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ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ

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Presentation on theme: "ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ"— Presentation transcript:

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2 ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
ΑΡΤΗΡΙΑΚΗ ΥΠΕΡΤΑΣΗ & ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ Κωνσταντίνος Π. Μακαρίτσης Παθολογική Κλινική Πανεπιστημίου Θεσσαλίας

3 Prevalence of hypertension is high
Prevalence of hypertension in people aged 20 years and older 2000 Prevalence of hypertension (%) 2025 GLB.IRB 071022b-Irbe Reference : Kearney PM et al.,Lancet. 2005;365: Kearney PM et al.,Lancet. 2005;365:

4 Curvilinear relation of blood pressure (BP) and cardiovascular risk.
A meta-analysis of individual data for 1,000,000 adults in 61 prospective studies. Lancet 360:1903, 2002.

5 Absolute risks of CAD (left) and stroke mortality (right) for each decade of life by usual systolic blood pressure (BP) level A meta-analysis of individual data for 1,000,000 adults in 61 prospective studies. Lancet 360:1903, 2002.

6 Hypertension is a leading cause for cardiovascular morbidity
36-Year Follow-up in Patients Aged Years1,2 Coronary Disease Stroke Peripheral Arterial Disease Heart Failure 50 45.4 40 Normotensive Biennial Age-Adjusted Rate per 1,000 Hypertensive 30 22.7 21.3 20 13.9 12.4 GLB.IRB 071022b-Irbe Reference : 1. Kannel W.B. et al., JAMA 1996; 275: 2. Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-90 9.5 9.9 10 7.3 6.2 6.3 5.0 3.3 3.5 2.4 2.0 2.1 Men Women 1. Kannel W.B. et al., JAMA 1996; 275: 2. Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-90

7 Global estimates suggest that less than 40% of hypertensives have both systolic and diastolic BP control, with similar estimates from the USA and other countries. Chobanian AV et al. The JNC 7 Report. JAMA 289, 2560–2571 (2003). Kearney P.M. et al. J Hypertens 22, 11–19 (2004). Mori H et al. Hypertens. Res. 29, 143–151 (2006). Rodriguez-Roca GC et al. Hypertens. Res. 32, 753–758 (2009).

8 Worldwide blood pressure control rates in treated hypertensive patients are low
Germany 33.6 Canada 41.0 Japan* 55.7 England 29.2 Greece 49.5 USA 53.1 China 28.8 Taiwan 18.0 GLB.IRB 071022b-Irbe Mexico 21.8 Turkey 19.8 Egypt 33.5 South Africa* 47.6 Kearney P.M. et al., J Hypertens 2004; 22: 11–19; * Data for men only

9 Prevalence of stroke Prevalence of stroke by age and sex (NHANES: ). Source: NCHS and NHLBI.

10 ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
Approximately 795,000 people in the United States have a stroke each year, of which about 610,000 are a first attack; and 6.4 million Americans are stroke survivors. Stroke is also estimated to result in 134, 000 deaths annually and is the third leading cause of death in the USA behind heart disease and cancer. Stroke. 2011;42:

11 Stroke is the third leading cause of death worldwide
14 13 12 12 10 10 9 8 7 All deaths (%) 6 5 4 Reference Group 8 – Keep slide 2 Coronary Cancer Stroke Injury Respiratory HIV/AIDS heart disease tract infection HIV/AIDS = human immunodeficiency virus/acquired immune deficiency syndrome Reference: 1. World Health Organization. Global burden of stroke Available at:

12 Κύρια αίτια θανάτου στην Ελλάδα-2005
(ανά πληθυσμού) ΣΝ Ca ΑΕΕ

13 Projections of stroke events in men and women in EU and EFTA countries, 2000 to 2025 (solely due to the demographic changes) European Fair Trade Association Iceland, Norway, and Switzerland, Truelsen T, et al, WHO, 2004

14 Impact of cardiovascular disease on life expectancy
Atherothrombosis reduces life expectancy by approximately 8–12 years in patients aged over 60 years* 25 -7.4 years -9.2 years -12 years 20 Average remaining life expectancy at age 60, years (men) 15 10 5 Reference: Peeters A et al. Eur Heart J Mar;23(6): Group 6,7,8 – Keep Slide Group 5 – Keep Slide but add other comparators and data about quality of life/dependency Healthy History of cardiovascular disease History of AMI History of stroke AMI, acute myocardial infarction Peeters A et al. Eur Heart J 2002;23:458–466.

15 ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
ΑΡΤΗΡΙΑΚΗ ΥΠΕΡΤΑΣΗ & ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ PRIMARY PREVENTION SECONDARY PREVENTION ACUTE CARE

16 ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
ΑΡΤΗΡΙΑΚΗ ΥΠΕΡΤΑΣΗ & ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ PRIMARY PREVENTION SECONDARY PREVENTION ACUTE CARE

17 Antihypertensive drug therapy is effective at reducing risk of CV events
Heart failure1 Fatal/Nonfatal stroke1 Fatal/Nonfatal CHD1 Vascular deaths -10 -16% -21% -20 Risk reduction (%) -30 071016a_Irbe GLB.IRB A meta-analysis of 17 hypertension trials that included the development of heart failure demonstrated significant treatment benefits.1 The incidence of heart failure was reduced by 52% (CI 41-62%) compared to the control or placebo subjects. It is clear that the benefits in reducing heart failure in placebo-controlled trials are comparable, if not superior, to the reductions in stroke and coronary heart disease quantified in meta-analysis of all trials.2 References: 1. Moser M, Herbert PR. Prevention of Disease Progression, Left Ventricular Hypertrophy and Congestive Heart Failure in Hypertension Treatment Trials. J Am Coll Cardiol 1996; 27: 2. Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA et al. Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: -38% -40 -52% -50 1. Moser and Herbert. J Am Coll Cardiol. 1996; 2. Collins R et al. Lancet 1990.

18 Effective blood pressure control reduces cardiovascular morbidity and mortality
Systolic–diastolic hypertension Isolated systolic hypertension Fatal and non- fatal events Fatal and non- fatal events Mortality Mortality 10 All Causes All Causes CV Non CV CV Non CV Stroke CHD Stroke CHD NS NS -10 Relative Risk Reduction (%) -20 <0.01 <0.01 0.02 GLB.IRB 071022b-Irbe Methods Meta-analysis of data from trials of active antihypertensive treatment compared with placebo have shown that blood pressure lowering reduces:1 Cardiovascular and total mortality Stroke Coronary events. Benefits have been shown in placebo-controlled trials that have used all major antihypertensive drug classes, including: Diuretics Beta blockers Calcium antagonists Angiotensin-converting enzyme (ACE)-inhibitors Angiotensin receptor antagonists. Benefits have been proven: In patients with systolic-diastolic hypertension In elderly patients with isolated-systolic hypertension. Reference : Cifkova R, et al. for the ESH/ESC Hypertension Guidelines Committee. Practice guidelines for primary care physicians: 2003 ESH/ESC hypertension guidelines. J Hypertens. 2003;21:1011–1053 <0.001 0.01 <0.001 -30 <0.001 -40 ESH/ESC guidelines consider systolic values of <139 mmHg and diastolic values of <89 mmHg to be normal <0.001 Event reduction in patients on active antihypertensive treatment vs placebo or no treatment CHD: coronary heart disease; CV: cardiovascular -50 Cifkova R, et al. J Hypertens. 2003;21:1011–1053.

19 2 mmHg decrease in mean systolic blood pressure
Blood pressure reductions of as little as 2 mmHg reduce the risk of cardiovascular events by up to 10% Meta-analysis of 61 prospective, observational studies One million adults 12.7 million person-years 7% reduction in risk of ischemic heart disease mortality GLB.IRB 071022b-Irbe Methods Data from a meta-analysis of 61 prospective, observational studies has provided powerful evidence that throughout middle and old age, blood pressure (BP) is strongly and directly related to vascular mortality.1 These findings show, for example, that a 10 mmHg lower systolic BP is associated over the long-term with a 40% lower risk of stroke death and a 30% lower risk of death from ischemic heart disease (IHD) or other vascular causes. Importantly, within each decade of life between 40 and 89 years the proportional difference in the risk of vascular death associated with a given absolute difference in mean BP is roughly equivalent down to at least 115 mmHg for systolic BP and 75 mmHg for diastolic BP (below which there is little evidence). Thus, there was no evidence of a J curve across all middle and older age groups. Perhaps most striking is the practical implications of these data: even a small, 2 mmHg fall in mean systolic BP would be associated with large absolute reductions in premature deaths and disabling strokes.1 As shown here, a 2 mmHg lower mean systolic BP could lead to a 7% lower risk of IHD death and a 10% lower risk of stroke death.1 Reference : Lewington S, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903–1913. 2 mmHg decrease in mean systolic blood pressure 10% reduction in risk of stroke mortality Lewington S et al. Lancet. 2002;360:1903–1913.

20 ΑΕΕ & Υπερήλικες (INDANA Study) Είναι ωφέλιμη η αντιυπερτασική αγωγή
Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials Lancet 1999:353: 7 κλινικές μελέτες vs. placebo ή χωρίς αγωγή υπερτασικοί >80 ετών The Gueyffier meta-analysis examined data from 7 morbidity and mortality studies that included patients over 80. Together these studies included only 1670 patients Είναι ωφέλιμη η αντιυπερτασική αγωγή στους άνω των 80 ετών?

21 Η αγωγή μειώνει τα ΚΑ συμβάματα αλλά όχι την ολική θνητότητα
Μετα-ανάλυση INDANA Treatment better Control better 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 ΑΕΕ (-34%) Η αγωγή μειώνει τα ΚΑ συμβάματα αλλά όχι την ολική θνητότητα Ολική Θνητότητα (+6%- NS) Μείζονα ΚΑ συμβάματα (-22%) The benefits of antihypertensive treatment are clear and significant in terms of reduction in stroke, CV events and heart failure. BUT, a slight increase in total mortality is observed and this result is at odds with what is observed in younger patients Double-blind All trials Καρδιακή Ανεπάρκεια (-39%) Gueyffier F et al. Lancet 1999:353:

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23 HYVET STUDY INDAPAMIDE  PERINDOPRIL N Engl J Med 2008;358:

24 HYVET STUDY INDAPAMIDE  PERINDOPRIL N Engl J Med 2008;358:

25 BP & PRIMARY STROKE PREVENTION
There is no definitive evidence that that any class of antihypertensive agents offers special protection against stroke. There is a greater reduction in stroke risk with greater BP reduction. In most trials, however, the less-intensive therapy did not test a goal <140/90 mm Hg. Stroke (Feb);42:517–584. Lancet. 2003;362:1527–1535.

26 Τhe JNC 7 report. JAMA. 2003;289:2560 –2572.

27 Recommendations In agreement with the JNC 7 report, regular BP screening and appropriate treatment, including both lifestyle modification and pharmacological therapy, are recommended (Class I; Level of Evidence A) 2. Systolic BP should be treated to a goal of <140 mm Hg and diastolic BP to <90 mm Hg because these levels are associated with a lower risk of stroke and cardiovascular events (Class I; Level of Evidence A). 3. In patients with hypertension with diabetes or renal disease, the BP goal is <130/80 mm Hg (Class I; Level of Evidence A). Stroke (Feb);42:517–584.

28 ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
ΑΡΤΗΡΙΑΚΗ ΥΠΕΡΤΑΣΗ & ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ PRIMARY PREVENTION SECONDARY PREVENTION ACUTE CARE

29 ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
ΑΡΤΗΡΙΑΚΗ ΥΠΕΡΤΑΣΗ & ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ PRIMARY PREVENTION SECONDARY PREVENTION ACUTE CARE

30 BLOOD PRESSURE IN ACUTE STROKE
Elevations in blood pressure > 160 mmHg are detected in >60% of patients with acute stroke. Both elevated and low blood pressures are associated with poor outcome after stroke. For every 10-mm Hg increase > 180 mm Hg, the risk of neurological deterioration increased by 40% and the risk of poor outcome increased by 23%. There are several questions about the management of arterial hypertension in the setting of acute stroke. Unfortunately, definite answers to these questions are not available yet. Stroke. 2007;38:

31 BLOOD PRESSURE IN ACUTE STROKE
Theoretical reasons for lowering blood pressure include > reducing the formation of brain edema > lessening the risk of hemorrhagic transformation > preventing further vascular damage > forestalling early recurrent stroke Conversely, aggressive treatment of blood pressure may lead to neurological worsening by reducing perfusion pressure to ischemic areas of the brain. Excessively high blood pressure is associated with an increased risk of symptomatic hemorrhagic transformation. Stroke. 2007;38:

32 BLOOD PRESSURE IN ACUTE STROKE
Guidelines for the Early Management of Adults With Ischemic Stroke. Stroke. 2007;38: Vemmos et al found that among patients with most subtypes of ischemic stroke, elevated blood pressure was correlated with a past history of hypertension or severity of neurological impairments. They also found a U-shaped relationship between death and admission blood pressure. Both elevated and low admission levels were associated with high rates of early and late death. They also correlated death due to brain injury and brain edema with high initial blood pressure levels. Vemmos KN et al. J Hum Hypertens. 2004;18:253–259.

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34 AHA/ASA Recommendations for BP Management in Acute Ischemic Stroke
Patients eligible for treatment with intravenous thrombolytics or other acute reperfusion intervention and SBP >185 mm Hg or DBP >110 mm Hg should have BP lowered before the intervention. A persistent SBP of >185 mm Hg or a DBP >110 mm Hg is a contraindication to intravenous thrombolytic therapy. After reperfusion therapy, keep SBP <180 mm Hg and DBP <105 mm Hg for at least 24 hours. Patients who have other medical indications for aggressive treatment of BP should be treated. Stroke. 2007;38:

35 AHA/ASA Recommendations for BP Management in Acute Ischemic Stroke
For those not receiving thrombolytic therapy, BP may be lowered if it is markedly elevated (SBP >220 mm Hg or DBP >120 mm Hg). A reasonable goal would be to lower BP by approximately 15%-25% during the first 24 hours after onset of stroke. In hypotensive patients, the cause of hypotension should be sought. Hypovolemia and cardiac arrhythmias should be treated and in exceptional circumstances, vasopressors may be prescribed in an attempt to improve cerebral blood flow. Stroke. 2007;38:

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37 AHA/ASA Recommendations for BP Management in Acute Cerebral Hemorrhage
1. If SBP is >200 mm Hg or MAP is >150 mm Hg, consider aggressive reduction of BP. 2. If SBP is >180 mm Hg or MAP is >130 mm Hg and ICP may be elevated, consider monitoring ICP and reducing BP to keep cerebral perfusion pressure between 60 and 80 mm Hg. 3. If SBP is >180 mm Hg or MAP is >130 mm Hg and there is no evidence of or suspicion of elevated ICP, consider modest BP reduction (eg, MAP of 110 mm Hg or target blood pressure of 160/90 mm Hg). Stroke. 2007;38:2001–2023.

38 2029 patients were allocated to treatment groups (1017 candesartan, 1012 placebo).
During 6 months’ follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (adjusted HR:1.09, 95% CI 0.84–1.41; p=0.52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio 1.17, 95% CI 1.00–1.38; p=0.048). Lancet. 2011 Feb 26;377(9767):

39 If anything, the evidence suggested a harmful effect.
The observed effects were similar for all secondary endpoints (including death from any cause, vascular death, ischaemic or haemorrhagic stroke, MI, stroke progression, and renal failure). There was no indication that careful blood-pressure lowering treatment with ARB candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested a harmful effect. Lancet. 2011 Feb 26;377(9767):

40 Lancet. 2011 Feb 26;377(9767):

41 ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
ΑΡΤΗΡΙΑΚΗ ΥΠΕΡΤΑΣΗ & ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ PRIMARY PREVENTION SECONDARY PREVENTION ACUTE CARE 41

42 ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
ΑΡΤΗΡΙΑΚΗ ΥΠΕΡΤΑΣΗ & ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ PRIMARY PREVENTION SECONDARY PREVENTION 42

43 BP & SECONDARY STROKE PREVENTION
Although numerous randomized trials and meta-analyses support the importance of treatment of hypertension for prevention of primary cardiovascular disease in general and stroke in particular, few trials directly address the role of BP treatment in secondary prevention among persons with stroke or TIA. A meta-analysis of randomized trials showed that antihypertensive medications reduced the risk of recurrent stroke after stroke or TIA. Stroke. 2011;42:

44 BP & SECONDARY STROKE PREVENTION
The meta-analysis included 7 randomized trials performed through 2002. Together these trials included 15,527 participants with ischemic stroke, TIA, or intracerebral hemorrhage (ICH) randomized from 3 weeks to 14 months after the stroke event and followed up for 2 to 5 years. Stroke. 2003;34:

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46 Characteristics of Included Trials
Study; Quality Drug (daily dose); Control Other Antihypertensive Therapy, % Stroke Type, % Subjects (Centers) Follow-Up Interval, years Carter 1970; B Thiazide diuretic mg±methyldopa (750 mg); control ? “IS” 100 99 (1) 2–5 HSCSG 1974, A Deserpidine 1 mg and methylclothiazide 10 mg; placebo IS/ICH 96 TIA 4 452 (10) 2.8 Dutch TIA 1993; A Atenolol (50 mg); placebo IS 66 TIA 34 1473 (56) 2.6 PATS 1995; A Indapamide (2.5 mg); placebo IS 71 5665 (44) 2 ICH 14 TIA 12 SAH 2 TEST 1995; A Atenolol ? mg; placebo IS/ICH 67 720 (21) 2.5 TIA 20 HOPE 2000; A Ramipril; placebo 64† “Stroke” & TIA 100 1013 (267†) 5† PROGRESS 2001; A Perindopril 4 mg; placebo 51 IS 70 2561 (172) 4.1 ICH 11 TIA 23 Perindopril 4 mg + indapamide 2.5 mg; double-placebo 50 3544 (172) TIA 22 Stroke. 2003;34:

47 Η ραμιπρίλη μείωσε τον κίνδυνο εμφάνισης πρώτου ΑΕΕ
Η ραμιπρίλη μείωσε τον κίνδυνο εμφάνισης πρώτου ΑΕΕ HOPE STUDY 32% (P = ) Relative risk of stroke = 0.68 (P = ) Bosch et al. BMJ 2002;324:699–702 47

48 HOPE: Major end-points
RRR(%) with RAMIPRIL vs. PLACEBO Ενώ η θεραπεία με βιταμίνη E δεν παρουσίασε καμία επίδραση στις καρδιαγγειακές εκβάσεις, η Ραμιπρίλη μείωσε σημαντικά το κύριο σύνθετο τελικό σημείο του εμφράγματος του μυοκαρδίου, του αγγειακού εγκεφαλικού επεισοδίου και του θανάτου καρδιαγγειακής αιτιολογίας κατά 22%. Η καρδιαγγειακή θνησιμότητα μειώθηκε κατά 26% στην ομάδα της Ραμιπρίλης σε σύγκριση με τους ασθενείς που λάμβαναν εικονικό φάρμακο. Η Ραμιπρίλη μείωσε επίσης την επίπτωση του εμφράγματος του μυοκαρδίου κατά 20%, όπως επίσης και το αγγειακό εγκεφαλικό επεισόδιο κατά 32%. Yusuf S et al. Effects of an angiotensin-converting-enzyme inhibitor, Ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. New England Journal of Medicine 2000; 342:145-53 48

49 PROGRESS Collaborative Group
Randomised trial of a perindopril-based blood- pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack PROGRESS Collaborative Group Active treatment: combination of perindopril 4 mg/day and indapamide 2.0–2.5 mg/day at the physician’s discretion Lancet 2001; 358:

50 Antihypertensive therapy in patients at risk of stroke: PROGRESS
Compared with placebo, systolic/diastolic BP was reduced by an overall average of 9.0/4.0 mmHg (SE 0.3/0.2), with no evidence of attenuation Compared with placebo, combination therapy provided greater BP reductions than monotherapy (12.3/5.0 mmHg vs 4.9/2.8 mmHg) Significant reduction in stroke: 28% RRR (95% CI 17–38; p<0.0001) The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) found that, compared with placebo, combination treatment with the ACE inhibitor perindopril 4 mg/day and the diuretic indapamide reduced the risk of stroke in both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack (TIA) (p<0.01).1 The Heart Outcomes Prevention Evaluation (HOPE) trial found that treatment with the ACE inhibitor ramipril significantly reduced the risk of stroke in patients at risk of such events (risk reduction [RR]=0.68, p<0.001).2 References 1. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001;358: 2. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. N Engl J Med 2000;342: PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.

51 Reductions in systolic and diastolic BP: PROGRESS
Active treatment versus placebo R 6 12 18 24 30 36 42 48 54 Follow-up (months) 60 80 100 120 140 160 BP (mmHg) Systolic Diastolic Placebo Active Active = flexible regimen based on perindopril 4 mg/day with the addition of indapamide 2.0–2.5 mg/day at the physician’s discretion Reference: 1.PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.

52 ΣΥΜΠΕΡΑΣΜΑΤΑ Cumulative incidence of stroke among participants
assigned active treatment and those assigned placebo PROGRESS STUDY Perindopril + Indapamide 28% 28% μείωση του κινδύνου Lancet 2001; 358: PROGRESS STUDY

53 PROGRESS: Secondary prevention in both hypertensive and nonhypertensive subjects
Relative risk reduction (95%CI) Events/patients Activea Placebo Favours active Favours placebo Secondary stroke Hypertensive / /1452 32% (17, 44%) Nonhypertensive 144/ /1602 27% (8, 42%) Total stroke / /3054 28% (17, 38%) Major vascular events Hypertensive 240/ /1452 29% (16, 40%) Nonhypertensive 218/ /1602 24% (9, 37%) Total events 458/ /3054 26% (16, 34%) 2.0 0.5 1.0 aActive = Perindopril ± Indapamide. Total n=6105 Hazard ratio Reference: 1.PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.

54 Effects of study treatment on stroke and major vascular events in subgroups of patients
Lancet 2001; 358: PROGRESS STUDY

55 Η μονοθεραπεία με περινδοπρίλη δεν μείωσε τη συχνότητα υποτροπής ΑΕΕ
Η μονοθεραπεία με περινδοπρίλη δεν μείωσε τη συχνότητα υποτροπής ΑΕΕ PROGRESS P < 0.05 Reduction in relative risk of recurrent stroke (%) P < 0.05 The PROGRESS study enrolled 6,105 patients with a history of stroke within the 5 previous years.1 Around half (2,916) were hypertensive (SBP 160 mmHg or DBP 90 mmHg). Patients received perindopril 4 mg daily or placebo. Patients who had no contraindication for diuretics also received indapamide 2.5 mg daily (2.0 mg daily in Japan). The blood pressure reduction in patients who received combination therapy was around twice that of patients who received monotherapy. Monotherapy did not significantly reduce the risk of stroke compared with placebo, whereas combination therapy did. This pattern was the same in patients with and without hypertension. These results emphasize the importance of blood pressure reduction in reducing the incidence of recurrent stroke, even in patients without high blood pressure. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001;358:1033–1041. P = ns P = ns Perindopril 4 mg alone (n = 1,281) Perindopril 4 mg + Indapamide 2.5 mg (n = 1,770) Blood pressure reduction (SBP/DBP, mmHg) 5/3 12/5 PROGRESS Collaborative Group. Lancet 2001;358:1033–1041

56 Effects of study treatment on stroke subtypes, major vascular events, and deaths
Lancet 2001; 358: PROGRESS STUDY

57 Effect of Lowering Blood Pressure on Stroke, Myocardial Infarction, All Vascular Events, and Death
Outcome Trials Events Subjects Rate in Control Group, % OR 95% CI P HeterogeneityP Odds ratio (OR) and 95% confidence intervals (CI) determined using a random effects model. Stroke, all 7 1577 15 527 11.5 0.76 0.63–0.92 0.005 0.01 Stroke, fatal 329 2.4 0.56–1.03 0.08 0.16 Stroke, nonfatal 1268 9.2 0.79 0.65–0.95 0.042 Myocardial infarction, all 6 555 15 428 4.0 0.63–0.98 0.03 0.19 Vascular events, all 2225 16.0 0.66–0.95 0.002 Death, vascular 852 5.9 0.86 0.70–1.06 0.066 Death, all 1427 9.6 0.91 0.79–1.05 0.18 0.17 Stroke. 2003;34:

58 Effect of Drug Class, Prior Blood Pressure Status and Stroke Type on Stroke, Myocardial Infarction, and All Vascular Events Outcome Stroke, All Trials/Subjects OR (95% CI) MI, All Trials/Subjects Vascular Events, All Trials/Subjects All trials 7/15 527 0.76 (0.63–0.92) 6/15 428 0.79 (0.63–0.98) 0.79 (0.66–0.95) Drug class ACE-I 2/3574 0.93 (0.75–1.14) 0.74 (0.56–0.98) 0.83 (0.61–1.13) β-RA 2/2193 0.93 (0.72–1.20) 0.94 (0.60–1.45) 1.01 (0.81–1.27) Diuretic 3/6216 0.68 (0.50–0.92) 1.06 (0.63–1.78) 2/6117 0.75 (0.63–0.90) Diuretic and ACE-I 1/3544 0.55 (0.44–0.68) 0.55 (0.38–0.79) 0.57 (0.48–0.68) Non β-RA 5/13 334 0.71 (0.57–0.90) 4/13 235 0.72 (0.57–0.92) 0.73 (0.60–0.89) Baseline BP High blood pressure 3/1271 0.74 (0.45–1.22) 2/1172 0.85 (0.60–1.19) Any 4/14 256 0.75 (0.60–0.94) 0.78 (0.63–0.97) Stroke type     Ischemic stroke 2/1572 0.58 (0.24–1.40) 1/1473 1.04 (0.77–1.41) All stroke 5/13 955 0.78 (0.63–0.96) Stroke. 2003;34:

59 ACE-I plus diuretic appears to be the most effective intervention
Heterogeneity between drug classes in reducing recurrent stroke is apparent: β-receptor antagonists do not seem to reduce any vascular events Diuretics alone reduced stroke but not MI ACE-I reduced MI but not stroke ACE-I plus diuretic appears to be the most effective intervention

60 MOSES STUDY 1405 pts / Mean follow-up: 2.5 years Stroke Jun;36(6):

61 Systolic and diastolic blood pressure among patients assigned eprosartan (Epro) or nitrendipine (Nitren). MOSES STUDY Figure 2. Systolic and diastolic blood pressure among patients assigned eprosartan (Epro) or nitrendipine (Nitren). Schrader J et al. Stroke 2005;36:

62 Η ερποσαρτάνη μείωσε τον κίνδυνο υποτροπής ΑΕΕ έναντι της νιτρενδιπίνης
MOSES STUDY * P = 0.014 * P = 0.026 * P = 0.061 The MOrbidity and mortality after Stroke – Eprosartan compared with nitrendipine for Secondary prevention (MOSES) study compared eprosartan 600–800 mg with nitrendipine 10–20 mg over 4 years.1 The study was placebo-controlled, randomized, open-label, blinded endpoint (PROBE). The 1,405 patients had cerebral ischaemia, a transient ischaemic attack, prolonged reversible neurological deficit or intracerebral haemorrhage in the 24 months before enrolment. They also had hypertension requiring treatment (sitting SBP >140 mmHg, DBP >90 mmHg). Blood pressure control in the two studies was similar, with around 70 % of patients in each group reaching the target blood pressure. Compared with nitrendipine, eprosartan significantly reduced the primary endpoint, which was the incidence of cardio- and cerebrovascular events (including recurrent events) and mortality . Eprosartan also significantly reduced the incidence of cerebrovascular events compared with nitrendipine. Schrader J. Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOSES). Stroke 2005;36:1218–1226. * P vs Nitrendipine † Includes recurrent events Schrader J et al. Stroke 2005;36:1218–1226.

63 MOSES STUDY 1405 pts / Mean follow-up: 2.5 years A reduction in TIAs accounted for most of the benefit in cerebrovascular events, with no significant difference in ischemic strokes, and a more traditional analysis of time to first cerebrovascular event did not show a benefit of eprosartan. Stroke Jun;36(6):

64

65 – trial design ® * Initially compared with ASA plus clopidogrel
Mean follow-up: 2.5 years 2x2 factorial design involving 20,333 stroke patients ER-DP + ASA (200 mg/25 mgX2) Clopidogrel* (75 mg) ER-DP + ASA + Telmisartan (5,000 pts) Clopidogrel* + Telmisartan (5,000 pts) Telmisartan (80 mg) ER-DP + ASA + Placebo (5,000 pts) Clopidogrel + Placebo (5,000 pts) Patients participating in the trial were randomised, in double-blind fashion, to one of four treatment groups: ER-DP + ASA (25 mg/200 mg) bid; clopidogrel placebo qd; telmisartan (80 mg) qd Clopidogrel (75 mg) qd; ER-DP + ASA placebo bid; telmisartan (80 mg) qd telmisartan placebo qd Each treatment group will have 5,000 randomised patients assigned to it. Assuming no interaction between any of the combinations of treatments in the factorial design, the study is also capable of detecting a 25% stroke hazard reduction on telmisartan vs. placebo with >99% power at the 5% two-sided significance level. A 25% hazard reduction was observed in the LIFE trial for losartan compared to atenolol in hypertensive patients with LVH. In fact, to detect a 25% stroke hazard reduction on telmisartan vs. placebo with 90% power at the 5% two-sided significance level, only 4,000 patients (and 510 strokes) are required. Placebo * Initially compared with ASA plus clopidogrel Cerebrovasc Dis. 2007; 23: 368–380. 65

66 Kaplan–Meier Curves of the Cumulative Probability of Recurrent Stroke (Primary Outcome).
Figure 1. Kaplan–Meier Curves of the Cumulative Probability of Recurrent Stroke (Primary Outcome). During a mean follow-up of 2.5 years, 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% CI, 0.86 to 1.04; P=0.23). Hazard ratios were calculated with the use of the Cox model, which was adjusted for baseline age, use of angiotensin-converting–enzyme inhibitors, diabetes status, and modified Rankin Scale score. Yusuf S et al. N Engl J Med 2008;359:

67 ® Kaplan–Meier Curves of the Cumulative Probability of a
Major Cardiovascular Event or New-Onset Diabetes (Secondary Outcome). Figure 2. Kaplan–Meier Curves of the Cumulative Probability of a Major Cardiovascular Event or New-Onset Diabetes (Secondary Outcome). A composite of major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11) (Panel A). Hazard ratios were calculated with the use of the Cox model, which was adjusted for baseline age, use of angiotensin-converting–enzyme inhibitors, diabetes status, and modified Rankin Scale score. New-onset diabetes occurred in 125 of 7306 patients patients (1.7%) in the telmisartan group and 151 of 7283 patients (2.1%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10) (Panel B). Yusuf S et al. N Engl J Med 2008;359:

68 N Engl J Med 2008;359: There was no significant difference in primary and secondary endpoints between patients on ASA with ER-DP or patients on clopidogrel and those on telmisartan and placebo. Telmisartan was not associated with a reduction in recurrent stroke (hazard ratio [HR], 0.95; 95% CI, 0.86 to 1.04; P=0.23) or major cardiovascular events (HR, 0.94; 95% CI, 0.87 to 1.01) during mean 2.5-year follow-up. More aggressive treatment with other antihypertensive medications in the placebo group reduced the difference in BP between the treatment groups (systolic BP differed by 5.4 mmHg at 1 month and 4.0 mmHg at 1 year) and may have reduced the impact of telmisartan treatment on stroke recurrence. 68

69 After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.

70 ONTARGET STUDY N Engl J Med 2008;358:

71 ONTARGET STUDY N Engl J Med 2008;358:

72

73 TRANSCEND STUDY Patients intolerant to ACE inhibitors were enrolled if they had established coronary artery, peripheral vascular or cerebrovascular disease, or diabetes with end-organ damage. After a 3-week run-in period, 5926 patients, many of whom were receiving concomitant proven therapies, were randomised to receive telmisartan 80 mg/day (n=2954) or placebo (n=2972). The primary outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure. Lancet 2008; 372: 1174–83

74 TRANSCEND STUDY Lancet 2008; 372: 1174–83

75 TRANSCEND STUDY Lancet 2008; 372: 1174–83

76 TRANSCEND STUDY Lancet 2008; 372: 1174–83.

77

78 Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack
BP reduction is recommended for both prevention of recurrent stroke and prevention of other vascular events in persons who have had an ischemic stroke or TIA and are beyond the first 24 hours (Class I; Level of Evidence A). 2. Because this benefit extends to persons with and without a documented history of hypertension, this recommendation is reasonable for all patients with ischemic stroke or TIA who are considered appropriate for BP reduction (Class IIa; Level of Evidence B). Stroke. 2011;42:

79 Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack
3. An absolute target BP level and reduction are uncertain and should be individualized, but benefit has been associated with an average reduction of approximately 10/5 mm Hg, and normal BP levels have been defined as <120/80 mm Hg by JNC 7 (Class IIa; Level of Evidence B). 4. Several lifestyle modifications have been associated with BP reduction and are a reasonable part of a comprehensive antihypertensive therapy. These modifications include salt restriction; weight loss; consumption of a diet rich in fruits, vegetables, and low-fat dairy products; regular aerobic physical activity; and limited alcohol consumption (Class IIa; Level of Evidence C). Stroke. 2011;42:

80 Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack
5. The optimal drug regimen to achieve the recommended level of reduction is uncertain because direct comparisons between regimens are limited. The available data indicate that diuretics or the combination of diuretics and an ACEI are useful (Class I; Level of Evidence A). 6. The choice of specific drugs and targets should be individualized on the basis of pharmacological properties, mechanism of action, and consideration of specific patient characteristics for which specific agents are probably indicated (eg, extracranial cerebrovascular occlusive disease, renal impairment, cardiac disease, and diabetes) (Class IIa; Level of EvidenceB). (New recommendation). Stroke. 2011;42:

81

82

83 Chocolate consumption and cardiometabolic disorders:
systematic review and meta-analysis Seven (7) studies met the inclusion criteria (including 114,009 participants). None of the studies was a randomised trial, six were cohort studies, and one a cross sectional study. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels. BMJ. 2011;343:d4488

84 NEW Guidelines for the Prevention of Stroke

85 ΣΑΣ ΕΥΧΑΡΙΣΤΩ

86

87

88 5 Corti R, Flammer AJ, Hollenberg NK, Luscher TF
5 Corti R, Flammer AJ, Hollenberg NK, Luscher TF. Cocoa and cardiovascular health. Circulation 2009;119: 6 Balzer J, Heiss C, Schroeter H, Brouzos P, Kleinbongard P, Matern S, et al. Flavanols and cardiovascular health: effects on the circulating NO pool in humans. J Cardiovasc Pharmacol 2006;47(suppl 2):S122-7. 7 Buijsse B, Feskens EJM, Kok FJ, Kromhout D. Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study. Arch Intern Med 2006;166:411-7 8 Buijsse B, Feskens EJ, Kok FJ, Kromhout D. Cocoa intake in relation to blood pressure and cardiovascular mortality in elderly men. Circulation 2006;113:303. 9 Buijsse B, Weikert C, Drogan D, Bergmann M, Boeing H. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur HeartJ 2010;31: 10 Djousse L, Hopkins PN, Arnett DK, Pankow JS, Borecki I, North KE, et al. Chocolate consumption is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study. Clin Nutr 2011;30:182-7. 11 Faridi Z, Njike VY, Dutta S, Ali A, Katz DL. Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. Am J Clin Nutr 2008;88:58-63. 12 Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, et al. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 2008;138: 13 Janszky I, Mukamal KJ, Ljung R, Ahnve S, Ahlbom A, Hallqvist J. Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program. J Intern Med 2009;266: 14 Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 2007;85: 15 Mostofsky E, Levitan EB, Wolk A, Mittleman MA. Chocolate intake and incidence of heart failure: a population-based, prospective study of middle-aged and elderly women. Circ Heart Fail 2010;3:612-6. 16 Oba S, Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, et al. Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women. Br J Nutr 2010;103:453-9. 17 Allen RR, Carson L, Kwik UC, Evans EM, Erdman JW. Daily consumption of a dark chocolate containing flavanols and added sterol esters affects cardiovascular risk factors in a normotensive population with elevated cholesterol. J Nutr 2008;138: 18 Desch S, Schmidt J, Kobler D, Sonnabend M, Eitel I, Sareban M, et al. Effect of cocoa products on blood pressure: systematic review and meta-analysis. Am J Hypertens 2010;23: 19 Ding EL, Hutfless SM, Ding X, Girotra S. Chocolate and prevention of cardiovascular disease: a systematic review. Nutr Metab (Lond) 2006;3:2. 20 Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr 2005;81:611-4. 21 Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, et al. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 2005;46: 22 Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2008;88:38-50. 23 Jia L, Liu X, Bai YY, Li SH, Sun K, He C, et al. Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2010;92: 24 Ried K, Sullivan T, Fakler P, Frank OR, Stocks NP. Does chocolate reduce blood pressure? A meta-analysis. BMC Med 2010;8:39 29 Allen R, Carson LA, Kwik-Uribe C, Evans EM, Erdman JW. Daily consumption of flavanol rich dark chocolate bar with added sterol esters improves cardiovascular markers in a population with elevated cholesterol. FASEB J 2007;21:A338. 30 Balzer J, Rassaf T, Heiss C, Kleinbongard P, Lauer T, Merx M, et al. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. J Am Coll Cardiol 2008;51:

89

90 Lifestyle modifications for hypertension
Recommendation Expected systolic reduction Weight reduction Goal of BMI 18–25 Waist <89cm 5–20 mmHg per 10kg wt loss Diet Fruits, vegetables, low-fat dairy products, less fat 8–14 mmHg Sodium restriction <2.4g every day 2–8 mmHg Physical activity 30 mins of aerobic 4 times a week 4–9 mmHg Reduced Alcohol (1/2 for women) 60–340ml beer, 300ml wine, 90ml 80proof whiskey in men 2–4 mmHg Reference: 1. Sacco RL Stroke 2006;37:577.

91 Το όφελος της λοσαρτάνης προκύπτει κυρίως λόγω της μείωσης των ΑΕΕ
Το όφελος της λοσαρτάνης προκύπτει κυρίως λόγω της μείωσης των ΑΕΕ LIFE STUDY 9,193 pts with hypertension Losartan vs. Atenolol The LIFE study enrolled 9,193 patients with hypertension (SBP 160–200 mmHg, DBP 95–115 mmHg).1 Patients received losartan 50–100 mg or atenolol 50–100 mg for at least 4 years, with hydrochlorothiazide and additional antihypertensive treatment as required to reach target blood pressure. Similar reductions in blood pressure were observed in the two groups. However, losartan provided a significant reduction in the primary endpoint, a composite of cardiovascular mortality, stroke and myocardial infarction. This was primarily due to a reduction in the incidence of stroke. Dahlöf B, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995–1003. Dahlöf et al. Lancet 2002;359:995–1003 91

92 HOT* Trial: BP Control Reduces Cardiovascular Events in Diabetics
51% reduction Diabetes Subgroup Goal DBP (mmHg) Patients’ Number End SBP † (mmHg) End DBP †  90 501 143.7 85.2  85 141.4 83.2  80 499 139.7 81.1 † End BP = Mean BP from the 6th month of follow-up to the end of the study. 30 25 20 15 10 5 P = 0.005 24.4 18.6 11.9 CV events* per 1000 pt years HOT Trial: BP Control Reduces Cardiovascular Events in Diabetics Talking Points: The Hypertension Optimal Treatment (HOT) trial demonstrated fewer cardiovascular events with tighter control of diastolic blood pressure in patients with diabetes. Target goals and achieved levels of diastolic blood pressure are depicted on the right portion of the slide. One objective of the HOT trial was to assess the optimum target diastolic blood pressure in the treatment of hypertension. In the subgroup of patients with diabetes there was a 51% reduction in major cardiovascular events in target group <80 mmHg compared with target group <90 mmHg (P=.005). References: Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351(9118): *ΗΟT: Hypertension Optimal Treatment * Including MI, Stroke and CV deaths. Hansson L, et al. Lancet. 1998;351:1755–1762.

93 – endpoint definition ® Primary endpoint Time to recurrent stroke
Target is 1,715 strokes Secondary endpoints Vascular events (stroke, MI or vascular death) Vascular events or congestive heart failure New onset diabetes The PRoFESS® study will focus primarily on the recurrent stroke rate among patients randomised to ER-DP + ASA or to clopidogrel, and telmisartan or matching placebo. Stroke is defined as a new focal neurological deficit of vascular origin lasting more than 24 h, or evidence of a new brain infarct upon brain imaging. The stroke can be of any type. “Vascular events” is a composite outcome defined as time to the first stroke (non-fatal or fatal), or myocardial infarction (non-fatal or fatal), or vascular death. “Stroke or major haemorrhagic event” is a composite outcome. Major haemorrhagic events include those that result in significant disability based upon the judgment of the investigator, symptomatic intracranial haemorrhage, intraocular bleeding causing loss of vision, the need for a transfusion of 2 units of red blood cells or equivalent whole blood, or hospitalisation. Diagnosis of new diabetes occurring during the study period will be recorded. ARBs have demonstrated efficacy in reducing the onset of new diabetes in other patient groups. Diener HC, Sacco R, Yusuf S. Cerebrovasc Dis. 2007; 23: 368–380. 93

94 N Engl J Med Sep 18;359(12):

95 N Engl J Med Sep 18;359(12):

96 Stroke and cardiovascular events following TIA
1.0 0.9 Survival free of event 0.8 0.7 0.6 7 30 60 90 Days after TIA Stroke 10.5% All events 25.1% (Stroke, recurrent TIA, cardiovascular event, death) Reference: 1. Johnston et al. JAMA 2000;284:2901–2906

97

98 Μετα-ανάλυση INDANA 76% of participants were women
Cardiovascular Study in theElderly (CASTEL) European Working Party on High Blood Pressure in the Elderly (EWPHE) Coope and Warrender trial Systolic Hypertension in the Elderly Program Pilot (SHEP-P) Systolic Hypertension in the Elderly Program (SHEP) Swedish Trial in Old Patients with Hypertension (STOP) Syst-Eur 76% of participants were women The maximum age at baseline was 99 years. Τhe mortality rate was more than 20% Mean follow-up was 3·5 years. Less than 10% of patients were lost to follow-up in all trials The Gueyffier meta-analysis examined data from 7 morbidity and mortality studies that included patients over 80. Together these studies included only 1670 patients Gueyffier F et al. Lancet 1999:353:

99 ADVANCE trial Lancet 2007; 370: 829–40
Perindopril 4 mg Indapamide 1.25 mg 99

100 ADVANCE trial Lancet 2007; 370: 829–40
Perindopril 4 mg Indapamide 1.25 mg ADVANCE trial Lancet 2007; 370: 829–40 100

101 Trial (or group of trials) Predicted reduction in stroke
No. of events Treatment:Control Odds ratio (95% CI) (Treatment:Control) Treatment better Treatement worse (i) Strokes HDFP trial 102:158 MRC trial 222:234 SHEP 105:162 MRC trial 101:134 13 others 157:272 All trials 525:845 (Heterogeneity X2 4 = 4.2, NS) 38% SD 4% reduction achieved 2p< 0.5 1.0 Predicted reduction in stroke 3540% Reference: 1.Collins R, MacMahon S. Brit. Med. Bull. 1994;52:272–290.

102 Proportion with stroke (%)
Antihypertensive treatment in patients with prior stroke/TIA: PROGRESS Cumulative incidence of stroke during 4-year follow-up 4 3 2 1 5 10 15 20 Placebo Active Proportion with stroke (%) Follow-up (years) Number at risk Active Placebo Active = flexible regimen based on perindopril 4 mg/day with the addition of indapamide 2.0–2.5 mg/day at the physician’s discretion Reference: 1.PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.


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