3 Prevalence of hypertension is high Prevalence of hypertension in people aged 20 years and older2000Prevalence of hypertension (%)2025GLB.IRB071022b-IrbeReference :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) levelA 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 Years1,2Coronary DiseaseStrokePeripheral Arterial DiseaseHeart Failure5045.440NormotensiveBiennial Age-Adjusted Rateper 1,000Hypertensive3022.721.32013.912.4GLB.IRB071022b-IrbeReference :1. Kannel W.B. et al., JAMA 1996; 275:2. Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-909.59.9220.127.116.11.03.33.52.42.02.1MenWomen1. 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 Germany33.6Canada41.0Japan*55.7England29.2Greece49.5USA53.1China28.8Taiwan18.0GLB.IRB071022b-IrbeMexico21.8Turkey19.8Egypt33.5South Africa*47.6Kearney P.M. et al., J Hypertens 2004; 22: 11–19; * Data for men only
9 Prevalence of strokePrevalence 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 141312121010987All deaths (%)654ReferenceGroup 8 – Keep slide2CoronaryCancerStrokeInjuryRespiratoryHIV/AIDSheart diseasetract infectionHIV/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)ΣΝCaΑΕΕ
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 AssociationIceland, 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 years20Average remaining life expectancy at age 60, years (men)15105Reference:Peeters A et al. Eur Heart J Mar;23(6):Group 6,7,8 – Keep SlideGroup 5 – Keep Slide but add other comparators and data about quality of life/dependencyHealthyHistory of cardiovascular diseaseHistory of AMIHistory of strokeAMI, acute myocardial infarctionPeeters A et al. Eur Heart J 2002;23:458–466.
17 Antihypertensive drug therapy is effective at reducing risk of CV events Heartfailure1Fatal/Nonfatalstroke1Fatal/NonfatalCHD1Vasculardeaths-10-16%-21%-20Risk reduction (%)-30071016a_IrbeGLB.IRBA 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.2References: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%-501. 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 hypertensionIsolated systolic hypertensionFatal and non- fatal eventsFatal and non- fatal eventsMortalityMortality10All CausesAll CausesCVNon CVCVNon CVStrokeCHDStrokeCHDNSNS-10Relative Risk Reduction (%)-20<0.01<0.010.02GLB.IRB071022b-IrbeMethodsMeta-analysis of data from trials of active antihypertensive treatment compared with placebo have shown that blood pressure lowering reduces:1Cardiovascular and total mortalityStrokeCoronary events.Benefits have been shown in placebo-controlled trials that have used all major antihypertensive drug classes, including:DiureticsBeta blockersCalcium antagonistsAngiotensin-converting enzyme (ACE)-inhibitorsAngiotensin receptor antagonists.Benefits have been proven:In patients with systolic-diastolic hypertensionIn 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<0.0010.01<0.001-30<0.001-40ESH/ESC guidelines consider systolic values of <139 mmHg and diastolic values of <89 mmHg to be normal<0.001Event reduction in patients on active antihypertensive treatment vs placebo or no treatmentCHD: coronary heart disease; CV: cardiovascular-50Cifkova 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 studiesOne million adults12.7 million person-years7% reduction in risk of ischemic heart disease mortalityGLB.IRB071022b-IrbeMethodsData 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.1Reference :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 pressure10% reduction in risk of stroke mortalityLewington 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 ετώνThe Gueyffier meta-analysis examined data from 7 morbidity and mortality studies that included patients over 80. Together these studies included only 1670 patientsΕίναι ωφέλιμη η αντιυπερτασική αγωγήστους άνω των 80 ετών?
21 Η αγωγή μειώνει τα ΚΑ συμβάματα αλλά όχι την ολική θνητότητα Μετα-ανάλυση INDANATreatment betterControl better0.20.40.60.81.01.21.41.61.82.0ΑΕΕ (-34%)Η αγωγή μειώνει τα ΚΑ συμβάματα αλλά όχι την ολική θνητότηταΟλική 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 patientsDouble-blindAll trialsΚαρδιακή Ανεπάρκεια(-39%)Gueyffier F et al. Lancet 1999:353:
23 HYVET STUDYINDAPAMIDE PERINDOPRILN Engl J Med 2008;358:
24 HYVET STUDYINDAPAMIDE PERINDOPRILN 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.
27 RecommendationsIn 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.
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 strokeConversely, 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.
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:
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):
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:
47 Η ραμιπρίλη μείωσε τον κίνδυνο εμφάνισης πρώτου ΑΕΕ Η ραμιπρίλη μείωσε τον κίνδυνο εμφάνισης πρώτου ΑΕΕHOPE STUDY32%(P = )Relative risk of stroke = 0.68 (P = )Bosch et al. BMJ 2002;324:699–70247
48 HOPE: Major end-points RRR(%) with RAMIPRIL vs. PLACEBOΕνώ 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; 342:145-5348
49 PROGRESS Collaborative Group Randomised trial of a perindopril-based blood- pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attackPROGRESS Collaborative GroupActive treatment: combination of perindopril 4 mg/day and indapamide 2.0–2.5 mg/day at the physician’s discretionLancet 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 attenuationCompared 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).1The 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).2References1. 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 placeboR61218243036424854Follow-up (months)6080100120140160BP (mmHg)SystolicDiastolicPlaceboActiveActive = flexible regimen based on perindopril 4 mg/day with the addition of indapamide2.0–2.5 mg/day at the physician’s discretionReference:1.PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.
52 ΣΥΜΠΕΡΑΣΜΑΤΑ Cumulative incidence of stroke among participants assigned active treatment and those assigned placeboPROGRESS STUDYPerindopril + Indapamide28%28% μείωση του κινδύνουLancet 2001; 358: PROGRESS STUDY
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 ΑΕΕPROGRESSP < 0.05Reduction in relative risk of recurrent stroke (%)P < 0.05The PROGRESS study enrolled 6,105 patients with a history of stroke within the 5 previous years.1Around 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 = nsP = nsPerindopril 4 mg alone (n = 1,281)Perindopril 4 mg + Indapamide 2.5 mg (n = 1,770)Blood pressure reduction (SBP/DBP, mmHg)5/312/5PROGRESS 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 OutcomeTrialsEventsSubjectsRate in Control Group, %OR95% CIPHeterogeneityPOdds ratio (OR) and 95% confidence intervals (CI) determined using a random effects model.Stroke, all7157715 52711.50.760.63–0.920.0050.01Stroke, fatal3292.40.56–1.030.080.16Stroke, nonfatal12689.20.790.65–0.950.042Myocardial infarction, all655515 4284.00.63–0.980.030.19Vascular events, all222516.00.66–0.950.002Death, vascular8525.90.860.70–1.060.066Death, all14279.60.910.79–1.050.180.17Stroke. 2003;34:
58 Effect of Drug Class, Prior Blood Pressure Status and Stroke Type on Stroke, Myocardial Infarction, and All Vascular EventsOutcomeStroke, All Trials/SubjectsOR (95% CI)MI, All Trials/SubjectsVascular Events, All Trials/SubjectsAll trials7/15 5270.76 (0.63–0.92)6/15 4280.79 (0.63–0.98)0.79 (0.66–0.95)Drug classACE-I2/35740.93 (0.75–1.14)0.74 (0.56–0.98)0.83 (0.61–1.13)β-RA2/21930.93 (0.72–1.20)0.94 (0.60–1.45)1.01 (0.81–1.27)Diuretic3/62160.68 (0.50–0.92)1.06 (0.63–1.78)2/61170.75 (0.63–0.90)Diuretic and ACE-I1/35440.55 (0.44–0.68)0.55 (0.38–0.79)0.57 (0.48–0.68)Non β-RA5/13 3340.71 (0.57–0.90)4/13 2350.72 (0.57–0.92)0.73 (0.60–0.89)Baseline BPHigh blood pressure3/12710.74 (0.45–1.22)…2/11720.85 (0.60–1.19)Any4/14 2560.75 (0.60–0.94)0.78 (0.63–0.97)Stroke type Ischemic stroke2/15720.58 (0.24–1.40)1/14731.04 (0.77–1.41)All stroke5/13 9550.78 (0.63–0.96)Stroke. 2003;34:
59 ACE-I plus diuretic appears to be the most effective intervention Heterogeneity between drug classes inreducing recurrent stroke is apparent:β-receptor antagonists do not seem toreduce any vascular eventsDiuretics alone reduced stroke but not MIACE-I reduced MI but not strokeACE-I plus diuretic appears to bethe most effective intervention
60 MOSES STUDY1405 pts / Mean follow-up: 2.5 yearsStroke Jun;36(6):
61 Systolic and diastolic blood pressure among patients assigned eprosartan (Epro) or nitrendipine (Nitren).MOSES STUDYFigure 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 = 0.061The 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 eventsSchrader J et al. Stroke 2005;36:1218–1226.
63 MOSES STUDY1405 pts / Mean follow-up: 2.5 yearsA 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):
65 – trial design ® * Initially compared with ASA plus clopidogrel Mean follow-up: 2.5 years2x2 factorial design involving 20,333 stroke patientsER-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) qdClopidogrel (75 mg) qd; ER-DP + ASA placebo bid;telmisartan (80 mg) qdtelmisartan placebo qdEach 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 clopidogrelCerebrovasc 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.
73 TRANSCEND STUDYPatients 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
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:
83 Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysisSeven (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
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;166:411-78 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;8:3929 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:
90 Lifestyle modifications for hypertension RecommendationExpected systolic reductionWeight reductionGoal of BMI 18–25Waist <89cm5–20 mmHgper 10kg wt lossDietFruits, vegetables, low-fat dairy products, less fat8–14 mmHgSodium restriction<2.4g every day2–8 mmHgPhysical activity30 mins of aerobic 4 times a week4–9 mmHgReduced Alcohol(1/2 for women)60–340ml beer, 300ml wine, 90ml 80proof whiskey in men2–4 mmHgReference: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 ΑΕΕLIFE STUDY9,193 pts with hypertensionLosartan vs. AtenololThe LIFE study enrolled 9,193 patients with hypertension (SBP 160–200 mmHg, DBP 95–115 mmHg).1Patients 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;359:995–100391
92 HOT* Trial: BP Control Reduces Cardiovascular Events in Diabetics 51% reductionDiabetes SubgroupGoal DBP (mmHg)Patients’ NumberEnd SBP †(mmHg)End DBP † 90501143.785.2 85141.483.2 80499139.781.1† End BP = Mean BP from the 6th month of follow-up to the end of the study.30252015105P = 0.00524.418.611.9CV events* per 1000 pt yearsHOT Trial: BP Control Reduces Cardiovascular Events in DiabeticsTalking 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 strokesSecondary endpointsVascular events (stroke, MI or vascular death)Vascular events or congestive heart failureNew onset diabetesThe 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
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-Eur76% of participants were womenThe 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 trialsThe Gueyffier meta-analysis examined data from 7 morbidity and mortality studies that included patients over 80. Together these studies included only 1670 patientsGueyffier F et al. Lancet 1999:353:
101 Trial (or group of trials) Predicted reduction in stroke No. of eventsTreatment:ControlOdds ratio (95% CI)(Treatment:Control)TreatmentbetterTreatementworse(i) StrokesHDFP trial 102:158MRC trial 222:234SHEP 105:162MRC trial 101:13413 others 157:272All trials 525:845(Heterogeneity X2 4 = 4.2, NS)38% SD 4%reduction achieved2p<0.51.0Predicted reduction in stroke3540%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: PROGRESSCumulative incidence of stroke during 4-year follow-up43215101520PlaceboActiveProportion with stroke (%)Follow-up (years)Number at riskActivePlaceboActive = flexible regimen based on perindopril 4 mg/day with the addition of indapamide2.0–2.5 mg/day at the physician’s discretionReference:1.PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.