Hypertension Canada CHEP Guidelines for the Management of Hypertension. What s new in the treatment of hypertension? What s still really important?

Transcription

1 Hypertension Canada CHEP Guidelines for the Management of Hypertension What s new in the treatment of hypertension? What s still really important? 1

2 Presenter Disclosure Relationships with commercial interests: Grants/Research Support: Novartis, Boehringer-Ingelheim, Astra-Zeneca, Servier Speakers Bureau/Honoraria: Merck, Abbott, Servier, Tribute, Forest, Boehringer-Ingelheim, Sanofi, Janssen, Bayer, Pfizer, Valeant, Mylan Advisory Boards: Bayer, Merck, Abbott, Amgen, Takeda, Servier, Boehringer-Ingelheim, Jansen, Sanofi, Valeant, Novartis 2

3 Mitigating Potential Bias The information presented is based on recent information that is explicitly evidence-based. This presentation and all the recommendations involving clinical medicine are based on evidence that was vetted by the Canadian Hypertension Education Program. The presentation has been developed for dissemination by Hypertension Canada. 3

4 CHEP Guidelines What s new? New thresholds and targets for high risk patients (SPRINT) Assessing clinic blood pressures using automatic electronic (oscillometric) monitors Adopting healthy behaviours is integral to the management of hypertension (focus on potassium supplementation Updating the treatment of patients with hypertension with concurrent coronary artery disease 4

5 CHEP Guidelines What s still important? The diagnosis of hypertension should be based on out-of-office measurements The management of hypertension is all about global cardiovascular risk management and vascular protection The most important step in prescription of antihypertensive therapy is achieving patient buy-in and adherence 5

6 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 6

7 Recommended Office BP Treatment Targets Treatment consists of health behaviour ± pharmacological management Population SBP DBP High Risk 120 NA Diabetes < 130 < 80 All others* < 140 < 90 * Target BP with AOBP < 135/85 7

8 SPRINT Research Question Examine effect of more intensive high blood pressure treatment than is currently recommended Randomized Controlled Trial Target Systolic BP Intensive Treatment Goal SBP < 120 mm Hg Standard Treatment Goal SBP < 140 mm Hg SPRINT design details available at: ClinicalTrials.gov (NCT ) Ambrosius WT et al. Clin. Trials. 2014;11:

9 Major Inclusion Criteria 50 years old Systolic blood pressure : mm Hg (treated or untreated) oscillometric BP x 3 at intervals of 5 minutes Additional cardiovascular disease (CVD) risk Clinical or subclinical CVD (excluding stroke) Chronic kidney disease (CKD), defined as egfr 20 <60 ml/min/1.73m 2 Framingham Risk Score for 10-year CVD risk 15% At least one Age 75 years

10 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 Frail or institutionalized elderly Inconclusive Evidence: Diabetes mellitus Prior stroke egfr < 20 ml/min/1.73m2 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 10

11 Primary Outcome and Primary Hypothesis Primary outcome CVD composite: first occurrence of Myocardial infarction (MI) Acute coronary syndrome (non-mi ACS) Stroke Acute decompensated heart failure (HF) Cardiovascular disease death Primary hypothesis* CVD composite event rate lower in intensive compared to standard treatment *Estimated power of 88.7% to detect a 20% difference - based on recruitment of 9,250 participants, 4-6 years of follow-up and loss

12 Systolic BP During Follow-up Year 1 Mean SBP mm Hg Mean SBP mm Hg Standard Intensive Average SBP (During Follow-up) Standard: mm Hg Intensive: mm Hg Average number of antihypertensive medications Number of participants

13 Primary Outcome NNT=61 The SPRINT Research Group, NEJM, Nov 9 th,

14 Primary Outcome SPRINT Primary Outcome and its Components Event Rates and Hazard Ratios Intensive No. of Events Rate, %/year Standard No. of Events Rate, %/year HR (95% CI) P value (0.64, 0.89) <0.001 All MI (0.64, 1.09) Non-MI ACS (0.64, 1.55) All Stroke (0.63, 1.25) All HF (0.45, 0.84) CVD Death (0.38, 0.85) 0.005

15 New Guideline post-sprint For high-risk patients, aged 50 years, with systolic BP levels >/=130 mm Hg, intensive management to target a systolic BP </=120 mm Hg should be considered. Intensive management should be guided by automated office BP measurements. Patient selection for intensive management is recommended and caution should be taken in certain high-risk groups. 15

16 Office BP Measurement Methods Office (attended): Auscultatory (mercury, aneroid) not recommended Non-automated oscillometric (electronic) Automated office (unattended): AOBP Oscillometric (electronic) 16

17 2015 Recommendation on BP Measurement AOBP: Measurement using electronic (oscillometric) devices in the upper arm Provider outside the room/area (mitigates white coat effect) Multiple readings Mean automatically calculated 17

18 New Recommendation BP Measurement Automated office blood pressure (AOBP) is the preferred method of performing in-office BP measurement. 3 6 measurements Automated Office (unattended, AOBP) Oscillometric (electronic) 18

19 Taking BP: Proper technique X

20 Oscillometric measure of BP

21 Predictive value of AOBP AOBP predicts end-organ damage Systolic AOBP correlates with LVMI similarly to awake ABPM AOBP and 24-h ABPM have similar predictive ability for microalbuminuria AOBP is more strongly associated with cimt (compared to OBPM) 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:

22 Studies comparing AOBP measurement with Awake ABPM AOBPs Equivalent to Awake ABPs Myers MG, et al. Can Fam Physician 2014;60:127-32; Myers MG. J Clin Hypertens 2014;16:83-6; Myers MG. J Hypertens 2012;30:1894-8; Myers MG, et al. Family Practice 2012;29:376-82; Myers MG, et al. BMJ 2011;342:d286; Myers MG. J Hypertens 2010;28:703-8; Myers MG, et al. J Hypertens 2009;27:280-6; Myers MG, et al. Blood Press Monit 2009;14:108-11; Myers MG, Godwin M. J Clin Hypertens 2007;9:

23 Predictive Value of AOBP The CHAP Study AOBP Predicts Cardiovascular Events 3627 community-dwelling residents, aged >65 yrs, untreated for hypertension part of the CHAP trial BpTRU device in community pharmacies f/u 4.9 ± 1.0 yrs for fatal and non-fatal CV events Myers MG, et al. Hypertension 2015;66: Kaczorowski J, et al Preventive Medicine 46:

24 Predictive Value of AOBP Cardiovascular Events Systolic Blood Pressure Diastolic Blood Pressure Systolic BP Hazard Ratio < ( ) (referent) ( ) ( ) ( ) ( ) ( ) ( ) Diastolic BP Hazard Ratio < ( ) (referent) ( ) ( ) ( ) Myers MG, et al. Hypertension 2015;66:

25 Health Behaviour Management Intervention Target Reduce foods with added sodium 2000 mg /day Weight loss BMI <25 kg/m 2 Alcohol restriction < 2 drinks/day Physical activity minutes 4-7 days/week Dietary patterns DASH diet Smoking cessation Smoke-free environment Waist circumference Men < 102 cm Women < 88 cm Potassium supplementation NEW RECOMMENDATION 25

26 Systematic Reviews Showing Significant Effect of Potassium on BP Author Year RCTs Total N Pooled effect SBP Pooled effect DBP Notes Cappuccio (-6.6 to -5.2) -3.4 (-4.0 to -2.8) Mixed status, days, participants;?all RCTs Whelton (-4.3 to -1.9) (-3.4 to -0.5) Mixed status; 4d-3yrs; N Geleijnse NR -2.4 (-3.8 to -1.1) (-2.6 to -0.5) Mixed status; >2 wks duration Dickinson (-8.6 to 0.8) (-25.2 to 2.7) -1.5 (-6.2 to 3.1) -5.0 (-12.5 to 2.4) Cochrane; hypertensive only; >8wks; N; still significant heterogeneity; one trial not pooled no ss dec in BP van Bommel (-8.5 to -5.7) -9.5 (-10.8 to -8.1) -4.9 (-5.8 to -4.0) -6.4 (-7.3 to 5.6) Hypertensive pts with high Na diet; heterogeneity dec. after exc. of outlier Aburto (-5.2 to -1.8) (-3.1 to -0.9) Binia (2.4 to -7) (1.3 to 5.7) Mixed status; >4 wks; measured urinary K Pts not on anti-htn Rx; mixed status; >=4wks; 26

27 Increased Potassium intake decreases BP: Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. Aburto et al, BMJ

28 Risk of Hyperkalemia with K Supplementation Identify those at Risk of Hyperkalemia with Potassium supplementation Prior to advising increase in potassium intake, the following kinds of patients who are at high risk of hyperkalemia, should be assessed for suitability, and monitored closely: Patients taking renin-angiotensin-aldosterone inhibitors Patients on other drugs that can cause hyperkalemia (trimethoprim and sulfamethoxazole, amiloride, triamterene) Patients with CKD (GFR < 45mL/min) Patients with baseline serum potassium > 4.5 mmol/l 28

29 Change in Recommendation: Hypertension in CAD Prior recommendation: For patients with stable angina, β-blockers are preferred as initial therapy. CCBs may also be used. New recommendation: For patients with hypertension and stable angina pectoris but without prior HF, MI or coronary artery bypass surgery, either a beta blocker or a calcium channel blocker can be used as initial therapy. 29

30 Beta blocker vs. CCB in treatment of CAD The APSIS Trial Cumulative percentage survival Fatal events Cumulative event free survival Non Fatal The curves were not extended beyond 5 years as few patients were followed thereafter APSIS: metoprolol vs verapamil in stable angina pectoris No difference: CV events (30.8% v 29.3%) CV mortality 4.7% vs 4.7%), Non-fatal CV events 26.1 v 24.3% Hjemdahl P. et al. Favourable long term prognosis in stable angina pectoris: an extended follow up of the angina prognosis study in Stockholm (APSIS); Heart 2006;92:

31 As required to achieve blood pressure control: CCB strategy: Verapamil sustained release + Trandolapril + HCTZ Non-CCB strategy: Atenolol + HCTZ, + Trandolapril CCB vs. Non-CCB in treatment of CAD The INVEST trial - 22,000 HT patients with CAD - Primary Outcome: Alive, Free of MI or Stroke - Total FU: 61,807 pt-y, mean FU 2.7y, - Annual event rate = 3.6% Pepine JC et al. JAMA (21):

32 Out-of-Office BP Measurements Out of office assessment is the preferred means of hypertension diagnosis Measurement using electronic (oscillometric) upper arm devices is preferred over auscultation 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. Identifies white coat hypertension and masked hypertension. 32

33 Cardiovascular Risk Factors in Hypertensive Patients 8 out of 10 hypertensive patients have at least 1 additional risk factor Gee ME, Bienek A, McAlister FA, et al. Factors Associated With Lack of Awareness and Uncontrolled High Blood Pressure Among Canadian Adults With Hypertension. Can J Cardiol. 2012;28:

34 Stratification of total CV risk by categories of HTN 2013 ESH Guidelines, J Hypertension, 31, 2013

35 Clinical Case 1, 62, diabetes + HTN x 12 years Rx: metformin, Diamicron MR & statin For BP: ramipril 5 mg die & hctz 12.5 mg die No retinopathy/ nephropathy No hx of IHD or CVA Physical exam: - BMI = /88; HR = 78/min - Clear lungs - Heart: RR, S1S2 N, S3S4, murmur - Good peripheral pulses What is your plan?

36 ACCOMPLISH: Design 74% of patients were treated with 2 antihypertensive agents Amlodipine 10 + benazepril 40 mg Free add-on antihypertensive agents* Amlodipine 5 mg + benazepril 40 mg Screening Randomization Amlodipine 5 mg + benazepril 20 mg Benazepril 20 mg + HCTZ 12.5 mg Benazepril 40 mg + HCTZ 12.5 mg Titrated to achieve BP<140/90 mmhg; <130/80 mmhg in patients with diabetes or renal insufficiency Benazepril 40 mg + HCTZ 25 mg Free add-on antihypertensive agents* 14 Days Day 1 Month 1 Month 2 Month 3 Year 5 *Beta blockers; alpha blockers; clonidine; (loop diuretics). Jamerson KA et al. Am J Hypertens. 2003;16(part2)193A

37 Systolic Blood Pressure Over Time mm Hg Baseline characteristics BMI, kg/m Diabetes, % 60.4 Previous MI, % 23.6 Unstable angina, % 11.5 Coronary-artery bypass grafting, % 21.3 Previous stroke, % 13.1 LVH, % mmHg ACEI / HCTZ N=5733 CCB / ACEI N=5713 BP < 140/90 BP < 130/80 DM, CKD Difference of 0.7 mmhg p<0.05* mmhg Month Patients *Mean values are taken at 30 months F/U visit DBP: 71.1 DBP: 72.8

38 Kaplan Meier for Primary Endpoint (Cardiovascular death, Non-fatal myocardial infarction, Non-fatal stroke, Hospitalization for unstable angina, Coronary revascularization procedure (PCI or CABG), Resuscitated sudden death) Cumulative event rate ACEI / HCTZ CCB / ACEI 20% Risk Reduction p = Time to 1 st CV morbidity/mortality (days) HR (95% CI): 0.80 (0.72, 0.90) INTERIM RESULTS Mar 08

39 Treatment of Hypertension in association with Diabetes Mellitus: Summary Threshold equal or over 130/80 mmhg and TARGET below 130/80 mmhg Diabetes with Nephropathy without Nephropathy ACE Inhibitor or ARB 1. ACE Inhibitor or ARB or 2. DHP-CCB or Thiazide diuretic A combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmhg systolic or >10 mmhg diastolic above target. Combining an ACEi and a DHP-CCB is recommended. > 2-drug combinations Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB Combinations of an ACEI with an ARB are specifically not recommended in the absence of proteinuria More than 3 drugs may be needed to reach target values for diabetic patients If Creatinine over 150 µmol/l or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired 2015

40 Diuretics in Hypertension Thiazide and Thiazide-like Diuretics BA (%) T½ (h) Duration (hrs) HTCZ Chlorothiazide CLD Bendroflumethiazide Indapamide Metolazone Loop Diuretics Bumetanide Potassium- Sparing Diuretics Furosemide Torsemide Amiloride Triamterene 83 (55) * 3.0 (3.0) * 7 9 Spironolactone > Eplerenone NA *Parentheses denote active metabolite. The half-life of one active metabolite, potassium canrenoate, is 15 h. BA = bioavailability; T½ = half-life; DOA = duration of action; NA = unknown. Reprinted from Brater DC. In: Principles of Pharmacology: Based Concepts and Clinical Applications. 1995: , with permission from Springer Science and Business Media; Delyani JA, et al. Cardiovasc Drug Rev 2001; 19: ; Rosenberg J, et al. Cardiovasc Drug Ther 2005; 19: ; Sica DA. Congest Heart Fail 2003; 9:

41 Comparative Effects of HCTZ (12.5 mg 25 mg) and Other Anti-hypertensive Drugs as Assessed by 24-hour ABPM 0 HCTZ ACE inhibitors ARBs Beta blockers Calcium antagonists Reduction in Blood Pressure (mmhg) N = 14 SBP DBP N = 5 N = 7 p < N = 3 N = 5 ABPM = ambulatory blood pressure monitoring; SBP = systolic blood pressure; DSP = diastolic blood pressure. Messerli FH, JACC, 2011, (57)

42 Clinical Case 2, 82, retired judge; elevated BP x 1 year Autonomous. Plays golf 3 days/week No hx of IHD or CVA Physical exam: - BMI = /68; HR = 76/min - Clear lungs. - Heart: RR, S1S2 N, S3S4, murmur - Good peripheral pulses What is your plan?

43 The Trial: International, multi-centre, randomised double-blind placebo controlled Inclusion Criteria: Exclusion Criteria: Aged 80 or more, Standing SBP < 140mmHg Systolic BP; mmHg Stroke in last 6 months + diastolic BP; <110 mmhg, Dementia Informed consent Need daily nursing care Primary Endpoint: All strokes (fatal and non-fatal) + Perindopril 2 mg Indapamide SR 1.5 mg + Perindopril 4 mg Placebo Placebo Target blood pressure 150/80 mmhg + Placebo + Placebo M-2 M-1 M0 M3 M6 M9 M12 M18 M24 M60

44 Blood pressure separation mmhg Blood Pressure (mmhg) Median follow-up I 1.8 years Placebo Indapamide SR +/- perindopril mmhg Follow-up (years)

45 All stroke (30% reduction) P=0.055

46 Total Mortality (21% reduction) P=0.019

47 Treatment of Isolated Systolic Hypertension without Other Compelling Indications TARGET <140 mmhg, < 150 mmhg for age > 80 years Health Behaviour Management Thiazide diuretic ARB Long-acting DHP CCB CONSIDER Nonadherence Secondary HTN Interfering drugs or lifestyle White coat effect Dual therapy Triple therapy *If blood pressure is still not controlled, or there are adverse effects, other classes of antihypertensive drugs may be combined (such as ACE inhibitors, alpha blockers, centrally acting agents, or nondihydropyridine calcium channel blocker). 2015

48 Clinical Case 3, 72, hypertensive x 5 years Rx: Dyazide, ½ tablet/ day FRS = 18 % Autonomous; lives in own house with spouse Physical exam: - BMI = /92; HR = 78/min - Lungs: clear - Heart: RR, S1S2 N, S3S4, holosystolic II/VI at apex - Good peripheral pulses What is your plan?

49 SPRINT Treatment Algorithm 50 years FRS 15 % This a SPRINT type patient! Intensive Treatment BP goal: SBP 120

50 PATIENTS TAKING SINGLE PILL COMBINATIONS - HIGHER ADHERENCE RATES Sherrill B, et al. J Clin Hypertens. 2011;13(12):

51 Odds ratios (and corresponding 95% CIs) of nonfatal cardiovascular (CV) outcomes as a whole, coronary heart disease, or cerebrovascular events associated with an initial combination of blood pressure lowering agents, with respect to initial monotherapy Giovanni Corrao et al. Hypertension. 2011;58: Copyright American Heart Association, Inc. All rights reserved.

52 Thank you!