Hypertension Putting the Guidelines into Practice

Transcription

1 Hypertension 2018 Putting the Guidelines into Practice Ally P.H. Prebtani Professor of Medicine Internal Medicine, Endocrinology & Metabolism McMaster University Canada

2 Faculty: Metabolism, Faculty Disclosure Ally P. H. Prebtani, BScPhm, MD, FRCPC Professor of Medicine, Internal Medicine, Endocrinology & McMaster University Relationships with financial sponsors: Consultant: Servier Speakers Bureau: Servier Potential for conflict(s) of interest: Servier develops and benefits from the sale of products that might be discussed in this program. Disclosure of Investigational Use or Off-Label Use of Medical Devices, Products or Pharmaceuticals I will discuss or describe in my presentation at the meeting the investigational or unlabelled ( off-label ) use of a medical device, product, or pharmaceutical that is classified by Health Canada as investigational for the intended use.

3 Mitigating Potential Bias All the recommendations involving clinical medicine are based on evidence that is accepted within the profession. All scientific research referred to, reported, or used is in the support or justification of patient care. Recommendations conform to the generally accepted standards. Independent content validation. The presentation will mitigate potential bias by ensuring that data and recommendations are presented in a fair and balanced way. Potential bias will be mitigated by presenting a full range of products that can be used in this therapeutic area. Information of the history, development, funding, and the sponsoring organizations of the disclosure presented will be discussed.

4 Learning Objectives After active participation in the workshop, participants will be able to: 1. Be aware of what is new in hypertension and the guidelines 2. Accurately diagnose hypertension. 3. Formulate an approach to refractory hypertension 4. Decide when to refer

5 William Osler The young physician starts life with 20 drugs for each disease, and the old physician ends life with one drug for 20 diseases.

6 Benefits of lowering mild to moderate BP For every 10/5 mmhg lowering of BP 1,2,3 % reduction Stroke 35 40% Myocardial infarction (MI) 20 25% Heart failure (HF) 50% 1. MacMahon S, Peto R, Cutler J et al. Lancet 1990;335: Collins R, Peto R, MacMahon S et al. Lancet 1990;335: Staessen JA, Fagard R, Lutgarde T et al. Lancet 1997;350:

7

8 Hypertension Diagnostic Algorithm 1. Out of office assessment is the preferred means of hypertension Dx 2. Measurement using electronic (oscillometric) upper arm devices is preferred over auscultation ABPM = ambulatory blood pressure measurement AOBP = automated office blood pressure

9 Ways to Measure BP 1. AOBP (Automated Office) : Electronic (oscillometric) devices in upper arm HCP outside the room/area (mitigates white coat effect) Multiple readings Mean automatically calculated 2. ABPM 24hr (Ambulatory 24hr) 3. HBPM (Home) 9

10 Out-of-Office BP Measurements Out-of-office measurement identifies white coat hypertension and masked hypertension ABPM has better predictive ability than OBPM and is the recommended out-of-office measurement method HBPM has better predictive ability than OBPM and is recommended if ABPM is not tolerated, not readily available or due to patient preference ABPM = ambulatory blood pressure measurement HBPM = home BP measurement OBPM = office BP measurement

11 Out-of-Office BP Measurements are More Highly Correlated With BP-Related Risk LVH Albumin excretion ratio SBP OBP HBPM ABPM SBP DBP OBP HBPM ABPM DBP Indexes of hypertensive target organ damage Indexes of hypertensive target organ damage Mulè G, et al. J Cardiovasc Risk 2002;9:123-9.

12 Predictive value of AOBP AOBP predicts end-organ damage Systolic AOBP correlates with LVMI similarly to awake ABPM (Ambulatory) AOBP & 24-h ABPM have similar predictive ability for uacr AOBP is more strongly associated with cimt (compared to OBPM) More closely approximates ABPM than routine office BPs (mitigates white coat effect)1-3 Is more predictive of end organ damage (LVMI, proteinuria and cimt), similar to ABPM4-6 cimt: Carotid Intima Media Thickness LVMI: Left Ventricular Mass Index Campbell NRC, et al. J Hum Hypertens 2007;21:588-90; Andreadis EA, et al. Am J Hypertens 2011;24:661-6; Andreadis EA, et al. Am J Hypertens 2012;25: Beckett L, et al. BMC Cardiovasc Disord 2005;5:18; 2. Myers MG, et al. J Hypertens 2009;27:280-6;2 3. Myers MG, et al. BMJ 2011;342;d286;4. Campbell NRC, et al. J Hum Hypertens 2007;21:588-90; 5. Andreadis EA, et al. Am J Hypertens 2011;24:661-6; 6. Andreadis EA, et al. Am J Hypertens 2012;25:

13 Usual Office BP Threshold Values for Initiation of Pharmacological Treatment Population SBP DBP High Risk (SPRINT population) >130 NA Diabetes >130 >80 Moderate-to-high risk (TOD or CV risk factors)* >140 >90 Low risk (no TOD or CV risk factors) >160 >100 TOD = target organ damage *AOBP threshold >135/85 1 3

14 Recommended Office BP Treatment Targets Treatment consists of health behaviour ± pharmacological management * Target BP with AOBP < 135/85 1 4

15 New Thresholds/Targets for the High-Risk Patient Post-SPRINT Clinical or sub-clinical cardiovascular disease OR Chronic kidney disease (non-diabetic nephropathy, proteinuria <1 g/d, * estimated glomerular filtration rate ml/min/1.73m2) OR Estimated 10-year global cardiovascular risk 15% OR Age 75 years There was an increased risk of renal deterioration, potassium abnormalities and hypotension with intensified therapy Patients with one or more clinical indications should consent to intensive management Used AOBP * Four variable MDRD equation Framingham Risk Score, D'Agastino, Circulation 2008

16 New Thresholds/Targets for the High-Risk Patient Post-SPRINT: Who does this NOT apply to? Limited or No Evidence: Heart failure (EF <35%) or recent MI (within last 3 months) Indication for, but not currently receiving, a beta-blocker Institutionalized elderly Inconclusive Evidence: Diabetes mellitus Prior stroke egfr < 20 ml/min/1.73m 2 Contraindications: Patient unwilling or unable to adhere to multiple medications Standing SBP <110 mmhg Inability to measure SBP accurately Known secondary cause(s) of hypertension

17 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 83 NUMBER 3 MARCH 2016

18 First Line Treatment of Adults with Systolic/Diastolic Hypertension Without Other Compelling Indications IF BP NOT CONTROLLED CONSIDER TARGET <135/85 mmhg (automated measurement method) INITIAL TREATMENT Nonadherence Secondary HTN Interfering drugs or lifestyle White coat effect Health behaviour management Thiazide/ thiazide-like* ACEI ARB Long-acting CCB Betablocker Single pill combination** * Longer-acting (thiazide-like) diuretics are preferred over shorter-acting (thiazide) diuretics BBs are not indicated as first line therapy for age 60 and above Renin angiotensin system (RAS) inhibitors are contraindicated in pregnancy and caution is required in prescribing to women of child bearing potential **Recommended SPC choices are those in which an ACE-I is combined with a CCB, an ARB with a CCB, or an ACE-I or ARB with a diuretic esp if target BP >20/10

19 Diuretic Type Meta-Analysis vs. Placebo Both types of diuretics reduced CV events, cerebrovascular events, & HF Only thiazide-like diuretics (chlorthalidone, indapamide) additionally reduced coronary events and all-cause mortality unlike HCTZ Event Thiazide-Type Thiazide-Like CV 0.67 ( ) 0.67 ( ) Coronary 0.81 ( ) 0.76 ( ) Cerebrovascular 0.52 ( ) 0.68 ( ) Heart Failure 0.36 ( ) 0.47 ( ) All-cause Mortality 0.86 ( ) 0.84 ( ) Olde Engberink RH. Hypertension 2015;65(5):

20 Mean change from baseline at week 12 Chlorthalidone > Effective vs HCTZ in BP Reduction 0 Ambulatory SBP Ambulatory DBP P= HCTZ (n=18) Chlorthalidone (n=16) -14 P<0.001 Kruskal-Wallis test used with Dunn s test for multiple comparisons; comparison between baseline and Wilcoxon signed rank test results. Mean 24h SBP was significantly lower for the chlorthalidone group than for the HCTZ group at week 4 ( vs mmhg, respectively, P=0.019) and week 12 ( vs mmhg, respectively, P=0.013). Intent-to-treat population. Pareek AK, et al. J Am Coll Cardiol 2016;67(4):379-89

21 Choice of Pharmacological Treatment Individualized treatment Compelling indications: Ischemic Heart Disease Recent ST Segment Elevation-MI or non-st Segment Elevation-MI Left Ventricular Systolic Dysfunction Stroke Left Ventricular Hypertrophy Non Diabetic Chronic Kidney Disease Renovascular Disease Diabetes Mellitus With Nephropathy Without Nephropathy Global Vascular Protection for Hypertensive Patients Statins if >/= additional CV risk factors? Aspirin once blood pressure is controlled

22 Evidence in Compelling Indications

23 Low Sodium

24 Impact of health behaviours on BP Intervention Diet and weight control (BMI < 25; WC < **) Systolic BP (mmhg) Diastolic BP (mmhg) Reduced salt/sodium intake < 2g/d Reduced alcohol intake (heavy drinkers) < 2 drinks/day DASH diet Physical activity (30-60 minutes 4-7 days/week) Relaxation therapies Multiple interventions Clinical Guideline : Methods, evidence and recommendations National Institute for Health and Clinical Excellence (NICE) May

25 Definition & Epidemiology Resistant HTN BP above target 3 optimally dosed Rx including thiazide or ACEI/ARB or DHP-CCB BP at target 4 or more drugs > CV Mortality & Morbidity (CHF, Stroke, CKI, MI) Due to HTN, Co-morbidities, EOD 20% of adults 8-12% primary care 11-21% specialized clinics Pseudo-resistance limits actual prevalence

26 Suboptimal therapy Not on diuretic Extracellular volume expansion Salt Poor compliance Combo pill, HBPM Secondary hypertension Primary hyperaldosteronism, NSAIDs, EtOH Office or "white coat" hypertension Pseudo-hypertension technique

27 How to Evaluate? r/o Pseudo-resistance White-coat 40% HBPM ABPM Technique Non-adherance Suboptimal regimen Look for secondary HTN 10% in tertiary care

28 Secondary HTN Endocrine Pheo, Cushing s, Primary Hyperaldosteronism Hypercalcemia, Thyroid Renal RAS, CKD Cardiac Coarctation OSA Drugs/Toxins

29 Meds/Toxins Padwal et al. CMAJ 2014

30 General Work-Up

31 Work-Up Secondary HTN Creatinine, Potassium TSH, Ca Sleep study Aldosterone/Renin? Imaging for RAS 24hr UFC 24hr urine metanephrines/catacholamines Echo prn

32 Effective Meds Modifications Optimal dosing & drugs Thiazide/Thiazide-like diuretics ACEI/ARB DHP-CCB Mineralocorticoid receptor antagonists (Spironolactone) Beta-blockers Non-DHP CCB (Diltiazem, Verapmil) Furosemide (loop) Volume excess GFR < 30-50mL/min Alpha-blockers Amiloride, DRI (Alikiseren), Clonidine, Methyldopa, Minoxidil, Hydralazine

33 Spironolactone (PATHWAY-2) Spiro 25-50mg/day vs placebo, bisoprolol, doxazosin Drug resistant HTN (A + C + D) RCT crossover trial BP < 135mmHg in 60% Williams B et al, Lancet, Sept 2015

34 Mechanisms Na retention Low renin ACTH dep Aldo hypersecretion Chronic stress via ACTH hypersecretion Gene mutations Zona Glomerulosa responsiveness Williams B et al, Lancet, Sept 2015

35 Approach Padwal et al. CMAJ 2014

36 Padwal et al. CMAJ 2014

37 Adherence improved by a multi-pronged approach Assess adherence at every visit Take pills on regular schedule with routine daily activity e.g. brushing teeth Simplify regimens using long-acting once-daily dosing Utilize fixed-dose combination pills Utilize unit-of-use packaging e.g. blister packaging Replacing with single pill combinations

38 Advantages of Single Pill Combinations (SPCs) SPC therapy is associated with better adherence vs. free combinations 1 A regimen featuring initial prescription of SPC leads to better BP control 2 Initial combination therapy is associated with risk of CV events than monotherapy 3,4 1. Sherrill B, et al. J Clin Hypertens 2011;13: ; 2. Feldman RD, et al. Hypertension 2009;53:646-53; 3. Corrao G, et al. Hypertension 2011;58:566-72; 4. Gradman AH, et al. Hypertension 2013;61(2):

39 SPC Combining an ACEI/ARB With CCB/Diuretic as First Line Rx 2 key studies establishing the utility of SPCs as first line: HOPE-3. N Engl J Med 2016;374(21): Pivotal study demonstrating the superiority of an SPC (ARB/diuretic) vs. Placebo ACCOMPLISH. N Engl J Med 2008;359(23): Demonstration of efficacy of ACEI/CCB SPC vs. active control

40 Other Strategies Bedtime dosing of one agent Combination therapy with different MOA Once daily long-acting agents Blister packaging Self-monitoring BP Education families and patient Multi-D RNs, RDs, pharmacists Base on compelling indications CHF, DM, MI/CAD, CKD, Stroke

41 When to refer to HTN specialist? Truly refractory Secondary cause of HTN Intolerance to many medications End organ damage requiring more specialized care

42 hypertension.ca For patients: Free access to the latest information and resources For professionals: Accredited 15.5 hour interdisciplinary training program Free monthly news updates, featured research and educational resources Become a member for special privileges and savings

43 Question 1 The SPRINT study included all patients but one of the following: a. Prior stroke b. egfr < 50ml/min c. Already on BP meds d. CAD/MI

44 Question 2 What method of BP monitoring is least accurate and least predictive of outcomes? a. Home automated (HBPM) b. Office automated (AOBP) c. 24hr ambulatory (ABPM) d. Office sphygamometer

45 Question 3 What is the most under-diagnosed cause of Secondary HTN? 1. Cushing s 2. Primary Hyperaldosteronism 3. Pheochromocytoma 4. Coarctation of the Aorta

46 Question 4 In a patient with Diabetes and Nephropathy, what would be your 1 st line therapy for HTN? 1. ACEI or ARB 2. Beta Blocker 3. Calcium Channel Blocker 4. Thiazide

47 Question 5 All of the following drugs can cause HTN except? 1. NSAIDs 2. OCP s 3. Sudafed 4. Codeine

48 Question 6 Beta blockers are 1 st line therapies in all of the following except? 1. Stable Angina 2. Diabetes Mellitus 3. CHF with LV dysfunction 4. Recent MI

49 Take Home Messages Move towards automated BP measurements AOBP Use of HBPM/ABPM Don t forget Lifestyle measures Global Vascular Health Lipids, smoking, Statins, DM Think about compelling indications Patient buy in for adherence Combo pills, once daily forms Aldosterone antagonists Consider target SBP < 120 for High Risk Patients SPRINT esp LV dysfunction If the patient is not at target, ask why? Ask about salt intake, EtOH, Adherance, OSA Proper BP technique Home BP monitoring/abp 2º HTN

50 Cases 1. 55yo man with HTN and LV dysfunction 2. 60yo woman with HTN, DM and proteinuria 3. 70yo man with HTN and stroke a week ago 4. 48yo man with recent MI, LV function normal, no DM 5. 39yo woman with new HTN and K 3.6, otherwise health 6. 49yo man office BP 145/92, otherwise healthy & no EOD 7. 65yo man CKD egfr 45, proteinuria; no DM or CVA