Understanding Coronary Artery Disease and Acute Coronary Syndrome

1. Coronary Artery Disease & Acute Coronary Syndrome Anthony J. Viera, MD, MPH, FAHA Professor and Chair

2. Objectives • Describe the appropriate work-up for chest pain based on clinical factors • Know the first-line medications for CAD and recognize important side effects and contraindications • Define acute coronary syndrome, explain diagnostic criteria • Describe management of ACS • Review of post-MI care

3. Scope of the problem • Coronary artery disease leads to angina, mycocardial infarction, and cardiac death, which together comprise coronary heart disease (CHD) • CHD is responsible for about 1/3 of deaths among people 35 years and older • 17 million Americans have stable coronary artery disease • Each year, 800,000 additional people have an initial CAD event

4. Presentation • Most commonly, the diagnosis of CAD is suspected based on a history of chest pain • When patient presents with chest pain, the first step is to consider serious causes, including acute coronary syndrome, which we will discuss in the second half • For patients not considered to have ACS, the next step is to consider the possibility of stable CAD

5. Diagnosing CAD • It is extremely important to consider the patient’s pretest probability for having flow-limiting CAD • Guides decision-making for next steps • Low pre-test = no further testing, consider other causes • High pre-test = consider consult for catheterization • Intermediate = further risk-stratification/testing

6. History • Age and sex • Characteristics of the pain: location, radiation, severity, duration and frequency, factors that provoke & relieve • Associated symptoms such as shortness of breath or radiation • History of angina, myocardial infarction, coronary revascularisation or other CVD • Cardiovascular risk factors

7. Physical exam • Signs of other cardiovascular disease • Non-coronary causes of angina such as severe aortic stenosis or cardiomyopathy • Exclude other causes of chest pain

8. Marburg Heart Score • High negative predictive value so helpful at ruling out CAD • 1 point for each • Woman >64 or man > 54 years • Known CAD, cerebrovascular dz, or peripheral vascdz • Pain worse with exercise • Pain not reproducible with palpation • Pt assumes pain is cardiac • 98% of patients with score 2 or less will not have CAD • A score >2 is not particularly helpful because only 23% of such patients will have CAD

9. Can get a more refined estimate of pre-test probability • Based on three things: • Kind of chest pain • Sex of the patient • Age of the patient • Kind of chest pain • Typical angina = substernal, onset with exertion or stress, relief by rest • Atypical = two of those three • Non-anginal = 1 or none of those three

10. Consult a chart • Diamond and Forrester • Available online at many sites including www.fpnotebook.com • Realize that men 40 years and older and women 60 years and older with typical angina have a high pretest probability • Pretest probability is very low in both sexes if none of the criteria are present

11. Next step Obtain an EKG • Presence of Q waves • Bundle branch blocks • ST or T wave changes that may make interpretation of a stress EKG difficult

12. Testing zone • Low risk patient: avoid stress testing (higher risk of false positives) • High risk patient: Consider referral for coronary angiogram

13. Intermediate probability from around 10% to 90% • Can patient exercise? • Stress test is a first-line option for most men and women • Stress imaging test if baseline EKG, prior revascularization, and if diabetes mellitus • Pharmacologic stress test if unable to exercise • For patients with an intermediate or high pretest probability of, stress testing with imaging has a higher sensitivity and specificity for the diagnosis of obstructive CAD

14. Stress test is negative • Reassuring – not a guarantee • Stress test has limited sensitivity and specificity • Manage risk factors • Re-evaluate as indicated

15. Stress test is positive • Means further testing usually warranted – not a guarantee • Depending on post-test probability, consider imaging test if first test was not imaged or consider consult for coronary angiogram

16. Note that computed tomography… • May play an increasing role • CT is an accurate non-invasive alternative to diagnose CAD, and can reduce the need for coronary angiography • Alternative first-line diagnostic test for patients with atypical or typical CP

17. Managing CAD • Goals are to prevent progression of disease and reduce likelihood of cardiovascular disease events, ultimately reducing mortality • ABCs = aspirin or other antiplatelet, blood pressure lowering medication, cholesterol (which should be a statin), and smoking cessation and symptom management

18. Antiplatelet • Aim is to reduce platelet aggregation at plaque sites to reduce chances of thrombosis • Aspirin is first-line with its benefit well-established; usual dose is 81-mg (baby ASA) • 30 patients need to be treated for about 30 months to prevent 1 CVD event • Over the same time period, 1 bleeding event occurs for every 111 patients treated

19. Clopidogrel • For patients allergic to aspirin or in whom aspirin is contraindicated, clopidogrel is an alternative • Dose is 75-mg once daily • Also indicated for patients following acute coronary syndrome or stent placement • Otherwise it should not be added to aspirin in patients with stable CAD

20. Blood pressure meds • Blood pressure lowering medications help reduce the myocardial oxygen demand and prevent left ventricular hypertrophy • For patients who have CAD, especially post-myocardial infarction, beta-blockers should be prescribed, even if not hypertensive • Reduce heart rate (goal 50-60), increase diastolic filling time, decrease contractility • β-blockers also help reduce anginal symptoms

21. Benefits also well-established • 23% reduction in the odds of death in long term trials, with NNT of 42 for 2 years • Most evidence is available for propranolol, timolol, and metoprolol • Typically use metoprolol, but carvedilol and labetalol are other alternatives • β-blockers with intrinsic sympathomimetic activity such as pindolol should be avoided in CAD patients

22. CCBs • If β-blockers are contraindicated or not tolerated, long-acting CCB is an alternative • Amlodipine for example, shown to reduce CVD events • Not as effective in reducing angina symptoms

23. ACE-inhibitors • Help prevent ventricular remodeling that can occur after an MI • Reduce CVD mortality with NNT of 17 over 3 years to prevent one death • Thus, important adjunct to β-blocker therapy • Diabetics and those with hypertension • Angiotensin receptor blockers (ARBs) can be used if patient cannot tolerate ACE-inhibitor due to cough • ACE and ARB should not be used together

24. Cholesterol • Statins are the main-stay • Multiple studies: reduce events and mortality • All patients with CAD regardless of LDL level • Aim for at least a moderate dose (40 mg of lovastatin, pravastatin, or simvastatin, 20 mg of atorvastatin, or 5 to 10 mg of rosuvastatin) • High dose in those at higher overall risk who can tolerate

25. Side effects • Severe side effects are rare • Rhabdomyolysis occurs in less than 1 out of 1000 • But myalgias are fairly common, 1-2 out of 100, and overall discontinuation occurs in about 6% • Limit simvastatin to no more than 20mg if patient also on amlodipine due to cytochrome P450 metabolism which can lead to elevated levels of simvastatin  increase risk of myopathy

26. Other considerations • Statins are first-line • Drugs such as fibrates and niacin can be added if further triglyceride lowering (e.g., if TGs remain >200 mg/dl) or HDL increase is a goal, but evidence on patient-oriented outcomes is weak

27. Smoking cessation • For any patients who are smokers, a #1 priority should be getting them to quit • Evidence based guidelines recommend assessing and documenting smoking status at each visit and offering smoking cessation therapies for those interested in quitting

28. Last “S” – symptom control • Already talked about the anti-anginal benefits of B-blockers and CCBs • Nitrates • Sublingual on hand for acute symptoms • Add long-acting nitrate (either oral or transdermal) when patient continues to experience angina • Improve exercise tolerance, reduce episodes • Patients can develop “nitrate tolerance” – a nitrate free interval may help mitigate this • Isosorbidedinitrate can be dosed at 8am and 4pm, for example, starting at 10mg and titrating

29. Persistent symptoms • If angina despite β-blocker, CCB, and long-acting nitrate, a next step is to consult with cardiology for consideration of revascularization if warranted, or use of newer agents such as ranolazine, which is a sodium channel blocker

30. Acute Coronary Syndrome • Generally, signifies unstable plaque in the coronary artery that either has ruptured or is in the process of rupturing • Refers to two clinical presentations: either ST elevation MI or non-ST elevation ACS. Note that the terms NSTEMI (non-ST elevation myocardial infaction) and unstable angina are now lumped into this NSTE-ACS category • The reason is that unless patient has ST elevations, ACS presentations are indistinguishable

31. Myocardial infarction • Thrombosis leads to necrosis of myocardium • Release of myocardial biomarkers • Within three hours after presentation, 80% of patients with AMI will have troponin elevations • Troponin elevations persist for up to 2 weeks Prompt recognition of possible ACS is key • If patient with chest pain is suspected of having ACS, he/she should be evaluated in the emergency department (if presenting to clinic)

32. Making the diagnosis • History • Electrocardiogram • Serum biomarkers

33. Making the diagnosis • History • New onset angina – usually a pressure • Increasing in frequency or duration or with less exertion • Rest angina (usually more than 20 minutes) • No ECG changes indicative of ischemia (i.e., no ST depression or transient ST elevation or new TWI)and no biomarker elevation = non-ST elevation ACS

34. Suggestive symptoms • Include radiation of pain to one or especially both arms • Pain associated with nausea, vomiting or diaphoresis • Pain described as similar to previous MI

35. Initial management of ACS • The traditional ABCs and ACLS • Airway, breathing, circulation • O2, IV, monitor • “MONA” greets at the door • Morphine 2-4 mg IV push • Oxygen • Nitroglycerin – remember to ask men about recent use of a PDE5 inhibitor like sildenafil b/c can drop BP • Aspirin (162-325 mg chewed and swallowed) unless severe allergy or sensitivity • If no signs heart failure and not bradycardic, beta-blocker, such as metoprolol 5mg IV q5 mins X3 doses as tolerated • Start or change to 80mg atorvastatin qd • Correct electrolyte abnormalities, esp hypokalemia and hypomagnesemia

36. STEMI • Patients with ST segment elevation MI (this includes new LBBB) should have a prompt evaluation by cardiology for reperfusion by percutaneous coronary intervention (PCI) • If PCI unavailable, fibrinolytics should be administered within 90-120 minutes, assuming no contraindications • Most will also get unfractionated heparin • Additional antiplatelet therapy (in addition to aspirin) either clopidogrel or ticagrelor or prasugrel

37. NSTE-ACS • Choosing between either an ischemia-guided strategy or an early invasive strategy

38. NSTE-ACS management • Remember that thrombolytics are NOT indicated because of increased risk of reinfarction and other complications • Decide on early invasive or not • If hemodynamically unstable or severe LV dysfunction, persistent rest angina, worsening mitral regurg, or sustained ventricular arrhythmia = early invasive • For others, TIMI risk score

39. TIMI risk score 0 or 1 for each: • Age 65 or older • At least three CHD risk factors (HTN, DM, HLP, smoking, positive early family history) • Prior coronary stenosis 50% or more • ST segment deviation on admission • Two or more anginal episodes in last 24 hrs • Elevated troponin • Aspirin in past 7 days

40. TIMI • Calculators in smartphone apps and on-line • Low risk if score 0 to 2 AND no ST depression and troponin not elevated • High risk of 5 or higher (score 5 =>26% risk of serious CVD event at 14 days; score 6-7 = 41%) • Intermediate or high risk should be considered for early invasive strategy

41. Based on strategy, but all get dual antiplatelet therapy and anticoagulant therapy Early invasive - going to receive • ASA + another antiplatelet agent like clopidogrel or ticagrelor (cardiologist preference; may also receive glycoprotein2b/3a inhibitor) • Anticoagulation • Unfractionated heparin or bivalirudin Conservative • ASA + clopidogrem or ticagrelor • Anticoagulation • Unfractionated heparin or enoxaparin

42. “Possible” ACS • Probably the majority of patients we admit for chest pain to rule out MI fit into the category of “possible” ACS • Nondiagnostic ECG and initially normal (i.e., nonelevated troponin level) • Observe for 12 hours or more from symptom onset, following symptoms and measuring troponin and obtaining ECG serially, e.g., every 6 hours • No further concern for ACS = stress test • ACS confirmed – manage as we discussed

43. Post-MI care • In the absence of an absolute contraindication, aspirin indefinitely • In general, patients who had a STEMI or a stent placed will be on dual antiplatelet therapy (e.g., aspirin plus clopidogrel) for one year • Beta-blocker • ACE-inhibitor, esp if diabetes, heart failure, ejection fraction <40% or hypertension

44. Post-MI care (cont) • Smoking cessation / maintenance = so important • Statin • BP control • If diabetic, glycemic control, striving for A1C <7% • Cardiac rehabilitation – refer if center available • Major depression develops in almost 20% of patients after MI, and over 33% have significant symptoms • Places patients at increased risk of adverse outcomes • Attention to symptoms of depression and treat if indicated

45. Thank you!anthony.viera@duke.edu