Milestones in Acute Myocardial Infarction

1. 1 Milestones in Acute Myocardial Infarction Celebrating 10 Years of Insights from the National Registry of Myocardial Infarction

2. Cardiovascular Disease: Problems/Opportunities • 58 million Americans have one or more types of cardiovascular disease • Approximately 1 million Americans will have a new/recurrent myocardial infarction this year • Coronary heart disease is the single largest cause of death in the United States • Estimated direct/indirect cost: • Coronary heart disease $95.6 billion/year • Congestive heart failure $20.2 billion/year 1998 Heart and Stroke Statistical Update, American Heart Association

3. The Role of Observational Studies • Collect data on selected demographics, practice patterns, and outcomes; describe variations and trends • Complement controlled, randomized trials by comparing data with large groups of patients treated under “real world” conditions • Examine treatment effects on subgroups • Access and analyze clinical issues at less cost than in clinical trials • Generate hypotheses for more complete examination in clinical trials

4. Major Observational Studies • Cooperative Cardiovascular Project • Framingham Heart Study • Myocardial Infarction Triage and Intervention (MITI) • National Registry of Myocardial Infarction (NRMI) • Nurses’ Health Study • Physicians’ Health Study

5. The Framingham Heart Study • Collecting data for over 50 years • 5,209 adult residents of Framingham, MA (2,873 women and 2,336 men) • Collects data from • standardized biennial cardiovascular examinations • daily surveillance of hospital admissions • death information • information from physicians and other sources outside the clinic

6. Framingham Heart Study Contributions • Identified major risk factors associated with heart disease, stroke, diabetes, and other diseases • Identified hypotheses for clinical trials • Created new and larger emphasis for preventive medicine • Over 1,000 published articles

7. The Nurses' Health Study • Collecting data prospectively for nearly 25 years • 121,700 women aged 30 to 55 • Collects data on diet, exercise, smoking, hormone use, alcohol use • Still in contact with 90% of the original participants

8. The Nurses' Health Study Contributions • Demonstrated • drinking coffee does not increase risk of MI • HRT reduces risk of MI and osteoporosis • second hand smoke increases risk of heart disease • Vitamin E can protect against heart disease • Over 250 published articles

9. 1 NRMI: Leadership in Observational Databases • 1990–1994 • Over 350,000 patients • 1,073 hospitals • Identified delays in thrombolytic therapy • 1994–1998 • 771,653 patients • 1,506 hospitals • Assisted in decreasing door to drug time • 1998 - 2000 • Over 500,000 patients • Approximately 1,600 hospitals • Identified untreated eligibles, timely reperfusion, and use of adjunctive therapies

10. NRMI 4 • Initiated in July 2000 • Includes approximately 1,600 hospitals • Collects information on pre-hospital care • Emphasizes process improvement • Provides customized reporting for hospital systems • Identifies eligible untreated patients • Collects information on TNK, GP IIb/IIIa inhibitors, combination therapies • Evaluates of additional medications/procedures • Monitors outcomes such as clinical events and mortality • Compatible with current ACC/AHA guidelines for AMI care

11. NRMI Goal Improve AMI patient care through evaluation/ assessment of care delivery systems Purpose Collect, analyze, and disseminate observational data related to outcomes and quality of care for AMI patients Rationale Ongoing assessment of practice is critical for improving patient care

12. NRMI Publications *additional abstracts and articles are expected for 2000

13. Trends Study validation Time to treatment Diagnosis and treatment of women AMI subgroups Seasonality Use of cardiac procedures Complications of MI/safety Bundle branch block ACE inhibitors JCAHO/ORYX NRMI Highlights

14. National Trends in AMI Management:Door to Drug Time with Thrombolysis NRMI 1 NRMI 2 NRMI 3 (Activase only)(All lytics) (All lytics) 91 60 75th percentile, 52 39 34 25th percentile, 22 NRMI 1:Includes patients where initial ECG was the method of MI diagnosis NRMI 2 and 3: Includes patients with ST on 1st 12-lead ECG results, where 1st 12-lead ECG date/time = 1st 12-lead ECG with ST and/or BBB date/time Non-transfer-in patients

15. National Trends in AMI Management:Door to Balloon Time in PPTCA NRMI 2 NRMI 3 116 108 Includes patients with ST on 1st 12-lead ECG results, where 1st 12-lead ECG date/time = 1st 12-lead ECG with ST and/or BBB date/time (non-transfer-in patients)

16. National Trends in AMI Management:Hospital Length of Stay 7.5 NRMI 1 NRMI 2 NRMI 3 6.8 4.6 3.5 Non-transfer-in patients

17. National Trends in AMI Management: Medications Used Within 24 Hours NRMI 1 NRMI 2 NRMI 3 Non-transfer-in patients

18. NRMI Study Validation Background • Compared NRMI 2 to the Cooperative Cardiovascular Project (CCP) Objective • To evaluate whether or not the simpler case identification and data abstraction processes used in NRMI 2 are comparable to the more rigorous processes used in the CCP Every et al. JACC 1999

19. Hospital-level Comparison: Baseline Characteristics Adapted from Every N, et al. JACC 1999

20. Hospital-level Comparison:Process of Care and Outcomes Adapted from Every N, et al. JACC 1999

21. Patient-level Comparison: Hospital Course Adapted from Every N, et al. JACC 1999

22. NRMI Study Validation: Conclusions • The simpler case identification and data abstraction processes used in NRMI are comparable to the more rigorous processes used in the CCP • NRMI is less expensive to administer and maintain, provides timely and continuous feedback, allows ongoing involvement in data collection and analysis, and facilitates QI activities • In summary, the NRMI is a valid outcomes measurement tool Every N, et al. JACC 1999

23. NRMI: Time to Treatment Studies • Time to treatment • Established factors that can lead to delays in treatment • Suggested areas for process improvement and quality control • Consultation • Compared the time used for consultation to patient outcomes • Door-to-drug time • Identified that longer door-to-drug time increases rates of mortality • Angioplasty • Examined the relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for AMI

24. Factors Influencing Time to Treatment with rt-PA Background • Very early administration of thrombolytic therapy for AMI has significantly reduced mortality Objectives • To evaluate factors which influence • the time from symptom onset to hospital presentation • the time from hospital presentation to the onset of thrombolytic treatment Maynard C, et al. Am J Cardiol 1995

25. Factors that Predict Time to Treatment *Age coded as (1) <60, (2) 61-74, and (3) >75 years of age Maynard C, et al. Am J Cardiol 1995

26. Factors Influencing Time to Treatment: Conclusions • To shorten time to treatment, thrombolytic treatment should be initiated in the Emergency Department • Reducing time to treatment allows more patients to benefit from thrombolytic therapy • The effectiveness of programs aimed at reducing time to treatment should be subject to continuing quality improvement surveillance Maynard C, et al. Am J Cardiol 1995

27. Factors Influencing the Time to Thrombolysis in AMI Background • The extent of myocardial salvage and the magnitude of mortality reduction in patients with AMI are directly related to how early drug is given after the onset of symptoms and how quickly reperfusion occurs Objective • The Time to Thrombolysis Substudy of the NRMI identified factors that delay thrombolytic treatment of patients with ST-segment elevation AMI Lambrew CT, et al. Arch Intern Med 1997

28. Time to Treatment: Cardiac Consultation by Gender P = .001 P = .001 Lambrew CT, et al. Arch Intern Med 1997

29. Time to Treatment: Bedside vs Telephone Consultation P = .001 P = .001 Lambrew CT, et al. Arch Intern Med 1997

30. Time to Treatment: Conclusions • Hospital practices and policies can significantly delay treatment of patients with AMI • Delays in hospital arrival for women are compounded by delays in decisions and initiation of therapy in those women who receive consultation compared with men • ED physicians should have the authority to initiate thrombolytic therapy • Monitoring should be part of a multidisciplinary, continuous QI effort Lambrew CT, et al. Arch Intern Med 1997

31. Consultation Before Thrombolytic Therapy in AMI Background • In-hospital delay is often the largest factor impacting time-to-thrombolytic treatment. Time-consuming ED protocols and practices may explain some of these delays Objectives • To determine whether patients for whom consultation was obtained before initiation of therapy differ in presenting characteristics from their counterparts for who consultation was not obtained • To ascertain differences in time to treatment due to consultation • To determine if time delays associated with consultation affect outcomes Al-Mubarak N, et al. Am J Cardiol 1999

32. ST segment elevation Race (white) Presence of chest pain Male gender ST segment depression MI sx to ECG (per 10 min) History of PTCA HMO vs commercial insurance History of CABG Age >70 years LBBB RBBB Pulmonary edema Normal ECG Odds ratio Factors that Predict Use of Consultation 95% CIP value 0.825 .0001 0.890 .0001 0.928 .047 0.949 .01 0.956 .025 1.003 .0001 1.084 .04 1.088 .009 1.126 .0001 1.184 .0001 1.195 .029 1.278 .0001 1.390 .0001 1.391 .0001 Al-Mubarak N, et al. Am J Cardiol 1999 0.5 0 1.5 2 Consultation Less likely More likely

33. Elapsed Door-to-drug Time After Hospital Arrival No consultation Consultation 0 60 120 180 Al-Mubarak N, et al. Am J Cardiol 1999

34. Consultation Before Thrombolytic Therapy: Conclusions • Consultation was sought in 64% of patients although presenting features were typical, rather than atypical, in most patients • Consultation significantly delayed the administration of lytic therapy and was associated with increased hospital mortality • This study led to the empowerment of ED physicians to initiate thrombolytic therapy Al-Mubarak N, et al. Am J Cardiol 1999

35. Longer Door-to-drug Time Associated with Increased Mortality Background • It has been recommended that all hospitals work to decrease door-needle-time, yet the relationship between door-needle-time and mortality had not been examined Objective • To evaluate whether longer door-to-needle times increase the rate of mortality Cannon et al. JACC 2000 (Abstract, Suppl A)

36. Odds for Mortality Associated with Longer Door-to-drug Time P=0.0001 P=0.01 P=NS n=28,624 n=33,867 n=11,616 n=10,316 Cannon et al. JACC 2000 (Abstract, Suppl A)

37. Longer Door-to-drug Time: Conclusions • Delays in door-to-needle times over 60 minutes increases the rate of mortality • Delays in door-to-needle times over 30 minutes increases the development of left ventricular dysfunction post-MI • These data provide direct evidence of the need to reduce door-to-needle times in order to improve the chances of survival post AMI Cannon et al. JACC 2000 (Abstract, Suppl A)

38. Symptom-onset-to-balloon Time and Door-to-balloon Time with Mortality in Patients Undergoing Angioplasty for AMI Background • Rapid time to treatment with thrombolytic therapy is associated with lower mortality in patients with AMI. However, data on time to primary angioplasty and its relationship to mortality are inconclusive Objective • To test the hypothesis that more rapid time to reperfusion results in lower mortality with primary angioplasty Cannon CP, et al. JAMA 2000

39. Relationship Between Symptom-onset-to-balloon Time Intervals and Mortality P=0.17 P=0.21 P=0.35 P=0.65 P=0.95 Adapted from Cannon CP, et al. JAMA 2000

40. Relationship between Door-to-Balloon Time Intervals and Mortality P<0.001 P<0.001 P=0.01 P=0.29 P=0.35 Adapted from Cannon CP, et al. JAMA 2000

41. Time to Treatment in Angioplasty: Conclusions • More rapid time to reperfusion results in lower mortality with primary angioplasty • Physicians and health care systems should work toward reducing door-to-balloon times to less than 90 minutes (plus or minus 30 minutes) • Door-to-balloon time should be considered when choosing a reperfusion strategy Cannon CP, et al. JAMA 2000

42. Women: Risk of AMI, Treatment Patterns, and Outcomes • Women have a worse prognosis than men after AMI • Women present at an older age, may have more advanced disease, often have coexisting conditions, and may get less aggressive referral, diagnosis, and treatment • Two key studies have used the NRMI database to examine sex-based differences in patients with AMI

43. Thrombolytic Therapy Demographics Adapted from Chandra NC et al. Arch Intern Med 1998 P <.001

44. Mortality in Men and Women, by Age  Adapted from Chandra NC et al. Arch Intern Med 1998

45. Treatment of Women with MI: Conclusions • Women have higher mortality rates and are less likely to receive thrombolytic therapy, cardiac catheterization, coronary artery bypass surgery, aspirin, heparin, and beta-blockers • These findings contribute to the growing body of evidence suggesting that women receive insufficient referral and treatment for AMI Chandra NC et al. Arch Intern Med 1998

46. Sex-based Differences in Early Mortality Background • To further investigate mortality patterns among women with AMI, Vaccarino and colleagues analyzed NRMI 2 data Objective • To test the hypothesis that younger, but not older, women have higher in-hospital mortality rates than their male peers Vaccarino V, et al. N Engl J Med. 1999

47. Rates of Mortality During Hospitalization, by Age P <0.001 Vaccarino V, et al. N Engl J Med. 1999

48. Sex-based Differences in Early Mortality After MI: Conclusions • The younger the women, the greater the relative risk for mortality compared to men • The risk for mortality is greater for women less than 75 years, but after the age of 75, the risk for men is greater • Under the age of 50, women have a 2:1 greater risk for mortality • Younger women with MI are a high-risk group Vaccarino V, et al. N Engl J Med. 1999

49. Sex-based Differences in AMI: Conclusions • Many earlier observational studies on AMI did not analyze sex-based differences • The size and scope of the NRMI databases allow identification of important findings on the treatment of women: • younger women with AMI are a high risk group requiring special attention • substantial differences exist in the way women and men are treated for AMI • Further research is warranted

50. Seasonality in AMI • Seasonal patterns in mortality from AMI have been established. However, it is unclear if a seasonal rhythm for onset of AMI exists. • Two studies used NRMI databases was to determine if there is a seasonal variation in the occurrence of AMI and if so, if it is present in all geographic areas.