drug-related problem
DESCRIPTION
DRUG-RELATED PROBLEM. CHD RISK FACTORS. Modifiable Total- and LDL-Cholesterol HDL-Cholesterol Diabetes Mellitus Hypertension (SBP140 mmHg, DBP90 mmHg or on antihypertensive therapy) Smoking Left Ventricular Hypertrophy Non-Modifiable - PowerPoint PPT PresentationTRANSCRIPT
DRUG-RELATED PROBLEM
CHD RISK FACTORS
Modifiable Total- and LDL-Cholesterol HDL-Cholesterol Diabetes Mellitus Hypertension (SBP140 mmHg, DBP90
mmHg or on antihypertensive therapy) Smoking Left Ventricular Hypertrophy
Non-Modifiable Age (male45 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% efficacyRequires anaesthesiaRisk 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 PROPHYLAXISWARNING:
Patients with underlying structural heart disease receiving long-term 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 FACTORSHigh 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 ValveModerate Risk: Age 65-75 year Diabetes Mellitus Coronary Artery Disease with Preserved LVFLow 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 1.3% 1.9%RF 1.5% 2.9%
No RF 1.0% 0.5%
Bleeds 1.7% 0.9%> 75 y.o.
Strokes 3.6% 4.8%RF 4.2% 7.2%
No RF 2.5% 1.8%
Bleeds 4.2% 1.6% (p=0.04)
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=523Standard
Adjusted-Dose Warfarin (INR 2-3)
N=521Low Intensity
Fixed-DoseWarfarin
(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