Presentation on theme: "Ranexa™ for Chronic Angina An Unmet Need"— Presentation transcript:
1Ranexa™ for Chronic Angina An Unmet Need 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMRanexa™ for Chronic Angina An Unmet NeedEugene Braunwald, MD, FACCHarvard Medical SchoolBrigham and Women’s Hospital
22. Chronic Angina—An Unmet Need (CM) 4/13/2017 4:00 PMCM-2There 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 Physiciansof London. 1772;2:59-67.
3Epidemiology of Chronic Angina 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMEpidemiology of Chronic AnginaAHA reports that at least 6.6 million Americans suffer with angina pectorisDespite therapeutic advances> 13 million episodes of angina a week in the US> 1000 episodes of angina every minuteGrowing prevalence of chronic angina due to reductions in cardiovascular mortalityImproved treatment of angina is an important goal
4Comorbid Conditions Complicate Therapy 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMComorbid Conditions Complicate TherapyStudies of VA patients with CAD demonstrate the following comorbidity incidence ratesDiabetes: 26% to 31%COPD: 13% to 22%Peripheral vascular disease: 16% to 28%Congestive heart failure: 20%Rumsfeld, 1999.
5Persistent Angina Despite Current Drug Therapy 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMPersistent Angina Despite Current Drug TherapyDespite 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 conductionIt would be desirable to develop an anti-anginal drug without these limitations†Pepine, 1994.
6Persistent Angina Despite Percutaneous Intervention (PCI) 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMPersistent Angina Despite Percutaneous Intervention (PCI)Angina at 1-yr follow-up by events during or after initial PCI1 yr after PCI for. . .Symptom relief (N = 1403)Treatment of acute myocardial infarction (N = 352). . . the overall prevalence of angina was 26%Events, nAngina at follow-up, %Events occurring after post-PCI discharge onlyMINo157625.2Yes4438.6CABG152226.39815.3Repeat PCI137024.125034.0Holubkov R, et al. NHLBI Dynamic Registry. Am Heart J. 2002;144:
7Persistent Angina Despite Optimal Revascularization 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMPersistent Angina Despite Optimal Revascularization1 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.*VARIABLE12 MO AFTER INTERVENTIONSTENTING GROUPSURGERY GROUPP valueFree of angina (%)78.989.5<0.001Free of antianginal medication (%)21.141.5Free of angina and antianginal medication (%)19.138.4~ 60% to 80% are still taking anti-anginal medications~ 10% to 20% still have anginaSerruys PW, et al. for the ARTS Study Group. N Engl J Med. 2001;344:
8Self Rating of Health for Angina Patients 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMSelf Rating of Health for Angina Patients100Normal US populationAngina patients9080Generalhealth70Vitality60SF36 scores5040302010PhysicalfunctionBodily painChen AY, et al. Med Decis Making. 1996;16:
9Angina Frequency and Depression 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMAngina Frequency and Depression1957 patients completed SAQ 7 mo after ACSHistory of depression documented in 526 (26.7%) patients following ACSStrong correlation of angina frequency with depression5045403530% depression252015105NoneMonthlyWeeklyDailyAngina frequencyACS = acute coronary syndromeSAQ = Seattle Angina QuestionnaireRumsfeld JS, et al. Am Heart J. 2003;145:492.
10Unmet Need of Chronic Angina 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMUnmet Need of Chronic AnginaAngina continues in many patients despite medical therapy and mechanical revascularizationThe personal burden can deprive many patients of their functional independence, forcing them to downsize their livesThe economic toll of angina places a huge burden on patients, their families, the healthcare system, and society
11Unmet Need of Chronic Angina 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMUnmet Need of Chronic AnginaWhen 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.
12Novel Therapies Needed for a Growing Angina Burden 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMNovel Therapies Needed for a Growing Angina Burden64Patients,millions219002000
13Angina—Evolution of Therapy 2. Chronic Angina—An Unmet Need (CM)4/13/2017 4:00 PMAngina—Evolution of TherapyNitrates blockCABGCCBPCIRanexa™TREATMENTO2 demandO2 supply + + ? +ATP/OLikely mechanisms