1. Secondary Prevention Goal: Prevention of recurrent events
Life style changes – exercise, smoking, weight
Hypertension
Diabetes
Aspirin
ACE/ARB
Influenza vaccine
LIPID LOWERING - CONTROVERSIAL
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2. Lipid Lowering in the Elderly
Ref: Electronic Publication. Braunwald’s Heart Disease
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3. Limitations of Lipid Control
Benefits in most trials did not start for 3-5 years
TNT – excluded patients above the age of 75
High dose statins may be associated with more myopathy: CKD, old age, Frailty, Multisystem disease, Drug interactions
? Use the lowest effective dose.
TREATING TO NEW TARGETS
N ENGL J MED 2005; 352: 1425
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4. Pharmacologic Therapy
NITROGLYCERIN
BETA
BLOCKER
CALCIUM
CHANNEL
IMPROVE SUPPLY ++ - +
LOWER DEMAND
++++
ACUTE BENEFIT
+++
CHRONIC BENEFIT
+/-
+++++
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5. Nitrates Mechanism: NO contributor, vasodilate
Physiology: Reduce preload, afterload, Dilate collaterals, counteract spasm
Action: Rapid onset
Administration: iv, sl, buccal, topical, (PO)
Limitations
Tachyphylaxis rapidly develops
Hypotension, tachycardia
MAINSTAY FOR ALL PATIENTS WITH ANGINA
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6. Pitfalls of nitrates in elderly
Postural hypotension
Rapid absorption with Isosorbide dinitrate
Interaction with alpha blockers (BPH in men)
Bradycardia
Volume depletion
Approaches
Isosorbide mononitrate
Topical nitrates
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7. Beta Blockers
Mechanism: Competitive inhibition at beta 1 and beta 2 receptors
Physiology: Reduce demand through slower heart rate, lower BP, and reduced contractility
Action: Variable onset, usually slow
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8. BETA Blockers Pitfalls in Elderly
Titrate to resting heart rate – sick sinus syndrome
? Role of pacemaker for therapy
Inadequate doses to achieve reduced contractility
Short actions of drugs – metoprolol, atenolol – multiple dosing.
CNS penetration – lipophilic
Favor nadolol, atenolol
Only anti-anginal with evidence for prolonging life in patients post MI
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9. Calcium Channel Blockers
Mechanism: Vascular Smooth muscle relaxation and reduced contractility
Physiology:
Demand reduced by reducing BP, contractility, and heart rate (for some)
Supply improved by blocking spasm
Action: Duration longer, rapid onset
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10. Calcium Channel Blockers
Limitations in elderly
Dihydropyridines induce reflex tachycardia
Contraindicated in low EF patients post MI
Edema formation (venous insufficiency)
Sick sinus syndrome – non dihydropyridines, combinations with beta blockers
Constipation
Postural hypotension
Role: “triple therapy”
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11. Dose: 500 mg bid increasing to 1000 mg bid
Added to existing antianginals
Contraindications:
• With pre-existing QT prolongation
• With hepatic impairment (Child-Pugh Classes A [mild], B [moderate] or C [severe])
• On QT prolonging drugs
• On potent and moderately potent CYP3A inhibitors, including diltiazem
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12. Ranolazine: Most recenta Anti-anginal
Piperazine derivative
Anti-ischemic effect without effect on heart rate or blood pressure
Inhibits late Ina (slowly inactivating component of sodium current) = reduce intracellular calcium and sodium overload
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13. Effects of Ranolazine With Atenolol, Amlodipine, or Diltiazem on Exercise Tolerance and Angina Frequency in Patients With Severe Chronic Angina
Randomized, 3-group parallel, double-blind, placebo-controlled trial of 823 eligible adults.
Patients received twice-daily placebo or 750 mg or 1000 mg of ranolazine
Treadmill exercise 12 hours (trough) and 4 hours (peak) after dosing was assessed after 2, 6 (trough only), and 12 weeks of treatment.
Trough exercise duration increased by seconds … vs 91.7 seconds in the placebo group (P = .01).
The increases did not depend on changes in blood pressure, heart rate, or background antianginal therapy and persisted throughout 12 weeks.
JAMA. 2004;291:
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14. Ranolazine: MERLIN-TIMI 36 JAMA. 2007;297:1775-1783
6560 patients over 442 sites (17 countries)
ACS, TIMI > 3
Placebo v IV then po ranolazine (1000 mg bid)
Endpoint: Occurrence of Death, MI, Recurrent Ischemia Result: No Difference
Median follow: 348 days
Context Ranolazine is a novel antianginal agent that reduces ischemia in patients with
chronic angina but has not been studied in patients with acute coronary syndromes (ACS).
Objective To determine the efficacy and safety of ranolazine during long-term treatment
of patients with non–ST-elevation ACS.
Design, Setting, and Patients A randomized, double-blind, placebo-controlled,
multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who
were treated with ranolazine (initiated intravenously and followed by oral ranolazine
extended-release 1000 mg twice daily, n=3279) or matching placebo (n=3281), and
followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for
Less Ischemia in Non−ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial
between October 8, 2004, and February 14, 2007.
Main Outcome Measures The primary efficacy end point was a composite of cardiovascular
death, myocardial infarction (MI), or recurrent ischemia through the end
of study. The major safety end points were death from any cause and symptomatic
documented arrhythmia.
Results The primary end point occurred in 696 patients (21.8%) in the ranolazine group
and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence
interval [CI], ; P=.11). The major secondary end point (cardiovascular
death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine
group and 625 (19.2%) in the placebo group (HR, 0.96;95%CI, ; P=.50).
Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine
and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, ; P=.87).
Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with
the placebo group (494 [16.1%]; HR, 0.87; 95% CI, ; P=.03). QTc prolongation
requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%)
receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic
documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and
placebo (102 [3.1%]) groups (P=.84). No difference in total mortality was observed
with ranolazine compared with placebo (172 vs 175; HR, 0.99;95%CI, ; P=.91).
Conclusions The addition of ranolazine to standard treatment for ACS was not effective
in reducing major cardiovascular events. Ranolazine did not adversely affect
the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide
support for the safety and efficacy of ranolazine as antianginal therapy.
Trial Registration clinicaltrials.gov Identifier: NCT
JAMA. 2007;297:
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15. Ranolazine: Limitations in Elderly
Side effects more common
Dizziness
Constipation, Nausea, dyspepsia, abdominal pain
Asthenia
Headache
QT prolongation due to drug interactions
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16. Dr. MS: Referred for Angiography
ABNORMAL CORONARY CIRCULATION
Proximal LAD: 99 % stenosis, site of prior stent.
·Mid LAD: 80 % stenosis.
·D1: 80 % stenosis.
·D2: 99 % stenosis.
·Mid circumflex: 40 % stenosis.
·Mid RCA: 99 % stenosis.
·Distal RCA: 60 % stenosis.
RPDA: 90 % stenosis.
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17. Non-medical Therapies
All therapy requires lifestyle changes and drugs for secondary prevention of ischemic events
Revascularization
Surgical (1968)
Percutaneous (1978)
PCI v. Surgery
Medical v. Intervention
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18. Percutaneous Coronary Interventions
Lesion angioplasty POBA
Atherectomy and occluded vessels
Adjunctive Platelet Therapies
Stenting – BMS, DES
Bare Metal
Drug Eluting
Efficacy: Equivalent to surgical intervention in short term relief
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19. Coronary Bypass Graft Surgery
Indications
Symptomatic – refractory to medical therapy
Prognostic
Left main stenosis > 50%
Three vessel disease +/- impaired LV function
Two vessel disease with LAD involvement
Risks – Mortality 1-2%, increased by gender, emergency surgery, LV function, reoperation
Advances – Off Pump, Limited access, Arterial Conduits
Comparisons – anti-anginal effect long term 85%
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20. STS Database for CABG Only 1997-2000 J Am Coll Surg 2003;197:347–357
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22. Survival and Comorbidities
Table 3. Independent Risk Factors for 4-Year Mortality in the Development Cohort in the Multivariable Analysis
Lee, S. J. et al. JAMA 2006;295:
Copyright restrictions may apply.

23. TIME: One Year results JAMA 2003 289:1117
Switzerland
Patients over 75
Chronic stable angina
148 optimized Med
153 invasive
Similar outcomes for symptoms, QOL, Death or Nonfatal Infarction
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24. COURAGE N Engl J Med 2007;356:1503-16. Chronic Stable Angina
Average age 61
85% Male
86% White
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25. Alternative Therapies of Angina
Vitamin E
Garlic
Gingko Biloba
Salmon oil
Red Algae
Chelation Therapy
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26. Dr. MS Decision: PCI of LAD
Readmitted emergently with severe pain and palpitations – RCA ischemia and atrial fibrillation
Converted to NSR, RCA revascularized
Referred for cardiac rehab – completely asymptomatic
2 years later – recurrent angina then ACS – new RCA lesion.
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27. Angina pectoris is a classic syndrome of ischemia
Conclusions:
Angina pectoris is a classic syndrome of ischemia
Evaluation depends on a history – 95% specific; In the elderly it often has reduced sensitivity
Clinical assessment focuses on stability and high risk cases
Therapy always involves secondary prevention, but not all is proven for elderly patients
Drug therapy can be effective with caution.
Interventional therapies work well. They do NOT always offer survival benefit.
Drug therapy should be mastered for those in whom intervention carries risks
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