1. PHARMACOTHERAPY OF HYPERTENSION Based on New Guidelines Fariborz Nikaeen; MD Interventional cardiologist 2 november 2015

2. Prevalence of Hypertension Adults have elevated Blood Pressure Patients with HTN Diagnosed HTN 78% Treated HTN 68% Uncontrolled HTN 38% Resistant HTN 9% Patients with HTN Diagnosed HTN Treated HTN Uncontrolled HTN HTN=Hypertension

3. Only relying on manual office pressures misses out on white coat and masked hypertension Manual Office BP mmHg Ambulatory BP mmHg Hypertension Normotension White Coat Hypertension Masked Hypertension 200 180 160 140 120 100 120140160180200 135 2014

4. The prognosis of masked hypertension Prevalence is approximately 10% in hypertensive patients. 0 5 10 15 20 25 30 35 Normal 23/685 White coat 24/656 Uncontrolled 41/462 Masked 236/3125 CV events per 1000 patient-year CV Events Okhubo et al. J. Am. Coll. Cardiol. 2012;46;508-515 2014

5. What’s The Worst That Could Happen?

6. Importance OF HTN HTN is the most important modifiable CV risk factor HTN is the commonest cause of premature death HTN is the commonest cause of CKD & commonest cause of ESRD in elderly Continuum of increasing CV risk from SBP 115mmHg CV mortality doubles for every10/5 increase in BP>120/70 High BP causes: 35% of all cardiovascular deaths 50% of all stroke deaths 25% of all CAD deaths 50% of all congestive heart failure

7. Benefits of Lowering BP

8. New Guidelines for Hypertension National Institute for Health and Clinical Excellence (NICE), 2011 Kidney Disease: Improving Global Outcome (KDIGO), 2012 European Society of Hypertension/European Society of Cardiology, (ESH/ESC), 2013 American Diabetes Association (ADA), 2014 American Society of Hypertension and the International Society of Hypertension (ASH/ISH), 2014 Eighth Joint National Committee (JNC8), 2014

13. JNC 8 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults

14. JNC 8 (2014 Hypertension Guideline Management Algorithm) 1

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16. PopulationGoal BP, mm Hg Initial Drug Treatment Options General ≥60 y<150/90Nonblack: thiazide-type diuretic, ACEI, ARB, or CCB Black: thiazide-type diuretic or CCB General <60 y<140/90Nonblack: thiazide-type diuretic, ACEI, ARB, or CCB Black: thiazide-type diuretic or CCB Diabetes<140/90Thiazide-type diuretic, ACEI, ARB, or CCB CKD<140/90ACEI or ARB

17. Start one drug, titrate to maximum dose, and then add a second drug Start one drug and then add a second drug before achieving maximum dose of the initial drug Begin with 2 drugs at the same time, either as 2 separate pills or as a single pill combination Strategies to Dose of Antihypertensive Drugs

18. Ratio of Incremental SBP lowering effect at “standard dose”– Combine or Double? Incremenal SBP reduction ratioObserved/Expected (additive)

19. BP lowering effects from antihypertensive drugs  Dose response curves for efficacy are relatively flat  80% of the BP lowering efficacy is achieved at half-standard dose  Combinations of standard doses have additive blood pressure lowering effects

20. key issues must be addressed during the initial office evaluation of a person with elevated BP readings:  Documenting that the BP is elevated  Defining the presence or absence of TOD related to hypertension 3. Screening for other CV risk factors that often accompany hypertension 4. Estimating the person’s absolute risk for CV and renal disease 5. Assessing whether the person is likely to have an identifiable cause of HTN (secondary HTN) and should have further diagnostic testing to confirm or exclude that diagnosis 6. Obtaining data that may be helpful in the initial and subsequent choices for therapy.

21. GENERAL RULES 1-Decrease CV mortality :ACEI ;ARBs, Diuretics, 2-Age:Elderly,Middle age,Women at reproductive age 3- Race/Ethnicity : Blacks,African-American,whites,…. 4- Concomitant disease & Conditions: BPH,CRF,Asthma, … 5- Compelling indications:Post MI,CKD, stroke,DM,CHF, CAD,… 6-Long acting Drugs : Patient compliance 7-Start low (dosage)&go slow

26. Treatment of Hypertension CONSIDER Nonadherence Secondary HTN Interfering drugs or lifestyle White coat effect Dual Combination Triple Therapy Lifestyle modification Thiazide diuretic ACEI Long-acting CCB TARGET <140/90 mmHg For age<60 & <150/90 mmHg For age ≥60 ARB Initial therapy 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

27. Treatment of Isolated Systolic Hypertension CONSIDER Nonadherence Secondary HTN Interfering drugs or lifestyle White coat effect Thiazide Amlodipin Dual therapy Triple therapy Lifestyle modification therapy ARB or ACEI TARGET : SBP 60 years *If blood pressure is still not controlled, or there are adverse effects, other classes of antihypertensive drugs may be combined

28. Choice of Pharmacological Treatment for Hypertension Compelling indications: Stable IHD Recent ST Elevation-MI or non-ST Elevation-MI LV Systolic Dysfunction Cerebrovascular Disease Non Diabetic CKD Diabetes Mellitus With Nephropathy Without Nephropathy

29. Treatment of HTN in Patients with Stable IHD Caution should be exercised when combining (Verapamil Or Diltiazem) +beta-blocker If abnormal systolic left ventricular function: avoid (Verapamil or Diltiazem) Dual therapy with an ACEI +ARB are not recommended in the absence of refractory CHF The combination of an ACEi and CCB is preferred 1. Beta-blocker 2. Long-acting CCB Stable angina ACEI are recommended for most patients with established CAD* ARBs are not inferior to ACEI in IHD Short-acting nifedipine

30. Treatment of HTN in Patients with Recent STEMI or NSTEMI Amlodipine* (Avoid diltiazem, verapamil) Beta-blocker +ACEI (or ARB) Recent myocardial infarction CHF? NO YES Long-acting CCB If beta-blocker contraindicated( Asthma, COPD, Heart Block,….) or not effective *

31. Treatment of HTN with LV Systolic Dysfunction If additional therapy is needed: Diuretic (Thiazide for hypertension; Loop for volume control Or eGFR,30cc/min) Spironolactone : for CHF NYHA-FC II-IV or post MI (clinical HF Or LVEF<40% Or DM) Systolic LV dysfunction ACEI(or ARB)+Beta blocker (carvedilol Or metoprolol) Up titrate doses of ACEI or ARB If ACEI and ARB are contraindicated: Hydralazine + Isosorbide dinitrate If additional antihypertensive therapy is needed: ACEI / ARB Combination Amlodipine Verapamil Diltiazem

32. Treatment of HTN in Association With Stroke Acute Stroke: Onset to 72 Hours Treat extreme BP elevation (systolic > 220 mmHg, diastolic > 120 mmHg) by 15-25% over the first 24 hour with gradual reduction after. Acute ischemic Stroke Avoid excessive lowering of BP which can exacerbate ischemia

33. Strongly consider blood pressure reduction in all patients after the acute phase of stroke or TIA. Target BP < 140/90 mmHg An ACEI / diuretic combination is preferred Stroke TIA Combinations of an ACEI with an ARB are not recommended Treatment of HTN in Association With Stroke Acute Stroke: After72 Hours

34. Treatment of HTN in Patients with Non Diabetic CKD Chronic kidney disease and proteinuria * ACEI(or ARB)±Diuretic(Thiazide Or Loop) Combination with other agents Target BP: < 140/90 mmHg * albumin:creatinine ratio [ACR] > 30 mg/mmol or urinary protein > 500 mg/24hr Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB Combinations of a ACEI and a ARB are specifically not recommended in the absence of proteinuria

35. Treatment of Hypertension in association with Diabetes Mellitus

36. Treatment of HTN in DM without CKD Threshold ≥130/80 mmHg and Target below 130/80 mmHg * Combinations of an ACEI with an ARB are specifically not recommended

37. If eGFR <30 ml/min, a Furosemide should be substituted for a thiazide THRESHOLD equal or over 130/80 mmHg and TARGET below 130/80 mmHg DIABETES with Nephropathy ACE Inhibitor or ARB IF ACEI and ARB are contraindicated or not tolerated, SUBSTITUTE: Long-acting CCB Thiazide Addition of one or more of Long-acting CCB or Thiazide 3 - 4 drugs combination may be needed Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB Treatment of HTN in DM +CKD

38. The use of the combination of ACE inhibitor with an ARB should only be considered in selected and closely monitored Patients with Refractory CHF or Marked proteinuria.