Individual management of arterial hypertension. Doumas Michael, Internist Lecturer, Aristotle University, Thessaloniki
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1 Individual management of arterial hypertension Doumas Michael, Internist Lecturer, Aristotle University, Thessaloniki
2 From Population to Individual Management of Arterial Hypertension
3 Epidemiologic impact on mortality of blood pressure reduction in the population Prevalence % After Intervention Reduction in BP Before Intervention Reduction in SBP (mmhg) % Reduction in Mortality Stroke CHD Total Adapted from Whelton, P. K. et al. JAMA 2002;288:
4 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 2 mmhg decrease in mean SBP 7% reduction in risk of IHD mortality 10% reduction in risk of stroke mortality Prospective Studies Collaboration. Lancet. 2002;360:
5 52 yr old woman non smoker TC: 202 mg/dl HDLC: 61 mg/dl No diabetes BP: 162/94 mmhg Mrs Ariadni Low-risk 10y CV risk: 0.6% BP: 157/89 mmhg 10y CV risk: 0.5%
6 67 yr old man Diabetes Smoker TC: 268 mg/dl HDLC: 28 mg/dl BP: 160/95 mmhg Mr Thrasivoulos High-risk Smoking cessation BP lipid control 3.7% 10y CV risk: 5.3% BP: 155/90 mmhg 10y CV risk: 5.3%
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8 "Individualized Care" Risk factors considered Non-pharmacological therapy tried Monotherapy or combination therapy is instituted Considerations for choice of initial therapy: Renin status Age Coexisting cardiovascular conditions Other conditions
9 Stratification of CV risk in four categories Blood pressure (mmhg) Other risk factors, OD or disease Normal SBP or DBP High normal SBP or DBP Grade 1 HT SBP or DBP Grade 2 HT SBP or DBP Grade 3 HT SBP 180 or DBP 110 No other risk factors Average risk Average risk Low added risk Moderate added risk High added risk 1 2 risk factors Low added risk Low added risk Moderate added risk Moderate added risk Very high added risk 3 or more risk factors, MS, OD or diabetes Moderate added risk High added risk High added risk High added risk Very high added risk Established CV or renal disease Very high added risk Very high added risk Very high added risk Very high added risk Very high added risk 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.
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11 Einstein Not everything that can be counted counts, and not everything that counts can be counted. Αυτά που είναι μετρήσιμα δεν είναι πάντα χρήσιμα και αυτά που είναι χρήσιμα δεν είναι πάντα μετρήσιμα
12 Addressing the Complexity of Hypertension
13 The Challenge of Personalized Antihypertensive Treatment How to improve prognosis to identify the patients in need of further treatment? Who to treat? How to identify more effective therapeutic opportunities tailored to the individual How patient? to treat?
14 J Hypertension, November 2009
15 Initiation of antihypertensive treatment Other risk factors, OD or disease Normal SBP or DBP High normal SBP or DBP Grade 1 HT SBP or DBP Grade 2 HT SBP or DBP Grade 3 HT SBP 180 or DBP 110 No other risk factors No BP intervention No BP intervention Lifestyle changes for several months then drug treatment if BP uncontrolled Lifestyle changes for several weeks then drug treatment if BP uncontrolled Lifestyle changes + immediate drug treatment 1 2 risk factors Lifestyle changes Lifestyle changes Lifestyle changes for several weeks then drug treatment if BP uncontrolled Lifestyle changes for several weeks then drug treatment if BP uncontrolled Lifestyle changes + immediate drug treatment 3 or more risk factors, MS, OD or diabetes Diabetes Lifestyle changes Lifestyle changes Lifestyle changes and consider drug treatment Lifestyle changes + drug treatment Lifestyle changes + drug treatment Lifestyle changes + drug treatment Lifestyle changes + immediate drug treatment Established CV or renal disease Lifestyle changes + immediate drug treatment Lifestyle changes + immediate drug treatment Lifestyle changes + immediate drug treatment Lifestyle changes + immediate drug treatment Lifestyle changes + immediate drug treatment
16 -30% -21% -23% -39% Beckett NS et al. N Engl J Med 2008;358:
17 60 50 INVEST (CAD pts) 30 ONTARGET (high risk pts, mainly with CAD) 3 CV events (%) CV events (%) Adjusted HR >110 to 120 to > to > to > to > >160 On-treatment SBP (mmhg) On-treatment SBP (mmhg) 0 30 VALUE (High risk pts) 35 TNT (CAD pts) 5 Cardiac events (%) CV events (%) Adjusted HR 0 < 120 >120 to 130 to > to > >150 >160 to 160 to 170 to > On-treatment SBP (mmhg) > 100 On-treatment DBP (mmhg) 0 J hypertension 2009;27:
18 Should low-risk hypertensive patients be treated? Young patients? Mild hypertension?
19 One point of view individual treatment can only be justified if there is individual benefit
20 Stroke and blood pressure lowering: subgroup analysis from 17 RCTs Trial % Events Odds ratio (Relative risk red.) group control treatment Younger 43 % patients Older 34 % patients 1º prev. 38 % 2º prev. 38 % MacMahon & Rogers J Vasc Med Biol 1993;4:265-71
21 Stroke and blood pressure lowering: subgroup analysis from 17 RCTs Trial % Events Odds ratio (Relative risk red.) group control treatment Younger 2.3 % 1.3 % 43 % patients 1% Older 7.0 % 4.6 % 34 % patients 2.4% 1º prev. 3.2 % 2.0 % 38 % 1.2% 2º prev % 18.8 % 38 % 8.5% MacMahon & Rogers J Vasc Med Biol 1993;4:265-71
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23 Drug Costs in the US Drug name Cost for 30 day supply Enalapril 5 mg -20 mg $4 HCTZ mg $4 Atenolol 25 mg- 100 mg $4 Amlodipine (Norvasc) 5 mg $75 Amlodipine (generic) 5 mg $21
24 To treat or not to treat mild hypertension treat risk not blood pressure only absolute risks and benefits are relevant to patients the payer should choose the threshold
25 High-risk patients The earlier The better Attention to all CV risks
26 To treat or not to treat mild hypertension the payer should not choose the threshold
27 The Challenge of Personalized Antihypertensive Treatment How to improve prognosis to identify the patients in need of further treatment? How to identify more effective therapeutic opportunities tailored to the individual How patient? to treat?
28 The Many Faces of HT Therapy Today CCBs CCBs Centrally acting agents Centrally acting agents ARBs Diuretics Diuretics ACE inhibitors Beta Beta blockers blockers Hypertension
29 Reductions in Systolic Blood Pressure Among All Patients VA Cooperative Study of Responses to Single-Drug Therapy Hydrochlorothiazide Prazosin Captopril Clonidine Diltiazem Atenolol Placebo n = Change in SBP (mm Hg) from Baseline * *P 0.05 vs. captopril Materson BJ, et al. N Engl J Med. 1993;328: * SBP = systolic blood pressure *
30 Rates of Successful Treatment Were Similar for Most Single Drugs in White Men VA Cooperative Study of Responses to Single-Drug Therapy Successful Treatment (%) White Men <60 yr Clonidine Atenolol Captopril * * Diltiazem Prazosin HCTZ Placebo Successful Treatment (%) Clonidine Atenolol White Men 60 yr Diltiazem * Prazosin HCTZ Captopril Placebo *There were no clinically important differences (<15%) between the treatment groups spanned by the arrows. Treatment was considered to be successful if the diastolic blood pressure measured <95 mm Hg after 1 year.
31 ALLHAT Medication Use and BP Control * 1 Drug 2 Drugs 3 Drugs 4 Drugs Average # of Drugs Patients (%) 100% 80% 60% 40% 20% # of Drugs/Patient 0% 0 6 mon 1 yr 3 yr 5 yr Cushman WC, et al. J Clin Hypertens. 2002;4:
32 One tool fits all One drug for everybody
33 2007 ESH/ESC Guidelines Antihypertensive Treatment: Preferred Drugs Subclinical organ damage LVH Microalbuminuria Atherosclerosis (asympt) Renal dysfunction Clinical event Previous stroke Previous MI Angina pectoris Heart failure Atrial fibrillation Recurrent Permanent ESRD/Proteinuria Peripheral Artery Disease ACEI, CA, ARB ACEI, ARB CA, ACEI ACEI, ARB Any BP lowering agent BB, ACEI, ARB BB, CA Diu, BB, ACEI, ARB, Antialdo ARB, ACEI BB, non-dihydropiridine CA ACEI, ARB, Loop DIU CA 2007 ESH/ESC Guidelines. J Hypertens 2007; 25:
34 Benjamin Franklin Keep your eyes wide open before marriage, half shut afterwards. Keep your eyes wide open before treatment, and keep doing this afterwards.
35 M.T., woman, 54y BP: 156/88 mmhg No comorbidities LVMI: 152 g/m2 Lisinopril 20mg BP: 138/84 mmhg 9mon - Cough Manidipine 20mg BP: 140/85 mmhg LVMI: 123 g/m2 Valsartan 160mg-6mo BP: 141/83 mmhg LVMI: 149 g/m2
36 K.E., man, 62y BP: 155/95 mmhg No comorbidities LVMI: 163 g/m2 Irbesartan 150 to mon BP: 154/92 mmhg Indapamide 2.5 mg BP: 143/88 mmhg LVMI: 131 g/m2 Amlo 5 to 10mg- 9mon BP: 138/86 mmhg LVMI: 165 g/m2 Edema
37 Peeking at the Future
38 Beyond the HGP: What s Next? HapMap Chart genetic variation within the human genome Prote- Metabol-omics Exploring Microbial Genomes for Energy and the Environment
39 The Future Diuretics B-blockers Ca-antag ARBs ACE-inhibit Renin-inh Other Edema Cough Hypokalemia Sexual Dysf
40 Pharmacogenomics The right drug to the right patient Increased efficacy Decreased toxicity
41 Mission not accomplished (yet)
42 Hypertension poorly controlled worldwide Percentage of patients with controlled BP (<140/90 mm Hg) Belgium 25% Canada 16% China 3% England 6% France 33% Italy 9% Poland 4% Russia 6% Spain 16% USA 24% Erdine. European Society of Hypertension Scientific Newsletter 2000
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44 DH Lawrence's The Third Thing (Pansies 1929) Water is H20 Hydrogen two parts Oxygen one But there is a third thing That makes it water. And nobody knows what that is.
45 NPHS ( ): More Lifestyle Changes After Hypertension Diagnosis Are Needed Age Standardized Rates of Lifestyle Change After a Hypertension Diagnosis % -2.4% Percent % -0.1% 0 Smoking BMI 25+ Inactive Alcohol 9+ A B Can J Cardiol, ; 3:
46 Let s just go in and see what happens.
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49 υστυχώς είναι πραγματικότητα
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