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DRUG-RELATED PROBLEM

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

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DRUG-RELATED PROBLEM

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  1. DRUG-RELATED PROBLEM

  2. 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.)

  3. 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)

  4. 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

  5. DISEASE-INDUCED? P I R A T E S

  6. DRUG-INDUCED? • Alcohol (“Holiday Heart”) • Theophylline/Caffeine • Sympathomimetics • Thyroid Medications • MAO Inhibitors • Amphetamines • Cocaine • Digoxin

  7. 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

  8. CONTROL VRR Digoxin Class II (propranolol, metroprolol) Class IV (diltiazem, verapamil)

  9. 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)

  10. LONG-TERM (> 1 YEAR) ANTIARRHYTHMIC PROPHYLAXIS WARNING: 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)

  11. 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

  12. 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)

  13. 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)

  14. WARFARIN VS PLACEBO:SECONDARY PREVENTION EAFT(European Atrial Fibrillation Trial) ESPS2 (European Stroke Prevention Study) SIFA (Studio Italiano Fibrillazione Article)

  15. 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

  16. 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)

  17. 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

  18. WARFARIN VS ASA: AFASAK 2 (Atrial Fibrillation Aspirin Anticoagulation Study) SPAF II(Stroke Prevention in Atrial Fibrillation)

  19. 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)

  20. COMBINATION WARFARIN AND ASA SPAF III HIGH RISK STUDY (Stroke Prevention in Atrial Fibrillation) AFASAK 2 (Atrial Fibrillation Aspirin Anticoagulation Study)

  21. 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

  22. WARFARIN AND ASPIRIN: SPAF III (Lancet 1996)

  23. 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

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