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CM-1 Ranexa™ for Chronic Angina An Unmet Need Eugene Braunwald, MD, FACC Harvard Medical School Brigham and Women’s Hospital.

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Presentation on theme: "CM-1 Ranexa™ for Chronic Angina An Unmet Need Eugene Braunwald, MD, FACC Harvard Medical School Brigham and Women’s Hospital."— Presentation transcript:

1 CM-1 Ranexa™ for Chronic Angina An Unmet Need Eugene Braunwald, MD, FACC Harvard Medical School Brigham and Women’s Hospital

2 There is a strong disorder in the breast. The seat of it, and sense of strangling and anxiety with which it is attended, may make it not improperly be called angina pectoris.… Those who are afflicted with it, are seized, while they are walking with a painful and most disagreeable sensation in the breast, which seems as if it would take their life away, if it were to increase or to continue. Heberden. Medical Transaction, Royal College of Physicians of London. 1772;2:59-67. CM-2

3 CM-3 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

4 CM-4 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.

5 CM-5 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.

6 CM-6 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% Holubkov R, et al. NHLBI Dynamic Registry. Am Heart J. 2002;144:826-833. Events, n Angina at follow-up, % Events occurring after post-PCI discharge only MI No157625.2 Yes 4438.6 CABG No152226.3 Yes 9815.3 Repeat PCI No137024.1 Yes 25034.0 Angina at 1-yr follow-up by events during or after initial PCI

7 CM-7 Persistent Angina Despite Optimal Revascularization Serruys PW, et al. for the ARTS Study Group. N Engl J Med. 2001;344:1117-1124. 1 yr after optimal revascularization by stenting or surgery for relief of ischemia (ie, not to prolong survival) … ~ 60% to 80% are still taking anti-anginal medications ~ 10% to 20% still have angina T ABLE 3. S TATUS WITH R ESPECT TO A NGINA AND M EDICATION U SE AND Q UALITY OF L IFE A MONG S URVIVING P ATIENTS.* V ARIABLE 12 MO AFTER I NTERVENTION STENTING GROUP SURGERY GROUP P value Free of angina (%)78.989.5<0.001 Free of antianginal medication (%)21.141.5<0.001 Free of angina and antianginal medication (%) 19.138.4<0.001

8 CM-8 Chen AY, et al. Med Decis Making. 1996;16:169-177. Self Rating of Health for Angina Patients 0 10 20 30 40 50 60 70 80 90 100 Physical function Bodily pain Vitality General health SF36 scores Angina patients Normal US population

9 CM-9  1957 patients completed SAQ 7 mo after ACS  History of depression documented in 526 (26.7%) patients following ACS  Strong correlation of angina frequency with depression Rumsfeld JS, et al. Am Heart J. 2003;145:492. Angina Frequency and Depression 0 5 10 15 20 25 30 35 40 45 50 DailyWeeklyMonthlyNone % depression Angina frequency ACS = acute coronary syndrome SAQ = Seattle Angina Questionnaire

10 CM-10 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

11 CM-11 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.

12 CM-12 Novel Therapies Needed for a Growing Angina Burden 0 2 4 6 Patients, millions 19002000

13 CM-13  O 2 demand +++  O 2 supply ++?+  ATP/O 2 + Angina—Evolution of Therapy 1880 19651969 1975 19772004 TREATMENT Likely mechanisms Nitrates  block CABG CCB PCI Ranexa™ Ranexa™

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