ISCHEMIC HEART DISEASE

1. ISCHEMIC HEART DISEASE I

2. Chief Complaint "Doc, the drugs aren't working for my chest pain!”

3. HPI Jack Palmer is a 72-year-old man with coronary artery disease. He is an avid golfer and prefers to walk the course, but this is becoming progressively more difficult for him due to frequent angina. He has had two coronary artery bypass operations in the past. A coronary angiogram performed 1 month ago revealed significant disease in the RCA proximal to his graft but this was considered high risk for angioplasty. His dose of isosorbidemononitrate was increased at that time from 60 to 120 mg once daily. This had no effect on his angina. He is still using about 30 nitroglycerin tablets a week, and these do relieve his chest pain. He reports that most often the chest discomfort comes on with activity, such as walking up slight inclines on the golf course. The discomfort is located in the center of his chest and rated as a 3–4/10 on average. He reports that the chest discomfort slowly fades as he slows his activity. He also complains of occasional lightheadedness with a pulse around 50 bpm and SBP near 100 mm Hg.

4. PMH . Acute anterior wall MI with CABG in 1976 . Posterior lateral MI in 1990 and PTCA to the circumflex at that time . Redo CABG in 1998 . Ischemic cardiomyopathy . Heart failure with an ejection fraction of 40% . Dyslipidemia . COPD (mild) . Chronic low back pain . Depression

5. FH Noncontributory for premature coronary artery disease SH Retired dairy farmer, lives with wife, drinks occasionally, previous smoker—quit in 1998

6. Meds Carvedilol 6.25 mg twice daily Digoxin 0.25 mg once daily Lisinopril 5 mg once daily Furosemide 40 mg once daily Aspirin 325 mg once daily Isosorbidemononitrate, extended release 120 mg once daily

7. Meds Diltiazem, extended-release 240 mg once daily St. John's wort 300 mg three times daily Celecoxib 200 mg once daily Simvastatin 40 mg once daily Nitroglycerin 0.4 mg SL PRN

8. AII NKDA ROS No fever, chills, or night sweats. No recent viral illnesses. No shortness of breath; occasional cough with cold weather. No nausea, vomiting, diarrhea, constipation, melena, or hematochezia. No dysuria or hematuria. No myalgias or arthralgias.

9. Physical Examination Gen Pleasant, cooperative man in no acute distress VS BP 105/68, P 50, RR 22, T 36.4°C, Ht 5'11″, Wt 93 kg, waist circumference 43 in Skin Intact, no rashes or ulcers

10. Physical Examination HEENT PERRL; EOMI; oropharynx is clear Neck Supple, no masses; no JVD, lymphadenopathy, or thyromegaly Lungs Bilateral air entry is clear. No wheezes.

11. Physical Examination CV RRR, S1, S2 normal; no murmurs or gallops; PMI palpated at left fifth ICS, MCL Abd Soft, NT/ND; bowel sounds normoactive Genit/Rect Heme (–) stool

12. Physical Examination Ext No CCE; pulses 2+ throughout Neuro A & O x 3, CN II–XII intact; speech is fluent; no motor or sensory deficit; no facial asymmetry; tongue midline

13. MCV 77 m3 MCV 77 m3 Labs Na 137 mEq/L Glu98 mg/dL Hgb 11.8 g/dL K 4.8 mEq/L Cl103mEq/L Hct 35.1% CO2 21 mEq/L Plt187 x 103/mm3 BUN 24 mg/dL WBC7.9 x 103/mm3 SCr1.2 mg/dL MCV 77cm3 MCHC 29 g/dL

14. MCV 77 m3 MCV 77 m3 Labs Fasting lipid profile: Digoxin serum concentration: 1.8 mg/ml Chol202 mg/dL LDL 125 mg/dL HDL 38 mg/dL Trig 215 mg/dL

15. ECG Sinus rhythm, first-degree AVB, 50 bpm, old AWMI, no ST–T wave changes noted, QT/QTc 406/431 Assessment A 72-year-old man with poorly controlled angina on multiple medications who is a poor candidate for angioplasty Clinical Pearl The COURAGE trial made major headlines in 2007 by showing that coronary stenting with optimal medical therapy is no better at preventing future coronary events than optimal medical therapy alone in patients with stable coronary disease, potentially saving the US health care system $5 billion a year.14

16. Questions Problem Identification 1.a. What drug-related problems appear to be present in this patient? • Angina pectoris, poorly controlled on current drug therapy • Dyslipidemia, poorly controlled • More safe drug is recommended instead of Diltiazem because of his mild HF • Unsafe drug is been using Celecoxib due to increase risk of CVD • Safety dosage regimen issues ( digoxin ,aspirin ) • Metabolic syndrome (abdominal obesity, elevated triglyceride and low HDL-C )

17. 1.b. Could any of these problems potentially be caused or exacerbated by his current therapy? • Medical management of angina must take into consideration the patient’s hemodynamic status and left ventricular function. Although CCB and BB are both reasonable antianginal drugs, they are likely the cause of his relatively low heart rate and blood pressure and associated lightheadedness. According to the American Heart Association (AHA)/American College of Cardiology (ACC) guidelines, he should remain on a β-blocker such as carvedilol, if possible, to slow progression of systolic heart failure but diltiazem is a poor choice in a patient with left ventricular dysfunction as it is known to depress myocardial contractility.

18. • According to a recent statement by the AHA, selective COX-2 inhibitors such as celecoxib increase the risk of myocardial infarction, stroke, heart failure, and hypertension.

19. Questions Desired Outcome 2. What are the goals of pharmacotherapy for IHD in this case? Short term : Stabilize chest pain and discomfort and reduce and stabilize angina symptoms Prevent ischemia and subsequent infarction Improve exercise tolerance and quality of life Long term : Prevent primary or secondary CV event MI HF Stabilize the pattern of chest pain Decrease overall CV morbidity and mortality

20. Questions 3.a. Does this patient possess any modifiable risk factors for IHD? Therapeutic Alternatives • He has poorly controlled dyslipidemia. His LDL-C and triglycerides are too high, and his HDL-C is too low. Hypercholesterolemia is a significant cardiovascular risk factor, and risk is directly related to the degree of cholesterol elevation. (target LDL <100 mg/dL; <70 mg/dL in patients with CHD and multiple risk factors is reasonable ) Additional goals include HDL-C greater than 40 mg/dL and triglycerides less than 150 mg/dL. Because his triglycerides are in the range of 200–499 mg/dL, a secondary target is non-HDL cholesterol <130 mg/dL.

21. • Alcohol ingestion in small to moderate amounts (<40 g/day of pure ethanol) reduces the risk of coronary heart disease; however, consumption of large amounts (>50 g/day) or binge drinking of alcohol is associated with increased mortality from stroke, cancer, vehicular accidents, and cirrhosis •Body mass index is associated with an increased mortality ratio compared with individuals of normal body weight, and the objective for patients with IHD is to maintain or reduce to a normal body weight

22. • This patient meets the criteria for the definition of metabolic syndrome on the basis of abdominal obesity, elevated triglycerides,and low HDL-C. ATP III1 identified 6 components of the metabolic syndrome that relate to CVD: • 1) Abdominal obesity It presents clinically as increased waist circumference. Waist circumference ≥40 in (102 cm) in men and ≥35 in (88 cm) in women 2) Atherogenic dyslipidemia raised triglycerides and low concentrations of HDL cholesterol. HDL-C <40 mg/dL in men and <50 mg/dL in women Triglycerides ≥150 mg/dL

23. 3) Raised blood pressure ≥130/85 mm Hg 4) Insulin resistance ± glucose intolerance 5) Proinflammatory state recognized clinically by elevations of C-reactive protein (CRP), is commonly present in persons with metabolic syndrome.  6) Prothrombotic statecharacterized by increased plasma plasminogen activator inhibitor (PAI)-1 and fibrinogen, also associates with the metabolic syndrome.

24. • He is currently taking celecoxib for low back pain, which may put him at risk for cardiovascular events. • All NSAIDs are associated with an increased risk of serious (and potentially fatal ) adverse cardiovascular thrombotic events, including MI and stroke • Risk may be increased with duration of use or pre existing cardiovascular risk factors or disease

25. 3.b. What pharmacotherapeutic options are available for treating this patient's IHD? Discuss the agents in each class with respect to their relative utility in his care. • We use nitroglycerine to relieve acute symptom • Pharmacotherapy to prevent recurrent ischemic symptom -Beta blocker -Calcium channel blocker -Long acting nitrate -Ranolazine • Pharmacotherapy to prevent acute coronary syndromes and death ( vasoprotictive agent ) -Antiplatlet agent -Statin -ACE inhibitors and ARB -Control of risk factors

26. Nitrate • Nitrate therapy should be first step in managing acute attack for patient with chronic stable angina or for prophylaxis of symptoms.its leading to reductions in preload and afterload reduction of myocardial oxygen demand ,Nitrate –free interval (10-12 hours/day) is recommended to avoid tolerance development . Nitroglycerin (NTG) : Nitroglycerin concentrations are affected by the route of administration, with the highest concentrations usually obtained with intravenous administration, the lowest seen with lower oral doses Isosorbide dinitrate (ISDN): Chewable, oral, and transdermal products are acceptable for the long-term prophylaxis of angina, its given 1 tablet three to four time daily. Isosorbide mononitrate (ISMN):is available in two types of oral formulations: Regular release tablet : initial 5-20 mg BID with the 2 doses given 7 hours apart (eg. 8AM and 3PM )to decrease tolerance development Extended release tablet : initial 30-60 mg given once daily in the morning ;titrate upword as needed maximum daily dose : 240 mg

27. Calcium channel blockers (CCBs) Calcium channel antagonists have the potential advantage of improving coronary blood flow through coronary artery vasodilation as well as decreasing MVO2. Calcium antagonists may provide better skeletal muscle oxygenation, resulting in decreased fatigue and better exercise tolerance. Patients with conduction abnormalities and moderate to severe LV dysfunction (ejection fraction <35%) should not be treated with verapamil and Diltiazem whereas amlodipine may be safely used in many of these patients. We must consider that this patient has a relatively low heart rate and moderate LV dysfunction. Therefore, use of a negative inotrope such as diltiazem is inadvisable.

28. B-blockers β-blockers may be preferable because of less-frequent dosing and other properties inherent in β-blockade (e.g., potential cardioprotective effects, antiarrhythmic effects, lack of tolerance, and antihypertensive effects), as well as their antianginal effects and documented protective effects in post- MI patients. Decreased heart rate, decreased contractility, and a slight to moderate decrease in blood pressure with β-adrenergic receptor antagonism reduce MVO2 Carvedilol is a nonselective beta-adrenergic blocking agent with a1 blocking activity This patient has mild COPD but seems to be tolerating his carvedilol well at present.

29. Ranolazine Ranolazine exerts antianginal and anti-ischemic effects without changing hemodynamic parameters (HR & BP) Ranolazine doesn’t relieve acute angina attack.Has been shown to prolong QT interval We need to avoid grapefruit –contaning product or dose adjusment of ranolazine may be required St John’s wort may decrease the serum concentration of ranolazine With moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin), the ranolazine dose should be limited to 500 mg twice daily.

30. Antiplatelet

31. ACE inhibitors

32. Statins

33. Questions Optimal Plan 4. Given the patient information provided, construct a complete pharmacotherapeutic plan for optimizing management of his IHD .

34. 1) Stop using Deltiazm and replace it by amlodepine 5mg once daily 2) Stop using of carvidilol and replaced by metoprololtarterateXL 50mg once daily 3) we replace simvastatin by atrovastatines 40mg once daily 4) Decreas the dose of digoxin to .125 once daily 5) Adding of ranalozin 500mg BID6) Reduce the dose of aspirin to 162 mg once daily

35. 7) Initially continue the administration of isosorbidemononitrate 120mg QD,PO then after the patient condition is improved inc.the dose up to 240mg QD,PO8) Discontinue CELECOXIB and start with PARACETAMOL 500mg PRN, PO

36. Questions Outcome Evaluation 5. When the patient returns to the clinic in 2 weeks for a follow-up visit, how will you evaluate the response to his new antianginal regimen for efficacy and adverse effects?

37. Efficacy: We need to ask him : about the number and severity of anginal attacks and what provoke his anginal pain .and for how long its remain Does sublingual NTG relieve the pain? Have any attacks occurred at rest which is a sign of unstable angina and would require hospital admission?

38. Adverse effects: We need to Check vital signs.: heart rate and blood pressure We would ask if he had any of these symptoms dizziness, lightheadedness, headache, and facial flushing. Because we want to give him amlodipine instead of diltiazem we need to check if he had any edema We need to be careful about sign of bleeding

39. Questions Patient Education • 6. What information will you communicate to the patient about his antianginal regimen to help him experience the greatest benefit and fewest adverse effects?

40. Nitroglcerin SL • 1) Used at start of angina if the pain not released you can take another one after 5 mint and if the pain also not released you can take another one after 5 mint and if the pain is not reliesed after 5 mint you must to go to emergency beceuse of MI ( acute condition ) 2 ) Stor them away of heat and moisture and light Aspirine • 1) aspirin is give you some protection against recurrence MI or occurring of stroke • 2) if you feel any pain in your stomach or you see blood in the stool you must to tell your doctor

41. Metoprolol XL • 1) you must to check your pulse daily because this drug reduce the HR 2 ) you may feel dizziness or fatigue Celecoxib We stop using this drug because it increase the risk of MI and stroke ISMN This drug have high tolerance but you take it once daily so no tolerance will occur

42. Amlodipine We replace diltiazm by this drug because your HR is low and this drug has less effect on HR than diltiazm but may feel some dizziness and fatigue Ranalozine We give you this drug to improve your ischemic condition and this drug has also less effect on BP and HR so this good in your case because your pulse is low and your BP also low May have some nausea and constipation and headache