* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download 3% annual mortality rate
Survey
Document related concepts
Transcript
بسم هللا الرحمن الرحيم Current Treatment of Stable Angina By Ahmed Shafea Ammar MD, FACC Definition of Angina Definition Chronic stable angina (CSA) is defined as the predictable occurrence with exertion or emotional upset of pressure or a squeezing sensation in the substernal area of the chest and adjacent areas, due to transient myocardial ischemia. Angina equivalents (exertional breathlessness, fatigue, and/or nausea) may also occur with physical activity or emotional stress. Clinical Classification of Chest Pain Atherosclerosis Timeline Foam Cells Complicated Lesion/ Fatty Intermediate Fibrous Rupture Streak Lesion Atheroma Plaque Endothelial Dysfunction From First Decade From Third Decade Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104). From Fourth Decade Which Plaque Ruptures??? Vulnerable vs Stable Atherosclerotic Plaques Vulnerable Plaque Lumen Fibrous Cap Lipid Core • Thin fibrous cap • Inflammatory cell infiltrates: proteolytic activity • Lipid-rich plaque Stable Plaque Lumen Lipid Core Fibrous Cap • Thick fibrous cap • Smooth muscle cells: more extracellular matrix • Lipid-poor plaque Libby P. Circulation. 1995;91:2844-2850. Epidemiology of Chronic Angina AHA reports that at least 6.6 million Americans suffer with angina pectoris Despite therapeutic advances – > 13 million episodes of angina a week in the US – > 1000 episodes of angina every minute Growing prevalence of chronic angina due to reductions in cardiovascular mortality Improved treatment of angina is an important goal Comorbid Conditions Complicate Therapy Studies of VA patients with CAD demonstrate the following comorbidity incidence rates – Diabetes: 26% to 31% – COPD: 13% to 22% – Peripheral vascular disease: 16% to 28% – Congestive heart failure: 20% Rumsfeld, 1999. Noninvasive Risk Stratification High-Risk (>3% annual mortality rate) 1. Severe resting LV dysfunction (LVEF < 35%) 2. High-risk treadmill score (score -11) 3. Severe exercise LV dysfunction (LVEF < 35%) 4. Stress-induced large perfusion defect (particularly if anterior) 5. Stress-induced multiple perfusion defects of moderate size 6. Large, fixed perfusion defect with LV dilation or increased lung uptake (thallium-201) 7. Stress-induced moderate perfusion defect with LV dilation or increased lung uptake (thallium-201) 8. Echocardiographic wall motion abnormality (involving > 2 segments) developing at low dose of dobutamine ( 10 mg/kg/min) or at low heart rate (< 120 beats/min) 9. Stress echocardiographic evidence of extensive ischemia Intermediate-Risk (< 3% annual mortality rate) 1. Mild-moderate resting LV dysfunction (LVEF 35% to 49%) 2. Intermediate-risk treadmill score (-11 score 5) 3. Stress-induced moderate perfusion defect without LV dilatation or increased lung uptake (thallium-201) 4. Limited stress echocardiographic ischemia with a wall motion abnormality only at higher doses of dobutamine involving two Low-Risk (< 1% annual mortality rate) 1. Lowest treadmill score (score 5)??? 2. Normal or small myocardial perfusion defect at rest or with stress 3. Normal stress echocardiographic wall motion or no change of limited resting wall motion abnormality during stress ??? Prognostic Markers in Exercise Testing The Duke Treadmill Score (risk calculation) The Duke treadmill score = – exercise time in minutes on Bruce Protocol – minus 5x the ST-segment deviation (during or after exercise, in millimeters) – 4x the angina index (“0” if there is no angina, “1” if angina occurs, and "2" if angina is the reason for stopping the test). works well for both inpatients and outpatients, and equally well for men and women N Engl J Med 1991;325:849-53 Survival According to Risk Groups Based on Duke Treadmill Score Risk Group (Score) Low ( +5) Moderate (-10 to +4) High (< -10) Total 62% 34% 4% Survival 99% 95% 79% N Engl J Med 1991;325:849-53 4 –Year Annual Mortality 0.25% 1.25% 5.00% Use of Exercise Test Results in Patient Management need for additional testing (i.e. stress imaging) risk score predicted average annual mortality recommended treatment low <1% per year medical therapy intermediate 1% to 3% cardiac catheterization exercise imaging study >3% per year cardiac catheterization high-risk score * <5% pt with low-risk treadmill score will be identified as high risk after imaging * those with known LV dysfunction should have cardiac catheterization Therapy of Angina Goals of Current Therapy of Angina Control of Anginal Symptoms Reduction of MACE Drugs in angina and secondary prevention of coronary heart disease For chest pain Nitrates Beta-blockers Calcium antagonists For prognosis Asprin Statin Beta-blockers (after myocardial infarction) Calcium antagonists ACE inhibitor Strategies to control Anginal Symptoms Antianginal Medications ß-Blockers, Nitrates, and Calcium channel blockers (CCBs) ALL are effective antianginal and anti-ischemic agents. However There is no evidence that any of these drugs prolong life or reduce the incidence of MI in patients with CSA (J Cardiovasc Pharmacol Ther. 2004) β-Blockers Beta blockers Beta blockers decrease three major determinants of myocardial oxygen demand – Heart rate – Contractility – Systolic wall tension Beta blockers also allow improved perfusion of the subendocardium by increasing diastolic perfusion time Rebound Phenomena Sudden cessation of beta blocker therapy may precipitate myocardial infarction Those at risk include patients with angina and men over 50 years. Contraindications Asthma Peripheral Vascular Disease – Relative contraindication Raynauds Syndrome Heart failure – Those patients who are dependent on sympathetic drive Bradycardia / Heart block Adverse Drug Reactions Tiredness /fatigue Impotence Bradycardia Bronchospasm Nitrates Hemodynamic Effects of nitrates Dilatation of vessels Veins Arterioles Dilation of venous capacitance vessels Pre-load reduction PCP and PAP End diast. Ventricular pressure Coronary vessels Dilation of peripheral resistance vessels Dilation of coronary vessels After-load reduction Vasal resistance Resistance against cardiac-output Coronary/Venous spasm Coronary blood flow Cardiac output Diastolic wall tension O2 consumption O2 supply Optimized O2 balance PCP= pulmonary capillary pressure PAP= pulmonary arterial pressure The Value of Nitrates as Excellent Combination Partners 1. 2. 3. 4. Nitrates are safe, with rare interactions with other substances (no influence on hepatic metabolism of other drugs). Nitrates have no effect on plasma lipid & glucose levels such as beta-blockers, & do not provoke angina or peripheral edema such as calciumantagonists. Nitrates have beneficial CV effects, which are complementary to the effects of other CV drugs. Nitrates are cost-effective. Nitrates in management of stable angina For Immediate relief Treatment with glyceryl trinitrate/ISDN that can be given as a spray or sublingually. Long term Prophylaxis Treatment with Isosorbide Mononitrate that can be given either in a short-acting or a sustained release formulation. Different Available Nitrate Preparations •Glyceryl Trinitrate •Isosorbide Dinitrate •Isosorbide Mononitrate “nitrate free interval” Tolerance may occur to nitrates. A nitrate free interval of at least 8 hours has been recommended between doses. After overnight free period, sensitivity returns the next day. Adverse Drug Reactions Headache – Increase dose slowly Hypotension – GTN syncope Calcium Channel Blockers Anti-anginal Effects of CCBs CCBs reduce vascular tone and so produce vasodilatation – reduce after load and so myocardial work load Rate limiting CCBs reduce myocardial contractility – reduce myocardial oxygen requirements Rate limiting CCBs reduce heart rate – reduce myocardial oxygen requirement CCBS may also produce coronary vasodilatation – Of little importance or even dangerous Adverse Drug Reactions Ankle oedema – Affects 15-20% of patients and does not respond to diuretics Headache Flushing Palpitation Contraindications Evidence that the use of short acting CCBs (nifedipine) may precipitate acute MI or stroke Post MI – May increase morbidity and mortality in patients with impaired LV function Unstable angina – Evidence that dihydropyridines may increase infarction rate and death in the unstable patient Beta-blockers vs. calcium antagonists: angina relief. Reproduced from ACC/AHA 2002 guideline update for the management of patients with chronic stable angina,3 with permission. Beta-blockers vs. calcium antagonists: exercise time to 1 mm STdepression. Reproduced from ACC/AHA 2002 guideline update for the management of patients with chronic stable angina,3 with permission. New drugs for the treatment of angina pectoris and mechanisms of action Drug Probable mechanism TMZ Metabolic switch Ivabradine Slows heart rate; If channel inhibitor Ranolazin New: slow sodium channel inhibitor; old: metabolic e switch Nicorandil K-channel activator and nitrate like properties Strategies to Reduce MACE 1- Risk Factors Management 2- Asprin 3- Statin 4- B- blocker 5- ACEI 6- Surgery 7- ?? DES Risk Factor Management 1 (Level B), ↓1 year mortality by 50% 2 ( Level A), ↓ CV mortality by 18-20%) Level A = multiple RCTs Level B = single RCT or non RTs Level C= expert openion Risk Factor Management 3 4 ( Level B) 5 ( Level C) Risk Factor Management 6 LDL <100 mg/dl (Level A) Risk Factor Management Diabetes Melletis 7 Patients with angina should make efforts to optimize glycemic control. (Level C) ASPRIN Daily aspirin (81-325 mg) reduced CV mortality and morbidity with an ARR of 12 /1000 patients treated during a 15-month period. (Lancet. 1992; 340: 1421–1425) STATIN No specific trials with lipid-lowering agents have been conducted in patients with CSA. However, in the 4S trial, many patients had CSA and experienced a reduction in angina as well as in MACE Current guidelines recommend a target fasting LDL cholesterol level of <100 mg/dL in patients with CSA. The most recent NCEP-ATP III directive suggests a target of LDL <70 mg/dL for high-risk CAD patients. Β-blockers ß-Blockers have been shown to improve survival and reduce hospitalization in HF patients with an LVEF 40% and in survivors of acute MI. BB should be used as first-line therapy in patients with CSA who have reduced LV systolic function, provided that such patients are on background treatment with ACEI. Practice guidelines recommend that ß-blockers are the first choice of therapy for uncomplicated CSA. (N Engl J Med. 2005; 352: 2524–2533) ACEI ACEI should be used in all patients with CSA, who have : previous MI diabetes, hypertension, proteinuria, CKD LVEF <40% (Circulation. 2005;112:e255-e259.) In older patients with CAD, routine use of ACEI has been recommended on the basis of the positive results of the HOPE and EUROPA trials. CABG & PCI PCI and CABG relieve angina in 80% to 90% of patients. However, compared with medical therapy, these procedures do not prolong life or reduce the incidence of MI, except in patients with LMC disease and in those with 2- or 3vessel disease with decreased LV function (J Cardiovasc Pharmacol Ther. 2004) (2001) (2005) Class I Class IIa Patients with 1 or more significant lesions in 1 or more coronary arteries suitable for PCI with a high likelihood of success and low risk of morbidity or mortality. The vessel (s) to be dilated must subtend a moderate or large area of viable myocardium and have high risk. (Level of Evidence: B) It is reasonable that PCI be performed in patients with CCS class III angina and single-vessel or multivessel CAD who are undergoing medical therapy and who have 1 or more significant lesions in 1 or more coronary arteries suitable for PCI with a high likelihood of success and low risk of morbidity or mortality. (Level of Evidence: B) The recommendation class has been changed to IIa to reflect published data and Writing Committee consensus. Criteria regarding viable and high-risk myocardium have been deleted from this recommendation. CABG vs Medical TTT Gr = Coronary anatomy severity groups (9) (J Thorac Cardiovasc Surg 1996) 95% = 95% prox. Stenosis Hazard ratio = MR CABG vs PCI (J Thorac Cardiovasc Surg 1996) CABG vs PCI Different trials ARTS trial, repeat revascularization Arts MR CM-58 Percutaneous Coronary Angioplasty Compared With Exercise Training in Patients With Stable Coronary Artery Disease A Randomized Trial (Circulation. 2004;109:1371-1378.) ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention—Summary Article A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention) WRITING COMMITTEE MEMBERS Sidney C. Smith, Jr, MD, FACC, FAHA, Chair; Ted E. Feldman, MD, FACC, FSCAI*; John W. Hirshfeld, Jr, MD, FACC, FSCAI*; Alice K. Jacobs, MD, FACC, FAHA, FSCAI; Morton J. Kern, MD, FACC, FAHA, FSCAI*; Spencer B. King, III, MD, MACC, FSCAI; Douglass A. Morrison, MD, PhD, FACC, FAHA, FSCAI*; William W. O’Neill, MD, FACC, FSCAI; Hartzell V. Schaff, MD, FACC, FAHA; Patrick L. Whitlow, MD, FACC, FAHA; David O. Williams, MD, FACC, FAHA, FSCAI PCI vs Medical TTT Meta-analysis of randomised controlled trials (BMJ 321:73-77, 2000) PCI versus Exercise Training Evolution of Therapy PCI TREATMENT TMZ Ivbradine Ranolazine Nicorandil CCB CABG block Nitrates Likely mechanisms O2 demand O2 supply ATP/O2 1880 1965 + + + 1969 1975 1977 + + ? + 2004 + Persistent Angina Despite Current Drug Therapy Despite use of traditional anti-anginal agents (-blockers, CCBs, and nitrates), patients still reported an average of 2 anginal attacks/week† A significant percentage of patients have relative intolerance to full doses of -blockers, CCBs, and nitrates -blockers and many CCBs have similar depressive effects on BP, HR and/or AV nodal conduction It would be desirable to develop an anti-anginal drug without these limitations †Pepine, 1994. Persistent Angina Despite Percutaneous Intervention (PCI) 1 yr after PCI for. . . Symptom relief (N = 1403) Treatment of acute myocardial infarction (N = 352) . . . the overall prevalence of angina was 26% Angina at 1-yr follow-up by events during or after initial PCI Angina at Events, n follow-up, % Events occurring after post-PCI discharge only MI No 1576 25.2 Yes 44 38.6 CABG No 1522 26.3 Yes 98 15.3 Repeat PCI No 1370 24.1 Yes 250 34.0 Holubkov R, et al. NHLBI Dynamic Registry. Am Heart J. 2002;144:826-833. Persistent Angina Despite Optimal Revascularization 1 yr after optimal revascularization by stenting or surgery for relief of ischemia (ie, not to prolong survival) … TABLE 3. STATUS WITH RESPECT TO ANGINA AND MEDICATION USE AND QUALITY OF LIFE AMONG SURVIVING PATIENTS.* VARIABLE 12 MO AFTER INTERVENTION STENTING SURGERY GROUP GROUP P value Free of angina (%) 78.9 89.5 <0.001 Free of antianginal medication (%) 21.1 41.5 <0.001 Free of angina and antianginal medication (%) 19.1 38.4 <0.001 ~ 60% to 80% are still taking anti-anginal medications ~ 10% to 20% still have angina Serruys PW, et al. for the ARTS Study Group. N Engl J Med. 2001;344:1117-1124. Unmet Need of Chronic Angina Angina continues in many patients despite medical therapy and mechanical revascularization The personal burden can deprive many patients of their functional independence, forcing them to downsize their lives The economic toll of angina places a huge burden on patients, their families, the healthcare system, and society Unmet Need of Chronic Angina When angina cannot be eliminated by current drugs, it is often their additive effects on BP, HR, AV conduction, and other important side effects (depression, fatigue, sexual/sleep disorders, etc.) that preclude complete relief. Novel Therapies Needed for a Growing Angina Burden 6 4 Patients, millions 2 0 1900 2000 The 10 most important elements of stable angina management. Ahmed Shafea MD, FACC