Pharmacologic Management of Hypertension

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Magdalen Bertha Cunningham
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Current Concepts In Management of Fernando Vega, MD Secondary - Definition Renovascular Disease (The kidney doesn t get impressed by blood pressure)

Pyelonephritis Cushing s Disease Conn s Syndrome Pheochromocytoma Catecholamine secreting tumor Carcinoid Serotonin Secreting Tumor Secondary - Causes

Catecholamine secreting tumor Carcinoid Serotonin Secreting Tumor 2.

Disease Peripheral Vascular Disease Renal, abdominal bruits Femoral pulses Peripheral pulses, edema Retinopathy 2.

1 Current Concepts In Management of Fernando Vega, MD Secondary - Definition Renovascular Disease (The kidney doesn t get impressed by blood pressure) Renovascular stenosis Renal artery stenosis Fibromuscular hyperplasia Atherosclerosis Renal Parenchymal Disease Polycystic Kidney Glomerulonephritis Pyelonephritis Cushing s Disease Conn s Syndrome Pheochromocytoma Catecholamine secreting tumor Carcinoid Serotonin Secreting Tumor Secondary - Causes Renovascular Disease (The kidney doesn t get impressed by blood pressure) Renovascular stenosis Renal artery stenosis Fibromuscular hyperplasia Atherosclerosis Renal Parenchymal Disease Polycystic Kidney Glomerulonephritis Pyelonephritis Cushing s Disease Conn s Syndrome Pheochromocytoma Catecholamine secreting tumor Carcinoid Serotonin Secreting Tumor 2. Proper execution of Focused Physical Exam Other signs of end organ damage or secondary hypertension Fundi Hypertensive Heart Disease Cerebrovascular Disease Peripheral Vascular Disease Renal, abdominal bruits Femoral pulses Peripheral pulses, edema Retinopathy 2. Proper execution of Focused Physical Exam Retinopathy 2. Proper execution of Focused Physical Exam Fundi Fundi Fernando Vega, M.D. 1

Laboratory Evaluation Imaging Assess end

Proteinuria Renal ultrasound Renal function

causes Renal artery stenosis (fibromuscular

Syndrome Screen for risk factors (lipids,

2 Laboratory Evaluation Imaging Assess end organ damage ECG LVH Echocardiogram LVH Proteinuria Renal ultrasound Renal function (lytes, BUN, Cr,) Screen for treatable causes Renal artery stenosis (fibromuscular hyperp, atheroma) Cushings disease Conn s Syndrome Screen for risk factors (lipids, BS) Imaging Imaging - Imaging - Imaging Fernando Vega, M.D. 2

3 A brief word on renovascular hypertension: The most common correctable cause of 2º hypertension Incidence varies with clinical setting 1% in patients with mild hypertension 10 45% in white patients with severe or malignant HT Radiographic testing for renovascular disease is indicated only in Patients in whom the history or physical exam is suggested. When to suspect renovascular hypertension: Severe or refractory HT including retinal hemorrhages Or papilledema Abnormal creatinine may be secondary to bilateral disease An acute rise of BP over previous stable baseline Proven age of onset before puberty or above 50 An acute rise of Cr unexplained or after ACE or ARB Incidental finding of assymetric sizes (75% correlation) Abdominal bruit that lateralizes (40% sens, 95% spec) Negative family history for hypertension When to suspect other causes of secondary hypertension: Primary renal disease- elevated creatinine and proteinuria Pheochomocytoma triad of pounding headaches, palpitations and sweating Primary aldosteronism hypokalemia and low renin Cushings facies, central obesity, ecchymoses and muscle weakness Sleep Apnea- snoring, awake with HA, sommolence Coarctation decreased or lagging peripheral pulses, bruit Thyroid abnormalities Hyperparathyroidism Pharmacological Treatment Thiazide type diuretic for most Consider compelling factors or indications Compelling p gindications include age, ethnicity, And co-morbid conditions Compelling indication means a major improvement in outcome independent of blood pressure Pharmacological Treatment Compelling Indications Indication Systolic Heart Failure S/P Myocardial Infarct Proteinuric Chronic Renal Insuf High CAD risk Diabetes w/ proteinuria Diabetes w/o proteinuria Angina Atrial fib / rate control Atrial flutter / rate control ACE, ARB, ß-blk, hctz, ald-ant ACE, ß-blk, ald-ant ACE, ARB Diurtetic, poss ACE ACE, Diuretic, perhaps ACE ß-blk, CCB ß-blk, non dhp CCB ß-blk, non dhp CCB Pharmacological Treatment Likely to have Favorable Effect Indication Benign Prostatic Hypertrophy Essential tremor Hyperthyroidism Migraine Osteoporosis Raynaud s Alpha Blocker ß-blocker ß-blocker ß-bocker, CCB Diuretic Dhp CCB Fernando Vega, M.D. 3

Pharmacological Treatment Contraindications Pharmacological Treatment Relative Contraindication Condition Condition Angio Edema ACE inhibitor Bronchospastic disease ß-blocker Depression Reserpine

diuretic Renovascular disease ACE, ARB Efficacy: Generally, each agent are roughly equally effective - 30 to 50% hypertensive response. However, in a study of 1300: Wide inter-patient variability.

4 Pharmacological Treatment Contraindications Pharmacological Treatment Relative Contraindication Condition Condition Angio Edema ACE inhibitor Bronchospastic disease ß-blocker Depression Reserpine Liver Disease Methyldopa Pregnancy ACE, ARB 2º or 3º Heart Block ß-blocker, CCB Depression ß-blocker, central alpha-agonist Gout Diuretic Hyperkalemia Aldosterone ant, ACE, ARB Hypokalemia Thiazide diuretic Renovascular disease ACE, ARB Efficacy: Generally, each agent are roughly equally effective - 30 to 50% hypertensive response. However, in a study of 1300: Wide inter-patient variability. Example of enalapril and diltiazem: No predictable relationship with response from patient to patient. Differential response was most prominent in blacks. Older black people responded best to diltiazem or hctz. Younger blacks responded best to diltiazem. There were fewer differences between the drugs in white patients who responded equally to each of the different drug. Exception was to HCTZ Least effective in younger whites. No significant differences in side effects or quality / life Study of 56 hypertensive patients: Cross-over rotation of ACE-I, B-B, CC-B, diuretic, 36 patients received all four monthly cycles One-half of all the patients that attained target BP on monotherapy did not do so with the first assigned drug. The rotation increased the success of monotherapy from 39 per cent to 73 per cent. TOMHS Treatment of Mild hypertension Study: No significant differences in efficacy. Incidence of side effects was similar But the thiazide diuretic was associated with a higher frequency of erectile dysfunction. Correlations were found between A and B and also between C and D Fernando Vega, M.D. 4

5 Does the choice of drug affect the outcome? The same level of BP control provides the same degree of cardiac protection. General Lessons from MCR trials Medical Research Council Trial Found not difference in outcome between thiazide diuretic and propranolol Atenolol compared to HCTZ/amiloride Bt Beta blocker reduced dthe incidence id of cerebrovascular disease but doesn t reduce coronary events or cardiovascular or all-cause mortality. Diuretic therapy was associated with improvements in all of the end points. General Lessons from CAPPP trials Captopril Prevention Trial 10,986 patients Captopril vs Beta blocker and/or diuretic for six years: No difference in risk of a cardiovascular event However in a subsequent sub-group, diabetics had 40% reduction in the relative risk of all primary end points. General Lessons from STOP 2 and NORDIL study 6614 elderly/11,00 pts: Same conclusion. Newer drugs provide similar benefit. General Lessons from INSIGHT Trial: Same conclusion. Newer drugs provide similar benefit. No enhanced risk of stroke as in STOP Lessons from ALLHAT: 45,000 Patients with HT + an additional risk factor for CAD. Clorthalidone vs. lisinopril, amlodipine, doxazosin Primary outcome: fatal CHD, non-fatal MI. Secondary outcomes: all cause mortality, stroke, combined CVD events Doxazosin was prematurely terminated because of increased risk of CHF Efficacy/ control: hair splitting at 2-3 mm Hg over years. Incidence of primary outcome and all cause mortality were the same. Higher rate of CHF with amlodipine vs chlorthalidone Lisinopril (vs. clorthalidone) had a higher incidence of combined cardiovascular disease outcomes Fernando Vega, M.D. 5

6 More Lessons from ALLHAT: subgroups Observation observed across all subgroups m,w, b,nb, dm,y,o Amlodipine observations consistent with m,w,b, nb,dm, y,o. Lisionopril observations were consistent with gender, age, dm status, although a few outcome differences among subgroups: In blacks, increased risk of stroke and combined CVD among blacks with lisinopril over clorthalidone Biochemical differences Hyperkalemia with chlorthalidone Lessons from VALUE Trial: Quickly achieving adequate BP control in high risk patients is very important in groups at high risk Variations in cardiovascular outcomes among different antihypertensive drugs and trials can result from relatively small differences in achieved blood pressures. With equivalent BP control ARBS are at least as effective as CCB S. Incidence of new onset of diabetes is lower with ARB s. Higher rate of hyperglycemia with chlorthalidone The adverse metabolic effects did not result in incr CV mortality or morbidity in dm or non dm pt. THE END Fernando Vega, M.D. 6

Hypertension (JNC-8)

Hypertension (JNC-8) Southern California University of Health Sciences Physician Assistant Program Management and Treatment of Hypertension April 17, 2018, presented by Ezra Levy, Pharm.D.! The 8 th Joint