SECONDARY PREVENTION WORKSHOP. May 5, 2018

Transcription

1 SECONDARY PREVENTION WORKSHOP May 5, 2018

2 Disclosures Have received honourarium/speaker fees from Astra Zeneca Sanofi

3 Objectives 1. Examine the use of beta-blockers post-mi 2. Determine the benefits and risk of long term DAPT 3. Explore the benefits and risks of SGLT2 inhibitors

4 Case Jerry is 62 year old male who was admitted on May 3 rd with complaints of restrosternal chest pain. He had woken up with the chest pains and his wife had called 911. In the Emergency department 2 mm ST elevation was seen in leads II, III, avf and he underwent primary PCI receiving a DES stent (Xience) to the RCA

5 Should this gentleman receive a betablocker? A.Yes B.No C.Not sure

6 American College of Cardiology Guidelines 2011 Secondary Prevention Guidelines BB should be started and continued for 3 years in all patients with normal left ventricular function who have had an MI or ACS (Class I, B) It is reasonable to continue beta-blockers beyond 3 years as chronic therapy in all patients with normal left ventricular function (Class II, B) 2013 STEMI Guidelines BB during and after hospitalization (Class I, B) long-term duration of routine beta-blocker therapy in uncomplicated MI without HF or HTN has not prospectively been addressed 2014 NSTACS Guidelines It is reasonable to continue BBs in patients with normal LV function (Class IIa, C) Used with permission from C Bucci

7 European Society of Cardiology STEMI Guidelines (2017) The recommendation for BB initiation during hospital stay (in those without HF/LVD) has been downgraded from Class I to Class IIa Used with permission from C Bucci

8 NICE Guidelines (UK) Beta-blockers should be continued for at least 12 months after an MI in patients without left ventricular dysfunction or heart failure Not to offer people without left ventricular dysfunction or heart failure who have had an MI more than 12 months ago, treatment with a beta-blocker unless there is an additional clinical indication for a beta-blocker

9 New Zealand Best Practice Advisory Centre Guideline Beta-blocker be withdrawn 6-12 months after an acute MI in patients without heart failure or arrhythmias and who have undergone revascularization

10

11 With important exceptions, the evidence does not appear to support the use of beta-blockers in modern patients who have experienced MI those who have had their culprit artery stent and have only minor residual myocardial damage. Consideration could be given to offering a betablocker for 1 month to reduce repeated infarction and angina, but the trade-off would be slightly increased risk of heart failure Can J Cardiol 2017;33:

12 Benefits and risks of beta-blockers post MI Benefits reperfusion era Mortality IRR 0.98 ( ) Myocardial infarction IRR 0.72 ( ) Angina IRR 0.80 ( ) Benefit appeared limited to the first 30 days Analysis < 30 d, 30 d 1 year Risks Heart Failure IRR 1.10 ( ) Cardiogenic shock IRR 1.29 ( ) Drug discontinuation IRR 1.64 ( ) Am J Med 2014;127: Can J Cardiol 2017;

13 BB Evidence? Reperfusion Era - Chinese - 50% lytics - Average duration 15 days COMMIT Lancet 2005;366:

14 New Data: BB Post MI without HF (BMJ 2016) FAST-MI database Database up to 2005 Outcomes 30 days in whom beta-blockers started within 48 hours

15 BB Post MI without HF (BMJ 2016) Early BB (<48 hrs) was associated with a reduced 30 day mortality BB at discharge was not associated with a reduced in 1 year mortality (6.3% vs 7.3%. HR 0.85, p = 0.57) Stopping BB within first year was not associated with a higher rate of mortality at 5 years (7.6% vs 9.2%, HR 0.79, p=0.41)

16 Systematic Review Effect of long term ( > 1 year) beta-blocker therapy post- MI without left ventricular dysfunction 8 cohort studies included Methods variable definition of LVD (> 30% to > 50%) Inconsistent results 6/8 no significant difference in mortality Barry A. Pharmacotherapy DOI /pharm.02110

17 Cohort study French administrative database Beta-blocker d/c associated with CCB or antiarrhythmic association, pacemaker insertion Ongoing beta-blocker use associated with use of statin/ace/arb/antiplatelet/defibrillator placement Followed on average for 3.8 years Adjusted Crude HR for death or ACS was 1.17 ( ), death alone was not significant Adjusted crude HR for death after statin d/c was 2.57 Why were the drugs discontinued?

18 Case Jerry is 62 year old male who was admitted on May 3 rd with complaints of restrosternal chest pain. He had woken up with the chest pains and his wife had called 911. In the Emergency department 2 mm ST elevation was seen in leads II, III, avf and he underwent primary PCI receiving a DES stent (Xience) to the RCA What will you do with the beta-blocker?

19 Case 2 Duration of DAPT Jerry is a 63 year old male who had an MI 1 year ago (inferior wall), no heart failure. Has done well afterwards has returned to daily walks and golfing. A card given to him in hospital says Xience stent implanted may 3/18, 3 mm x 18 mm. No recurrent chest pain, pt complained of easy bruising but no signs of other bleeding, ECG is normal (no q waves). Current labs: Cr 90 umol/l (estimated CrCl 92 ml/min), Hg 136, WBC 6.2 Claudio is a 73 year old male who had NSTEMI 1 year ago. He experienced heart failure during initial presentation and then has had one recurrent episode (managed as out patient). EF is 33%. He received a Xience stent (3.25 mm x 15 mm and 3.5 mm x 18 mm) for lesions in RCA and Diagonal branch. He has not had recurrent angina. PMH: MI at age 68, DM II x 8years Current labs are: Cr 120 (estimated Cr Cl 58 ml/min), Hg 118 WBC 5.8 Hedy is a 74 year old female who had a NSTEMI 1 year ago. She underwent three vessel PCI DES x 3 (Xience) to LAD, RCA and OM1 (size of stents 3, 3.25 and 2.5). She was a smoker quit 5 years ago, hypertension, PUD - 5 years ago treated with triple therapy, osteoarthritis, increased cholesterol, family history of CAD (mother had MI at age 72), Current labs: Cr 100 (estimated CrCl 64 ml/min), Hg 116, WBC 7.2 Other meds include acetaminophen TID, Naproxen 220 mg prn (takes 3-4 x/month).

20

21

22

23

24 DAPT score

25 DAPT score Variable Score Age 75 years -2 Age 65 < 75-1 Age < 65 0 Current cigarette smoker 1 Diabetes mellitus 1 MI at presentation 1 Prior PCI or prior MI 1 Stent diameter < 3 mm 1 Paclitaxel-eluting stent (Taxus) 1 CHF or LVEF < 30% 2 Saphenous vein graft PCI 2 Score 2 is associated with favorable benefit/risk ratio for prolonged DAPT < 2 associated with unfavorable benefit/risk ratio Limitations: PCI population - Recent validation for MI population

26 PRECISE-DAPT - Based upon patients who received an elective, urgent or emergent PCI - Validated in PLATO and BERN PCI populations - Score 25 high bleeding risk consider < 12 mos (3-6 mos DAPT) Lancet 2017; 389:

27 Precise-DAPT

28

29 CALIBER - Determine events (ischemic/bleeding) after 1 year of DAPT - Based on electronic health record data, validated with PEGASUS TIMI 54 European Heart Journal (2017) 38,

30

31 Compares risk/benefit or DAPT/no DAPT over a period of up to 5 years

32 Jerry Claudio Hedy Would you? Shorten therapy (< 12 months) Lengthen therapy (additional 2 years) Stop at 1 year

33 Patients risk benefit Caliber CV Death/MI/Stroke Major Bleed No DAPT With DAPT No DAPT With DAPT Jerry Claudio Hedy Precise-DAPT Score Major bleed Event Jerry Claudio Hedy

34 Your decision??? Jerry 63 year old male who had an MI 1 year ago (inferior wall), no heart failure, Xience stent implanted may 3/18, 3 mm x 18 mm. No recurrent chest pain, pt complained of easy bruising but no signs of other bleeding, ECG is normal (no q waves). Current labs: Cr 90 umol/l (estimated CrCl 92 ml/min), Hg 136, WBC 6.2 Claudio 73 year old male who had NSTEMI 1 year ago. He experienced heart failure during initial presentation and then has had one recurrent episode (managed as out patient). EF is 33%. He received a Xience stent (3.25 mm x 15 mm and 3.5 mm x 18 mm) for lesions in RCA and Diagonal branch. He has not had recurrent angina. PMH: MI at age 68, DM II x 8years Current labs are: Cr 120 (estimated Cr Cl 58 ml/min), Hg 118 WBC 5.8 Hedy 74 year old female who had a NSTEMI 1 year ago. She underwent three vessel PCI DES x 3 (Xience) to LAD, RCA and OM1 (size of stents 3, 3.25 and 2.5). She was a smoker quit 5 years ago, hypertension, PUD - 5 years ago treated with triple therapy, osteoarthritis, increased cholesterol, family history of CAD (mother had MI at age 72), Current labs: Cr 100 (estimated CrCl 64 ml/min), Hg 116, WBC 7.2 Other meds include acetaminophen TID, Naproxen 220 mg prn (takes 3-4 x/month).

35

36 Jim is a 58 year old male admitted a COPD exacerbation/upper respiratory tract infection. PMH: DM type II, HTN, Peripheral arterial disease intermittent claudication (ABI 0.7), Stable angina Social history: Married, 2 kids, Medications covered by wife s plan, Smoker, Sedentary minimal exercise E.C ASA 81 mg daily, Metformin 1 g BID, Ramipril 10 mg daily, Chlorthalidone 25 mg daily, Bisoprolol 5 mg daily, Rosuvastatin 10 mg daily A1c 8.2 Team asks your opinion regarding adding empaglflozin or another SGLT2 inhibitor and is it important for his statin dose to be higher?

37 Statins and PAD

38 SGLT2 inhibitors & CV disease

39 Empagliflozin & PAD population

40

41 DKA & SGLT2 inhibitors 1.8 cases/1000 subjects Identified causes Surgery/periop period Reduction or cessation of insulin Low carbohydrate diet Acute coronary syndrome Infections Liver and kidney impairment May be with euglycemia

42 European Medicines Agency Healthcare professionals should exercise caution with SGLT2 inhibitors in patients with risk factors for ketoacidosis and inform patients of these factors. These include low insulin-producing capacity in the pancreas, a sudden drop in a patient s insulin dose, increased insulin requirement (due to illness, surgery or alcohol abuse) or conditions that can restrict food intake or lead to severe dehydration. In addition, EMA recommended temporarily stopping SGLT2 inhibitors in patients who are undergoing major surgery or are in hospital due to serious illness.

43 Product monograph Diabetic Ketoacidosis Clinical trial and post-market cases of diabetic ketoacidosis (DKA), a serious life-threatening condition requiring urgent hospitalization, have been reported in patients with type 2 diabetes mellitus (T2DM) treated with JARDIANCE and other sodium-glucose co-transporter 2 (SGLT2) inhibitors. Some cases of DKA have been fatal. A number of these cases have been atypical with blood glucose values below 13.9 mmol/l (250 mg/dl) (see Adverse Reactions). Patients should be assessed for diabetic ketoacidosis immediately if non-specific symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, anorexia, excessive thirst and unusual fatigue or sleepiness occur, regardless of blood glucose level, and JARDIANCE should be discontinued immediately. Interruption of treatment with JARDIANCE should be considered in type 2 diabetes patients who are hospitalized for major surgical procedures, serious infections or acute serious medical illnesses.

44 S A D M A N S

45 Summary 1. Examine the use of beta-blockers post-mi - Still start in hospital stop during follow-up 1 12 months 2. Determine the benefits and risk of long term DAPT - There are tools to help estimate risk & benefit 3. Explore the benefits and risks of SGLT2 inhibitors - While shown to be beneficial to reduce CV mortality, don t start (or continue them) in hospital