drug-related problem

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