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Hypertension 2017

Putting the Evidence into Practice. Hypertension 2017. Disclosures. Relationships with commercial interests : Grants/ Research Support: Speakers Bureau/ Honoraria : Consulting Fees : Data Safety and Monitoring:. Disclosure of Commercial Support.

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Hypertension 2017

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  1. Putting the Evidence into Practice Hypertension 2017

  2. Disclosures • Relationshipswith commercial interests: • Grants/Research Support: • Speakers Bureau/Honoraria: • Consulting Fees: • Data Safety and Monitoring:

  3. Disclosure of Commercial Support • This program has receivedfinancial support fromServier Canada in the form of an educationalgrant • This program has not receivedany in-kindsupport

  4. MitigatingPotentialBias • The information presentedisbased on recent information thatisexplicitly ‘‘evidence-based’’ and issolelybased on Hypertension Canada Guidelines

  5. Evidence-BasedAnnual Guidelines • Canada has the world’shighestreported national blood pressure control rates • Hypertension Canada isknown as the mostcredible source for evidence-based hypertension guidelines, withannual updates, a well-validatedreviewprocess and effective dissemination and implementation techniques across Canada

  6. Learning Objectives At the conclusion of thisactivity, participants willbe able to: • Applyappropriatemethods for making a diagnosis of hypertension • Implementevidence-basedthreshold and targetBPs • Integrate new guidelines for hypertension management including: • Use of longer-acting over shorter-acting diuretics • Use of single pillcombinations as a first-line treatment

  7. Hypertension 2017 What’s new? • Longer acting (thiazide-like) diuretics are preferredvs. shorter acting (thiazides) • Single pillcombinations as a first line treatment (regardless of the extent of BP elevation)

  8. Hypertension 2017 What’sstill important? • The diagnosis of hypertension shouldbebasedon out-of-office measurements; in the office, use automated office BP monitoring (AOBP) • The threshold and targetblood pressures are lowerin those at greaterrisk

  9. Hypertension Diagnostic Algorithm • Out of office assessmentis the preferredmeansof hypertension Dx • Measurementusingelectronic(oscillometric) upper arm devicesispreferred over auscultation ABPM= ambulatory blood pressure measurement AOBP = automated office blood pressure

  10. Out-of-Office Assessmentis the PreferredMeans of Diagnosing Hypertension Clinic BP as alternate method AOBP = automated office blood pressure OBPM = office BP measurement ABPM = ambulatory BP measurement HBPM = home BP measurement

  11. Out-of-Office BP Measurements • Out-of-office measurement identifies white coat hypertension and masked hypertension • ABPM has betterpredictiveabilitythan OBPM and is the recommended out-of-office measurementmethod • HBPM has betterpredictiveabilitythan OBPM and isrecommended if ABPM is not tolerated, not readilyavailable or due to patient preference ABPM= ambulatory blood pressure measurement HBPM = home BP measurement OBPM = office BP measurement

  12. Out-of-Office BP Measurements are More HighlyCorrelatedWith BP-RelatedRisk LVH Albumin excretion ratio SBP SBP DBP DBP Indexes of hypertensive target organ damage Indexes of hypertensive target organ damage Mulè G, et al. J Cardiovasc Risk 2002;9:123-9.

  13. 200 180 MASKED HYPERTENSION TRUE HYPERTENSION White Coatand Masked Hypertension 160 Ambulatory BP mmHg 140 135 Derived from Pickering TG, et al. Hypertension 2002:40:795-6. WHITE COAT HYPERTENSION 120 NORMOTENSION 100 120 140 160 180 200 100 Manual Office BP mmHg Derivedfrom Pickering TG, et al. Hypertension 2002:40:795-6.

  14. Criteria for the Diagnosisof Masked Hypertension

  15. about about higher 30% 10% in patients with diabetes in treated hypertensive patients in the general population Prevalence of Masked Hypertension and chronic kidney disease patients One out of three treated hypertensive patients has masked hypertension Andalib A, et al. Int Med J 2012;42:260-6

  16. The Prognosis of White Coatand MaskedHypertension 35 CV Events 30 25 20 CV events per 1000 patient-year 15 10 5 0 Normal Whitecoat Uncontrolled Masked Okhubo T, et al. J Am CollCardiol2005;46;508-15

  17. Automated Office (unattended, AOBP) Oscillometric (electronic) Automated Office BP MeasurementPreferred • Automated office blood pressure (AOBP) is the preferredmethod of performing in-office BP measurement

  18. Automated Office BP Measurement • 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 ABPM= ambulatory blood pressure measurement LVMI = left ventricular mass index cIMT= carotid intima media thickness • Beckett L, et al. BMC CardiovascDisord2005;5:18; 2. Myers MG, et al. J Hypertens2009;27:280-6; • 3. Myers MG, et al. BMJ 2011;342;d286;4. Campbell NRC, et al. J HumHypertens2007;21:588-90; • 5. Andreadis EA, et al. Am J Hypertens2011;24:661-6; 6. Andreadis EA, et al. Am J Hypertens 2012;25:969-73.

  19. AOBP Readings are Lowerthan OBP Readings and are More Similar to ABP Readings *The automated office blood pressure (BP) and awake ambulatory BP were similar, and both were lower than the routine manual BP obtained in community practice. 1. Beckett L et al , BMC Cardiovasc. Disord. 2005; 5: 18. 2. Myers MG et al, J. Hypertens. 2009; 27: 280. 3. Myers MG, et al. BMJ 2011; 342: d286.

  20. Hypertension 2017 What’sstill important? • The diagnosis of hypertension shouldbebasedon out-of-office measurements; in the office, use automatic office BP monitoring (AOBP) • The threshold and targetblood pressures are lowerin those at greaterrisk

  21. Usual Office BP Threshold Valuesfor Initiation of PharmacologicalTreatment AOBP = automated office blood pressure TOD = targetorgan damage SBP = systolicblood pressure DBP = diastolicblood pressure #Based on AOBP *AOBP threshold 135/85 mmHg

  22. Recommended Office BP TreatmentTargets Treatment consists of health behaviour ±pharmacological management #Based on AOBP *AOBP threshold 135/85 mmHg

  23. New Guideline Post-SPRINT • For high-risk patients, aged ≥ 50 years, withsystolic BP levels ≥130 mm Hg, intensive management to target a systolic BP ≤120 mm Hg shouldbeconsidered • Intensive management shouldbeguided by automated office BP measurements • Patient selection for intensive management isrecommended and caution shouldbetaken in certain high-risk groups

  24. SPRINT: SBPsAchieved Average no. of medications Intensive care: 2.8 Standard care: 1.8 The SPRINT Research Group, NEJM, Nov 9th, 2015

  25. SPRINT PrimaryOutcome NNT=61 The SPRINT Research Group, NEJM, Nov 9th, 2015

  26. New Thresholds/Targets for the High-Risk Patient Post-SPRINT: Whodoesthisapply to? Clinical or sub-clinicalcardiovasculardisease OR Chronickidneydisease (non-diabeticnephropathy, proteinuria <1 g/d, *estimatedglomerular filtration rate 20-59 mL/min/1.73m2) OR †Estimated 10-year global cardiovascularrisk ≥15% OR Age ≥ 75 years • There was an increasedrisk of renaldeterioration, potassium abnormalities and hypotension withintensifiedtherapy • Patients with one or more clinical indications should consent to intensive management * Four variable MDRD equation † Framingham Risk Score, D'Agastino, Circulation 2008

  27. New Thresholds/Targets for the High-Risk PatientPost-SPRINT: Whodoesthis NOT apply to? Limited or No Evidence: • Heartfailure (EF <35%) or recent MI (within last 3 months) • Indication for, but not currentlyreceiving, a beta-blocker • Institutionalizedelderly Inconclusive Evidence: • Diabetesmellitus • 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 • Knownsecondary cause(s) of hypertension

  28. Hypertension 2017 What’s new? • Longer acting (thiazide-like) diuretics are preferredvs. shorter acting (thiazides) • Single pillcombinationsshouldbeused as a first line treatment (regardless of the extent of BP elevation)

  29. Longer-acting DiureticsShouldbePreferred(i.e., thiazide-like are preferred to thiazides) Longer-acting (thiazide-like): chlorthalidone, indapamide Shorter-acting (thiazides): hydrochlorothiazide

  30. Thiazide-type vs. Thiazide-likeDiuretics: CV Events and Mortality Meta-analysis • Design: Meta-analysis of 21 RCTs of BP lowering comparing thiazide-type or thiazide-like diuretics vs. placebo or another antihypertensive on CV events and mortality • >500,000 person-years of observation combined • Thiazide-type: • Hydrochlorothiazide • Bendrofluazide • Chlorothiazide • Thiazide-like: • Indapamide • Chlorthalidone • OldeEngberink RH. Hypertension 2015;65(5):1033-40

  31. Diuretic Type Meta-Analysis vs. Placebo • Both types of diuretics reduced CV events, cerebrovascular events, and HF • Only thiazide-like diuretics additionally reduced coronary events and all-cause mortality • OldeEngberink RH. Hypertension 2015;65(5):1033-40

  32. Design: Meta-analysis of 14 RCTs (n=883) comparing HCTZ vs. indapamide/chlorthalidone on BP reduction • Compared according to 3 different dose levels: HCTZ 12.5, 25, 50 mg; chlorthalidone 6.25, 12.5, 25 mg; indapamide 1.5, 2, 2.5 mg • SBP reduction: • Indapamide vs. HCTZ: −5.1 mmHg (p=0.004) • Chlorthalidone vs. HCTZ: −3.6 mmHg (p=0.052) • Metabolic effects: • No differences between HCTZ vs. indapamide in adverse effects (K+, Na+, Cr, BG, cholesterol, uric acid); no data for HCTZ vs. chlorthalidone • Roush GC, et al. Hypertension. 2015 May;65(5):1041-6

  33. Head-to-Head for BP Lowering: HCTZ vs. Chlorthalidone or Indapamide • Meta-analysis • Used 3 dose levels to try to standardize dosing • Hydrochlorothiazide (12.5/25/50 mg) • Chlorthalidone (6.25/12.5/25 mg) • Indapamide (1.5/2.0/2.5 mg) • Outcomes: • BP lowering • Metabolic • CV events • Roush GC et al. Hypertension 2015;65:1041-6

  34. For BP Lowering, Hydrochlorothiazideis LESS Effective thanIndapamide or Chlorthalidone Chlorthalidone more effective than HCTZ (p=0.052) • Indapamide more effective than HCTZ (p=0.004) • Roush GC et al. Hypertension 2015;65:1041-6

  35. Indapamide and Hydrochorothiazide have SimilarEffects on Serum Potassium Levels • Roush et al. Hypertension. 2015;65:1041-1046

  36. Chlorthalidone vs. Hydrochlorothiazide for BP Lowering (Ambulatory BP Measurement) • Design: 12-week RCT (double-blind) • Population: stage 1 hypertension (140 -159/ 90-99 mmHg), India (n=54) • Intervention:chlorthalidone 6.25 vs. HCTZ 12.5 vs. HCTZ (controlled release) 12.5 mg • 1°outcomes: 24h ABPM baseline to weeks 4 & 12 •  SBP & DBP with chlorthalidone and HCTZ-CR (p<0.01), but not conventional HCTZ • Pareek AK, et al. J Am CollCardiol2016;67(4):379-89

  37. Chlorthalidone More Effective ThanHydrochlorothiazide in BP Reduction Ambulatory SBP Ambulatory DBP Mean change from baseline at week 12 P=0.007 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 (125.52 vs. 139.71 mmHg, respectively, P=0.019) and week 12 (121.87 vs. 136.64 mmHg, respectively, P=0.013). Intent-to-treat population. • Pareek AK, et al. J Am CollCardiol2016;67(4):379-89

  38. Summary: Longer-Acting DiureticsPreferred • Longer-acting (thiazide-like) diureticsappear more effective at reducingCV eventsand SBP & DBP thanshorter-acting (thiazide) diuretics

  39. Hypertension 2017 What’s new? • Longer acting (thiazide-like) diuretics are preferredvs. shorter acting (thiazide) • Single pillcombinationsshouldbeused as a first line treatment (regardless of the extent of BP elevation)

  40. Long-acting CCB Beta-blocker* Thiazide diuretic ACEi ARB First Line Recommendations Circa 1999-2016 TARGET < 140 mmHg systolic AND < 90 mmHg diastolic Health behaviour management 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 *Not indicated as first line therapy for patients over 60 yrs.

  41. Single pill combination** Long-acting CCB Beta-blocker† Thiazide/ thiazide-like* ACEI§ ARB § First Line Treatment of AdultswithSystolic/DiastolicHypertension WithoutOtherCompelling Indications TARGET <135/85 mmHg (automated measurement method) New 2017 INITIAL TREATMENT Health behaviour management * 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

  42. Advantages of Single PillCombinations (SPCs) • SPC therapy is associated with better adherence vs. free combinations1 • A regimen featuring initial prescription of SPC leads to better BP control2 • Initial combination therapy is associated with ↓ risk of CV events than monotherapy3,4 Sherrill B, et al. J ClinHypertens2011;13:898-909; Feldman RD, et al. Hypertension 2009;53:646-53; Corrao G, et al. Hypertension 2011;58:566-72; Gradman AH, et al. Hypertension 2013;61(2):309-18.

  43. SPCsImproveAdherence -20 -10 0 10 20 Favors free equivalents Favors single pill • Sherrill B, et al. J ClinHypertens. 2011;13(12):898-909

  44. Incremental BP-LoweringEffect at Standard Doses: Combine or Double? Incremental SBP reduction ratio observed/expected (additive) • Wald DS, et al. Am J Med 2009;122:290-300

  45. At Low Doses the Adverse Effects of Most AntihypertensivesApproachthose of Placebo 30 30 Calcium Channel Blockers Thiazides 20 20 10 10 Side effect prevalence (%-placebo rate) 0 0 -10 -10 1 1/2 1/2 4 4 1/4 1/4 1 2 2 Dose as a proportion of the standard dose • Law, M R et al. BMJ 2003;326:1427

  46. Initial SPC TherapyImprovesBP Control Rates: STITCH Study • Cluster randomized controlled trial - hypertension in family practices • Simplified algorithm featuring initial therapy with low-dose antihypertensive single drug combination vs. conventional guideline-based care • Low-dose - by splitting usual starting dose in half • Practitioners randomly assigned to use STITCH care or usual stepwise management according to CHEP guidelines • Feldman RD, et al. Hypertension 2009;53(4):646-53

  47. STITCH Study: Results Absolute difference: 12.0% 95% CI 1.5-22.4% P = 0.026 Relative difference: 23% • Feldman RD, et al. Hypertension 2009;53(4):646-53

  48. Initial CombinationTherapyReduces CV Risk(observationalstudy) • Corrao G, et al. Hypertension 2011;58(4):566-72

  49. Initial CombinationTherapyReduces CV Risk (observationalstudy) 0 0.25 0.5 0.75 1.00 1.25 Combination Therapy Better Add-on Better • Gradman AH, et al. Hypertension 2013;61(2):309-18

  50. 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):2009-20 Pivotal study demonstrating the superiority of an SPC (ARB/diuretic) vs. Placebo ACCOMPLISH. N Engl J Med 2008;359(23):2417-28Demonstration of efficacy of ACEI/CCB SPC vs. active control

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