candidates for internal mammary graft
utilization, given a possible survival
advantage over PCI.
INVASIVE MANAGEMENT
• There is no data on the impact of using sirolimus-eluting,
paclitaxel-eluting stents or brachytherapy on re-stenosis
after PCI in dialysis patients, but these techniques may
improve the long-term outcome of dialysis patients after
PCI.
• Follow up after PCI: The clinical detection of restenosis
after initially successful coronary artery intervention may
be more difficult in the dialysis patient because symptoms
can mimic those resulting from recurrent ischemic disease.
Provocative stress imaging should be considered to detect
clinically silent re-stenosis 12-16 wks after PCI.