Michael J Unruh, MD Renal Associates of West Michigan, PC

Transcription

1 Michael J Unruh, MD Renal Associates of West Michigan, PC

2 None

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4 The Definition of Hypertension 1940s: >210/ s: >180/ s: >160/ (JNC I): >160/ (JNC III): >140/ (JNC V): >130/ (JNC VII): >120/ (JNC 2013):?

5 Definition of hypertension (JNC 7) (no compelling indications) Normal: < 120 and < 80 Pre-HTN: or Stage 1: or Stage 2: >160 or > 100

6 Definition of hypertension (JNC 7) (with compelling indications) Normal: < 120 and < 80 Pre-HTN: and < 80 Stage 1: or Stage 2: >160 or > 100 Compelling indications: 1. Cardiovascular disease 2. Diabetes mellitus 3. Chronic kidney disease

7 Definition of hypertension JNC 2013? In June, ESH/ESC recommended a SBP goal of mmhg in patients under the age of 80 Goal DBP was less than 85 mmhg While HHS has not yet approved JNC 2013, it is expected to follow suit: Goal blood pressures <140/90 in hypertension and chronic kidney disease Goal blood pressure <140/80 in diabetes mellitus Goal systolic blood pressure <150 if age 80 or older Ideal systolic blood pressure

8 Prevalence of hypertension Hypertension is the most common primary diagnosis in this country 50 million Americans affected (28%) 1 in 5 adults NHANES data % know they have hypertension 45% are being treated 34% are at goal by JNC VII criteria Healthy People 2010 goal: from 28% to 16% Actually increased to 39% by 2006

9 Hypertension facts Starting at 115/75: For every rise in SBP of 3-4 mmhg, the risk of heart attack increases by 20% and stroke by 12% Starting at 115/75: For every rise in SBP of 20 mmhg or DBP of 10 mmhg, the risk of heart attack or stroke doubles If left untreated, 60% of prehypertension will progress to stage 1 hypertension in 4 years

10 Hypertension facts Patients with risk factors and a SBP of : lowering SBP by 12 mmhg will prevent one death for every 11 patient treated over 10 years Patients with compelling indications and a SBP of : lowering SBP by 12 mmhg will prevent one death for every 9 patients treated over 10 years

11 Hypertension has momentum Age causes hypertension Increased aortic and peripheral vascular stiffness Hypertension causes hypertension Endothelial damage and smooth muscle hypertrophy increase blood pressure Currently in the US: Most patients need 2 or more drugs to reach goal Most patients with diabetes need 3-4 drugs to reach goal

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13 Basic treatment algorithm <120 and <80: no intervention and <80: encourage lifestyle modification and risk factors: lifestyle 3 or more risk factors: lifestyle + meds Any compelling indication: lifestyle + meds >140 or >90: lifestyle + meds

14 Assessing risk Risk factors: Hyperlipidemia Smoking Family history Compelling indications: Cardiovascular disease Diabetes mellitus Chronic kidney disease Insulin resistance Sedentary lifestyle

15 Lifestyle Modifications Weight loss and systolic blood pressure: 1 kg loss can lead to 1 mmhg SBP reduction (up to 6 mmhg) Sodium intake and systolic blood pressure: Normal: 150 mmol (3.5g) Reduced: 100 mmol (2.3g) 2 mmhg drop Extreme reduction: 50 mmol (1.2g) 7 mmhg drop DASH diet: 50 mmol (1.2g) 9 mmhg drop Exercise Moderation of alcohol intake

16 Pathophysiology of Hypertension Basic hemodynamics Cardiac output (heart rate and stroke volume) Peripheral vascular resistance Neuro-hormonal axis Renin-Angiotensin-Aldosterone System (RAAS) Catecholamines Small bed vascular resistance Endothelial dysfunction Vasoactive substances

17 RAAS Zaman MA, Oparil S, and Calhoun DA. Drugs targeting the renin angiotensin aldosterone system. Nat Rev Drug Disc 2003; 1: 621.

18 Initial treatment Hypertension is extraordinarily heterogeneous There is no single holy grail of hypertension therapy Targeting patient specific pathology is only in early stages Works best in known secondary hypertension For the most part, first line therapy is still one size fits all

19 First line drugs by class A ACE inhibitors / ARBs B β-blockers (?) C Calcium channel blockers D Thiazide-type Diuretics

20 ACE Inhibitors / ARBs Should be used in diabetics regardless of proteinuria Not recommended as dual therapy in most patients Recommended as tolerated in patients with heart failure or post-myocardial infarction ACEI / ARB may reduce fasting glucose Lab monitoring: initial therapy, increased dose, addition of new med, yearly monitoring

21 ACE Inhibitors / ARBs Mechanism of Action: Angiotensin II Receptor Blockers Causes vasodilation, decreased aldosterone production/ secretion, and decreased vasopressin secretion Angiotensin Coverting Enzyme Inhibitors Block conversion of Angiotensin I to Angiotensin II

22 A note on β-blockers β-blockers are going out of favor as a first line med in the general population Higher stroke risk Higher all-cause mortality ESH/ESC specifically recommends against use, except in: Post-myocardial infarction Heart failure Atrial fibrillation Only atenolol is evidence-based β-blockers are not as effective at lowering central BP This may result in increased cardiovascular outcomes

23 β-blockers Types: β-1 specific: atenolol, metoprolol, nebivolol Nonselective: propranolol Nonselective + α: carvedilol, labetalol Side effects: Impaired exercise tolerance Can increase fasting glucose levels (4-6mg/dl) and cause weight gain Can cause pulmonary exacerbation, lethargy, nightmares, and decreased sexual drive

24 Calcium channel blockers Two classes: Dihydropyridines: ending in -ipine Non-dihydropyridines: the others Dual calcium channel blockade can provide an additive BP lowering effect Long acting agents are not contraindicated in heart failure Amlodipine can help with pulmonary hypertension Verapamil may help with left ventricular remodeling in diastolic heart failure

25 Thiazide-type diuretics MUST have a salt restricted diet for efficacy Dose thiazides adequately: HCTZ mg/day reduces BP No evidence of effect on CV outcomes! Chlorthalidone mg/day reduces BP, CV outcomes Indapamide mg/day reduces BP, CV outcomes Chlorthalidone and Indapamide are thus the drugs of choice in this class Thiazides augment the BP lowering effect of other drugs when used in combination (more than a purely additive effect)

26 Thiazide-type diuretics Side effects: Might increase fasting glucose by 4-6 mg/dl Can cause hypokalemia Can cause hyponatremia Increase serum uric acid Preventing thiazide induced hypokalmeia may prevent increase in fasting glucose Lab monitoring: initial therapy, increased dose, addition of new med, yearly monitoring

27 Drugs for special populations Blacks: calcium channel blockers and thiazides possible more effective than ACE inhibitors / ARB Women of child bearing age: no ACEI / ARB without pregnancy counseling Elderly: thiazides most effective but monitor for electrolyte complications Diabetics: ACEI / ARB and thizaide combination is first line

28 Drugs for special populations Lung disease: dual calcium channel blockers Post MI: β-blockers are first line Heart failure: β-blockers are first line Anxiety disorder: dual catecholamine blockade (α- and β- blocker) and an SSRI Subclinical anxiety (pseudo-pheochromocytoma): paroxysms of hypertension without overt anxiety

29 Brief, Confusing Slide Heart Failure Post-MI High CAD risk Thiazide β-blocker ACEI ARB CCB Aldosterone antagonist x x x x x x x x x x x x x x x Clinical Trial Basis ACC/AHA HF guideline; MERIT-HF; COPERNICUS, CIBIS, SOLVD; AIRE, TRACE, Val-HeFT; RALES ACC/AHA post-mi guideline; BHAT; SAVE, CAPRICORN, EPHESUS/VALIANT ALLHAT; HOPE, ANBP2; LIFE; CONVINCE, ONTARGET Diabetes mellitus x x x x NKF-ADA guideline; UKPDS; ALLHAT Chronic kidney disease Stroke x x x x x NKF guideline; CAPPP; RENAAL; IDNT, REIN, AASK PROGRESS, LIFE Adapted from Chobanian AV et al. JAMA.2003;289:

30 Common medications Lisinopril: 10-40mg 1 /day Enalapril: 5-20mg 2 /day Valsartan: mg 2 /day* Losartan: mg 1 /day Atenolol: mg 2 /day* Metoprolol: mg 2 /day Carvedilol: mg 2 /day Labetalol: mg 2-3 /day*

31 Common medications Amlodipine: 5-10mg 1 /day Nifedipine ER: 30-90mg 1/ day Diltiazem ER: mg 1 /day Verapamil SR: mg 2 /day* HCTZ: 25-50mg 2 /day* Chlorthalidone: 25-50mg 1 /day Spironolactone: mg 2 /day

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33 Resistant hypertension Resistant hypertension Not meeting goal on maximum doses of 3 meds including a diuretic Uncontrolled hypertension Not meeting goal but non-adherence or inadequate therapy persists

34 Resistant Hypertension Characteristics: Older Higher baseline blood pressure Chronic kidney disease Diabetes mellitus Obesity Excessive sodium intake Left ventricular hypertrophy African American Female

35 Uncontrolled hypertension Non-adherence is one of the main factors contributing to perceived resistance Adherence needs to be actively assessed On average in the primary care setting, 40% of patients will stop initial therapy within the first year Switch to generics, low cost combinations, or 3 month supplies Referral: non-adherence rates dropped to 16% when patients saw a hypertension specialist

36 Uncontrolled hypertension Dose inadequacy is the other main factor contributing to perceived resistance Maximize dosage (especially of thiazides) Review dosage intervals Review lifestyle modifications (EVERY TIME) Re-enforce salt restriction for diuretic efficacy Look for interfering substances NSAIDs, alcohol, diet pills, decongestants Encourage home monitoring

37 Secondary hypertension Chronic kidney disease Drug-induced (NSAIDs, antidepressants, stimulants) Obstructive sleep apnea (OSA) Renal artery stenosis Primary aldosteronism Hypercortisolism (Cushing disease) Thyroid disease Hyperparathyroidism Pheochromocytoma Oral contraceptive use

38 Secondary hypertension Suspect secondary HTN with new onset, severe, or rapidly accelerating HTN OSA is the most common unrecognized cause Drug-induced is also very common RAS can be associated with intolerance of ACEI/ARB by renal function 25-30% Creatinine increase expected Hyperaldosteronism is more prevalent than previously estimated Hypokalemia is probably a late manifestation

39 Drug classes Second line (in my personal favorite order): Aldosterone antagonists Alpha blockers Direct vasodilators Central alpha agonists Others (population specific use only): Long acting nitrates Loop diuretics Direct renin inhibitor

40 Aldosterone antagonists Spironolactone, eplerenone Primary aldosteronism more prevalent that previously thought Effective dosage may be as high as mg twice a day Aldosterone escape can be a mechanism of resistant HTN Not a function of random renin/aldosterone levels Effective at dosage of 25-50mg per day Obese patients generate more aldosterone

41 Aldosterone antagonists Indicated in low dose for heart failure Eplerenone less likely to cause gynecomastia Very weak diuretics (even with thiazides) except in edematous states Lab monitoring: initial therapy, increased dose, addition of new med, yearly monitoring

42 Alpha-1 blockers Doxazosin, Terazosin Once daily dosing to be dosed at night Likely not as effective if patient is already on carvedilol or labetalol Can help with benign prostatic hypertrophy and may increase insulin sensitivity May worsen heart failure Side effects: first pass orthostasis, headache, fatigue

43 Direct vasodilators Hydralazine, minoxidil Hydralazine is a potent arterial vasodilator Needs to be dosed 3 times a day Minoxidil is a potent venous vasodilator Not recommended to use in combination Common side effects: Edema (use in combination with a diuretic) Tachycardia (use in combination with a β-blocker)

44 Central alpha agonists Clonidine Patch is available but less effective than the equivalent oral dose The pill needs to be dosed 3 times a day for 24 hour coverage Every 8 hour dosing is the most effective Common side effects: fatigue, dry mouth, CNS depression, constipation, urinary retention Rebound hypertension will occur if stopped suddenly Significant dependence on renal clearance α-methyldopa still occasionally used

45 Long acting nitrates Used specifically in the post-mi and angina population Not a recommended routine second line agent May have a role in elderly-associated isolated systolic hypertension and diastolic heart failure Caveat: specifically designed to not have 24-hour coverage

46 Loop diuretics Furosemide, Bumetanide, Torsemide Can be antihypertensive, but only in edematous states complicated by kidney disease Kidney disease prolongs clearance Not recommended for egfr > 30 ml/min/1.73m 2 Lab monitoring: initial therapy, increased dose, addition of new med, yearly monitoring

47 Direct renin inhibitor Aliskerin (Tekturna) available since March 2007 Equivalent to ACEI / ARB / CCB in combination with thiazides but no data for monotherapy AVOID trial: reduced proteinuria, no clinical benefit ALTITUDE trial: increased non-significant rate of hypotension, stroke As a result of the above trials, not recommended to combine with ACEI or ARB therapy Lab monitoring: initial therapy, increased dose, addition of new med, yearly monitoring

48 Common medications Spironolactone: 25-50mg 1-2 /day Eplerenone: 25-50mg 1-2 /day Doxazosin: 1-8mg 1 /day at bedtime Terazosin: 1-5 mg 1 /day at bedtime Clonidine: mg 3 /day Hydralazine: mg 3 /day Minoxidil: 5-20mg 2 /day Furosemide: mg 3-4 /day Bumetanide: 1-3 mg 2 /day Torsemide: mg 1 /day Aliskiren: mg 1 /day

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50 Chronic kidney disease Hypertension present ~85% of the time Based on the MDRD study: 65% of patients with an GFR of 85 ml/min/1.73m2 95% of patients with an GFR of 15 ml/min/1.73m2

51 Chronic kidney disease Due to: Sodium retention Increased renin-angiotensin activity Enhanced sympathetic nervous system activity Decreased nitric oxide synthesis due to uremia Hyperparathyroidism induced vasoconstriction Hypercalcemia induced vasoconstriction Erythropoietin therapy

52 Chronic kidney disease BP goals (KDIGO 2011), likely JNC 2013 If no proteinuria, <140/90 If proteinuria present, less than 130/80 BP goals in diabetes mellitus (ADA 2013) Less than 140/80, though a goal of less than 130/80 may be appropriate in some individuals

53 Chronic kidney disease SODIUM RESTRICTION! More effective than valsartan with normal sodium diet Loop diuretics Particularly when GFR < 30 ml/min/1.73m2 Longer acting (bumetanide, torsemide) Volume expansion may be present despite lack of edema ACEI/ARB, CCB, aldosterone antagonists remain effective

54 End stage kidney disease Dialysis BP is misleading Predialytic pressures typically overestimates Postdialytic pressures typically underestimates Ambulatory and home pressures preferred Optimal pressure Unclear Mortality clearly high if SBP >160 predialysis However, mortality also increased if <140/90 predialysis Lower pressures associated with more access thrombosis

55 End stage kidney disease Hypertension in dialysis patients is volume until proven otherwise Estimated dry weight BP normalizes or symptoms of hypovolemia appear Post dialysis BP normalized and no edema or orthostasis May be complicated by: Antihypertensives High dialytic sodium bath Short dialysis sessions

56 End stage kidney disease Effective drugs include: ACE inhibitors ARBs Calcium channel blockers Beta-blockers in selected patients Clonidine Direct vasodilators

57 End stage kidney disease Unique issues High sodium bath Leads to sodium uptake during dialysis Solution: use a lower sodium or variable sodium bath Hypertension during dialysis Poorly understood Associated with worse outcomes May respond to carvedilol

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59 Trials ALLHAT (2002): ACEI vs CCB vs TD ASCOT (2005): CCB+ACEI vs BB+TD VALUE (1998): ARB vs CCB INVEST (2003): BB+ACEI vs CCB+ACEI TROPHY (2006): ARB vs placebo HOPE (2000): ACEI+others vs others LIFE (2002): ARB+TD vs BB+TD Others: RENAAL, SHEP, ACCORD, DREAM, FACET, ABCD, ADVANCE, HOT, AVOID, ALTITUDE, ACCOMPLISH

60 Bibliography 1. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: Whaley-Connell AT, Sowers JR, Stevens LA, et al. CKD in the United States: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) Am J Kidney Dis 2008; 51:S Buckalew VM Jr, Berg RL, Wang SR, et al. Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group. Am J Kidney Dis 1996; 28: Diabetes Care 2013;36 (suppl 1) January Zaman MA, Oparil S, and Calhoun DA. Drugs targeting the renin angiotensin aldosterone system. Nat Rev Drug Disc 2003; 1: Minutolo R, Agarwal R, Borrelli S, et al. Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease. Arch Intern Med 2011; 171: Buter H, Hemmelder MH, Navis G, et al. The blunting of the antiproteinuric efficacy of ACE inhibition by high sodium intake can be restored by hydrochlorothiazide. Nephrol Dial Transplant 1998; 13: Günal AI, Duman S, Ozkahya M, et al. Strict volume control normalizes hypertension in peritoneal dialysis patients. Am J Kidney Dis 2001; 37: Alborzi P, Patel N, Agarwal R. Home blood pressures are of greater prognostic value than hemodialysis unit recordings. Clin J Am Soc Nephrol 2007; 2: Robinson BM, Tong L, Zhang J, et al. Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2012; 82: Mailloux LU. The overlooked role of salt restriction in dialysis patients. Semin Dial 2000; 13: Fishbane S, Natke E, Maesaka JK. Role of volume overload in dialysis-refractory hypertension. Am J Kidney Dis 1996; 28: Santos SF, Peixoto AJ. Revisiting the dialysate sodium prescription as a tool for better blood pressure and interdialytic weight gain management in hemodialysis patients. Clin J Am Soc Nephrol 2008; 3: Katzarski KS, Charra B, Luik AJ, et al. Fluid state and blood pressure control in patients treated with long and short haemodialysis. Nephrol Dial Transplant 1999; 14: Tomson CR. Blood pressure and outcome in patients on dialysis. Lancet 2009; 373: Tai DJ, Lim TW, James MT, et al. Cardiovascular effects of angiotensin converting enzyme inhibition or angiotensin receptor blockade in hemodialysis: a meta-analysis. Clin J Am Soc Nephrol 2010; 5: Hörl MP, Hörl WH. Drug therapy for hypertension in hemodialysis patients. Semin Dial 2004; 17: Flanigan MJ, Khairullah QT, Lim VS. Dialysate sodium delivery can alter chronic blood pressure management. Am J Kidney Dis 1997; 29: Inrig JK, Patel UD, Toto RD, Szczech LA. Association of blood pressure increases during hemodialysis with 2-year mortality in incident hemodialysis patients: a secondary analysis of the Dialysis Morbidity and Mortality Wave 2 Study. Am J Kidney Dis 2009; 54:881.