Cardi-OH ECHO - Hypertension Thursday, March 7, 2019 1 Advances - PowerPoint PPT Presentation

Cardi-OH ECHO - Hypertension Thursday, March 7, 2019 1

Advances in Hypertension Pharmacotherapy Michael B. Holliday, MD Associate Professor Department of Family and Community Medicine University of Cincinnati 2

Disclosure Statements The following planners, speakers, moderators, and/or panelists of the CME activity have financial relationships with commercial interests to disclose: • Adam T. Perzynski, PhD reports being co-founder of Global Health Metrics LLC, a Cleveland- based software company and royalty agreements for forthcoming books with Springer publishing and Taylor Francis publishing. • Siran M. Koroukian, PhD reports ownership interests in American Renal Associates, and Research Investigator subcontract support from Celgene Corporation. • George L. Bakris, MD reports partial salary from Bayer as FIDELIO PI, partial salary from Janssen as CREDENCE Steering Committee, partial salary from Vascular Dynamics as Calm-2 Steering Committee, and receiving honorarium as a consultant to Merck, NovoNordisk. • These financial relationships are outside the presented work. All other planners, speakers, moderators, and/or panelists of the CME activity have no financial relationships with commercial interests to disclose. 3

Objectives • Identify BP targets for hypertension pharmacologic treatment • Use a patient-centered approach to arrive at more effective anti-hypertensive regimens • Prescribe potentially underutilized medications to achieve blood pressure treatment goals 4

Determinants of Patient-centered Pharmacotherapy • Diagnosis threshold and treatment targets • Effective drug combinations • Interventions that increase adherence to therapy 5

Accurate Diagnosis of Hypertension Corresponding Values of SBP/DBP for Clinic, HBPM, Daytime, Nighttime and 24-Hour ABPM Measurements Daytime Nighttime 24-Hour Clinic HBPM ABPM ABPM ABPM 120/80 120/80 120/80 100/65 115/75 130/80 130/80 130/80 110/65 125/75 140/90 135/85 135/80 120/70 130/80 160/100 145/90 145/90 140/85 145/90 ABPM = ambulatory blood pressure monitoring.; BP = blood pressure; DBP = diastolic blood pressure; SBP = systolic blood pressure; HBPM = home blood pressure monitoring 6

Accurate Diagnosis of Hypertension Out-of-Office Blood Pressure Uses andAdvantages Measurement Helps identify WCH and masked • hypertension Rationale: Multiple readings throughout the day may • Provides a better risk • reveal patterns in blood pressure and prediction than office-based periods when control is inadequate. monitoring Improves patient adherence • cardiac (LVH) and renal • Reduces costs • (albuminuria) consequences Take readings 1 week per month, 2 • of hypertension thanoffice readings in the AM and PM, throw out the readings first day and get 24 values for a week q month. Pickering TG, White W. J Clin Hypertens. 2008; 10:850-855; Izzo JL, Sica DA, Black HR, eds, and the Council for High Blood Pressure Research (American Heart Association). Hypertension Primer: The Essentials of High Blood Pressure, 4 th ed. Philadelphia: Lippincott 7 Williams & Wilkins; 2008: 339-342

Accurate Diagnosis of Hypertension 8

Estimating CVD Risk 9

Adherence • Urine studies show partial nonadherence in over 1/2 of patients and no drug in 1/3 • Promising interventions • Regimen simplification • Reduction of out-of-pocket costs • Team-based collaborative care • Self-monitoring of BP Hypertension. 2017;70:5-9 10

Hypertension ChangePackage Algorithm Set BP goal and initiate therapy with: 1. Lifestyle modification Widely acceptable and effective • 2. Low dose ACE-I/diuretic or ARB/diuretic combination* algorithm using inexpensive IS BLOOD PRESSURE CONTROLLED? combinationtherapy. YES NO May lead to under-dosing of • Up-titration of combination therapy successfully to the highestdose HCTZ (failure to intensify dose). YES Reinforce lifestylemodification Encourage self-monitoring of home BP Effective dose for BP reduction • NO and CV outcome for HCTZ is 25- Add dihydropyridine calcium channel blocker and up-titrate 50 mg day, not 12.5-25 mg/day Continue current therapy. YES Reinforce lifestylemodification Encourage self-monitoring of home BP commonly used in primary care NO settings. Add on spironolactone (25-50 mg/day), consider changing HCTZ to chlorthalidone Evidence of increased BP control • If BP is still elevated… Reinforce lifestyle modification Consider medicationnon-adherence rates and reduction in BP control Encourage self-monitoring of home BP Consider white coateffect Add β –blocker **, ! -blocker or guanfacine *** However , BP gap exists between Consideraddinghydralazine in addition to above medications • African Americans and non- Consider interfering agents (e.g. NSAIDs,excess alcohol) * If pregnant or pregnancy potential, avoid using ACE-I or African Americanhypertensives ARB spironolactone Consider secondaryetiologies with use of this algorithm. CONSIDER CONSULTATION WITHA HYPERTENSION ** Avoid starting a beta blocker if pulse<70 or on a non- SPECIALIST dihydropyridine calcium channel blocker *** Guanfacine has similar mechanism of action as clonidine and is once daily instead of 3 times per day 11

Hypertension Drug Treatment Algorithm In addition to lifestyle change: Start a thiazide diuretic (chlorthalidone 25 mg ½ tab once daily – will need pill cutter]) • This algorithm was recommended in OR SPRINT trial, with chlorthalidone the Amlodipine 5 mg oncedaily preferred thiazide-like diuretic – BLOOD PRESSURE ATGOAL? especially for African-American patients. YES NO • Non-African-American patients Addan ACEI/ARB (e.g. lisinopril 10-40 mgonce daily or losartan 50- 100 mgonce daily. YES could also start with ACEI or ARB. Can be added at Step 1 if CKDpresent (esp with proteinuria) or BP> 20 mmHgabove goal • Very effective in achieving even NO SBPs < 120 mmHg. If onchlorthalidone, increase to 25 mgonce daily If onamlodipine,increase to 10 mg/day YES • No significant disparity in BP NO NO lowering or outcome benefit similar Addamlodipine 5-10 mgonce daily). Addchlorthalidone to 12.5-25 mg/dayonce daily across race/ethnicity was seen in the YES NO SPRINT trial. Addspironolactone 25-50 mgonce daily if K<4.5 YES NO • May be better option in practices Adda beta blocker if HR >70 (e.g. metoprolol ER 50 -200 mg daily) or YES with large numbers of African- guanfacine 1-3 mgdaily (not clonidine) NO American hypertensives since uses Continue current therapy Consider non-adherence issues, secondary causes of HTN, additional agents like chlorthalidone rather than HCTZ as hydralazine or minoxidil,or referral to a HTN specialist initial therapy. 12

Thiazide-type Diuretic Doses in Hypertension Morbidity Trials • Doses used in outcome trials Dose of Thiazide (mg/d) Trial Drug using thiazide type diuretics. VA CSPM&M HCTZ 100 • ACCOMPLISH trial is the one trial that used doses HDFP chlorthalidone 25-100 equivalent to 12.5-25 HCTZ. It is also the only trial showing MRC I bendroflumethiazide 10 inferior benefit of thiazide-type 5-10 diuretics compared to CCBs or bendroflumethiazide HCTZ HAPPHY 50-100 any other class of antihypertensives. EWPHE HCTZ/triamterine 25-50 • There is a tendency to under- MRC Elderly HCTZ/amiloride 25-50 dose diuretics, and doing so SHEP chlorthalidone 12.5-25 sacrifices both BP lowering and clinical benefit. ALLHAT chlorthalidone 12.5-25 • Summary: 25mg or less of ACCOMPLISH HCTZ 12.5-25 HCTZ may compromise the benefits of thiazide diuretics SPRINT chlorthalidone 12.5-25 (as well as its BP-lowering potency). 13

Pharmacokinetics A rationale for the Half- Relative Oral Onset Peak Duration Vd life selection of Potentcy* Bioavail (h) (h) (h) (h) chlorthalidone over HCTZ 3-4 L/kg 6-9 12 1 ~70% 2 4-6 HCTZ: (single (single 40%protein dose) dose) Among thedifferences • bound 8-15 16-24 (long- (long- between the two term term include chlorthalidone’s dosing) dosing) longer half-life and Chlorthalidone 3-13L/kg 1 ~65% 2-3 2-6 40 24-48 (single (single duration of action. 75% protein dose) dose) The half-life of bound 45-60 48-72 • (long- (long- chlorthalidone is 60-72 98% term term distribution hours, yielding more dosing) dosing) intoRBC potent and smoother BP Indapamide 20 ~93% 1-2 <2 14 Up to36 control, more gradual onset of diuretic action with less urinary urgency, and patients 24-72 4-6 40-60 are more tolerant to Amlodipine missed doses. * Per most pharmacology texts; Carter BL, Ernst ME, Cohen JD. Hypertension Note: amlodipine also • 2004;43:4-9 research suggests otherwise. has a very long half-life Abernathy DR, Cardiol 1992; 80:31-36 14

CalciumChannel BlockerHalf-Life Amlodipine, like • chlorthalidone, has a very long half-life (40-60 hrs) and consequently more tolerant of misseddoses. It has a significant evidence • base demonstrating reduction of CVD events, and thus can be prescribed as an initial or add-on agent. It is effective regardless of • age, race, or renal function. In patients with kidney • dysfunction, it should be combined with either an Figure 1. Drug half-life for calcium channel Sica DA. J Clin Hypertens 2005; 7(4) blockers in the presence of renal failure. AML = Supp 1: 21-26 ACEI or ARB (but not both) amlodiphine; DIL = dilatiazem; FEL = felodipine; ISR = isradipine; NIF = nifedipine; NIM = nimodipine; VER = verapamil 15