# Presentation: 778039

## RanexaTM for Chronic Angina An Unmet Need

**Eugene Braunwald, MD, FACC**
**Harvard Medical School**
**Brigham and Women’s Hospital**

## 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-**

## 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.**

## 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%**

**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 |  |  |
|    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 |

**Angina at 1-yr follow-up by ****events during or after initial PCI**

## Persistent Angina DespiteOptimal Revascularization

**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**. STATUS WITH RESPECT TO ANGINA AND MEDICATION USE AND QUALITY OF LIFE AMONG SURVIVING PATIENTS.*

| VARIABLE | 12 MO AFTER INTERVENTION |  |  |
| --- | --- | --- | --- |
|  | STENTINGGROUP | SURGERY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 |

## 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**

**SF36 scores**

** ****Angina patients**

**Normal US population**

## 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

**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**

**Daily**

**Weekly**

**Monthly**

**None**

**% depression**

**Angina frequency**

**ACS = acute coronary syndrome**
**SAQ = Seattle Angina Questionnaire**

## 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

**Novel Therapies Needed for a Growing Angina Burden**

**0**

**2**

**4**

**6**

**Patients, **
**millions**

**1900**

**2000**

## Angina—Evolution of Therapy

** ****O****2**** demand ****	****+****	****+****	****	****+**
** ****O****2**** supply****	****+****	****	****+****	****?****	****+**
** ****ATP/O****2 ****	****	****	****	****	****	****+**

**Angina—Evolution of Therapy**

**1880 ****	****1965****	****1969 ****	****1975 ****	****1977****	****2004**

**TREATMENT**

**Likely****mechanisms**