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Current Concepts in Pharmachotherapy in Hypertension

Current Concepts in Pharmachotherapy in Hypertension. Brig Afsar Raza FCPS (Medicine), FCPS( Cardiology), MRCP(UK), CCST Cardiology (UK) Commandant Army Cardiac Centre Consultant Cardiologist & Physician. Army Cardiac Centre Lahore Pakistan. Hypertension : High Prevalence

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Current Concepts in Pharmachotherapy in Hypertension

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  1. Current Concepts in Pharmachotherapy in Hypertension Brig Afsar Raza FCPS (Medicine), FCPS( Cardiology), MRCP(UK), CCST Cardiology (UK) Commandant Army Cardiac Centre Consultant Cardiologist & Physician Army Cardiac Centre Lahore Pakistan

  2. Hypertension : High Prevalence & Growing Incidence in Pakistan • Accounts for over 100,000 deaths a year or • 12% of all cause mortality . • Overall 18% of adults in Pakistan suffer from • hypertension: 21.5% in urban areas and 16.2% • in rural areas. • One in every 3 adults over age 45 suffer from • hypertension. • Very few Pakistanis with hypertension (<3%) have • their B.P controlled. PROCOR: 7/25/99 The National Health Survey in Pakistan published in 1998 by (PMRC)

  3. Levels of blood-pressure control in different countries: Only 3% controlled in Pakistan * Percent of Patients Controlled 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% US Germany Finland Spain Australia Scotland Canada India England Pakistan** * Controlled defined as <140/90 mm Hg; other countries <160/95 mm Hg J Hum Hypertens 1997;11(4):213-220 ** 3% controlled: Data from Pakistan Hypertension League

  4. Benefits of Lowering BP Average Percent Reduction Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure 50%

  5. Benefits of Lowering BP Ref : EWPHE, LANCET, 1985; 1349-1954 SHEP, JAMA’ 1991; 265: 3255-3264

  6. To Prevent Target Organ Damage • Heart • Left ventricular hypertrophy • Angina or prior myocardial infarction • Prior coronary revascularization • Heart failure • Brain • Stroke or transient ischemic attack • Chronic kidney disease • Peripheral arterial disease (PVD) • Eye: Retinopathy

  7. Benefits of Lowering BP In stage 1 HTN and additional CVD risk factors, achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.

  8. Goals of Therapy • Reduce CVD and renal morbidity and mortality. • Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease. • Achieve SBP goal especially in persons >50 years of age.

  9. Blood Pressure Classification

  10. TreatmentOverview • Goals of therapy • Lifestyle modification • Pharmacologic treatment • Algorithm for treatment of hypertension • Followup and monitoring

  11. Is it just BP control which is required or ...... Traditional Treatment Approach New Treatment Approach Hypertension systemic disease Hypertension disease of blood vessels Hemodynamics altered Vascular biology altered Control BP & Treat vasculature (Endothelium) Treat Blood Pressure

  12. CV Risk Factors affect Prognosis & Guide Treatment (JNC 7 Report) • >95% of hypertensives have • Other CV risk factors* • Cigarette smoking • Obesity • Physical inactivity • Dyslipidemia • Diabetes mellitus • Microalbuminuria or • estimated GFR <60 mL/min • Age (>55 years for men, • >65 years for women) • Family history of premature CVD High-risk Hypertension 95% Hypertension with CV risk factors: Patients highly vulnerable for target organ damage JNC 7 Report JAMA, May 21, 2003- Vol 289, No. 19 *Stern N, et al. J Intern Med. 2000;203-210

  13. Identifiable Causes of Hypertension • Sleep apnea • Drug-induced or related causes • Chronic kidney disease • Primary aldosteronism • Renovascular disease • Chronic steroid therapy and Cushing’s syndrome • Pheochromocytoma • Coarctation of the aorta • Thyroid or parathyroid disease

  14. Lifestyle Modification

  15. Classification and Management of BP for adults *Treatment determined by highest BP category. †Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.

  16. Special Considerations • Compelling Indications • Other Special Situations • Obesity and the metabolic syndrome • Peripheral arterial disease • Hypertension in older persons • Postural hypotension • Hypertension in women • Hypertension urgencies and emergencies

  17. Compelling Indications

  18. Compelling Indications for Individual Drug Classes

  19. Compelling Indications for Individual Drug Classes

  20. Other Special Situations

  21. Hypertension in OlderPersons • More than two-thirds of people over 65 have HTN. • This population has the lowest rates of BP control • Threshold for treatment Diastolic > 90mm Hg and systolic > 150-160 mm Hg over 3-6 months observation(despite life style intervention) • Lower initial drug doses may be indicated to avoid symptoms • Thiazide or CCB(Dihydroyridine). ACE or ARB may be added

  22. Postural Hypotension • Decrease in standing SBP >10 mmHg, when associated with dizziness/fainting, more frequent in older SBP patients with diabetes, taking diuretics or venodilators drugs. • BP in these individuals should be monitored in the upright position. • Avoid volume depletion and excessively rapid dose titration of drugs.

  23. Hypertension in Women • Oral contraceptives may increase BP, and BP should be checked regularly. In contrast, HRT does not raise BP. • Development of HTN—consider other forms of contraception. • Pregnant women with HTN should be followed carefully. Methyldopa, BBs, and vasodilators, preferred for the safety of the fetus. ACEI and ARBs contraindicated in pregnancy.

  24. Hypertension in Pregnancy • May be due to pre existing essential HTN or pre-eclampsia. • Methyl dopa is safe • B Blockers are effective & safe in 3rd trimester • Modified release prep of Nifedepine • IV Labetalol for hypertensive crises • ACE and ARBs best avoided

  25. Accelerated Hypertension(Diasstolic >140 mm Hg) • Requires hospitalization. • IV not necessary • Rapid reduction not recommended can reduce organ perfusion; cerebral or myocardial ischemia • Long acting CCB(Amlodipineor modified release Nifedipine) or B Blocker to start with to reduce BP 100-110 mm Hg. Then ACE/ARB • may be added • Na Nitroprusside by infusion is the drug of choice if IV necessary

  26. Pheochromocytoma • Long term remedy is surgery. • Alpha Blockers(Phenoxybenzamine) for short term management of episodes • Tachycardia can be controlled with careful use of BBs • Phentolamine for short term during surgery

  27. Causes of Resistant Hypertension • Improper BP measurement • Excess sodium intake • Inadequate diuretic therapy • Medication • Inadequate doses • Drug actions and interactions (e.g., nonsteroidal anti-inflammatory drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptives) • Over-the-counter (OTC) drugs and herbal supplements • Excess alcohol intake • Identifiable causes of HTN

  28. ESH/ESC & ADA Guidelines

  29. ADA Treatment Recommendations for Diabetic Patients with Hypertension • Recommended target blood pressure • Systolic <130 mm Hg • Diastolic <80 mm Hg • Drug therapy mandatory above 140 mm Hg systolic and 90 mm Hg diastolic • Recommended first-line agents for patients with microalbuminuria or clinical albuminuria • ARBs and ACE-Is ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker. American Diabetes Association. Diabetes Care. 2002;25(Suppl 1):S71-S73.

  30. ADA Treatment Recommendations for Diabetic Nephropathy • Both ACE-Is and ARBs are first-line agents for treatment of albuminuria/nephropathy • Initial choice in diabetic nephropathy for hypertensive and nonhypertensive patients with type 1 diabetes • ACE-Is • Initial choice in diabetic nephropathy for hypertensive patients with microalbuminuria or clinical albuminuria and type 2 diabetes • ARBs • If one class is not tolerated, the other should be substituted American Diabetes Association. Diabetes Care. 2002;25(Suppl 1):S85-S89. ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker.

  31. ACE Inhibition Beyond Hypertensive Control

  32. Endothelium-Focus of New Research Arteriole lumen Endothelium Largest organ of the human body

  33. Causes and consequences of Endothelial Dysfunction Vasospasm (coronory, cerebral) Heart failure Reocclusion Diabetes Hypertension Endothelial dysfunction Hyperhomocystenemia Reperfusion injury Hyperlipidemia Peripheral artery disease Immune reaction Inflammatory disease Atherosclerosis Adopted from Rubanyi GM. J Cardiovasc Pharmacol. 1993;22(suppl 4):S1-S4

  34. Additional Considerations in Antihypertensive Drug Choices • Potential favorable effects • Thiazide-type diuretics useful in slowing demineralization in osteoporosis. • BBs useful in the treatment of atrial tachyarrhythmias/fibrillation, migraine, thyrotoxicosis (short-term), essential tremor, or perioperative HTN. • CCBs useful in Raynaud’s syndrome and certain arrhythmias. • Alpha-blockers useful in prostatism. • Spironlactone in Conn,s syndrome

  35. Additional Considerations in Antihypertensive Drug Choices • Potential unfavorable effects • Thiazide diuretics should be used cautiously in gout or a history of significant hyponatremia. • BBs should be generally avoided in patients with asthma, reactive airways disease, or second- or third-degree heart block. • ACEIsand ARBs are contraindicated in pregnant women or those likely to become pregnant. • ACEIs should not be used in individuals with a history of angioedema. • Aldosterone antagonists and potassium-sparing diuretics can cause hyperkalemia.

  36. Conclusion • According to baseline BP and presence or absence of complications, therapy can be initiated either with a low dose of a single agent or with a low-dose combination of 2 agents • Most patients with hypertension will require 2 or more antihypertensive drugs to achieve BP goals • Choice of therapy has to be individualized keeping in view the associated co morbid conditions Chobanian AV et al. JAMA. 2003;289:2560-2572. Guidelines Committee. J Hypertens. 2003;21:1011-1053.

  37. ThankYou

  38. 1976-1980 1988-1991 1991-1994 1999-2000 Trends in Awareness, Treatment, and Control of Hypertension in the US* 100 90 80 73% 70% 68% 70 59% 60 55% 54% 51% Percentage of Population 50 40 34% 31% 29% 27% 30 20 10% 10 0 Aware Treated Controlled† *Data for 1999-2000 were computed (M. Wolz, unpublished data, 2003) from the National Heart, Lung, Blood Institute and data for National Health and Nutrition Examination Surveys II and III (phases 1 and 2) are from The Sixth Report of the Joint National Committee on Prevention Detection, Evaluation and Treatment of High Blood Pressure. High blood pressure is systolic blood pressure of 140 mm Hg or diastolic blood pressure90 mm Hg, or taking antihypertensive medication. †Systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg. Chobanian AV et al. JAMA. 2003;289:2560-2572.

  39. 48.3 CAD Death Rate per 10,000 Person-Years 37.4 80.6 31.0 34.7 43.8 25.5 23.8 38.1 24.6 20.6 16.9 25.3 100+ 13.9 25.2 10.3 24.9 12.8 11.8 90-99 12.6 80-89 8.8 11.8 160+ 75-79 8.5 70-74 140-159 9.2 <70 Diastolic BP(mm Hg) 120-139 <120 Systolic BP(mm Hg) Effect of Systolic and Diastolic Blood Pressure on Coronary Heart Disease Mortality: MRFIT Adapted from Neaton JD, Wentworth D. Arch Intern Med. 1992;152:56-64. 

  40. CVD Risk Factors • Hypertension* • Cigarette smoking • Obesity* (BMI >30 kg/m2) • Physical inactivity • Dyslipidemia* • Diabetes mellitus* • Microalbuminuria or estimated GFR <60 ml/min • Age (older than 55 for men, 65 for women) • Family history of premature CVD (men under age 55 or women under age 65) *Components of the metabolic syndrome.

  41. CVD Risk • HTN prevalence ~ 50 million people in the United States. • The BP relationship to risk of CVD is continuous, consistent, and independent of other risk factors. • Each increment of 20/10 mmHg doubles the risk of CVD across the entire BP range starting from 115/75 mmHg. • Prehypertension signals the need for increased education to reduce BP in order to prevent hypertension.

  42. ESH/ESC 2003: Cardiovascular Risk Stratification Blood Pressure (mm Hg) Other Risk Factors and Disease History NormalSBP 120-129or DBP 80-84 High-NormalSBP 130-139or DBP 85-89 Grade 1SBP 140-159or DBP 90-99 Grade 2SBP 160-179or DBP 100-109 Grade 3SBP ≥180or DBP ≥110 No other risk factors Averagerisk Averagerisk Lowadded risk Moderateadded risk Highadded risk 1-2 risk factors Lowadded risk Lowadded risk Moderateadded risk Moderateadded risk Very highadded risk ≥3 risk factors,target organ damage, or diabetes Moderate added risk Highadded risk Highadded risk Highadded risk Very highadded risk Associated clinical conditions Highadded risk Very high added risk Very highadded risk Very highadded risk Very highadded risk Guidelines Committee. J Hypertens. 2003;21:1011-1053.

  43. Category Systolic Diastolic (mmHg) (mmHg) Optimal <120 and <80 Normal <130 and <85 High-normal 130-139 or 85-89 Hypertension Stage 1 140-159 or 90-99 Stage 2 160-179 or 100-109 Stage 3 >180 or 110 JNC Classification of Blood Pressure for adults age 18 and older

  44. In hypertension With Controlled BP Mortality Risk is Still Higher Than in Normotensive Relative risk of death Hypertensives treated and not controlled Normotensives Hypertensives, treated and controlled High risk of mortality in patients with controlled BP points out to other causes of target Organ damage (e.g endothelial dysfunction) Hawlk RJ et al, Hypertension. 1989;13(suppl):1-20-1-32.

  45. Without Compelling Indications With Compelling Indications Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Stage 1 Hypertension(SBP 140–159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Stage 2 Hypertension(SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved.Consider consultation with hypertension specialist. Algorithm for Treatment of Hypertension Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices

  46. ACE InhibitorsBenefits Beyond Anti Hypertensive Effects “ Data collected from various studies suggested that treatment of hypertension with ACE Inhibitors could prevent endothelial dysfunction independent of systemic anti hypertensive effect.” Medical clinics of North America 1998

  47. Circulating vs tissue ACE Circulating ACE 10% • Circulating ACE (endocrine) • Plasma • Tissue ACE (autocrine/paracrine) • Vasculature (endothelium) • CNS • Adrenal • Heart • Kidney • Reproductive organs • Lung Tissue ACE 90% Tissue ACE Mainly Responsible For Target Organ Damage Dzau VJ.Arch Intern Med. 1993;153:937-942

  48. ACE Inhibition Vasculoprotective Effect Kininogens Angiotensinogen Kallikreinin Renin Bradykinins Angiotensin I ACE Inhibition ACE Inhibition Inactive Peptides Angiotensin II ACE Inhibition in vascular endothelium Ang II; Bradykinin; NO

  49. Laboratory Tests • Routine Tests • Electrocardiogram • Urinalysis • Blood glucose, and hematocrit • Serum potassium, creatinine, or the corresponding estimated GFR, and calcium • Lipid profile, after 9- to 12-hour fast, that includes high-density and low-density lipoprotein cholesterol, and triglycerides • Optional tests • Measurement of urinary albumin excretion or albumin/creatinine ratio • More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved

  50. Hypertension & CV Diseases (JNC 7) Its More Than High Blood Pressure

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