Pharmacologic Management Of Hypertension

Pharmacologic Management ofHypertensionSecondary Hypertension - DefinitionCurrent ConceptsInManagement of HypertensionFernando Vega, MD¾ Renovascular Disease¾ (The kidney doesn’t get impressed by blood pressure)¾ Renovascular stenosis – Renal artery stenosis¾ Fibromuscular hyperplasia¾ Atherosclerosis¾ Renal Parenchymal Disease¾ Polycystic Kidney¾ Glomerulonephritis¾ Pyelonephritis¾ Cushing’s Disease¾ Conn’s Syndrome¾ Pheochromocytoma¾ Catecholamine secreting tumor¾ Carcinoid¾ Serotonin Secreting TumorSecondary Hypertension - Causes¾ Renovascular Disease¾ (The kidney doesn’t get impressed by blood pressure)¾ Renovascular stenosis – Renal artery stenosis¾ Fibromuscular hyperplasia¾ Atherosclerosis¾ Renal Parenchymal Disease¾ Polycystic Kidney¾ Glomerulonephritis¾ Pyelonephritis¾ Cushing’s Disease¾ Conn’s Syndrome¾ Pheochromocytoma¾ Catecholamine secreting tumor¾ Carcinoid¾ Serotonin Secreting TumorHypertension – Clinical Approach2. Proper execution of Hypertension Focused Physical Exam¾Other signs of end organ damage or secondary hypertension¾Fundi¾Hypertensive Heart Disease¾Cerebrovascular Disease¾Peripheral Vascular Disease¾Renal, abdominal bruits¾Femoral pulses¾Peripheral pulses, edemaHypertension – RetinopathyHypertension – Retinopathy2. Proper execution of Hypertension Focused Physical Exam2. Proper execution of Hypertension Focused Physical Exam¾FundiFernando Vega, M.D.¾Fundi1

Pharmacologic Management ofHypertensionHypertension – Clinical ApproachLaboratory EvaluationHypertension – Imaging Assess end organ damage– ECGLVH– EchocardiogramLVH– 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)Hypertension – ImagingHypertension - ImagingFernando Vega, M.D.Hypertension – ImagingHypertension - Imaging2

Pharmacologic Management ofHypertensionHypertension – Clinical ApproachA brief word on renovascular hypertension:¾The most common correctable cause of 2º hypertension¾Incidence varies with clinical setting¾1% in patients with mild hypertension¾ 10 – 45% in white patients with severe or malignant HTHypertension – Clinical ApproachWhen to suspect renovascular hypertension:¾ Severe or refractory HT including retinal hemorrhagesOr papilledema¾Abnormal creatinine may be secondary to bilateral disease¾ An acute rise of BP over previous stable baseline¾ Proven age of onset before puberty or above 50¾ An acute rise of Cr unexplained or after ACE or ARB¾Incidental finding of assymetric sizes (75% correlation)Radiographic testing for renovascular disease is indicated only inPatients in whom the history or physical exam is suggested.¾ Abdominal bruit that lateralizes (40% sens, 95% spec)¾ Negative family history for hypertensionHypertension – Clinical ApproachHypertension – Clinical ApproachPharmacological TreatmentWhen to suspect other causes of secondary hypertension:¾ Primary renal disease- elevated creatinine and proteinuria¾ Pheochomocytoma – triad of pounding headaches,palpitations and sweating¾ Primary aldosteronism – hypokalemia and low renin¾ Cushings – facies, central obesity, ecchymoses andmuscle weakness¾ Sleep Apnea- snoring, awake with HA, sommolence¾Thiazide type diuretic for most¾Consider compelling factors or indications¾Compellingpg indications include age,g , ethnicity,y,And co-morbid conditions¾Compelling indication means a major improvementin outcome independent of blood pressure¾Coarctation – decreased or lagging peripheral pulses, bruit¾ Thyroid abnormalities¾ HyperparathyroidismHypertension – Clinical ApproachPharmacological Treatment – Compelling IndicationsIndicationAntihypertensive DrugsHypertension – Clinical ApproachPharmacological Treatment – Likely to have FavorableEffectIndicationAntihypertensive DrugsACE, ß-blk, ald-antBenign Prostatic HypertrophyAlpha BlockerACE, ARBEssential tremorß-blockerHigh CAD riskDiurtetic, poss ACEHyperthyroidismß-blockerDiabetes w/ proteinuriaACE,Migraineß-bocker, CCBDiabetes w/o proteinuriaDiuretic, perhaps ACEOsteoporosisDiureticAnginaß-blk, CCBRaynaud’sDhp CCBSystolic Heart FailureACE, ARB, ß-blk, hctz, ald-antS/P Myocardial InfarctProteinuric Chronic Renal InsufAtrial fib / rate controlß-blk, non dhp CCBAtrial flutter / rate controlß-blk, non dhp CCBFernando Vega, M.D.3

Pharmacologic Management ofHypertensionHypertension – Clinical ApproachHypertension – Clinical ApproachPharmacological Treatment – ContraindicationsPharmacological Treatment – Relative ContraindicationConditionAntihypertensive DrugsConditionAntihypertensive DrugsAngio EdemaACE inhibitorDepressionß-blocker, central alpha-agonistBronchospastic eiHHyperkalemiak l iAld tAldosteroneant,t ACE,ACE ARBLiver DiseaseMethyldopaHypokalemiaThiazide diureticPregnancy2º or 3º Heart BlockACE, ARBß-blocker, CCBRenovascular diseaseACE, ARBTreatment Strategies*********General Lessons from clinical trials: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 predictablerelationship with response from patient to patient.DiffDifferentialti l response was mostt prominentit ini blacks.bl kOlder black people responded best to diltiazem or hctz.Younger blacks responded best to diltiazem.There were fewer differences between the drugs in whitepatients who responded equally to each of the differentdrug. Exception was to HCTZ – Least effective inyounger whites.No significant differences in side effects or quality / lifeTreatment Strategies*********Treatment Strategies*********General Lessons from clinical trials:General Lessons from clinical trials:Study of 56 hypertensive patients:TOMHS Treatment of Mild hypertension Study:Cross-over rotation of ACE-I, B-B, CC-B, diuretic, 36 patientsreceived all four monthly cyclesNo significant differences in efficacy.One-half of all the patients that attained target BP onpy did not do so with the first assignedgdrug.gmonotherapyThe rotation increased the success of monotherapy from39 per cent to 73 per cent.Incidence of side effects was similarBut the thiazide diuretic was associated with a higherfrequency of erectile dysfunction.Correlations were found between A and B and also betweenC and DFernando Vega, M.D.4

Pharmacologic Management ofHypertensionTreatment Strategies*********General Lessons from clinical trials:Treatment Strategies*********General Lessons from MCR trialsMedical Research Council TrialDoes the choice of drug affect the outcome?Found not difference in outcome between thiazide diuretic andpropranololThe same level of BP control provides the same degree ofcardiac protection.Atenolol compared to HCTZ/amilorideB t blockerBetabl k reducedd d ththe iincidenceidoff cerebrovascularbldisease but doesn’t reduce coronary events orcardiovascular or all-cause mortality.Diuretic therapy was associated with improvements in all ofthe end points.Treatment Strategies*********General Lessons from CAPPP trialsCaptopril Prevention Trial – 10,986 patientsCaptopril vs Beta blocker and/or diuretic for six years:Treatment Strategies*********General Lessons from STOPHypertension 2 and NORDIL study6614 elderly/11,00 pts:Same conclusion. Newer drugs provide similar benefit.No difference in risk of a cardiovascular eventHowever inHi a subsequentbt sub-group,bdi b ti hdiabeticshadd 40%reduction in the relative risk of all primary end points.Treatment Strategies*********General Lessons from INSIGHT Trial:Treatment Strategies*********Lessons from ALLHAT:45,000 Patients with HT an additional risk factor for CAD.Clorthalidone vs. lisinopril, amlodipine, doxazosinSame conclusion. Newer drugs provide similar benefit.No enhanced risk of stroke as in STOPPrimary outcome: fatal CHD, non-fatal MI. Secondaryoutcomes: all cause mortality, stroke, combined CVD eventsDoxazosin was prematurely terminated because ofincreased risk of CHFEfficacy/ control: hair splitting at 2-3 mm Hg over years.Incidence of primary outcome and all cause mortality were thesame.Higher rate of CHF with amlodipine vs chlorthalidoneLisinopril (vs. clorthalidone) had a higher incidence ofcombined cardiovascular disease outcomesFernando Vega, M.D.5

Pharmacologic Management ofHypertensionTreatment Strategies*********Treatment Strategies*********More Lessons from ALLHAT: subgroupsLessons from VALUE Trial:Observation observed across all subgroups m,w, b,nb, dm,y,oQuickly achieving adequate BP control in high risk patients isvery important in groups at high riskAmlodipine observations consistent with m,w,b, nb,dm, y,o.Lisionopril observations were consistent with gender, age, dmstatus, although a few outcome differences among subgroups:In blacks, increased risk of stroke and combined CVDamong blacks with lisinopril over clorthalidoneBiochemical differencesVariations in cardiovascular outcomes among differentantihypertensive drugs and trials can result from relativelysmall differences in achieved blood pressures.With equivalenti l t BP controlt l ARBS are att lleastt as effectiveff tias CCB’S. Incidence of new onset of diabetes is lowerwith ARB’s.Hyperkalemia with chlorthalidoneHigher rate of hyperglycemia with chlorthalidoneThe adverse metabolic effects did not result in incr CVmortality or morbidity in dm or non dm pt.THE ENDFernando Vega, M.D.6

Management of HypertensionManagement of Hypertension Fernando Vega, MD Secondary Hypertension - Definition ¾Renovascular Disease ¾(The kidney doesn’t get impressed by blood pressure) ¾Renovascular stenosis – Renal artery stenosis ¾Fibromuscular hyperplasia ¾Atherosclerosis ¾Rena