DRUG-RELATED
PROBLEM
CHD RISK FACTORS
Modifiable
  Total- and LDL-Cholesterol
  HDL-Cholesterol
 Diabetes Mellitus
 Hypertension (SBP140 mmHg, DBP90
mmHg or on antihypertensive therapy)
 Smoking
 Left Ventricular Hypertrophy
Non-Modifiable
 Age (male45 y.o., female 55 y.o. or
postmenopausal not receiving HRT)
 Family History of CHD (male 55 y.o.,
female 65 y.o.)
SIGNS / SYMPTOMS
 Loss of organized atrial
contractions (“atrial kick”)
which contributes to
approximately 18% of CO
 VRR 130-180 bpm,
irregularly irregular
 Palpitations, chest discomfort,
 exercise tolerance, SOBOE,
dyspnea on exertion
  CO (confusion, fatigue,
weakness, dizziness)
DISEASE-INDUCED?
 Valvular / Rheumatic Heart
Disease (20%)
 Nonvalvular / Non-Rheumatic
Heart Disease
Cardiovascular (65%):
- MI, HT, pericarditis, cardiomyopathy,
CABG
Pulmonary:
- PE, pneumonia, COPD
Endocrine (25%):
- Thyrotoxicosis
 Lone (3-10%)
 No identifiable cause
DISEASE-INDUCED?
P
I
R
A
T
E
S
DRUG-INDUCED?
 Alcohol (“Holiday Heart”)
 Theophylline/Caffeine
 Sympathomimetics
 Thyroid Medications
 MAO Inhibitors
 Amphetamines
 Cocaine
 Digoxin
TREATMENT
REQUIRED?
 Control Ventricular Response
Rate (VRR):
 < 100 bpm at rest
 Relieve symptoms
 Improves hemodynamics
 Prevent ventricular fibrillation
 Restore and maintain normal
sinus rhythm (NSR):
 Duration of arrhythmia (< 1 yr)
 Underlying disease process
 Left atrial size (< 5 cm)
 Reduce risk of stroke
CONTROL VRR
Digoxin
Class II (propranolol, metroprolol)
Class IV (diltiazem, verapamil)
RESTORE AND
MAINTAIN NSR
 Direct-Current Cardioversion
(DCC):
85% efficacy
Requires anaesthesia
Risk of sinus arrest
Indicated for symptomatic patients (i.e.
chest pain, pulmonary edema, syncope)
 Pharmacologic (50-90% efficacy):
Class Ia (procainamide, quinidine)
Class Ic (propafenone)
Class III (amiodarone, sotalol)
LONG-TERM (> 1 YEAR)
ANTIARRHYTHMIC
PROPHYLAXIS
WARNING:
Patients with underlying structural
heart disease receiving longterm Class I antiarrhythmics
have an increased risk of
mortality.
Recommend:
Several recurrences
Severe symptoms during episode
Not Recommended:
First episode
Reversible causes (post-CABG,
alcohol, hyperthyroid)
STROKE RISK
FACTORS
High Risk: >5% thromboembolic rate/year
 Prior Stroke/TIA/Systemic Embolus
 History of hypertension
 Poor Left Ventricular Function
 Age > 75 years
 Rheumatic Mitral Valve Stenosis
 Prosthetic Heart Valve
Moderate Risk:
 Age 65-75 year
 Diabetes Mellitus
 Coronary Artery Disease with Preserved
LVF
Low Risk (15% of patients):
1% thromboembolic rate/year
 Age < 65 years
 No Clinical/Echocardiographic Evidence of
CVD
BLEEDING
RISK FACTORS
 Elevated INR
 High variability in INR
 > 3 comorbid conditions
(renal failure, female, diabetes,
cerebrovascular disease)
 Severe hypertension
 Previous GI/GU bleed
 Seizure disorder
 Risk of falling
 Age > 75 years (controversial)
 Alcoholism (controversial)
WARFARIN VS PLACEBO:
PRIMARY PREVENTION
AFASAK (Atrial Fibrillation Aspirin
Anticoagulation Study)
SPAF (Stroke Prevention in Atrial
Fibrillation)
BAATAF (Boston Area Anticoagulation
Trial)
CAFA (Canadian Atrial Fibrillation
Anticoagulation Study)
SPINAF (Stroke Prevention in
Nonrheumatic Atrial Fibrillation)
WARFARIN VS PLACEBO:
SECONDARY PREVENTION
EAFT (European Atrial Fibrillation
Trial)
ESPS2 (European Stroke Prevention
Study)
SIFA (Studio Italiano Fibrillazione
Article)
WARFARIN VS PLACEBO:
META-ANALYSIS
 Overall reduction in the
incidence of stroke:
 68% (p<0.001)
 Absolute annual reduction:
 3.1% (NNT = 32)
 Annual frequency of major
bleeding events:
1.3% (warfarin)
1.0% (placebo)
Arch Intern Med 1994;154:1449-57
ASA VS PLACEBO:
PRIMARY PREVENTION
AFASAK (Atrial Fibrillation Aspirin
Anticoagulation Study)
SPAF (Stroke Prevention in Atrial
Fibrillation)
SPAF III LOW RISK STUDY (Stroke
Prevention in Atrial Fibrillation)
ASA VS PLACEBO:
META-ANALYSIS
 Overall reduction in the
incidence of stroke:
 21 % (p=0.05) (heterogeneous)
 Absolute annual reduction:
 1.8 % (8.1 TO 6.3%)
Arch Intern Med 1997;157:1237-40
Ann Intern Med 1999;131:492-501
J Gen Intern med 2000;15:56-67
WARFARIN VS ASA:
AFASAK 2 (Atrial Fibrillation Aspirin
Anticoagulation Study)
SPAF II (Stroke Prevention in Atrial
Fibrillation)
WARFARIN VS ASPIRIN:
SPAF II (Lancet 1994)
WARFARIN
ASA
 75 y.o.
Strokes
RF
No RF
Bleeds
1.3%
1.9%
1.5%
1.0%
2.9%
0.5%
1.7%
0.9%
3.6%
4.8%
4.2%
2.5%
7.2%
1.8%
4.2%
1.6% (p=0.04)
> 75 y.o.
Strokes
RF
No RF
Bleeds
COMBINATION
WARFARIN AND ASA
SPAF III HIGH RISK STUDY
(Stroke Prevention in Atrial
Fibrillation)
AFASAK 2 (Atrial Fibrillation Aspirin
Anticoagulation Study)
WARFARIN AND ASPIRIN:
SPAF III (Lancet 1996)
1044 “high risk” patients
•poor LVF
(recent CHF / EF<0.25)
•SBP>160 mmHg
•Prior stroke/TIA
•Female> 75 y.o.
N=523
Standard
Adjusted-Dose
Warfarin
(INR 2-3)
N=521
Low Intensity
Fixed-Dose
Warfarin
(INR 1.2-1.5)
AND
ASA 325 mg/day
WARFARIN AND ASPIRIN:
SPAF III (Lancet 1996)
6th ACCP CONFERENCE
ON ANTITHROMBOTIC
THERAPY (January 2001)
Any High Risk Factor OR > 1
Moderate Risk Factor:
Warfarin (INR 2-3; target 2.5)
One Moderate Risk Factor:
ASA 325 mg/day OR
Warfarin (INR 2-3; target 2.5)
Low Risk (Age < 65 yr, No evidence of
CVD):
ASA 325 mg/day