4/25/15 Pharmacologic Interven1on in Hypertension: 2015 Larry Warmoth, M.D. Nephrologist Chief of Staff, Covenant Medical Center Associate Professor of Nephrology, Texas Tech School of Medicine Life1me Risk of Developing Hypertension Beginning at Age 65 100 Men Women 80 60 40 20 0 Risk of hypertension (%) 0 2 4 6 8 10 12 14 16 18 20 Years Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHg Vasan RS, et al. JAMA. 2002; 287:1003-1010. www.hypertensiononline.or Copyright 2002, American Medical g Association. 1 4/25/15 Frequency Distribu1on of Untreated HTN by Age Hypertension – Why a Nephrologist???? Isolated Systolic HTN Systolic Diastolic HTN Isolated Diastolic HTN Accurate BP measurement History • Who checks your paents BP? • Angina/MI Stroke: Complicaons of HTN, Angina may improve with • You or Staff b-blockers • IF Staff – Do they know what to listen for or do they use automated eQuipment • Seated properly and Quietly for 5 minutes • Asthma, COPD: Preclude the use of b-blockers • Appropriate size cuff • Inflate 20-30 mmHg above loss of radial pulse • Heart failure: ACE inhibitors indicaon • Deflate at 2mmHg per second • DM: ACE preferred • 1st sound SBP ; Disappearance of Korotkoff sound (phase 5) is DBP • Confirm Elevated blood pressure within 2 weeks • Polyuria and nocturia: Suggest renal impairment • Caffeine, exercise, and smoking should be avoided for at least 30 minutes before BP measurement. • The auscultatory method should be used. • 24 hour ambulatory BP monitoring History-contd. Iden1fiable Causes of HTN • Claudicaon: May be aggravated by b-blockers, atheromatous RAS • Sleep apnea may be present • Drug-induced or related causes • Gout: May be aggravated by diureIcs • Chronic kidney disease • Use of NSAIDs: May cause or aggravate HTN • Primary aldosteronism • Family history of HTN: Important risk factor • Renovascular disease • Family history of premature death: May have been due to HTN • Chronic steroid therapy and Cushing’s syndrome • Pheochromocytoma • Coarctaon of the aorta • Thyroid or parathyroid disease 2 4/25/15 Cardiovascular Risk factors History-contd. • Hypertension • Family history of DM : Paent may also be DiabeIc • Cigarece smoking • CigareLe smoker: Aggravate HTN, independently a risk factor for CAD • Obesity (body mass index ≥30 kg/m2) and stroke • Physical inacIvity • High alcohol: A cause of HTN • Dyslipidemia • High salt intake: Advice low salt intake • Diabetes mellitus • Albuminuria or esImated GFR <60 mL/min • Age (older than 55 for men, 65 for women) • Family history of premature cardiovascular disease (men under age 55 or women under age 65) Examina1on Examina1on-contd. • Appropriate measurement of BP in both arms • Thorough examinaon of the heart and lungs • Opc fundi • Abdomen for enlarged kidneys, masses, and abnormal aorIc • Calculaon of BMI ( waist circumference also may be useful) pulsaon • Auscultaon for caroId, abdominal, and femoral bruits • Lower extremiIes for edema and pulses • Palpaon of the thyroid gland. • Neurological assessment Development of JNC-8 Rou1ne Labs • Commissioned by the NHLBI in 2008 • Panel members appointed • EKG. • Developed focused critical questions relevant to practice • Urinalysis W/ albumin/creanine and protein/creanine raos. • Conducted a systematic search of pertinent literature • Limited to randomized controlled trials (RCTs) published between • Blood glucose and hematocrit; serum potassium, BUN, creanine 1966 and 2009 (eGFR), and calcium. • Included patients age 18 or older with hypertension • HDL cholesterol, LDL cholesterol, and triglycerides. • Sample size of 100 patients or more • Results must have included “hard” outcomes • Subsequent search of studies from 2009 to 2013 required samples of 2000 or more patients James PA et al. JAMA 2014;311:507-20. 3 4/25/15 Development of JNC-8 Development of JNC-8 • 3 critical questions for adults with hypertension • Does initiating antihypertensive pharmacologic therapy at • In 2013, the NHLBI decides that it will no specific blood pressure thresholds improve health outcomes? longer publish clinical guidelines [When to start therapy?] • Proposes to work collaboratively with other organizations • Does treatment with antihypertensive pharmacologic therapy to a specified blood pressure goal lead to improvements in • The appointed panel members for JNC-8 decided to health outcomes? [How low should I go?] publish their findings independently • Do various antihypertensive drugs or drug classes differ in • Published online in JAMA in December 2013 comparative benefits and harms on specific health outcomes? • Received no endorsements from other organizations [What drug do I use?] James PA et al. JAMA 2014;311:507-20. James PA et al. JAMA 2014;311:507-20. But Wait…There’s More JNC-8 Recommendations • A multitude of other hypertension guidelines were also • In patients >60 years of age, start medications at blood published in 2013: pressure of >150/90mm Hg and treat to goal of • AHA/ACC/CDC advisory algorithm <150/90mm Hg • American Society of Hypertension/International Society of Hypertension (ASH/ISH) • European Society of Hypertension and European Society of • In patients >60 years of age, treatment does not need to Cardiology (ESH/ESC) be adjusted if achieved blood pressure is lower than • Canadian Hypertension Education Program (CHEP) goal and well-tolerated James PA et al. JAMA 2014;311:507-20. JNC-8 Recommendations JNC-8 Recommendations • In patients <60 years of age, start medications at blood • For the non-black population (including diabetes), pressure of >140/90mm Hg and treat to goal of initial antihypertensive treatment may include a <140/90mm Hg thiazide, ACEI, ARB, or CCB • For the black population (including diabetes), initial • In all adult patients with diabetes or chronic kidney antihypertensive treatment should include a thiazide or disease, start medications at blood pressure of CCB >140/90mm Hg and treat to goal of <140/90mm Hg • For all patients with CKD, initial (or add-on) therapy for hypertension should include an ACEI or ARB James PA et al. JAMA 2014;311:507-20. James PA et al. JAMA 2014;311:507-20. 4 4/25/15 Initial Drug Selection for HTN JNC-8 Recommendations • What happened to the beta-blockers (BB)? • Initiate therapy according to recommendations • Most evidence for BB is from atenolol • If BP is not at goal in one month, increase dose or add a • Does not meet current FDA criteria for a once-daily drug • Losartan Intervention for Endpoint reduction (LIFE) study second agent from recommended classes • Compared losartan vs. atenolol in pts. with HTN & LVH • If patient is still not at goal, add a third drug from • Primary outcome of CV death, MI, or stroke recommended classes • Overall 13% RRR with losartan vs. atenolol (p=0.021) • Do not use an ACEI and ARB together • Driven mainly by 25% reduction in risk of stroke (p=0.001) • Drugs from other classes may be used if additional BP • BB still recommended for many patients with comorbid lowering is needed or if contraindications exist conditions (CHF, CAD, etc.) • Refer to HTN specialist whenever necessary James PA et al. JAMA 2014;311:507-20. Dahloff B et al. Lancet 2002;359:995-1003. Comparisons to Other Guidelines BP Goal JNC-7 JNC-8 ASH/ISH ESC/ESH CHEP Age < 60 <140/90 <140/90 <140/90 <140/90 <140/90 Age 60-79 <140/90 <150/90 <140/90 <140/90 <140/90 Age 80+ <140/90 <150/90 <150/90 <150/90 <150/90 Diabetes <130/80 <140/90 <140/90 <140/85 <130/80 CKD <130/80 <140/90 <140/90 <130/90 <140/90 Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8. Comparisons to Other Guidelines JNC-7 JNC-8 ASH/ISH ESC/ESH CHEP Non-black Thiazide Thiazide, <60:ACEI, Thiazide, Thiazide, (no DM or ACEI, ARB, ARB ACEI, ARB, ACEI, ARB CKD) CCB >60:CCB, CCB, BB (BB if <60) thiazide Black (no Thiazide Thiazide, Thiazide, Thiazide, Thiazide, DM or CCB CCB ACEI, ARB, ARB (BB if CKD) CCB, BB <60) Diabetes ACEI, ARB, CCB, ACEI, ARB, ACEI, ARB ACEI, ARB, CCB, BB, thiazide CCB, CCB, thiazide thiazide thiazide CKD ACEI, ARB ACEI, ARB ACEI, ARB ACEI, ARB ACEI, ARB Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8. 5 4/25/15 Hypertension: Pharmacologic Treatment Pharmacologic Treatment of Hypertension • SelecIon of IniIal Therapy Treatment OpIons • Demographics • Diure&cs • Concomitant Diseases and Therapies • ACE inhibitors • Quality of Life • Angiotensin II receptor blockers • Cost • Calcium channel blockers • Drug InteracIons • Beta blockers • Alpha blockers • Centrally acIng alpha agonists • Direct vasodilators • Peripheral adrenergic blockers Arch Inter Med 1997 Hypertension Hypertension Carbonic anhydrase inhibitors • TherapeuIc OpIons: DiureIcs • Promote sodium and water excreIon at various sites of the nephron • Loop diurecs Thiazide diuretics • Thiazide/Thiazide-like diureIcs diureIcs • Potassium-sparing diureIcs • Carbonic Anhydrase Inhibitors Potassium-sparing diuretics Loop diuretics 6 4/25/15 Hypertension Hypertension • DiureIcs: Pharmacodynamics • DiureIcs: Compelling Indicaons* • Decreased intravascular (blood) fluid volume • Isolated Systolic Hypertension • Decreased extravascular (edema) fluid volume • CongesIve Heart Failure • Decreased blood pressure • DiureIcs: Possible Favorable Effects • Osteoporosis (thiazides) • DiureIcs: Possible Unfavorable Effects • Diabetes • Gout • Renal Insufficiency Hypertension Hypertension • DiureIcs: PotenIal Adverse Effects • DiureIcs: Consideraons • Electrolyte disturbances • Useful for paents with ISH, African Americans, CHF • potassium, magnesium, sodium, calcium • Different