Management of Hypertension: An Overview & Update

1. Management of Hypertension:An Overview & Update 11/12/11 Marcus Weiser, DO PGY3 Chief Resident Via Christi Family Medicine

2. Outline • Classification • Causes • History, PE, initial testing • Antihypertensive agents • Monotherapy & combination therapy

3. Hypertension • Sustained elevation of arterial systemic blood pressure • Single most common diagnosis at US family physician office visits (coded at 11.1%) • Age 20-50 usually affected • 29% of US adults • Prevalence increases with age

4. Hypertension • Baseline high blood pressure at age 50 reduces life expectancy by about 5 years.1 • Associations • Erectile dysfunction, ophthalmologic conditions, osteoporosis, anxiety, chronic kidney disease, obstructive sleep apnea, coronary artery disease, cerebrovascular disease, peripheral arterial disease, congestive heart failure, dementia

6. Types • Prehypertension (SBP 120-139 or DBP 80-89) • Stage I (SBP 140-159 or DBP 90-99) • Confirm within 2 months • Stage II (SBP > 159 or DBP > 99) • Evaluate within 1 month (within 1 week if > 180/110) • Type I (vasoconstriction, high renin, high SBP) • Treat with ACE, ARB, BB • Type II (Na dependent, low renin, high DBP) • Treat with diuretics, CCB

7. ICD-10 codes • I10 essential (primary) hypertension • ICD-10-CA modification in Canada • I10.0 benign hypertension • I10.1 malignant hypertension • I11 hypertensive heart disease • I11.0 hypertensive heart disease with (congestive) heart failure • I11.9 hypertensive heart disease without (congestive) heart failure • ICD-10-CA modification in Canada - 4th character extensions were deleted to allow for use of dual classification for added specificity • I12 hypertensive renal disease • I12.0 hypertensive renal disease with renal failure • I12.9 hypertensive renal disease without renal failure • ICD-10-CA modification in Canada - 4th character extensions were deleted to allow for use of dual classification for added specificity • I13 hypertensive heart and renal disease • I13.0 hypertensive heart and renal disease with (congestive) heart failure • I13.1 hypertensive heart and renal disease with renal failure • I13.2 hypertensive heart and renal disease with both (congestive) heart failure and renal failure • I13.9 hypertensive heart and renal disease, unspecified • ICD-10-CA modification in Canada - 4th character extensions were deleted to allow for use of dual classification for added specificity • I15 secondary hypertension • I15.0 renovascular hypertension • I15.1 hypertension secondary to other renal disorders • I15.2 hypertension secondary to endocrine disorders • I15.8 other secondary hypertension • I15.9 secondary hypertension, unspecified • ICD-10-CA modification in Canada • 5th digits assigned to specify • 0 benign or unspecified • 1 malignant • R03.0 elevated blood-pressure reading, without diagnosis of hypertension

8. CKD (any cause) Renal Artery Stenosis Cushing Syndrome Primary Hyperaldosteronism Hyper/Hypothyroidism Hyperparathyroidism Pheochromocytoma Obstructive Sleep Apnea Coarctation of the Aorta Black Licorice Medications BP Cuff too small Arm position Caffeine Nicotine Substance Abuse/Intoxication Short sleep duration Alcohol Use Salt intake? Impatience, hostility Causes

9. History • Symptoms • Medications • Corticosteroids, OCPs, NSAIDs, venlafaxine, buspirone, carbamazepine, clozapine, bromocriptine, cyclosporin, tacrolimus, EPO • Past Medical History • DM, CAD, CHF, DSLD, Thyroid/Renal Dz • Social History • Dietary sodium, stress, smoking, alcohol intake, activity level, St. John’s wort, ergot-containing herbal preparations, cocaine, anabolic steroids, narcotic withdrawal, meth, PCP

10. Physical Exam • Proper blood pressure measurement • Seated in chair with back in calm, quiet, warm room for at least 5 minutes. Bare arm elevated so elbow is level with heart. No smoking or caffeine 1 hour prior • Cuff width > 2/3 arm diameter • Cuff length > 2/3 arm circumference • Average of 2 measurements • Carotid bruits • Cardiac auscultation • Abdomen • Extremities

11. Serum Potassium Serum Creatinine Fasting Blood Glucose Fasting Lipid Panel Urinalysis Electrocardiogram - Uniformly recommended by 4 expert panels (CHEP, ESH/ESC, ICSI, JNC7) Hematocrit Serum Calcium Serum Sodium Serum Uric Acid Urine Albumin/Creatinine Ratio - Recommended by some, not all 4 panels Initial Testing

12. Additional Testing to Consider • PTH • TSH • 24 hour urine metanephrine • Plasma Aldosterone • Plasma Renin • Dexamethasone supression test • Sleep study • RAS imaging

13. Agents • Ace-inhibitors (ACEs) • Angiotensin Receptor Blockers (ARBs) • Calcium Channel Blockers (CCBs) • Beta Blockers (BBs) • Thiazide Diuretics (TZD) • Loop Diuretics (Loops) • Aldosterone Antagonists • Alpha Blockers • Other agents

14. ACEs & ARBs • Special Indications • ACE • CHF (SOLVD, AIRE, TRACE) • Post-MI (SAVE) • Diabetes (UKPDS, HOPE) • CKD (REIN, AASK, CAPTOPRIL) • Recurrent Stroke Prevention (PROGRESS) • High CAD Risk (ALLHAT, HOPE, ANBP2) • ARB • CHF (Val-HeFT) • Diabetes • CKD (RENAAL, IDNT, CAPTOPRIL)

15. ACEs & ARBs • Contraindications • Pregnancy, Angioedema, Renovascular Disease, Hyperkalemia, Acute Renal Failure • Monitor • Creatinine, Potassium • Agents • Benazepril or Lisinopril (20mg to 40mg PO daily) • Enalapril, Ramipril • Losartan, Olmesartan, Valsartan

16. Calcium Channel Blockers • Special Indications • High CAD risk (ALLHAT, CONVINCE) • Migraines • Raynaud’s • Angina (non-dihydropyridine) • Atrial Fibrillation (non-dihydropyridine) • Atrial Flutter (non-dihydropyridine)

17. Calcium Channel Blockers • Contraindications • 2nd or 3rd degree heart block • Agents • Amlodipine (5mg to 10mg PO daily) • Nifedipine, Nicardipine, Felodipine

18. Beta Blockers • Special Indications • CHF (MERIT-HF, COPERNICUS, CIBIS) • Post-MI (BHAT, CAPRICORN) • Angina, Atrial Fibrillation, Atrial Flutter, Tremor, Migraine • Contraindications • Asthma, COPD, 2nd or 3rd degree heart block, Depression, Acute CHF • Avoid abrupt cessation • Agents • Metoprolol (50mg to 200mg PO BID) • Carvedilol (3.125mg to 25mg PO BID) • Atenolol, Nebivolol, Labetalol, Esmolol, Propranolol, Timolol

19. Beta BlockersInappropriate first-line treatment • JNC8 • Worse BP control (LIFE) • Worse CV outcome prevention (LIFE) • Increased mortality (ASCOT) • Higher risk of stroke 2 • More side effects 2 • Increased risk of type II diabetes 3

20. Thiazide Diuretics • Special Indications • High CAD risk (ALLHAT) • Recurrent stroke prevention (PROGRESS) • DM without proteinuria (ALLHAT) • Edema • Osteoporosis

21. Thiazide Diuretics • Contraindications • Stage IV CKD, Gout, Hyponatremia, Acute Renal Failure • Monitor • Creatinine, Potassium, Sodium • Agents • Chlorthalidone (12.5mg to 25mg PO daily) • Hydrochlorothiazide, Indapamide, Metolazone

22. Thiazide equivalence? • Chlorthalidone vs HCTZ • Chlorthalidone use has sharply declined over the last 20 years for reasons unknown 4

23. ACCOMPLISH

24. Chlorthalidone vs HCTZ • Amlodipine appears superior to HCTZ

25. ALLHAT • Secondary Outcome

26. Chlorthalidone vs HCTZ • Amlodipine appears superior to HCTZ • Chlorthalidone appears superior to Amlodipine

27. ALLHAT • Secondary Outcome • Lower rate of combined CVD with Chlorthalidone

28. Chlorthalidone vs HCTZ • Amlodipine appears superior to HCTZ • Chlorthalidone appears superior to Amlodipine • Chlorthalidone appears superior to Lisinopril

29. ACE-I Beats Diuretic (ANBP2) • Rate of events per year

30. Chlorthalidone vs HCTZ • Amlodipine appears superior to HCTZ • Chlorthalidone appears superior to Amlodipine • Chlorthalidone appears superior to Lisinopril • Enalapril appears superior to HCTZ

31. Thiazide equivalence? • Chlorthalidone vs HCTZ • Chlorthalidone use has sharply declined over the last 20 years for reasons unknown 4 • No evidence that HCTZ improves cardiovascular outcomes • Large body of evidence in major trials (ALLHAT) showing cardiovascular event reduction and outcome benefit with chlorthalidone • Chlorthalidone has much longer half-life, is 1.5-2.0 times more potent, and has slightly more hypokalemia (7-8% patients require treatment 5,6)

32. Thiazide Diuretics • Chlorthalidone superior reduction of nighttime BP, compared to HCTZ 7 • 13.5 mmHg vs 6.4 mmHg • Chlorthalidone (12.5-25mg) vs HCTZ (25-50mg) • Agents • Chlorthalidone (12.5mg to 25mg PO daily) • Hydrochlorothiazide, Indapamide, Metolazone

33. Loop Diuretics • Special Indications • CHF, Edema • Contraindications • Gout, Acute Renal Failure • Monitor • Creatinine, Electrolytes • Agents • Torsemide (5mg to 10mg PO daily) • Furosemide, Bumetanide

34. Aldosterone Antagonists • Special Indications • CHF (RALES) • Post-MI (EPHESUS) • Contraindications • Gout, Hyperkalemia, Acute Renal Failure • Monitor • Creatinine, Potassium • Agents (ASCOT) • Spironolactone (25mg to 50mg once daily) • Amiloride, Triamterene

35. ASCOT • Patients with uncontrolled hypertension on 3 antihypertensive agents • Spironolactone 25mg once daily added as 4th agent • Mean BP drop of 22/10 at one year follow-up

36. Alpha Blockers • Special Indications • BPH • Contraindications • High CV risk (ALLHAT) • Agents • Doxazosin, Prazosin, Terazosin

37. Other Agents • Clonidine • Methyldopa • Hydralazine • Tekturna • Minoxidil • Isosorbide dinitrate/mononitrate

38. Low . . . but how low is too low? • Treatment goal < 140/90 • < 130/80 in diabetics per JNC7 recommendation • ACCORD, INVEST • BP targets below 140/90 overall do not improve morbidity or mortality • DBP < 70 increases risk of death, MI, stroke

39. Lifestyle ModificationsFirst-Line Treatment • Sodium Restriction (2-8 mmHg) • DASH (8-14 mmHg) • Fruits, vegetables, low-fat dairy, reduced fat • Aerobic physical activity (4-9 mmHg) • Weight Reduction • (5-20 mmHg per 10 kg lost) • Moderate alcohol (2-4 mmHg) • Smoking Cessation *From JNC7 Express Report, 2003

40. Sequential treatment Avoid excessive dosing First-line agents Avoid similar agents Avoid excessive dosing Other agents Monotherapy vs Multi-Drug Therapy

41. Monotherapy – 1st line agents • 1. Thiazide • Chlorthalidone 12.5mg daily, titrate to 25mg? • 2. ACE/ARB • Benazepril or Lisinopril 20mg daily • Titrate up to 40mg, possibly beyond • 3. Calcium Channel Blocker (dihydropyridine) • Amlodipine 5mg daily • Titrate up to 10mg once daily

43. Monotherapy • Sequential treatment • Try one agent, titrate up • If inadequate control, switch instead of add • Each first-line agent will normalize BP in 30-50% of patients 8,9 • 49.1% chance a different agent will control Stage I Hypertension following failure of initial agent 10 • May prevent unnecessary multi-drug treatment • JNC7 recommendation for uncontrolled stage I hypertension on monotherapy is to optimize dose or add 2nd medication • Addition of a second drug from a different class should be initiated when use of a single drug in adequate doses fails to achieve the BP goal

44. Combination Therapy • Consider combination for Stage 2 • Add if sequential monotherapy fails • Drugs for each compelling indication • ACCOMPLISH • Include a diuretic • Consider Spironolactone as 4th agent (ASCOT) • First-line agents

45. ACCOMPLISH

46. ACCOMPLISH

47. ACCOMPLISH

48. Combination Therapy • Drugs for each compelling indication • ACCOMPLISH • Include a diuretic • First-line agents • Consider Spironolactone as 4th agent (ASCOT)

49. Resistant Hypertension • Uncontrolled on 3 medications • Controlled on 4 or more medications • Must include a diuretic

50. CKD (any cause) Renal Artery Stenosis Cushing Syndrome Primary Hyperaldosteronism Hyper/Hypothyroidism Hyperparathyroidism Pheochromocytoma Obstructive Sleep Apnea Coarctation of the Aorta Licorice Medications BP Cuff too small Arm position Caffeine Nicotine Substance Abuse/Intoxication Short sleep duration Alcohol Use Salt intake? Impatience, hostility Causes