Cardiovascular Pharmacotherapy Update

Transcription

1 Cardiovascular Pharmacotherapy Update Debby Caraballo, PharmD, PhC, BCPS April 30 th 2011

2 Objectives Review recent updates in cardiovascular pharmacotherapy Discuss the updates to Afib, UA/NSTEMI, STEMI/PCI and CHF National Guidelines Understand the place in therapy of new agents (dronedarone, prasugrel, dabigatran) Review recent consensus statements (Gkycemic control, TZDs, PPIs)

3 What s new? 2009 ACC/AHA/SCAI STEMI/ PCI Update 2009 ACC/AHA CHF Update 2010 ESC Afib Update 2010 HFSA CHF Update 2011 ACCF/AHA/HRS Afib Update 2011 AHA/ACCF Afib Update (Dabigatran) 2011 AHA/ACC NSTEMI Update

4 Acute Coronary Syndromes

5 STEMI ACC/AHA 2004 Focused Update 2007 Focused Update 2009 (ACC/AHA/SCAI) (STEMI and PCI update; last Focused Update for PCI was in 2005)

6 2009 Focused Update GPIs New data to show all three available agents are equal Role of thienopyridines Routine use uncertain Thienopyridines Loading dose Prasugrel ASA dose

7 2009 STEMI Focused Update PPIs and clopidogrel interaction Genetic polymorphisms Genetic testing Bivalirudin HORIZONS-AMI

8 STEMI Update- Prasugrel TPD TRITON-TIMI 38 Pro-drug (one-step only) Quicker onset Same offset (wait 5-7 d before surgery) Higher risk for bleed v. clopidogrel Superior for ischemic events No genetic polymorphisms

9 STEMI Update- PPIs and Clopidogrel CYP2C19 In-vitro interaction COGENT trial Omeprazole most documented One study suggested pantoprazole OK Writing committee cannot make a recommendation (later on..consensus 2010 )

10 STEMI Update- Bivalirudin Bivalirudin added as a reasonable antiocoagulant option for PCI (Class I LOEB) HORIZONS-AMI New recommendation Bivalirudin reasonable in STEMI pts undergoing PCI at high risk for bleed (Class IIa LOE B)

11 PPIs and Clopidogrel Consensus ACCF/ACG/AHA 2010 (Focused Update to ACCF/ACG/AHA 2008 Expert Consensus on Reducing the GI Risks of Antiplatelet Therapy and NSAID Use)

12 PPIs and Clopidogrel Consensus, cont. Concern for interaction Based on genetic polymorphisms with clopidogrel CYP2C19 30% non-responders => Worse outcomes PPIs (except for pantoprazole) metabolized by CYP 2C19 In vitro data

13 PPIs and Clopidogrel Consensus, cont. No data to support one PPI No prospective trials directly compare different PPIs in patients treated with clopidogrel Retrospective observational studies (>20,000 pts) No difference in CV outcomes H2RAs alternative for low GIB risk

14 PPIs and Clopidogrel Consensus, cont. Risk Factors (RFs) for GIB Age Anticoagulants Steroids NSAIDs (including ASA) Helicobacter pylori infection Risk increases the more RFs are present

15 PPIs and Clopidogrel Consensus, cont. Risk for GIP = 4X with ASA alone If bleed Discontinuation of drug worse CV outcomes Evaluate each patient for bleeding risk PPIs underused No data on H2 antagonists (H2As) Suggest to consider pantoprazole or H2As

16 PPIs Consensus- Summary Consider risk factors PPIs or H2As better than no tx PPIs better than H2As in pts with h/o GIB Routine use of H2As or PPIs not recommended PK interaction with PPIs and clopidogrel Most documented with omeprazole Potential clinically important Role genetic testing uncertain

17 Clopidogrel and genetic testing FDA boxed warning on genetic polymorphism Test patients Consider alternative regimens 150 mg po BID based on N=10 study CYP2C19 Genetic polymorphism accounts for 12% clopidogrel response Higher doses studied no improved outcomes CURRENT-OASIS7*; GRAVITAS Subgroup benefited from 150mg X 1 week

18 UA/NSTEMI 2011 Focused Update 2007 ACC/AHA Guidelines 2011 ACC/AHA Focused Update

19 UA/NSTEMI 2011 Focused Update Effient added as an option if UA/NSTEMI and PCI is planned Plavix is still the only option for conservative strategy (non-invasive)

20 Everybody Needs: (Unless negative for CAD in stress test) ASA BETA BLOCKER ACE STATIN PLAVIX/ EFFIENT ALWAYS BET on ACE of SPades

21 ATRIAL FIBRILLATION

22 ESC 2010 Update Ahead of the game Dronedarone Dabigatran CHADSVAsc HASBLED

23 Dronedarone Antiarryhtmic NOT THE NEW AMIODARONE Chemical structure related NOT SAFE in CHF; Amiodarone is safe in CHF! ANDROMEDA trial Increased mortality in NYHA III-IV or recent hospitalization for CHF Contraindicated in QTc > 500ms

24 Dronedarone No IV; Amiodarone has IV Shorter duration of action More favorable ADR profile Better option for younger patients Maintenance of SR Drug interactions..

25 Dabigatran First in its class (but a lot more to come!) Oral direct thrombin inhibitor Approved in US for stroke prevention in NON-VALVULAR Afib Approved in EU for VTE Px

26 Dabigatran No monitoring No bridging Better than warfarin for stroke Same as warfarin for bleeding $$$$ (~$240/month out of pocket; $70-$110/ mo copay) Oral anticoagulants

27 Atrial Fibrillation Goals of therapy Symptom control Stroke prevention Stroke Prevention Strategy Stroke risks Bleeding risks CHADS 2 CHADS-Vasc HAS-BLED

28 CHADS 2 SPAF CHADS CHF (1 POINT) AGE > 75YO (1 POINT) DIABETES (1 POINT) STROKE/TIA/VALVULAR DISEASE (2 POINTS) CHADS >/= 2 warfarin CHADS< 2 ASA or warfarin

29 Example 65YOF Afib w/ RVR Rate controlled PMH- HTN, hypothyroidism, depression NKDA CHADS= 1 (ASA or warfarin) CHADS= 1 ~ 2% annual risk of stroke

30 CHADSVasc CHF (1 POINT) AGE > 65 (1 POINT) Age > 75 (2 POINTS!) Antiplatelet effect lower with age; 300 falls in one year for ICH Female sex RR 1.6 Previous MI PAD

31 Example 65YOF Afib w/ RVR Rate controlled PMH- HTN, hypothyroidism, depression NKDA CHADSVasc= 3 (~3.2% annual risk of stroke) CHADS of 0= 1.9% CHADSVAsc 0= 0%

32 Example Stroke prevention strategy Warfarin ASA plus clopidogrel dabigatran

33 Did you just sa ASA plus clopidogrel?! Cardioembolic stroke ASA or Warfarin NOT clopidogrel Update from AHA/ASA/ACC 2011 ACTIVE-A ASA plus clopidogrel better than ASA alone Same bleeding as warfarin OK for pts not wanting testing done

34 HAS-BLED Bleeding risk stratification tool Endorsed by ESC and EHRA HTN (uncontrolled >160 SBP) Abnormal liver/renal function Bleeding Hx or predisposition (anemia) Labile INR (<60%) Elderly (>65%) Drugs/alcohol concomitantly

35 Atrial Fibrillation INR range has been proposed for the elderly But it is not based on any large trial evidence 2-fold increase in stroke risk at INR INR < 2.0 not recommended

36 Atrial Fibrillation- Rate Control RACE II trial (2010) Strict <110 bpm at 6min walk test and <80 bpm at rest Lenient < 110 bpm at rest Strict control seems unnecessary Lenient is not inferior to strict Lenient is more convenient May may be adopted in permanent AF

37 CHF

38 2009 AHA/ACC Update TZDs Preserved EF still no mortality benefit No new drugs. Avoid dronedarone in CHF III-IV

39 TZDs Consensus 2010 Based on data rosiglitazone associated with increased CV risks No data on pioglitazone RECORD, PROactive No mortality benefit data Only antihypreglycemic with mortality data is metformin Avoid TZDs if possible

40 ACC/AHA CHF 2009 Focused Update ISDN/ Hydralazine African-Americans with moderate to severe symptoms on optimal therapy with ACEs, BBs and diuretics. (Class I LOE B) Lack of data in patients intolerant of ACEIs Still a therapeutic option in such patients (Class IIb LOE C)

41 Just a reminder PRIORITZE life-saving drugs! ACEs or ARBs BBs Aldosterone antagonists SrCr >2 or 2.5 in males K > 5.0 ISDN/Hydralazine Digoxin Diuretics

42 CHF with Preserved LV Still no mortality benefit with any drug class Same mortality with LV systolic dysfunction Treat comorbidities Patient education Salt restriction Symptoms Medication adherence

43 Glycemic Control Consensus SUGAR NICE Tight glycemic control vs. less strict glycemic control Increased mortality with tight control

44 What was that again?!? 2009 ACC/AHA/SCAI STEMI/ PCI Update 2009 ACC/AHA CHF Update 2010 ESC Afib Update 2010 HFSA CHF Update 2011 ACCF/AHA/HRS Afib Update 2011 AHA/ACCF Afib Update (Dabigatran) 2011 AHA/ACC NSTEMI Update PPI Consensus TZDs, Glycemic Control Consensus

45 Drugs, drugs and more drugs Prasugrel Dabigatran Dronedarone ASA + Plavix (new regimen) Bivalirudin (added recommendation)

46 Questions?