Target dose achievement of evidencebased medications in patients with heart failure with reduced ejection fraction attending a heart failure clinic

Transcription

1 Target dose achievement of evidencebased medications in patients with heart failure with reduced ejection fraction attending a heart failure clinic June Chen 1, Charlotte Galenza 1, Justin Ezekowitz 2,3, Finlay McAlister 2,4, Kaitlin Rafuse 5, Ann-Marie Sande 6 and Sheri Koshman 3 1 Pharmacy Services, Alberta Health Services; 2 Canadian VIGOUR Centre, University of Alberta; 3 Division of Cardiology, Faculty of Medicine and Dentistry, University of Alberta; 4 Division of General Internal Medicine, Faculty of Medicine and Dentistry, University of Alberta; 5 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta; 6 Heart Function Clinic, Mazankowski Alberta Heart Institute, Alberta Health Services, Edmonton, AB

2 Presenter Disclosure No current or past relationships with commercial entities Speaking fees for current program: o No speaking fee o Complimentary registration for today s session 2

3 Commercial Support Disclosure This program has received no financial or inkind support from any commercial or other organization 3

4 Background For patients with HF with reduced ejection fraction (HFrEF), guidelines recommend: o Angiotensin-converting enzyme inhibitors (ACEi) / angiotensin receptor blockers (ARB) and beta-blockers (BB) at evidence-based target doses (EBTD) Evidence-based medications are utilized in practice, but doses used are often lower than recommended Few studies report: o Target dose achievement of both ACEi/ARB and BB o Titration patterns o Reasons for not reaching target doses 4

5 Objectives Primary To determine the proportion of patients who achieved EBTD of both an ACEi/ARB and BB at any time within 6 months of the first clinic visit 5

6 Objectives Secondary To determine the proportion of patients who achieved: o EBTD of ACEi/ARB and BB at 6 months o EBTD of individual drugs within and at 6 months o Maximally tolerated doses (MTD) of individual drugs at 6 months To describe reasons for not achieving target doses 6

7 Methods Study Design Retrospective chart review Consecutive adult patients entering the MAHI Heart Function Clinic between October 2012 to February 2015 Inclusion LVEF < 45% > 1 encounter within 12 months Exclusion At EBTD of both an ACEi/ARB and BB at baseline Documented contraindication, allergy, or intolerance to ACEi/ARB or BB at baseline 7

8 Methods Definitions EBTD and 6-month time-frame: Canadian Cardiovascular Society (CCS) HF guidelines / compendium Maximally tolerated dose (MTD): As documented in the medical records, or implied from documentation of the highest dose of medication that the patient or clinician would take or prescribe due to adverse effects 8

9 Methods Definitions Reasons for not achieving EBTD: Explicitly documented or implied from pre-defined objective parameters limiting up-titration o ACEi/ARB: SBP < 100 mmhg K+ > 5.5 mmol/l SCr > 30% from baseline o BB: SBP < 100 mmhg HR < 50 bpm 9

10 Statistical Analysis Categorical variables: o Percentages Continuous variables: o Normally distributed: Means (SD) o Not normally distributed: Medians (IQR) Analysis performed using the REDCap Tool, and Microsoft Excel 10

11 Results 359 screened 223 analyzed 136 excluded (37.9%) LVEF>45% (n=85) <2 encounters within 12 months of the 1 st clinic visit (n=21) At target doses of both an ACEi/ARB and BB at clinic entry (n=21) Ineligible for ACEi/ARB or BB at the 1 st clinic visit (n=9) 11

12 Baseline Characteristics (n=223) Characteristic Age years 67 (58-79) Males no. (%) 172 (77.1) NYHA no. (%) I 37 (16.6) II 95 (42.6) III 72 (32.3) Not documented 19 (8.5) LVEF % 27 (19-34) Duration of HF - months 2 (2-8) Not documented no. (%) 66 (29.6) Characteristic Hospitalizations for HF within previous 12 months no. (%) Heart failure cause no. (%) 105 (47.1) Non-ischemic 87 (39.0) Ischemic 84 (37.7) Not documented 57 (25.6) Systolic blood pressure 112 ( ) Heart rate beats/minute 70 (60-80) Serum potassium - mmol/l 4.4 ( ) Serum creatinine mmol/l 101 (79-123) 12

13 Baseline Characteristics (n=223) Medical History no. (%) Hypertension 128 (57.4) Coronary artery disease 115 (51.6) Atrial fibrillation/flutter 90 (40.4) Chronic kidney disease* 89 (39.9) Diabetes 66 (29.6) COPD 39 (17.5) Asthma 8 (3.6) Peripheral artery disease 7 (3.1) Medications no. (%) Beta-blocker 198 (88.8) ACE inhibitor 159 (71.3) ARB 34 (15.2) Diuretic (loop) 151 (67.7) MRA 100 (44.8) Digoxin 27 (12.1) Nitrate therapy (long-acting) 15 (6.7) Hydralazine 5 (2.2) *egfr<60ml/min/1.73m 2 13

14 Patients (%) Achievement of EBTD Both ACEi/ARB BB Baseline Within 6 months At 6 months 14

15 Patients (%) Achievement of EBTD or MDT % 41% 2% 13% 30% 46% Baseline 6 months Baseline 6 months ACEi/ARB BB Neither Maximally tolerated dose Target dose 15

16 Patients (%) Achievement of EBTD or MDT % 41% 90% 65% 2% 13% 30% 46% 8% 20% Baseline 6 months Baseline 6 months ACEi/ARB 3% BB 15% Neither Maximally tolerated dose Target dose 16

17 ACEi/ARB Doses at 6 Months ACEi (n=171) No. (%) Dose (mg/day) Target dose (mg/day) ACEi/ARB % of target dose = 62.5 (25-100) Ramipril 95 (55.6) 7.5 (5-10) 10 Perindopril 58 (33.9) 6 (4-8) 4 Lisinopril 11 (6.4) 20 (7.5-30) 20 Enalapril 5 (2.9) 15 (10-20) 20 Quinapril 2 (1.2) 25 ( ) 20 ARB n=33; individual data not shown 17

18 BB Doses at 6 Months BB (n=222) No. (%) Dose (mg/day) Target dose (mg/day) % of target dose = 50 (25-75) Bisoprolol 106 (47.7) 5 ( ) 10 Carvedilol 63 (28.4) 25 ( ) 50 Metoprolol 52 (23.4) 100 (50-150) 200 Atenolol 1 (0.5)

19 Reasons for Not Achieving EBTD Documented Reason ACEi/ARB (n=103) BB (n=173) Any reason 88 (85.4) 119 (68.8) Hypotension or SBP <100mmHg 62 (60.2) 62 (35.8) Hyperkalemia or K+ >5.5 mmol/l 19 (18.4) NR Renal dysfunction or SCr >30% from baseline 16 (15.5) NR Bradycardia or HR <50 beats/minute NR 24 (13.9) Maximally tolerated dose 11 (10.7) 14 (8.1) Improved LVEF 10 (9.7) 9 (5.2) Future up-titration planned 6 (5.8) 14 (8.1) Non-adherence 8 (7.8) 12 (6.9) Fluid overload 6 (5.8) 10 (5.8) Other 29 (28.2) 43 (24.9) 19

20 Patients (%) Overall Utilization of EBM Therapy ACEi/ARB BB MRA ACEi/ARB ACEi/ARB +BB +BB+MRA Baseline At 6 months 20

21 Discussion Overall utilization of EBM therapy was high, but target dose achievement of both ACEi/ARB and BB within 6 months was low (11%) o Consistent with previous studies (16-21%) o BB pose a particular challenge o Moderate doses are achieved in most Up-titration occurs, but is limited by various factors o Hypotension o Addition of an MRA 21

22 Discussion Suboptimal up-titration of ACEi/ARB and BB in 41% and 65% of patients, respectively o Opportunities for improvement Strategies to improve the achievement of target doses have been efficacious compared to usual care o Nurse- and pharmacist-led titration services achieved target doses in proportions as high as: ACEi/ARB - 61% of patients at 1 year BB - 82% of patients at 6 months 22

23 Limitations Retrospective chart review o Limited by the accuracy and completeness of documentation Time frame Decreased generalizability as a multidisciplinary, tertiary care HF clinic 23

24 Conclusions Overall utilization of evidence-based medications was high EBTD achievement of both ACEi/ARB and BB was low, but improved for individual agents Up-titration is attempted, but is limited by various factors - most achieve moderate doses Up-titration is suboptimal and opportunities for improvement exist 24

25 QUESTIONS?

26 ADDITIONAL SLIDES

27 Baseline Characteristics Characteristic n=223 Age* years 67 (58-79) Males no. (%) 172 (77.1) NYHA no. (%) I 37 (16.6) II 95 (42.6) III 72 (32.3) Not documented 19 (8.5) LVEF* % 27 (19-34) Duration of HF* - months 2 (2-8) Documented no. (%) 157 (70.4) *Median (IQR) Characteristic n=223 Hospitalizations for HF within previous 12 months no. (%) Heart failure cause no. (%) 105 (47.1) Non-ischemic 87 (39.0) Ischemic 84 (37.7) Not documented 57 (25.6) Device therapy no. (%) 54 (24.2) ICD 28 (12.6) Pacemaker 13 (5.8) CRT-D 13 (5.8) CRT 1 (0.4) 27

28 Baseline Characteristics *egfr<60ml/min/1.73m 2 Medical History no. (%) n=223 Dyslipidemia 148 (66.4) Hypertension 128 (57.4) Coronary artery disease 115 (51.6) Atrial fibrillation/flutter 90 (40.4) Chronic kidney disease* 89 (39.9) Diabetes 66 (29.6) COPD 39 (17.5) Stroke/TIA 31 (13.9) Ventricular arrhythmia 22 (9.9) Asthma 8 (3.6) Peripheral artery disease 7 (3.1) Medications no. (%) n=223 Beta-blocker ACE inhibitor 198 (88.8) 159 (71.3) ARB 34 (15.2) Diuretic (loop) 151 (67.7) MRA 100 (44.8) Digoxin 27 (12.1) Nitrate therapy (long-acting) 15 (6.7) Hydralazine 5 (2.2) Antiplatelet Anticoagulant 125 (56.1) 104 (46.6) Antiarrhythmic 17 (7.6) 28

29 Baseline Characteristics Clinical Features* SBP mmhg 112 ( ) HR beats/minute 70 (60-80) Na+ - mmol/l 139 ( ) K+ - mmol/l 4.4 ( ) SCr umol/l 101 ( ) *Median (IQR) 29

30 Dose Achieved at 6 Months ACE Inhibitor (n=171) No. (%) Dose (mg/day)* Target dose (mg/day) Mean dose achieved in clinical trials (mg/day) Ramipril 95 (55.6) 7.5 (5-10) 10 NR Perindopril 58 (33.9) 6 (4-8) 4 NR Lisinopril 11 (6.4) 20 (7.5-30) Enalapril 5 (2.9) 15 (10-20) Quinapril 2 (1.2) 25 ( ) 20 NA *Median (IQR) 30

31 Non-EBM EBM Dose Achieved at 6 Months ARB (n=33) No. (%) Dose (mg/day)* Target dose (mg/day) Mean dose achieved in clinical trials (mg/day) Candesartan 17 (51.5) 8 (8-16) Valsartan 11 (33.3) 80 (80-160) Telmisartan 2 (6.1) 60 (50-70) 80 NA 300 Irbesartan 1 (3.0) ( ) 300 NA Losartan 1 (3.0) 25 (25-25) Olmesartan 1 (3.0) 20 (20-20) 40 NA *Median (IQR) 31

32 Non-EBM EBM Dose Achieved at 6 Months Beta-Blocker (n=222) No. (%) Dose (mg/day)* Target dose (mg/day) Mean dose achieved in clinical trials (mg/day) Bisoprolol 106 (47.7) 5 ( ) Carvedilol 63 (28.4) 25 ( ) Metoprolol 52 (23.4) 100 (50-150) Atenolol 1 (0.5) 75 (75-75) 100 NA *Median (IQR) 32

33 Clinic Action ACE inhibitor / ARB All Patients (n=223) At target doses (n=120) Not at target doses (n=103) Up-titration 104 (46.6) 64 (53.3) 40 (38.8) Increase dose 84 (37.7) 59 (49.2) 25 (24.3) New 23 (10.3) 10 (8.3) 13 (12.6) Restart 13 (5.8) 6 (5.0) 7 (6.8) Median * number of uptitrations 1 (1-2) 1 (1-2) 1 (1-1) *Median (IQR) 33

34 Clinic Action ACE inhibitor / ARB All patients (n=223) At target doses (n=120) Not at target doses (n=103) Limiting up-titration 39 (17.5) 16 (13.3) 23 (22.3) Decrease dose 10 (4.5) 4 (3.3) 6 (5.8) Switch to/from ACEi/ARB ǂ 9 (4.0) 5 (4.2) 4 (3.9) Change agent ǂ 7 (3.1) 4 (3.3) 3 (2.9) Hold 10 (4.5) 3 (2.5) 7 (6.8) Discontinue 7 (3.1) 0 7 (6.8) No change 33 (32.0) Not prescribed ǂ Switch to an equivalent dose is 7 (6.8) assumed 34

35 Clinic Action Beta-Blocker All patients (n=223) At target doses (n=50) Not at target doses (n=173) Up-titration 98 (43.9) 30 (60.0) 68 (39.3) Increase dose 87 (39.0) 30 (60.0) 57 (32.9) New 16 (7.2) 0 16 (9.2) Restart 5 (2.2) 0 5 (2.9) Median * number of uptitrations 1 (1-2) 2 (1-3) 1 (1-2) *Median (IQR) 35

36 Clinic Action Beta-Blocker All Patients (n=223) At target doses (n=50) Not at target doses (n=173) Limiting up-titration 44 (19.7) 10 (20.0) 34 (19.7) Decrease dose 17 (7.6) 5 (10.0) 12 (6.9) Change agentǂ 29 (13.0) 5 (10.0) 24 (13.9) Hold 1 (0.4) 1 (2.0) 0 Discontinue 1 (0.4) 0 1 (0.6) No change 70 (40.5) Not prescribed 1 (0.6) ǂ Switch to an equivalent dose is assumed 36

37 MRA Utilization at 6 Months All patients (n=223) At ACEi/ARB EBTD (n=103) Not at ACEi/ARB EBTD (n=120) At BB EBTD (n=45) Not at BB EBTD (n=178) MRA 139 (62) 75 (73) 64 (53) 33 (73) 106 (60) 37

38 Diuretic Titration Within 6 Months Diuretic titration All patients (n=223) At ACEi/ARB EBTD (n=103) Not at ACEi/ARB EBTD (n=120) At BB EBTD (n=45) Not at BB EBTD (n=178) 104 (47) 38 (37) 66 (55) 15 (33) 89 (50) 38