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Hypertension Update

Hypertension Update. Prof. Ali. M. Kassem Head of Internal Medicine and Cardiology Department Sohag Faculty of Medicine Sohag University. Agenda. Past Vs today knowledge on hypertension Benefits of treating high BP Drugs used for hypertension

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Hypertension Update

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  1. Hypertension Update Prof. Ali. M. Kassem Head of Internal Medicine and Cardiology Department Sohag Faculty of Medicine Sohag University

  2. Agenda • Past Vs today knowledge on hypertension • Benefits of treating high BP • Drugs used for hypertension • When and how to initiate antihypertensive therapy ? • How to improve compliance to treatment ? • Summary

  3. Hyperextension in the past “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” Hay, Brit Med J, 1931

  4. Hyperextension in the past “The treatment of hypertension itself is a difficult and almost hopeless task in the present state of knowledge, and in fact for aught we know...the hypertension may be an important compensation mechanismwhich should not be tampered with, even were it certain that we could control it.” —Paul Dudley White, 1937

  5. Hypertension in the past “In a patient with mild benign hypertension, i.e., blood pressure <200/<100 mm Hg, there is no indication for use of hypotensive drugs. Continued observation is desirable and conservative treatment consisting of reassurance, mild sedatives, and weight reduction is indicated.” Friedberg. Diseases of Heart, 1946

  6. Major coronary event CV mortality All deaths CHF Stroke 2% 4% 4% 10% * 21% ** 23% *** 34% *** Older patients (mean >65 years) Younger patients (<65 years) 46% *** 49% *** 78% Hypertension today Treating Hypertension Reduces Cardiovascular Morbidity and Mortality Relative Risk Reduction (%) in Meta Analysis of Controlled Clinical Trials *P <0.05; **P <0.01; ***P <0.001 vs. baseline CHF = congestive heart failure; CV = cardiovascular Gueyffier F et al J Hum Hypertens 1996;10:1-8

  7. Results of PLACEBO CONTROLLED TRIALS Effect of Antihypertensive Drug Treatment on CardiovascularEvents % Reduction in Events ** CHF Strokes LVH CVD CHD events Fatal/Non-fatal Deaths Fatal/Non-fatal *Combined results from 17 randomized placebo controlled treatment trials (48.000 subjects) Diuretic or Beta-blocker based **All differences are statistically significant Moser,J Am Coll Cardiol. 1996;27:1214-1218; Arch Intern Med 1993;S76-S71

  8. BP Reductions as Small as 2 mmHg Reduce the Risk of CV Events by Up to 10% • Meta-analysis of 61 prospective, observational studies • 1 million adults • 12.7 million person-years 7% reduction in risk of IHD mortality 2 mmHg decrease in mean SBP 10% reduction in risk of stroke mortality Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.

  9. Benefits of Treatment • In clinical trials, anti-hypertensive therapy has been associated with mean reductions of: • 35 to 40% in stroke incidence • 20 to 25% of myocardial infarctions • >50% percent of heart failure • It is estimated that control of HTN to below 140/90 mmHg could prevent: • 19% of CHD events in men • 31% of CHD events in women • Optimal control of BP to below 130/80 mmHg could prevent: • 37% of CHD events in men • 56% of CHD events in women • Treating Stage 1 HTN can prevent 1 death for every 11 patients treated.

  10. HYPERTENSION TREATMENTS YearTreatment Non Drug Treatment 1922 Strict low-sodium diet 1929 Lumbar sympathectomy 1930s - 1950 Sedatives 1944 Kempner rice diet YearTreatment Early Antihypertensive Drugs 1930s Veratrum alkaloids 1940s Thiocyanates 1948 Antimalarials 1949 Reserpine Phenoxybenzamine 1950 Ganglion blockers 1951 Vasodilators Monamine oxidase inhibitors 1953 Central Alpha agonists

  11. -blockers ARBs Directvasodilators ACEinhibitors Thiazidesdiuretics Peripheralsympatholytics Ganglion blockers Veratrumalkaloids Central 2 agonists Calciumantagonists-non DHPs -blockers Calciumantagonists-DHPs Development of Antihypertensive Therapies Effectiveness Tolerability 1940’s 1950 1957 1960’s 1970’s 1980’s 1990’s 2001

  12. Drugs Used in Management of High Blood Pressure Drugs that Reduces Blood Volume Drugs Acts on Adrenergic System Drugs Acts on Renin Angiotensin Aldosterone System (RAAS)b Drugs Acts through Other Mechnismes Diuretics Beta-blockers Alpha-blockers Others ACE inhibitors Angiotensin II Blockers Calcium Channel Blockers Others

  13. Diuretics Thiazides Inhibit active exchange of Cl-Na in the cortical diluting segment of the ascending loop of Henle Cortex K-sparing Inhibit reabsorption of Na in the distal convoluted and collecting tubule Loop diuretics Inhibit exchange of Cl-Na-K in the thick segment of the ascending loop of Henle Medulla Loop of Henle Collecting tubule

  14. Thiazides Adverse Effects • K+, Mg+ (15 - 60%) • Na+ • Stimulation of neurohormonal activity • Hyperuricemia ,hypercalcremia ,hyperglycemia •Gastrointestinal side effects Sharpe N. Heart failure. Martin Dunitz 2000;43 Kubo SH , et al. Am J Cardiol 1987;60:1322 MRFIT, JAMA 1982;248:1465 Pool Wilson. Heart failure. Churchill Livinston 1997;635

  15. ß-Adrenergic Blockers Class I – nonselective:Propranolol Class II - β1 selective:Metoprolol, Atenolol, Bisoprolol Class III with vasodilating properties Nonselective : Carvedilol Selective : Nebivilol

  16. ß-Adrenergic Blockers Contraindications • Asthma (reactive airway disease) • AV block (unless pacemaker) • Symptomatic hypotension / Bradycardia

  17. Other agents that affect adrenergic function • Agents that prevent adrenergic transmission (reserpine, guanethedine, guanadrel) • Selective alpha-1 adrenergic receptor blockers (prazosin, terazosin, doxazosin) • Agents that act on the CNS (methyldopa, clonidine, guanabenz, guanfacine)

  18. Vasodilator Drugs • Calcium entry blockers (nifedipine ,amlodipine ,felodopine and others) • Potassium channel openers (minoxidil, diazoxide i.v., pinacidil) • Direct acting vasodilators (hydralazine, Na-nitroprusside i.v.) Common adverse effects: fall in BP  reflex tachycardia, fall Na/H2O retention

  19. ACE-i. Mechanism of Action VASOCONSTRICTION VASODILATATION ALDOSTERONE PROSTAGLANDINS VASOPRESSIN tPA Kininogen SYMPATHETIC Kallikrein Angiotensinogen RENIN BRADYKININ Angiotensin I A.C.E. Kininase II Inhibitor ANGIOTENSIN II Inactive Fragments

  20. Angiotensin II Receptor Blockers (ARB) RENIN Angiotensin IANGIOTENSIN II Angiotensinogen ACE Other pathways AT1 Receptor Blockers RECEPTORS AT1 AT2 Vasoconstriction Proliferative Action Vasodilatation Antiproliferative Action

  21. ACE-I. Contraindications • Intolerance (angioedema) • Bilateral renal artery stenosis • Pregnancy • Renal insufficiency (creatinine > 3 mg/dl) • Hyperkalemia (> 5.5 mmol/l) • Severe hypotension

  22. Goals of therapy All hypertensive patients BP < 140/90 mmHg Diabetic patients BP < 130/80 mmHg Patients with Renal Failure and proteinuria > 1g/24h BP < 125/75 mmHg 2007 ESH - ESC guidelines for the management of arterial hypertension. European Heart Journal Advance Access published June 11, 2007 JNC7 Report. JAMA 2003; 289: 2560-2572.

  23. Stratification of CV risk in four categories Blood pressure (mmHg) SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT: hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or non-fatal event. The term “added” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome.

  24. Journal of Hypertension 2007;25:1105-1187 Initiation of antihypertensive treatment

  25. JNC 7 Algorithm for Treatment of Hypertension 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. Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices JNC 7. JAMA. 2003; 289:2560f

  26. Choice of Antihypertensive Drugs The choice of a specific drug or a drug combination and the avoidance of others should take into account the following: • The previous favorable or unfavourable experience of the individual patient with the given class of compounds • The effect of drugs on cardiovascular risk factors in relation to the cardiovascular risk profile of the individual patient • The presence of subclinical organ damage, clinical cardiovascular disease, renal disease or diabetes which may be more favorably treated by some drugs than others • The presence of other coexisting disorders that may limit the use of particular classes of antihypertensive drugs • The possibilities of interactions with drugs used for other conditions • The cost of drugs, either to the individual patient or to the health provider, but cost considerations should never predominate over efficacy, tolerability and protection of the individual patient

  27. Combination therapy • Most patients with hypertension will require 2 or more antihypertensive medications to achieve their BP goals. • When BP is more than 20/10 mm Hg above goal, consideration should be given to initiating therapy with 2 drugs. • 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.

  28. ESH & ESC 2007 GuidelinesPossible combinations between some classes of antihypertensive drugs Thiazide diuretics Angiotensin receptor antagonists β-blockers Calcium antagonists α- blockers ACE inhibitors European Society of Hypertension & European Society of Cardiology2007 Guidelines for the Management of Arterial Hypertension, Journal of Hypertension 2007;25:1105-1187

  29. Inadequate Treatment • Barriers to controlling HTN include patient factors (e.g. non-adherence to medications) and healthcare provider factors ( e.g. inadequate BP measurement ) • Quality improvement measures have focused increasing attention on provider factors, particularly “therapeutic inertia”

  30. Inadequate Treatment .cont • “Clinician Inertia” • Fail to  drug dose when BP is below goal • Causes : • Inadequate knowledge • Competing time demands • “Soft clinical reasoning” “Wait until next visit.”“Let’s have you keep trying to lose wt” It’s probably white coat effect” JGenInternMed 2008; 23:588 AnnInternMed 2006; 144:525 Hypertension 2006;47:319

  31. Inadequate Treatment .cont “The measurement of BP is likely the clinical procedure of greatest importance that is performed in the worst manner.” (Norman Kaplan, M.D.) Lancet 2007; 370:591 “Health care professionals should take particular care to ensure that they are using accurate techniques to measure BP in all their patients.” (International Working Group, 2008)

  32. Medications that Can Interfere with Blood Pressure Control • Non-Narcotic Analgesics • Non-steroidal anti-inflammatory agents including aspirin • Selective COX-2 inhibitors • Sympathomimetic agents (decongestants, diet pills, cocaine) • Stimulants (methylphenidate, dexmethylphenidate, dextroamphetamine, amphetamine, methamphetamine, modafinil) • Alcohol • Oral contraceptives • Cyclosporine • Erythropoietin • Natural licorice • Herbal compounds (ephedra or ma huang)

  33. How to improve compliance to treatment ? • Inform the patient on the risk of hypertension and the benefit of effective treatment • Provide clear written and oral instructions about treatment and its possible side effects. • Tailor the treatment regimen to patient’s lifestyle and needs • Involve patient’s partner or family in information on disease and treatment plans • Dialogue with patient regarding adherence and be informed of his/her problems • Provide reliable support system and affordable prices

  34. Patient’s Follow-Up • Titration to BP control requires frequent visits in order to timely modify the treatment regimen in relation to BP changes and appearance of side effects • Once target BP has been obtained, the frequency of visits can be considerably reduced. However, excessively wide intervals between visits are not advisable • Patients at low risk or with grade 1 hypertension may be seen every months and regular home BP measurements may further extend this interval. Visits should be more frequent in high or very high risk patients

  35. Patient’s Follow-Up .cont • Follow-up visits should aim at maintaining control of all reversible risk factors as well as at checking the status of organ damage. • Treatment of hypertension should be continued for life because in correctly diagnosed patients cessation of treatment is usually followed by return to the hypertensive state. • Cautious downward titration of the existing treatment may be attempted in low risk patients after long-term BP control, particularly if non pharmacological treatment can be successfully implemented

  36. Thank You

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