Εχει θέση το πολυφάρμακο στον υπερτασικό ασθενή? Ανδρέας Πιτταράς MD.

Παρουσίαση με θέμα: "Εχει θέση το πολυφάρμακο στον υπερτασικό ασθενή? Ανδρέας Πιτταράς MD."— Μεταγράφημα παρουσίασης:

1 Εχει θέση το πολυφάρμακο στον υπερτασικό ασθενή? Ανδρέας Πιτταράς MD

2 Επιδημιολογία Επιδημιολογία  Η καρδιαγγειακή νόσος (ΚΑΝ) είναι η κύρια αιτία θνητότητας παγκοσμίως σε αναπτυγμένες και αναπτυσσόμενες χώρες 1  Η επιβάρυνση της ΚΑΝ προκαλείται από την υπέρταση,την υπερλιπιδαιμία και τους λοιπούς παράγοντες κινδύνου 2  Η υπέρταση συχνά συνυπάρχει με υπερλιπιδαιμία και λοιπούς παράγοντες κινδύνου 3,4  CVR ενισχύεται όταν η υπέρταση συνυπάρχει ακόμα και με ήπιες ή μέτριες αυξήσεις στους άλλους παράγοντες κινδύνου 4 1. World Health Organization. The World Health Report 2003: Shaping the Future. 2003; 2. Yusuf et al. Circulation. 2001;104:2746-2753; 3. NHANES III Phase 2 Morning Fasting Subset. 2000 Census Data; 4. De Backer et al. Eur J Cardiovasc Prev Rehabil. 2003;10(suppl):S1-S78.

3 Παγκόσμια θνητότητα 2002 Mortality (millions) World Health Organization. The World Health Report 2003: Shaping the Future. 2003. CVD Malignant neoplasms Injuries Respiratory infections COPD and asthma HIV/AIDS Perinatal conditions Digestive diseases Diarrhoeal diseases Tuberculosis Childhood diseases Malaria Diabetes

4 ΥΠΕΡΤΑΣΗ παράγοντας κινδύνου για καρδιαγγειακή θνητότητα Στεφανιαία νόσοςΑΕΕ Περιφερική αρτηριοπάθεια Καρδιακή Ανεπάρκεια Biennial age-adjusted rate per 1000 MenWomen Men Risk of CV events by hypertensive status in subjects aged 35 to 64 years, Framingham study, 36-year follow-up.

5 Παράγοντες κινδύνου και θνητότητα* Percentage of Mortality Attributable to Risk Factors *Based on The World Health Report 2003. Yach et al. JAMA. 2004;291:2616-2622. Developing countries Developed countries Blood pressure Tobacco Underweight Alcohol Cholesterol Unsafe sex Overweight Unsafe water, sanitation, hygiene Low fruit and vegetable intake Indoor smoke from solid fuels Physical inactivity

6 Επίπτωση Υπέρτασης* *Defined as systolic/diastolic blood pressure  140/90, (  160/95 for Taiwan)or receiving treatment. *Defined as systolic/diastolic blood pressure  140/90, (  160/95 for Taiwan) or receiving treatment. † South Korea is defined as men, aged 30-59. 1. Wolf-Maier et al. JAMA. 2003;289:2363-2369; 2. Data on file. Pfizer Inc, New York, NY; 3. WHO Collaborating Centre on Surveillance of Cardiovascular Disease Web site. Available at: www.cvdinfobase.ca. Accessed February 22, 2005. Prevalence (%) United States 1 Egypt 3 Japan 2 Italy 1 Sweden 1 England 1 Spain 1 Finland 1 Germany 1 010203040506070 Taiwan 3 Canada 1 South Korea 3 †

7 Worldwide Age-Adjusted Prevalence of Hypercholesterolaemia Tolonen et al. Int J Epidemiol. 2005;34:181-192. MenWomen  6.5 mmol/L  6.5 mmol/L or treatment  6.2 mmol/L  5.0 mmol/L SWI-TIC SWI-VAF GER-BRE SWE-NSW YUG-NOS CZE-CZE FRA-STR ICE-ICE UNK-GLA DEN-GLO BEL-GHE BEL-CHA UNK-BEL FRA-LIL FRA-TOU ITA-BRI LTU-KAU GER-EGE ITA-FRI AUS-NAW CAN-HAL POL-WAR SWE-GOT SPA-CAT AUS-PER POL-TAR CHN-BEI RUS-NOI RUS-NOC RUS-MOI USA-STA RUS-MOC 020406080100 Prevalence (%) Hypercholesterolaemia GER-BRE SWI-TIC SWI-VAF BEL-CHA CZE-CZE YUG-NOS SWE-NSW UNK-GLA LTU-KAU ICE-ICE BEL-GHE FRA-STR ITA-BRI FRA-LIL CAN-HAL DEN-GLO UNK-BEL FRA-TOU GER-EGE POL-WAR AUS-NEW ITA-FRI POL-TAR SPA-CAT SWE-GOT AUS-PER CHN-BEI RUS-MOC USA-STA RUS-MOI RUS-NOI RUS-NOC 020406080 100

8 MONICA: Συχνότητα αυξημένης ΑΠ & TChol σε 38 πληθυσμούς Tunstall-Pedoe et al. ESC. 2004 Average Prevalence (%) BP ≥130/80 mm Hg TC ≥5 mmol/L BP ≥140/90 mm Hg TC ≥5 mmol/L BP ≥140/90 mm Hg TC ≥5.5 mmol/L BP ≥160/95 mm Hg TC ≥6.5 mmol/L Men Women

9 Συνύπαρξη νόσων σε Υπερτασικούς Ασθενείς  Ισχαιμική καρδιοπάθεια (IHD) 20-30%  Συμφορητική καρδ. ανεπάρκεια (CHF) 10-20%  Δυσλιπιδαιμία 25-35%  Σ. Διαβήτης 10-15%  Αρρυθμίες 10-15%  Υπερτροφία της Αρ. Κοιλίας 10-40%  Νεφρική βλάβη 3 - 5%  Άσθμα 5 -10%  Περιφερική αρτηριοπάθεια 10-15%  Χωρίς άλλη νόσο (ανεπίπλεκτη) ~ 20%  Ισχαιμική καρδιοπάθεια (IHD) 20-30%  Συμφορητική καρδ. ανεπάρκεια (CHF) 10-20%  Δυσλιπιδαιμία 25-35%  Σ. Διαβήτης 10-15%  Αρρυθμίες 10-15%  Υπερτροφία της Αρ. Κοιλίας 10-40%  Νεφρική βλάβη 3 - 5%  Άσθμα 5 -10%  Περιφερική αρτηριοπάθεια 10-15%  Χωρίς άλλη νόσο (ανεπίπλεκτη) ~ 20% Am J Med 1996; 101 (Suppl 4A) : 50S - 55S

10 Trends in Awareness, Treatment, and Control of Hypertension in the US* 10% 31% 51% 29% 55% 73% 27% 54% 68% 0 10 20 30 40 50 60 70 80 90 100 Ενήμεροι Θεραπευμένοι Ρυθμισμένοι Ρυθμισμένοι † Percentage of Population 1976-1980 1988-1991 1991-1994 *Data represent percentage of adults 18 to 74 years of age who have systolic blood pressure  140 mm Hg, diastolic blood pressure  90 mm Hg, or are taking antihypertensive medication. † Systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg. Adapted from JNC VI. Arch Intern Med. 1997;157:2413-2446.

11 *BP <140/90 mm Hg. † Weighted average of total population. EUROASPIRE II Study Group. Eur Heart J. 2001;22:554-572. EUROASPIRE II: Μόνο οι μισοί στο στόχο θεραπείας ΑΠ Percentage of Patients Who Reached Goal* at Interview Among Those Using BP-Lowering Medication France United Kingdom Ireland Poland Greece Spain Belgium Hungary 0204060 80 Czech Republic Finland Germany Italy The Netherlands Slovenia Sweden Total † Total † % At Goal

12 HPS. Lancet. 2002;360:7. Downs. JAMA. 1998;279:1615. LIPID. N Engl J Med. 1998;339:1349. Sacks. N Engl J Med. 1996;335:1001. 4S. Lancet. 1995;345:1274. Shepherd. N Engl J Med. 1995;333:1301. % with CHD event Mean LDL-C level at follow-up (mg/dL) 0 5 10 15 20 25 30 90110130150170190210 CARE-Rx LIPID-Rx 4S-Rx CARE-PI LIPID-PI 4S-PI 2° Prevention 1° Prevention WOSCOPS-PI WOSCOPS-Rx AFCAPS-Rx AFCAPS-PI HPS-Pl HPS-Rx HPS-Pl w/revasc+ stroke CHD only PI=placebo Rx=treatment 70 HPS enrolled high-risk primary- and secondary-prevention patients. Relation Between CHD Events and LDL-C Outcomes in Statin Trials

13 Πολλοί ασθενείς δεν επιτυγχάνουν τον στόχο της LDL-C Pearson TA, et al. Arch Intern Med. 2000;160:459-467. 0 10 20 30 40 50 60 70 80 90 100 Low RiskHigh RiskCHD Diet/exercise (%) Drug therapy * (%) Percent of Patients Achieving Goal * Included statins (fluvastatin, lovastatin, pravastatin, simvastatin), gemfibrozil, bile acid sequestrants, niacin, psyllium fiber, or combination drug therapy 28286136119241081352n = 59 70 21 40 8 18

14 68 72.8 37 30.2 18 16.6 80 70 60 50 40 30 20 10 0 Low Risk High Risk CHD L-TAP (1996-1997) NHANES III (1988-1994) Patients (%) at Goal Jacobson TA et al. Arch Intern Med. 2000;160:1361-1369. Pearson TA et al. Arch Intern Med. 2000;160:459-467. Επίτευξη στόχων σε ασθενείς υπό θεραπεία

15 Percentage of Patients Who Reached Goal* at Interview Among Those Using Lipid-Lowering Medication EUROASPIRE II: Only Half of Patients With CHD Achieved Total Cholesterol Goals *TC <190 mg/dL (<5 mmol/L). † Weighted average of total population. EUROASPIRE II Study Group. Eur Heart J. 2001;22:554-572. Slovenia Greece Italy Spain United Kingdom Ireland Sweden Finland 0204060 80 The Netherlands Poland Czech Republic Hungary France Germany Belgium Total † % At Goal

16 <100 mg/dL) 100 – <130 mg/dL) 130 – <160 mg/dL) 160 – <190 mg/dL)  190 mg/dL) 14.3% 26.8% 33.7% 17.4% 7.7% Patients (%) Frequency of Hypertensive Patients by LDL-C Levels Η πλειονότητα των υπερτασικών έχει LDL-C ≥100mg/dl Adapted by Pfizer Inc, New York, NY, from the NHANES III Phase 2 Morning Fasting Subset. 2000 Census Data. (Unweighted N=7697; weighted sample=200,948,641).

17 Συνύπαρξη υπέρτασης και υπερλιπιδαιμίας αυξάνει τον κίνδυνο ανάπτυξης θανατηφόρας CVD Adapted from De Backer et al. Eur J Cardiovasc Prev Rehabil. 2003;10(suppl 1):S1-S78. Δυσλιπιδαιμία Υπέρταση TC 271 mg/dL) SBP 180 mm Hg TC 271 mg/dL) SBP 180 mm Hg Δυσλιπιδαιμία / Υπέρταση

18 Συνδυασμός ΣΑΠ & Λιπιδίων στην καρδιαγγειακή θνητότητα: MRFIT Neaton et al, for the Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992;152:56-64. 142+ 125-131 <182 182-202 203-220 221-244 Cholesterol quintile mg/dL SBP quintile (mm Hg) <118 118-124 132-141 21 13 6 23 8 10 6 18 11 6 4 17 8 8 Deaths/10,000 Patient-Years >245 14 5 6 3 12 17 n=316,099 12 9 6 3 34

19 Number of People With Diabetes in the Adult Population Worldwide for 2000 and 2010 Amos et al. Diabet Med. 1997;14:S1-S85; Zimmet et al. Nature. 2001;414:782-787. 14.2 m 17.5 m ↑23% World 2000: 151 million 2010: 221 million Increase: 46% 15.6 m 22.5 m ↑44% 26.5 m 32.9 m ↑24% 9.4 m 14.1 m ↑50% 1.0 m 1.3 m ↑33% 84.5 m 132.3 m ↑57%

20 Impact of Diabetes and Increasing Risk Factors on CV Death Rate: MRFIT *Increased systolic BP, elevated TC, smoking. Jamerson. Am J Hypertens. 2000;13:68S-73S. 140 120 100 80 60 40 20 0 0123 Age-Adjusted Cardiovascular Death Rate per 10,000 Person-Years No diabetes Diabetes Number of Risk Factors*

21 Νέα στρατηγική  Οι τρέχουσες ευρωπαικές και παγκόσμιες οδηγίες αναγνωρίζουν την εκτίμηση του συνολικού καρδιακού κινδύνου 1-3  Διαθέσιμα κλινικά εργαλεία πρόβλεψης συνολικού κινδύνου 2,4,5  Μεγαλύτερη μείωση κινδύνου μπορεί να επιτευχθεί στοχεύοντας στο συνολικό κίνδυνο και στους ξεχωριστούς καρδιαγγειακούς παράγοντες κινδύνου 6 1. World Health Organization, International Society of Hypertension Writing Group. J Hypertens. 2003;21:1983-1992; 2. De Backer et al. Eur Heart J. 2003;24:1601-1610; 3. European Society of Hypertension Guidelines Committee. J Hypertens. 2003;21:1011-1053; 4. Volpe et al. Am J Hypertens. 2004;17:1068-1074; 5. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497; 6. 1. World Health Organization, International Society of Hypertension Writing Group. J Hypertens. 2003;21:1983-1992; 2. De Backer et al. Eur Heart J. 2003;24:1601-1610; 3. European Society of Hypertension Guidelines Committee. J Hypertens. 2003;21:1011-1053; 4. Volpe et al. Am J Hypertens. 2004;17:1068-1074; 5. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497; 6. Emberson et al. Eur Heart J. 2004;25:484-491.

22 Current Guidelines Recognize the Relationship Among Risk Factors  The European Joint Task Force guidelines 1 : lower BP and lipid goals for patients at high total CV risk or with diabetes, CVD  The ESH/ESC 2 guidelines: SBP/DBP and other risk factors, such as diabetes, contributors to a patient’s risk stratification and subsequent prognosis  The WHO/ISH guidelines 3 : comprehensive risk-factor assessment for patients 1. De Backer et al. Eur Heart J. 2003;24:1601-1610; 2. European Society of Hypertension Guidelines Committee. J Hypertens. 2003;21:1011-1053; 3. World Health Organization, International Society of Hypertension Writing Group. J Hypertens. 2003;21:1983-1992.

23 Κλινικά εργαλεία εκτίμησης κινδύνου  European SCORE Project  Framingham Risk Score  PROCAM Score Volpe et al. Am J Hypertens. 2004;17:1068-1074.

24 SCORE: 10-Year Risk of Fatal CVD in High-Risk Regions De Backer et al. Eur Heart J. 2003;24:1601-1610. Chart should be used in all European countries excluding those considered low- risk (Belgium, France, Greece, Italy, Luxembourg, Spain, Switzerland, Portugal) 43322 65433 87655 1210987 76554 119876 161312109 2219171513 97654 1311986 161513119 2622191614 171412109 2420171513 3429252118 4741353026 22211 33222 54333 76544 44332 65543 98765 13111098 65433 97654 1210976 181513119 1210876 171412108 2420171412 3328242118 11111 21111 32221 43322 22211 33222 54433 76564 43322 65433 87654 1210876 86544 119865 16131198 2219151312 11100 11110 11111 22111 00000 00000 00000 00000 00000 00000 00000 11000 11111 21111 32221 43322 22211 33222 54332 765 1 4 54332 76543 108765 14121087 11100 11110 11111 22111 221 321 42 4567845678456784567845678456784567845678 180 160 140 120 180 160 140 120 180 160 140 120 180 160 140 120 180 160 140 120 SC  RE Systolic blood pressure © 2003 ESC Cholesterol mmol 40 50 55 60 65 Age 10-year risk of fatal CVD in populations at high CVD risk 150200250300 mg/dL WomenMen NonsmokerSmokerNonsmokerSmoker 15% and over 10%–14% 5%–9% 3%–4% 2% 1% <1% 4 11111 11 22 233

25 SCORE: 10-Year Risk of Fatal CVD in Low-Risk Regions DeBacker et al. Eur Heart J. 2003;24:1601-1610. 22211 33222 54433 76664 44333 76544 108766 14121199 54332 76544 108765 14121098 98655 1311987 1916141210 2623201715 11111 22111 32222 44333 32221 43322 55443 87655 33222 44332 65543 98765 65443 97655 1311987 1815131110 11110 11111 11111 22211 11111 22111 33222 44333 22111 32221 43322 65443 43322 65433 87654 1210876 00000 00000 11100 11111 00000 00000 00000 00000 00000 00000 00000 00000 11000 11111 11111 22211 11111 21111 22211 433 0 2 22211 33222 54332 76544 00000 00000 11000 11110 4567845678456784567845678456784567845678 180 160 140 120 180 160 140 120 180 160 140 120 180 160 140 120 180 160 140 120 SC  RE 15% and over 10%–14% 5%–9% 3%–4% 2% 1% <1% Systolic blood pressure © 2003 ESC Cholesterol mmol 40 50 55 60 65 Age 10-year risk of fatal CVD in populations at low CVD risk 150200250300 mg/dL WomenMen NonsmokerSmokerNonsmokerSmoker 2 11000 11110 11111 22111

26 ATP III: Framingham Point Scores Estimate of 10-Year Risk for Women Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. SBP mm Hg If Untreated <120 120-129 130-139 140-159  160 0123401234 HDL-C mg/dL Points  60 50-59 40-49 <40 0 1 2 Total Cholesterol <160 160-199 200-239 240-279  280 0 4 8 11 13 0 3 6 8 10 0245702457 0123401234 0112201122 Age 20-39 Nonsmoker Smoker 0909 Age 40-49 0707 Age 50-59 0404 Age 60-69 0202 Age 70-79 0101 AgePoints 20-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 -7 -3 0 3 6 8 10 12 14 16 If Treated 0345603456 Point Total 10-Year Risk, % <9 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24  25 <1 1 2 3 4 5 6 8 11 14 17 22 27  30 Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Age Total C HDL-C Systolic BP Smoking status Point total

27 ATP III: Framingham Point Scores Estimate of 10-Year Risk for Men Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. SBP mm Hg If Untreated <120 120-129 130-139 140-159  160 0011200112 HDL mg/dL Points  60 50-59 40-49 <40 0 1 2 Total Cholesterol <160 160-199 200-239 240-279  280 0 4 7 9 11 0356803568 0234502345 0112301123 0001100011 Age 20-39 Nonsmoker Smoker 0808 Age 50-59 0303 Age 60-69 0101 Age 70-79 0101 AgePoints 20-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 -9 -4 0 3 6 8 10 11 12 13 If Treated 0122301223 Point Total 10-Year Risk, % <0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16  17 <1 1 2 3 4 5 6 8 10 12 16 20 25  30 Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Age 40-49 0505 5 Age Total C HDL-C Systolic BP Smoking status Point total

28 Μακροχρόνια επίδραση μέτριων μειώσεων παραγόντων κινδύνου Emberson et al. Eur Heart J. 2004;25:484-491. 10% Reduction in BP 10% Reduction in Total-C + 45% Reduction in CVD =

29 Αξιολόγηση διαφορετικών στρατηγικών για καρδιαγγειακή πρόληψη στη μείωση του καρδιαγγειακού κινδύνου Adapted from Emberson et al. Eur Heart J. 2004;25:484-491. Predicted Reduction in Major CVD (%) Treatment Based on TC (statin) Treatment Based on BP (β-blocker, diuretic) Treatment Based on Overall Absolute Risk (ASA, statin, ACEI, β-blocker, diuretic) Treatment thresholds

30 “Overall risk reduction is the goal …(it) is best achieved by establishing global risk status, identifying modifiable components of that risk and then, in league with the patient, initiating the most efficient and least intrusive therapeutic strategy.” Volpe et al. Am J Hypertens. 2004;17:1068-1074.

31 Βιολογική βάση για συνολική αντιμετώπιση του καρδιαγγειακού Βιολογική βάση για συνολική αντιμετώπιση του καρδιαγγειακού  Atherosclerosis is a progressive disease 1  Risk factors in concert contribute to the development of atherosclerosis by causing endothelial dysfunction 2-4  Hyperlipidaemia causes endothelial dysfunction 5  Hypertension may affect vessel wall lipid uptake and metabolism, potentially contributing to atherosclerosis 5-8 1. Libby. In: Braunwald, Zipes, Libby, eds. Heart Disease. 2001:995-1006; 2. Ross. N Engl J Med. 1999;340:115-126; 3. Adapted from Mason. Cerebrovasc Dis. 2003;16(suppl 3):11-17; 4. Liao. Clin Chem. 1998;44:1799-1808; 5. Sposito et al. Eur Heart J Suppl. 2004;6(suppl G):G8- G12; 6. Taylor. Curr Hypertens Rep. 1999;1:96-101; 7. Gimbrone Jr et al. Ann NY Acad Sci. 2000;902:230-240; 8. Lee et al. J Biol Chem. 2001;276:13847-13851.

32 Intrinsic susceptibility—Genetic and environmental factors Widlansky ME et al. J Am Coll Cardiol. 2003;42:1149-1160. Κλασικοί Παράγοντες Κινδύνου Διαβήτης Τύπου ΙΙ Δυσλειτουργία Ενδοθηλίου Κάπνισμα Υπέρταση Ηλικία Υπερλιπιδαιμία Novel/Emerging Risk Factors Infection/Inflammation Physical inactivity Postprandial state Homocysteine Obesity Ενδοθηλιακή Δυσλειτουργία Impaired vasomotion/tone Prothrombotic state Proinflammatory state Proliferation in arterial wall Καρδιαγγειακά συμβάντα Δημιουργία & εξέλιξη αθηρωματικής βλάβης Ενεργοποίηση πλάκας / ρήξη Μείωση ροής αίματος λόγω θρόμβωσης & αγγειόσπασμου Ενδοθηλιακή δυσλειτουργία : Βαρόμετρο καρδιαγγειακού κινδύνου?

33 Libby P. In: Braunwald, Zipes, Libby, eds. Heart Disease. 2001:995-1006. Progression of Atherosclerosis LDL Monocytes Foam Cell Scavenger Receptor Macrophage Vascular Endothelium Cell Adhesion Molecule Oxidized LDL Internal Elastic Lamina MCP-1 Smooth Muscle Mitogens Smooth Muscle Proliferation Cell Apoptosis Smooth Muscle Migration IL-1

34 Integrated Perspective on CV Risk Factors and Vascular Disease CV Disease Endothelial Dysfunction Ross R. N Engl J Med. 1999;340:115-126 Oxidative Stress & Inflammation Courtesy of Preston Mason, PhD, and Robert Jacob, PhD. Modified from Ross. N Engl J Med. 1999;340:115-126.

35 1. Liao. Clin Chem. 1998;44:1799-1808; 2. Adapted from Mason. Cerebrovasc Dis. 2003;16(suppl 3):11-17. It has been hypothesized that, at the cellular level, risk factors lead to the development of vascular disease through the common pathway of endothelial dysfunction 1,2 Integrated Cellular Mechanisms of Cardiovascular Disease  NO Synthesis VasoconstrictionThrombosisSuperoxide  COX Activity Thromboxane A 2 Prostaglandin H 2 ProstacyclinInflammation Leukocyte adhesion Endothelial permeability Angiotensin II T-cell activation  Endothelin Vasoconstriction Calcium mobilization Endothelial Dysfunction DyslipidaemiaHypertensionDiabetesSmoking

36 Mechanism by Which Hypercholesterolaemia Interacts With and Disrupts NO Availability in the Endothelium Sposito et al. Eur Heart J Suppl. 2004;6(suppl G):G8-G12. Oxidized LDL LDL O2–O2–O2–O2– O2–O2–O2–O2– Inactivation + L-citrulline L-arginine 1 Reduced eNOS transcription Reduced mRNA stability  Production  ADMA Endothelial cell eNOS NADPH oxidase 2 3 – ↓NO

37 1. Taylor. Curr Hypertens Rep. 1999;1:96-101; 2. Gimbrone Jr et al. Ann NY Acad Sci. 2000;902:230-240; 3. Lee et al. J Biol Chem. 2001;276:13847-13851. In Patients With Hypertension, LDL-C Deposition Is Greatest in Areas of Disturbed Blood Flow  It has been hypothesized that hypertension causes disturbed flow, altering shear stress and biomechanical strain in the arterial wall 1,2  These altered biomechanical forces may lead to LDL-C accumulation in the arterial wall and promote LDL-C oxidation 3 Disturbed flow and altered shear stress

38 ↑ Atherogenic VLDL, VLDL-R IDL, LDL Hypertension can (a) increase the pressure-driven convection of atherogenic lipoproteins into the intima-media and (b) induce a pressure-related distension of the artery wall, facilitating the penetration and potential retention of atherogenic lipoproteins. Sposito et al. Eur Heart J Suppl. 2004;6(suppl G):G8-G12. Hypothesized Effects of Hypertension on Hypercholesterolaemia Pressure-driven convection Intima- media - Enhanced LP penetration LP retention Media - Pressure-induced distension - Stretching ↑ BP ↑ BP

39 Κλινικές πρακτικές για την αντιμετώπιση του καρδ/κού κινδύνου Κλινικές πρακτικές για την αντιμετώπιση του καρδ/κού κινδύνου  Ασθενείς με πολλαπλούς παράγοντες κινδύνου που πρέπει να παίρνουν αρκετά χάπια έχουν χαμηλή πιθανότητα παραμονής και συμμόρφωσης στη θεραπεία 1  Μειώνοντας τον αριθμό των χαπιών αυξάνουμε την συμμόρφωση 1,2 1. Chapman et al. AHA Scientific Sessions 2003; 2. Dezii. Manag Care. 2000;9(suppl):S2-S6.

40 Adherence in Patients Taking Both Antihypertensive and Lipid-Lowering Therapy Months Since Index Date* Nonadherent273536353634343439393636 Adherent LL/nonad AH 876666666565 Adherent AH/nonad LL 192221222323232421232320 Adherent AH and LL 4536373636373736343335380 10 20 30 40 50 60 70 80 90 100 Patients (%) 369121518212427303336 AH=antihypertensive; LL=lipid lowering. *Index date defined as date concomitant therapy (ie, second drug) was initiated. Chapman et al. AHA Scientific Sessions 2003.

41 Nonadherence and Patient Outcomes 1. Lipid Study Group. N Engl J Med. 1998;339:1349-1357; 2. Sacks et al. N Engl J Med. 1996; 335:1001-1009; 3. Lancet. 1994;344:1383-1389; 4. Shepherd et al. N Engl J Med. 1995;333: 1301-1307; 5. Downs et al. JAMA. 1998;279:1615-1622; 6. Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22; 7. West of Scotland Coronary Prevention Study Group. Eur Heart J. 1997;18:1718-1724; 8. Heeschen et al. Circulation. 2002;105:1446-1452; 9. Wei et al. Heart. 2002;88:229-233.  Studies have demonstrated that prolonged treatment with statins significantly reduces CV morbidity and mortality 1-9  Nonadherence to lipid-lowering therapy is linked to elevated cardiac morbidity and mortality 8,9

42 Pill Burden Predicts Nonadherence in Patients Taking Both Antihypertensive and Lipid-Lowering Therapy Chapman et al. AHA Scientific Sessions. 2003. Abstract. Αριθμός φαρμάκων Adjusted Odds Ratio for Adherence 0 1 2 3-5 6+ 0.51.01.52.02.5

43 Απλοποιώντας το σχήμα βελτιώνουμε τη συμμόρφωση Retrospective, database-based study of members of a national commercial pharmacy benefit manager (N=3942). Dezii. Manag Care. 2000;9(suppl):S2-S6. 100 Patients Adherent (%) 90 80 70 60 50 0123456789101112 Months Since Initiation of Therapy ~20% 1-pill combination therapy 2-pill therapy

44 Ταυτόχρονο ξεκίνημα 2 φαρμάκων βελτιώνει τη συμμόρφωση 1-30 days31-60 days61-90 days OR for Adherence* Time Between Start of Antihypertensive and Lipid-Lowering Therapies Retrospective cohort study in a large managed-care population (N=8406). *Relative odds of being adherent with both antihypertensive and lipid-lowering therapy at any point in time. Chapman et al. Poster presented at: AHA Scientific Sessions 2003.

45 Common Aspects of Successful Interventions  More instruction for patients –Written, verbal, programmed learning  Improve the convenience of care –Dose frequency, cost, work-site education  Involve patients in their care –Self-monitoring, tailoring doses  Reminders –Refills (phone, mail), doses (pill dispensers)  Reinforcement or rewards –Reduced visit frequency, payment for BP monitoring device Haynes et al. Lancet. 1996;348:383-386.

46 Φλέρτ με «Πολυχάπι»

47 «Polypill»: a strategy to reduce CVD by more than 80%  Αρτηριακή πίεση  LDL-C  Ομοκυστείνη  Αιμοπεταλιακή λειτουργία Wald et al BMJ Iune 2003 Προσπάθεια καθορισμού του συνδυασμού φαρμάκων και βιταμινών, καθώς και των δόσεων, για χρήση σε ένα δισκίο ημερησίως για επίτευξη μεγάλης μείωσης CVD, με ελάχιστες παρενέργειες

48 Πολυχάπι: Μείωση κινδύνου ισχαιμικής καρδιοπάθειας και ΑΕΕ σε 2 χρόνια σε ηλικία 55-64 Wald et al BMJ Iune 2003 % risk reduction (CI) Risk Factor Agent  RF IHD event STROKE LDL-CStatin  70mg/dl 61 (51-71) 17(9-25) BP 3 drugs ½ dose 11mmHg 46 (39-53) 63(55-70) Homocysteine Folic acid (0.8mg)  3μmol/l 16 (11-20) 24(15-33) Platelet Function Aspirin (75mg) 32 (23-40) 16(7-25) Combined effect ALL 88 (84-91) 80(71-87) Παρενέργειες: 8-15% (Διακ:1-2%, Θανατηφόρα συμβάντα:1/10000)

49 Ασπιρίνη Χαμηλής Δόση: 15 Μελέτες

50 Το 1/3 των ατόμων θα έχουν άμεσο όφελος, κερδίζοντας κατά μέσο όρο 11-12 χρόνια ζωής χωρίς καρδιακά επεισόδια ή ΑΕΕ (20 χρόνια για ηλικία 55-64) Wald et al BMJ Iune 2003

51 A “Poly-Portfolio” for Prevention: A Strategy to reduce subsequent events by up to 97% over 5 years Low to standard doses of antihypertensive therapy High-dose statin Aspirin Omega-3 Fish oil Cardiac Rehabilitation Diet Robinson J et al Am J Cardiol 2005;95:373-378

52 «Polymeal»: more natural, safer, probably tastier strategy to reduce CVD by more than 75% Franco O.et al BMJ Dec 2004 Συστατικά  Κινδύνου CVD (%) βιβλιογραφία Κρασί (150ml/day) 32 (23-41) Di Castelnuovo Ψάρι (114grX4/week) 14 (8-19) Whelton Μ. Σοκολάτα (100gr) 21 (14-27) Taubert Φρούτα-Λαχανικά (400gr) 21 (14-27) John Σκόρδο (2.7gr) 25 (21-27) Ackerman Αμύγδαλα (68gr) 12.5 (10.5-13.5) Jenkins, Sabate Συνδυασμός 76 (63-84)

53 Section 4: Lipid-Lowering Trials  Recent lipid trials have shown that statin treatment in addition to antihypertensive therapy led to further benefits in hypertensive patients with other risk factors 1,2  In the ASCOT-LLA study, 10 mg of atorvastatin given to controlled hypertensives who were slightly or nondyslipidaemic, led to significant reductions in CHD early in the study, and to early termination of the trial 1  In the CARDS study in patients with diabetes, many also having hypertension, 10 mg atorvastatin produced significant reductions in the primary end point that occurred early, and led to early termination of the trial 3 1. Sever et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158; 2. ALLHAT Officers and Coordinators. JAMA. 2002;288:2998-3007; 3. Colhoun et al. Lancet. 2004;364:685-696.

54 ASCOT Study Design n=5168 Atorvastatin 10 mg n=5137 Placebo RandomisedN=19,342 Amlodipine  Perindopril  Doxazosin GITs Moderate-Risk Hypertensive Patients Not Eligible for Lipid Lowering Eligible for Lipid Lowering Atenolol  Bendroflumethiazide  Doxazosin GITs 1. Study design adapted from Sever et al, for the ASCOT Investigators. J Hypertens. 2001;19:1139-1147; 2. Data from Sever et al. Lancet. 2003;361:1149-1158 Double-Blind Randomisation n=10,305

55 ASCOT-LLA: Patient Population Risk Factor Profile All patients in ASCOT-LLA had hypertension plus  3 risk factors for CHD Microalbuminuria/proteinuria Peripheral vascular disease Hypertension Age  55 years Male Smoker Family history of early coronary disease Type 2 diabetes Plasma TC:HDL-C  200 mg/dL Certain ECG abnormalities LVH Previous cerebrovascular events Patients With Risk Factor (%) Adapted from Sever et al, for the ASCOT Investigators. J Hypertens. 2001;19:1139-1147.

56 SBP (mm Hg) DBP (mm Hg) Baseline: 164/95 mm Hg Treated: 138/80 mm Hg ASCOT-LLA: Blood Pressure Changes Sever et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158. Years

57 ASCOT-LLA: Reductions in Total and LDL Cholesterol 200 150 100 (mg/dL) 15075 125 100 (mg/dL) Total Cholesterol (mmol/L) LDL Cholesterol (mmol/L) Years 1.3 mmol/L 1.0 mmol/L 1.2 mmol/L 1.0 mmol/L Sever et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158. Sever et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158.

58 HR = 0.64 (0.50-0.83) 0 1 2 3 4 0.00.51.01.52.02.53.03.5 Cumulative Incidence (%) Atorvastatin (10 mg) Placebo Trial was stopped early because of 36% reduction in events P=.0005 Years ASCOT-LLA: Primary End Point of Nonfatal MI and Fatal CHD Sever et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158. Final LDL-C  = −29%

59 Years 0 1 2 3 0.00.51.01.52.02.53.03.5 27% Reduction Cumulative Incidence (%) HR = 0.73 (0.56-0.96) P=.0236 ASCOT-LLA: Secondary End Point of Fatal and Nonfatal Stroke Sever et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158. Atorvastatin (10 mg) Placebo

60 Multiple risk intervention with a single pill combination (amlodipine/atorvastatin) helps patients to attain recommended target levels for blood pressure and lipids (The JEWEL Programme) JEWEL I UK and Canada JEWEL II 11 European countries 2245 patients achieved both country-specific BP and LDL-C goals JEWEL I (62.9%) JEWEL II(50.6%) Conclusion : Single-pill (amlodipine/atorvastatin) therapy is an effective and well-tolerated treatment, which helps physicians treat their patients to achieve both BP and LDL-C targets recommended by their local guidelines. Amlodipine/atorvastatin single-pill therapy should therefore improve management of total CV risk in patients requiring BP- and lipid-lowering therapy. FDR Hobbs, G Gensini, GBJ Mancini, AJ Manolis, oν behalf of the JEWEL Study Group FDR Hobbs, G Gensini, GBJ Mancini, AJ Manolis, oν behalf of the JEWEL Study Group

61 VALUE: Κύριο Τελικό Σημείο και διαφορές στη ΣΑΠ σε διάφορες χρονικές περιόδους Μήνες Συνολικά στη μελέτη 36–48 24–36 12–24 6–12 0–3 Τέλος μελέτης Favours amlodipine 1.02.00.5 ΚΥΡΙΟ ΤΕΛΙΚΟ ΣΗΜΕΙΟ  ΣΑΠ mmHg 1.4 1.6 1.8 2.0 3.8 1.7 2.2 3–62.3 Favours valsartan 4.0 Julius S et al. Lancet. June 2004;363.

62 Σε ασθενείς υψηλού κινδύνου εγκαιρη και γρήγορη αντιμετώπιση της υπερτασης

63 Common Aspects of Successful Interventions  More instruction for patients –Written, verbal, programmed learning  Improve the convenience of care –Dose frequency, cost, work-site education  Involve patients in their care –Self-monitoring, tailoring doses  Reminders –Refills (phone, mail), doses (pill dispensers)  Reinforcement or rewards –Reduced visit frequency, payment for BP monitoring device Haynes et al. Lancet. 1996;348:383-386.

64 Conclusions  There is a worldwide epidemic of CVD related to the high and growing prevalence of hypertension, dyslipidaemia, and other CV risk factors in developed and developing regions 1  Prompt, aggressive BP reduction improves CV outcomes in hypertensive patients 2,3  Lipid lowering leads to additional improvements in CV outcomes in treated hypertensive patients 4,5  Antihypertensive agents have reduced CV end points in large outcome trials 2,6,7  Statins have reduced CV end points in large clinical trials 4,8-10  Patients treated for multiple conditions can be helped to improve their medication adherence by using combination medications that reduce the pill burden 11,12 1. World Health Organization. The World Health Report 2003: Shaping the Future. 2003; 2. Julius et al. Lancet. 2004;363:2022-2031; 3. Williams. J Am Coll Cardiol. 2005;45: 813-827; 4. Sever et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158; 5. ALLHAT Officers and Coordinators. JAMA. 2002;288:2998- 3007; 6. ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997; 7. Nissen et al, for the CAMELOT investigators. JAMA. 2004;292:2217-2226; 8. Colhoun et al. Lancet. 2004;364:685-696; 9. Cannon et al. N Engl J Med. 2004;350:1495-1504; 10. LaRosa et al. N Engl J Med. 2005;352; 11. Chapman et al. AHA Scientific Sessions. 2003. Poster; 12. Dezii. Manag Care. 2000;9(suppl):S2-S6.