Update on HTN and ABPM. Raj Padwal Division of General Internal Medicine University of Alberta

Transcription

1 Update on HTN and ABPM Raj Padwal Division of General Internal Medicine University of Alberta

2 Disclosures Funding: CIHR, AIHS, HSF, UHF Research Collaboration: Novo Nordisk, CVRx Consulting: Vivus, Medtronic Speaking and other Honoraria: Abbott

3 Outline 1. Understand how to interpret ABPM. 2. Review the pros and cons of different methods to diagnose hypertension. 3. Discuss some current controversies in HTN management.

4 Epidemiology and Significance

5 European Society of Hypertension Classification of Blood Pressure Category Systolic Diastolic Optimal <120 and / or <80 Normal <130 and / or <85 High-Normal and / or Grade 1 (mild hypertension ) and / or Grade 2 (moderate hypertension) and / or Grade 3 (severe hypertension) 180 and / or 110 Isolated Systolic Hypertension (ISH) 140 and <90 The category pertains to the highest risk blood pressure *ISH=Isolated Systolic Hypertension. J Hypertens 2007;25:

6 Hypertension in Canada: Prevalence and Control Overall prevalence is 21% McAlister et al. CMAJ 2011

7 Life time risk of Hypertension in Normotensive Women and Men aged 65 years Risk of Hypertension % Risk of Hypertension % Women 80 Men Years to Follow-up Years to Follow-up JAMA 2002: Framingham data.

8 Diagnosing Hypertension

9 Blood Pressure Assessment: Patient preparation and posture Standardized Preparation: Patient 1. No acute anxiety, stress or pain. 2. No caffeine, smoking or nicotine in the preceding 30 minutes. 3. No use of substances containing adrenergic stimulants such as phenylephrine or pseudoephedrine (may be present in nasal decongestants or ophthalmic drops). 4. Bladder and bowel comfortable. 5. No tight clothing on arm or forearm. 6. Quiet room with comfortable temperature 7. Rest for at least 5 minutes before measurement 8. Patient should stay silent prior and during the procedure.

10 II. Criteria for the diagnosis of hypertension and recommendations for follow-up BP: / Clinic BP ABPM (If available) Home BPM Hypertension visit 3 >160 SBP or >100 DBP <160 / 100 or Hypertension visit 4-5 Diagnosis of HTN ABPM or HBPM Awake BP <135/85 and 24-hour <130/80 Awake BP >135 SBP or >85 DBP or 24-hour >130 SBP or >80 DBP < 135/85 Confirm with repeat Home BPM or ABPM >135/85 >140 SBP or >90 DBP < 140 / 90 Diagnosis of HTN Continue to follow-up Continue to follow-up Diagnosis of HTN Continue to follow-up Diagnosis of HTN Patients with high normal blood pressure (clinic SBP and/or DBP 85-89) should be followed annually.

11 Clinic, Home, Ambulatory (ABP) Blood Pressure Measurement Equivalence Numbers A clinic blood pressure of 140/90 mmhg has a similar risk of a: Description Blood Pressure mmhg Home pressure average 135 / 85 Daytime average ABP 135 / hour average ABP 130 / 80

12 ABPM Indications Chughtai and Peixoto. Hosp Phys 2003

13 Contraindications to ABPM 1. Not cooperative 2. Severe PVD or thrombocytopenia 3. Afib (relative): not accurate 4. Arm too big 5. Severe office HTN ( 220/120)

14 ABPM 1

15 ABPM 1

16 Information Provided by ABPM 1. Estimate of true overall 24 hour BP 2. Diurnal variation in BP 3. Variability in BP 4. Duration of action of drug

17 ABPM Normal Parameters BP should dip by 10-20% during sleep Chughtai and Peixoto. Hosp Phys 2003

18 ABPM 2

19 ABPM 2

20 ABPM 3

21 ABPM 3

22 ABPM 4

23 ABPM: Number of Readings Recommendation is at least 14 readings in the daytime (NICE Guidance). Minimum number is 2 per hour. We usually do a reading an hour at night.

24 ABPM 5

25 ABPM 5

26 ABPM 5 Ziemmsen. J Neurol Sci 2010

27 Home/Ambulatory SBP mmhg White Coat and Masked Hypertension Masked Hypertension Hypertension Normotension White Coat Hypertension Office SBP mmhg Derived from Pickering et al. Hypertension 2002: 40:

28 Prognosis of Masked Hypertension Prevalence of masked hypertension is approximately 10% in the general population but is higher in patients with diabetes J Hypertension 2007;25:

29 Prognostic Significance of Clinic vs. ABPM Dawes. BP Monit 2006

30 Prognostic Significance of Clinic vs. ABPM Dawes. BP Monit 2006

31 Diagnostic Utility of BP Measures NICE 2011 Guidance Document

32 Diagnostic Utility of BP Measures Hodgkinson. BMJ 2011

33 Cost-Effectiveness of ABPM Lovibond. Lancet 2011

34 Diagnosis of Hypertension: Key Points Non-automated office BP measurements are not accurate. This results in inappropriate management. Out-of-office measurement particularly ABPM should be used to confirm the diagnosis of HTN.

35 Bedtime Dosing of Antihypertensive Drugs

36 Predictive Role of Nighttime BP Hansen. Hypertension 2012

37 The MAPEC Trial

38 MAPEC Hypothesis: Bedtime chronotherapy leads to better BP control and reduces CV endpoints. Design: PROBE RCT Country: Spain Sample Size: 2156; mean age 56 Endpoints: 1. All-cause mortality and CVD events (huge composite endpoint) hour ABPM

39 MAPEC: Results Baseline awake systolic ABPM was 134 mm Hg. Baseline asleep systolic ABPM was 123 mm Hg.

40 MAPEC: Results

41 MAPEC Study: Issues Inconsistent numbers presented across trial publications. Is this truly an RCT with a predefined start and end? Original sample size in the protocol was Subsequent publication mentions 734 normotensive subjects uncertain if they are included in the main paper. Most of the literature in the field comes from a single centre and one group of investigators. Huge effect size from such a small, simple change.

42 Bottom Line: Bedtime Dosing Practical point: relatively simple intervention Conversely, I don t view the data as definitive yet. I don t routinely do it; however, I will in refractory hypertension. Also, in this group, I often use drugs that need bedtime dosing (alpha blockers and some CCBs).

43 Choice of Thiazide Diuretic for HTN Chlorthalidone vs. HCTZ

44 Pharmacologic Structure Chlorthalidone is often mislabeled as thiazidelike. It is a non-thiazide with a distinct pharmacological structure..that has similar pharmacological action (DCT NaCl symporter blockade) Kurtz. Hypertension 2012.

45 Thiazides and Non-thiazides Thiazides Hydrochlorothiazide Chlorothiazide Methychlothiazide Polythiazide Bendroflumethiazide Non-thiazides Chlorthalidone Indapamide Metolazone

46 Pharmacokinetics DRUG ONSET (h) PEAK T1/2 (h) Duration (h) HCTZ (single) 8-15 (long term) 12 (single) (long term) Chlorthalidone (single) (long term) (single) (long term) Carter BL. Hypertension 2004;43:4-9

47 BP Control Meta-analysis of 108 HCTZ and 20 chlorthalidone studies (n=10443) Comparisons are indirect, not head-to-head Dose Chlorthalidone is a more potent drug Ernst, ME. Am J Hypertens. 2010

48 MRFIT Trial Results MRFIT. JAMA 1986

49 Trial Results Trial Drug Result MRFIT Both + HDFP Chlorthalidone + ALLHAT Chlorthalidone + SHEP Chlorthalidone + Oslo BP HCTZ - MAPHY HCTZ - MRC HCTZ - Wing HCTZ - Amery HCTZ + MIDAS HCTZ + ANBP HCTZ + INSIGHT HCTZ + ACCOMPLISH HCTZ -

50 Diuretic Choice: Summary Thiazides and non-thiazides are similar and dissimilar properties. Chlorthalidone (non-thiazide) is more potent and can reduce BP more than HCTZ at equal doses. Non-definitive hard outcome indirect comparisons:?chlorthalidone better

51 Diuretic Choice: Practical Considerations Chlorthalidone: smallest dose available in Canada is 50 mg. Chlorthalidone: not commonly available in combos (atenolol only). HCTZ: many combos If BP controlled on HCTZ, I don t change. If I need to choose a fixed dose combo with a diuretic, I use perindopril indapamide or a HCTZ combo ($$ and coverage considered) In uncontrolled refractory hypertension, I will usually use chlorthalidone

52 Treatment Target in Mild HTN

53 Treatment of Mild Hypertension

54 Treatment of Mild Hypertension

55 Treatment of Mild Hypertension Primary Prevention Subjects with Mild HTN Total events 77 vs 90: Nearly all from one study Diao et al. Cochrane Collaboration 2013

56 Comments on This Review 1. Essentially reflects one study (that used BB in half the active treatment group) 2. Underpowered study not designed to specifically look at this subgroup. Randomization not stratified for this subgroup. 3. The authors excluded relevant studies: a) Non-placebo controlled studies (e.g., HDFP). b) Didn t have data for some studies (VA, Oslo, others) but number of events for these would have been small

57 Major Trials Including Patients with Mild Hypertension Trial (n) MRC y ANBP y Age BP Results for Primary Endpoint (intervention vs. control) Stroke events: 60 vs vs per 100 pt*y p<0.01 ARD 0.12% over 5 y Nonfatal and fatal CV events:138 vs vs. 2.5 per 100 pt*y P<0.05 ARD 0.5% over 4 y HDFP y Total mortality: 349 vs % vs. 7.7% P<0.01; ARD 1.3% over 5 y

58 Major Trials Including Patients with Mild Hypertension Trial (n) HDFP 7825 Age BP stratum Results for Primary Endpoint (intervention vs. control) Total mortality: 231 vs % vs. 7.4% P<0.01; ARD 1.5%

59 HDFP Mortality RRR HDFP. JAMA 1971

60 Canadian Hypertension Education Program Recommendations For Initiating Drug Therapy 1. Prescribe for DBP 100 or SBP 160 (Grade A). 2. Strongly consider for DBP 90 and TOD or other CV risk factors (Grade A). 3. Strongly consider for SBP 140 and TOD (Grade C for mild HTN).

61 Major Trials Including Patients with Mild Hypertension Trial (n) MRC y ANBP y HDFP y Age BP Results for Primary Endpoint (intervention vs. control) Stroke events: 60 vs vs per 100 pt*y p<0.01 ARD 0.12% over 5 y Nonfatal and fatal CV events:138 vs vs. 2.5 per 100 pt*y P<0.05 ARD 0.5% over 4 y Total mortality: 349 vs % vs. 7.7% P<0.01; ARD 1.3% over 5 y NNT over 1 year NNT over 10 y NNT over 10y for statins for CV event in high-risk patient is 11 and in mod risk pt. is 23.

62 Major Trials Including Patients with Mild Hypertension Trial (n) Age BP Results for Primary Endpoint (intervention vs. control) NNT over 1 year NNT over 10 y HDFP subgroup stratum Total mortality: 231 vs % vs. 7.4% P<0.01; ARD 1.5%

63 HDFP Trial Alderman. Hypertension 1983

64 II. Indications for Pharmacotherapy after diagnosis of hypertension (1) Patients at low risk with stage 1 hypertension ( /90-99 mmhg) lifestyle modification can be the sole therapy. Patients with target organ damage (e.g. left ventricular hypertrophy) ( /90-99 mmhg) Treat with pharmacotherapy Patients with chronic kidney disease should be considered for pharmacotherapy if the blood pressure is equal or over 140/90 mmhg Patients with diabetes should be considered for pharmacotherapy if the blood pressure is equal or over 140/90 mmhg

65 II. Indications for Pharmacotherapy after diagnosis of hypertension (2) Patients with other risk factors (over 90% of Canadians with hypertension have other risk factors) ( /90-99 mmhg despite lifestyle modification) Treat with pharmacotherapy Treatment Gap Alert: Many younger hypertensive Canadians with multiple cardiovascular risks are currently not treated with pharmacotherapy. Health care professionals need to be aware of this important care gap and recommend pharmacotherapy.

66 Treatment of Mild Hypertension: Key Points 1. All patients should be treated with lifestyle modification. 2. Decision to institute drug treatment should take into account global risk.

67 Renal Denervation

68 Resistant Hypertension Failure to achieve BP target despite treatment with three antihypertensive drugs (including a diuretic) at optimal doses. Prevalence is not well studied. Appears to be about 10-20% of hypertensive patients. Sarafidis. J Clin Hypertens 2011

69 Sympathectomy for Severe Hypertension Bilateral T8-L3 Sympathectomy Ray BS. Ann Surg 1949

70 Renal Sympathetic Denervation Papademetriou et al. Int J Hypertens 2011

71 Renal Sympathetic Denervation for Resistant Hypertension Source: Medtronic 73

72 Renal Sympathetic Denervation for Resistant Hypertension: SYMPLICITY HTN-2 RCT 6 month BP difference of 33/11 P< (n=106) Esler et al. Lancet

73 Renal Sympathetic Denervation: Safety Well tolerated one femoral pseudoaneurysm was the only adverse effect. Renal function similar at end of six months. Only half had ABPM measured; ABPM difference was 16/8 mm Hg between groups. Irreversible nature of the procedure Renal adverse effects? Stenosis, dilation Proteinuria Renal function

74 Renal Sympathetic Denervation: Key Point An emerging procedure Potential to be used in a large number of patients Long-term efficacy and safety data required.

75 Outline 1. Understand how to interpret ABPM. 2. Review the pros and cons of different methods to diagnose hypertension. 3. Discuss some current controversies in HTN management.