Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study Relationship of Blood Pressure, Antihypertensive Therapy, and Outcome in Ischemic Stroke Treated With Intravenous Thrombolysis: Retrospective Analysis From Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. Blood pressure 1 year after stroke: the need to optimize secondary prevention. The Australian Therapeutic Trial in Mild Hypertension. Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands) Blood Pressure Variability on Antihypertensive Therapy in Acute Intracerebral Hemorrhage: The Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study Ten-year legacy effects of baseline blood pressure ‘treatment naivety’ in the Second Australian National Blood Pressure study Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Blood pressure response under chronic antihypertensive drug therapy: the role of aortic stiffness in the REASON (Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind) study. On-treatment diastolic blood pressure and prognosis in systolic hypertension. Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial Controlling hypertension and hypotension immediately post stroke (CHHIPS)--a randomised controlled trial. Response to Antihypertensive Therapy in Older Patients With Sustained and Nonsustained Systolic Hypertension A Simplified Approach to the Treatment of Uncomplicated Hypertension: A Cluster Randomized, Controlled Trial Rationale, Design, and Progress of the ENhanced Control of Hypertension ANd Thrombolysis Stroke Study (ENCHANTED) Trial: An International Multicenter 2 × 2 Quasi-Factorial Randomized Controlled Trial of Low- vs. Standard-Dose rt-PA and Early Intensive vs. Guideline-Recommended Blood Pressure Lowerin
Objectives In many current guidelines , blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease ( CVD ) is based on absolute risk . However , in clinical practice , therapeutic decisions are often based on BP levels alone . We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure ( ANBP ) cohort , a seminal study establishing the efficacy of BP lowering in ‘ mild hypertensive ’ persons . Design A post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile . Setting and participants 3244 participants aged 35–69 years in a community-based r and omised placebo controlled trial of blood pressure-lowering medication . Interventions Chlorothiazide500 mg versus placebo . Primary outcome measures All-cause mortality and non-fatal events ( non-fatal CVD , congestive cardiac failure , renal failure , hypertensive retinopathy or encephalopathy ) . Results Treatment effects were assessed by HR , absolute risk reduction and number needed to treat . Participants had an average 5-year CVD risk in the intermediate range ( 10.5±6.5 ) with moderately elevated BP ( mean 159/103 mmHg ) and were middle aged ( 52±8 years ) . In a subgroup analysis , the relative effects ( HR ) and absolute effects ( absolute risk reduction and number needed to treat ) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality ( p for heterogeneity=0.04 ) . With respect to absolute benefit , drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 ( 10 to 64 ) , death from any cause with 45 ( 25 to 196 ) and major CVD events with 23 ( 12 to 193 ) . Conclusion Our analysis confirms that the benefit of treatment was substantial only in the high-risk tertile , reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation Background and Purpose — The optimal management of blood pressure ( BP ) in acute stroke remains unclear . For ischemic stroke treated with intravenous thrombolysis , current guidelines suggest pharmacological intervention if systolic BP exceeds 180 mm Hg . We determined retrospectively the association of BP and antihypertensive therapy with clinical outcomes after stroke thrombolysis . Methods — The SITS thrombolysis register prospect ively recorded 11 080 treatments from 2002 to 2006 .  BP values were recorded at baseline , 2 hours , and 24 hours after thrombolysis . Outcomes were symptomatic ( National Institutes of Health Stroke Scale score deterioration ≥4 ) intracerebral hemorrhage Type 2 , mortality , and independence at ( modified Rankin Score 0 to 2 ) 3 months . Patients were categorized by history of hypertension and antihypertensive therapy within 7 days after thrombolysis  :  Group 1 , hypertensive treated with antihypertensives ( n=5612 ) ; Group 2 , hypertensive withholding antihypertensives ( n=1573 ) ; Group 3 , without history of hypertension treated with antihypertensives ( n=995 ) ; and Group 4 , without history of hypertension not treated with antihypertensives ( n=2632 ) . For 268 ( 2.4 % ) patients , these data were missing . Average systolic BP 2 to 24 hours after thrombolysis was categorized by 10-mm Hg intervals with 100 to 140 used as a reference . Results — In multivariable analysis , high systolic BP 2 to 24 hours after thrombolysis as a continuous variable was associated with worse outcome ( P<0.001 ) and as a categorical variable had a linear association with symptomatic hemorrhage and a U-shaped association with mortality and independence with systolic BP 141 to 150 mm Hg associated with most favorable outcomes . OR ( 95 % CI ) from multivariable analysis showed no difference in symptomatic hemorrhage ( 1.09 [ 0.83 to 1.51 ] ; P=0.58 ) and independence ( 1.03 [ 0.93 to 1.10 ] ; P=0.80 ) but lower mortality ( 0.82 [ 0.73 to 0.92 ] ; P=0.0007 ) for Group 1 compared with Group 4 . Group 2 had a higher symptomatic hemorrhage ( 1.86 [ 1.34 to 2.68 ] ; P=0.0004 ) and mortality ( 1.62 [ 1.41 to 1.85 ] ; P<0.0001 ) and lower independence ( 0.89 [ 0.80 to 0.99 ] ; P=0.04 ) compared with Group 4 . Group 3 had similar results as Group 1 . Conclusions — There is a strong association of high systolic BP after thrombolysis with poor outcome . Withholding antihypertensive therapy up to 7 days in patients with a history of hypertension was associated with worse outcome , whereas initiation of antihypertensive therapy in newly recognized moderate hypertension was associated with a favorable outcome Background Many national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease ( CVD ) should no longer be based on BP level alone , but on absolute cardiovascular risk . While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP , clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “ untreated ” . Objective We aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals ( 45 - 65 years ) with mildly elevated BP ( systolic BP 140 - 159 mmHg and /or diastolic BP 90 - 99 mmHg ) stratified by absolute risk for primary prevention of CVD , but particularly in the low-risk ( < 10 % five-year absolute risk ) group . Methods R and omized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process . First , r and omized trials of BP-lowering therapy will be identified by ( 1 ) retrieving the references of trials included in published systematic review s of BP-lowering therapy , ( 2 ) retrieving studies published by the Blood Pressure Lowering Treatment Trialists ’ Collaboration ( BPLTTC ) , and ( 3 ) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memor and um on BP management . Posttrial follow-up studies will then be identified by forward citation search ing the r and omized trials identified in step 1 through Web of Science . The search will include r and omized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase . Age is the major determinant of absolute cardiovascular risk , so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile . The primary outcome will be all-cause mortality . Secondary outcomes will include cardiovascular mortality , fatal stroke , fatal myocardial infa rct ion , and death due to heart failure . Results The search es for existing systematic review s and BPLTTC studies were piloted and modified . The study is expected to be completed before June 2018 . Conclusions The findings of this study will contribute to the body of knowledge concerning the beneficial , neutral , or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk . Trial Registration PROSPERO International Prospect i ve Register of Systematic Review s : CRD42017058414 ; https://www.crd.york.ac.uk/ PROSPERO /display_record.asp?ID = CRD42017058414 ( Archived by WebCite ® at http://www.webcitation.org/6t6sa8O2Q BACKGROUND In 1989 , the European Working Party on High Blood Pressure in the Elderly started the double-blind , placebo-controlled , Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension . This report addresses whether the benefit of antihypertensive treatment varied according to sex , previous cardiovascular complications , age , initial blood pressure ( BP ) , and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per- protocol analysis . METHODS After stratification for center , sex , and cardiovascular complications , 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were r and omized . Active treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25 mg/d ) , titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg , to below 150 mm Hg . In the control group , matching placebo tablets were employed similarly . RESULTS In the intention-to-treat analysis , male sex , previous cardiovascular complications , older age , higher systolic BP , and smoking at r and omization were positively and independently correlated with cardiovascular risk . Furthermore , for total ( P = .009 ) and cardiovascular ( P = .09 ) mortality , the benefit of antihypertensive drug treatment weakened with advancing age ; for total mortality ( P = .05 ) , the benefit increased with higher systolic BP at entry , while for fatal and nonfatal stroke ( P = .01 ) , it was most evident in nonsmokers ( 92.5 % of all patients ) . In the per protocol analysis , active treatment reduced total mortality by 24 % ( P = .05 ) , reduced all fatal and nonfatal cardiovascular end points by 32 % ( P<.001 ) , reduced all strokes by 44 % ( P = .004 ) , reduced nonfatal strokes by 48 % ( P = .005 ) , and reduced all cardiac end points , including sudden death , by 26 % ( P = .05 ) . CONCLUSIONS In elderly patients with isolated systolic hypertension , stepwise antihypertensive drug treatment , starting with the dihydropyridine calcium channel blocker nitrendipine , improves prognosis . The per- protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths , 54 major cardiovascular end points , 29 strokes , or 25 cardiac end points . The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients Lowering blood pressure ( BP ) in stroke survivors reduces the risk of recurrent stroke . We tested the hypothesis that a nurse-led nonpharmacologic intervention would lower the BP of participants in an intervention group compared with a control group . A total of 349 patients who had sustained acute stroke or transient ischemic attack were r and omly assigned to either usual care or to 4 home visits by a nurse . During the visits , the nurse measured and recorded BP and provided individually tailored counseling on a healthy lifestyle . A total of 303 patients completed the 1-year follow up . No change in systolic BP was noted in either the intervention group or the control group . Because of an increase in diastolic BP in the control group ( P = .03 ) , a difference in mean diastolic BP between the 2 groups was found at follow-up ( P = .007 ) . Mean BP at follow-up was 139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group . Linear regression analysis demonstrated that BP at the point of discharge was the strongest predictor of BP 1 year later ( P < .0001 ) . The proportion of patients on antihypertensive medication increased in the intervention group ( P = .002 ) . Patients were compliant with antihypertensive therapy , and 92 % of the hypertensive patients in the intervention group followed the advice to see a general practitioner ( GP ) for BP checkups . At follow-up , 187 patients ( 62 % ) were hypertensive , with no difference in the rate of hypertension seen between the groups . Our data indicate that home visits by nurses did not result in a lowering of BP . Patients complied with antihypertensive therapy and GP visits in the case of hypertension . Nonetheless , the majority of patients were hypertensive at the 1-year follow up In the Australian Therapeutic Trial in Mild Hypertension treated patients had significantly lower cardiovascular mortality and a significantly lower incidence of cerebrovascular complications than patients given placebos .  There was , however , no difference in the incidence of nonfatal myocardial infa rct ion or other new manifestations of ischaemic heart disease . Although the evidence of benefit from treatment was clear-cut , the number of cardiovascular complications in the control group was small . This was due to several factors . Patients admitted to the trial had no preceding evidence of cardiovascular complications  , the blood pressure fell spontaneously to below 95 mm Hg in almost half the control group , and patients whose blood pressures rose to levels above 110 mm Hg were given treatment , but remained in the placebo group for analysis . In both treated and placebo groups , trial end-points occurred more frequently in persons whose average diastolic blood pressure during the study remained raised . Ischaemic heart disease and many cases of stroke are due to atherosclerotic arterial disease . This appears not to be favourably influenced by antihypertensive drug therapy Background and Purpose — High blood pressure ( BP ) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke . Whether BP influences the benefit or safety of intra-arterial treatment ( IAT ) is not known . We aim ed to assess the relation of BP with functional outcome , occurrence of symptomatic intracranial hemorrhage and effect of IAT .  Methods — This is a post hoc analysis of the MR CLEAN ( Multicenter R and omized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherl and s ) .  BP  was measured at baseline , before IAT or stroke unit admission . We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis . Effect of BP on the effect of IAT was tested with multiplicative interaction terms . Results — Systolic BP ( SBP ) had the best correlation with functional outcome . This correlation was U-shaped ; both low and high baseline SBP were associated with poor functional outcome . Higher SBP was associated with symptomatic intracranial hemorrhage ( adjusted odds ratio , 1.25 for every 10 mm Hg higher SBP [ 95 % confidence interval , 1.09–1.44 ] ) . Between SBP and IAT , there was no interaction for functional outcome , symptomatic intracranial hemorrhage , or other safety parameters ; the absolute benefit of IAT was evident for the whole SBP range . The same was found for diastolic BP . Conclusions — BP does not affect the benefit or safety of  IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion . Our data provide no arguments to withhold or delay IAT based on BP . Clinical Trial Registration — URL : http://www.is rct n.com . Unique identifier : IS RCT N10888758 Background and Purpose — The associations between early blood pressure ( BP ) variability and clinical outcomes in patients with intracerebral hemorrhage after antihypertensive therapy  , recently clarified by a post hoc analysis of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 ( INTERACT2 ) , were confirmed using the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-intracerebral hemorrhage study cohort . Methods — Patients with hyperacute ( <3 hours from onset ) intracerebral hemorrhage with initial systolic BP ( SBP ) > 180 mm Hg were registered in a prospect i ve , multicenter , observational study . All patients received antihypertensive therapy based on a predefined st and ardized protocol to lower and maintain SBP between 120 and 160 mm Hg using intravenous nicardipine . BPs were measured hourly during the initial 24 hours . BP variability was determined as SD and successive variation . The associations between BP variability and hematoma expansion ( > 33 % ) , neurological deterioration within 72 hours , and unfavorable outcome ( modified Rankin Scale , 4–6 ) at 3 months were assessed . Results — Of the 205 patients , 33 ( 16 % ) showed hematoma expansion , 14 ( 7 % ) showed neurological deterioration , and 81 ( 39 % ) had unfavorable outcomes . The SD and successive variation of SBP were 13.8 ( interquartile range , 11.5–16.8 ) and 14.9 ( 11.7–17.7 ) mm Hg , respectively , and those of diastolic BP were 9.4 ( 7.5–11.2 ) and 13.1 ( 11.2–15.9 ) mm Hg , respectively . On multivariate regression analyses , neurological deterioration was associated with the SD of SBP ( odds ratio , 2.75 ; 95 % confidence interval , 1.45–6.12 per quartile ) and the successive variation of SBP ( 2.37 ; 1.32–4.83 ) , and unfavorable outcome was associated with successive variation of SBP ( 1.42 ; 1.04–1.97 ) . Hematoma expansion was not associated with any BP variability . Conclusions — SBP variability during the initial 24 hours of acute intracerebral hemorrhage was independently associated with neurological deterioration and unfavorable outcomes . Stability of antihypertensive therapy may improve clinical outcomes Objectives : Current blood pressure ( BP ) management guidelines recommend that treatment thresholds for BP be based on absolute cardiovascular disease ( CVD ) risk rather than on elevated BP levels alone . Clinicians are concerned that delayed pharmacotherapy in individuals with high BP , but low CVD risk , may increase long-term CVD events . To investigate this , we examined differences in CVD events within the Second Australian National BP study ( ANBP2 ) for those previously on pharmacotherapy and those who were not , as well as fatal events in the 6-year post-trial period . Methods : Population consisted of ANBP2 participants without a prior CVD event . Adjusted Cox-regression hazard models were used to assess the effects of prior BP pharmacotherapy use on cardiovascular endpoints within ANBP2 . An extended 6-year follow-up analysis for cardiovascular and all-cause mortality was also conducted . Results : We found a higher in-trial CVD and all-cause mortality rate and incidence of new-onset diabetes for those on previous treatment versus those who were treatment-naive . We investigated whether this was an effect of the in-trial protocol , but this did not explain the observed differences . No difference in CVD or all-cause mortality at 10 years was observed between ‘ treatment-naive ’ and ‘ previous treatment ’ groups . Conclusion : We found no long-term adverse mortality associated with treatment naivety of elevated BP in an elderly hypertensive cohort , but this finding is likely to be confounded as seen by the lower in-trial mortality in the ‘ treatment-naive ’ group . Legacy effects need to be explored in r and omized trials of middle-aged population s where the clinical concern lies Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future OBJECTIVES We sought to evaluate the role of arterial stiffness on  blood pressure ( BP ) response to drug treatment . BACKGROUND Increased arterial stiffness ( pulse wave velocity [ PWV ] ) is associated with increased systolic blood pressure ( SBP ) . Antihypertensive drug therapy achieves better control of diastolic blood pressure ( DBP ) than SBP does , implying that increased PWV might be a predictor of the SBP response to treatment . METHODS The REASON ( Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind ) study is a r and omized , double-blind trial comparing atenolol versus perindopril/indapamide ;  375 patients with hypertension , with BP and PWV measurements at baseline and after 12 months of treatment , were divided into 3 tertiles according to baseline PWV and included in a post-hoc analysis . RESULTS After 12 months of treatment , BP differed significantly between PWV tertiles ( the third having the lowest response , p < 0.05 ) . Factors related to smaller BP decline were low baseline BP , high baseline PWV , need for a double dose of treatment , use of atenolol ( only for SBP response ) , and age ( only for DBP ) . Although DBP control did not differ in the PWV tertiles , SBP control was significantly associated with PWV level ( p = 0.001 ) as well as with the use of perindopril/indapamide ( p < 0.001 ) . The predictive value of PWV on BP response was independent of age , sex , mean BP , and cardiovascular risk factors . CONCLUSIONS Baseline PWV is a significant predictor of BP response to antihypertensive treatment , independent from age , the need for increasing drug dosage , and the presence of cardiovascular risk factors . Achievement of SBP control appears to be influenced by aortic stiffness as well as by angiotensin-converting enzyme inhibition BACKGROUND It has been suggested that low diastolic blood pressure ( BP ) while receiving antihypertensive treatment ( hereinafter called on-treatment BP ) is harmful in older patients with systolic hypertension . We examined the association between on-treatment diastolic BP , mortality , and cardiovascular events in the prospect i ve placebo-controlled Systolic Hypertension in Europe Trial . METHODS Elderly patients with systolic hypertension were r and omized into the double-blind first phase of the trial , after which all patients received active study drugs ( phase 2 ) . We assessed the relationship between outcome and on-treatment diastolic BP by use of multivariate Cox regression analysis during receipt of placebo ( phase 1 ) and during active treatment ( phases 1 and 2 ) . RESULTS Rates of noncardiovascular mortality , cardiovascular mortality , and cardiovascular events were 11.1 , 12.0 , and 29.4 , respectively , per 1000 patient-years with active treatment ( n = 2358 ) and 11.9 , 12.6 , and 39.0 , respectively , with placebo ( n = 2225 ) . Noncardiovascular mortality , but not cardiovascular mortality , increased with low diastolic BP with active treatment ( P < .005 ) and with placebo ( P < .05 ) ; for example , hazard ratios for lower diastolic BP , that is , 65 to 60 mm Hg , were , respectively , 1.15 ( 95 % confidence interval , 1.00 - 1.31 ) and 1.28 ( 95 % confidence interval , 1.03 - 1.59 ) . Low diastolic BP with active treatment was associated with increased risk of cardiovascular events , but only in patients with coronary heart disease at baseline ( P < .02 ; hazard ratio for BP 65 - 60 mm Hg , 1.17 ; 95 % confidence interval , 0.98 - 1.38 ) . CONCLUSIONS These findings support the hypothesis that antihypertensive treatment can be intensified to prevent cardiovascular events when systolic BP is not under control in older patients with systolic hypertension , at least until diastolic BP reaches 55 mm Hg . However , a prudent approach is warranted in patients with concomitant coronary heart disease , in whom diastolic BP should probably not be lowered to less than 70 mm Hg Objective To explore the likely optimum blood pressure ( BP ) level for patients with a history of cerebrovascular disease . Methods The Perindopril Protection Against Recurrent Stroke Study ( PROGRESS ) was a r and omized , placebo-controlled trial that established the beneficial effects of BP lowering in 6105 patients with cerebrovascular disease . The present study comprises two series of post hoc analyses . The first was design ed to investigate the effects of r and omized treatment on recurrent stroke by baseline BP levels , and the second was a corresponding observational analysis investigating the association between achieved follow-up BP levels and recurrent stroke risk . Results Analyses of the r and omized treatment comparisons showed that BP lowering with combination therapy produced similar risk reductions in each of four subgroups defined by baseline BP of less than 120 , 120–139 , 140–159 , and 160 mmHg or greater ( P homogeneity = 0.5 ) . The effects of single-drug therapy were also comparable across these subgroups ( P homogeneity = 0.2 ) , but consistently greater benefits were observed with combination compared to single-drug therapy . The analyses of achieved follow-up BP showed that the lowest risk of recurrence was among the one-quarter of participants with the lowest follow-up BP levels ( median 112/72 mmHg ) , and that risks rose progressively with higher follow-up BP levels . Minor side-effects were progressively more common at lower BP levels ( P homogeneity = 0.04 ) , but there was no excess of serious complications ( all P homogeneity > 0.2 ) . Conclusion These analyses provide no evidence of a J-curve relationship between BP level and stroke risk among patients with cerebrovascular disease , and identify no patient group among whom more intensive BP lowering would not be expected to produce greater risk reductions OBJECTIVES To assess the effects of acute pressor and depressor blood pressure ( BP ) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments . DESIGN A multicentre , prospect i ve , r and omised , double-blind , placebo-controlled titrated-dose trial . SETTING Five hospitals in Engl and . PARTICIPANTS Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either ( 1 ) symptom onset < 36 hours and hypertension , defined as systolic BP ( SBP ) < 160 mmHg ( depressor arm ) , or ( 2 ) symptom onset < 12 hours and hypotension , defined as SBP < or = 140 mmHg ( pressor arm ) . INTERVENTIONS Patients were allocated to either the pressor or the depressor arm depending on blood pressure at r and omisation . The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm . MAIN OUTCOME MEASURES The primary end point was death and dependency at 2 weeks , with dependency defined as a modified Rankin score < 3 . Secondary end points were the safety of acute pressor  ( 0 - 12 hours post stroke ) and  depressor  ( 0 - 36 hours post stroke )  BP manipulation  in stroke patients ; whether effects of BP reduction are influenced by stroke type ( ischaemic versus haemorrhagic ) ; whether alternative routes for administration of antihypertensive therapy ( including sublingual and intravenous ) are effective in dysphagic stroke patients ; whether effects of BP manipulation are influenced by the time to treatment ; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death . RESULTS 180 patients were recruited over the 36-month trial period , 179 in the depressor arm and one in the pressor arm ( who received placebo ) . No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo , although numbers recruited to the trial were lower than projected . Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo . Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups . Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group ( p = 0.05 ) . The pressor arm was closed early because of problems with recruitment , so no conclusions can be drawn regarding this therapy . CONCLUSIONS Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infa rct ion and haemorrhage and do not increase the likelihood of early neurological deterioration . The study was not sufficiently powered to detect a difference in disability or death at 2 weeks . However , the 3-month difference in mortality in favour of active treatment is of interest , although care must be taken in interpretation of the results . Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke , and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit Background The goal of the present study was to assess the effect of antihypertensive therapy on clinic ( CBP ) and ambulatory ( ABP ) blood pressures , on ECG voltages , and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension . Methods and Results Patients who were ≥60 years old , with systolic CBP of 160 to 219 mm Hg and diastolic CBP of < 95 mm Hg , were r and omized into the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) Trial . Treatment consisted of nitrendipine , with the possible addition of enalapril , hydrochlorothiazide , or both .  Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups : nonsustained hypertension ( < 140 mm Hg ) , mild sustained hypertension ( 140 to 159 mm Hg ) , and moderate sustained hypertension ( ≥160 mm Hg ) . At baseline , patients with nonsustained hypertension had smaller ECG voltages ( P < 0.001 ) and , during follow-up , a lower incidence of stroke ( P < 0.05 ) and of cardiovascular complications ( P = 0.01 ) than other groups . Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension ( P < 0.001 ) . The influence of active treatment on ECG voltages ( P < 0.05 ) and on the incidence of stroke ( P < 0.05 ) and cardiovascular events ( P = 0.06 ) was more favorable than that of placebo only in patients with moderate sustained hypertension . Conclusions Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension . The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension Notwithst and ing the availability of antihypertensive drugs and practice guidelines , blood pressure control remains suboptimal . The complexity of current treatment guidelines may contribute to this problem . To determine whether a simplified treatment algorithm is more effective than guideline -based management , we studied 45 family practice s in southwestern Ontario , Canada , using a cluster r and omization trial comparing the simplified treatment algorithm with the Canadian Hypertension Education Program guidelines . The simplified treatment algorithm consisted of the following : ( 1 ) initial therapy with a low-dose angiotensin-converting enzyme inhibitor/diuretic or angiotensin receptor blocker/diuretic combination ; ( 2 ) up-titration of combination therapy to the highest dose ; ( 3 ) addition of a calcium channel blocker and up-titration ; and ( 4 ) addition of a non — first-line antihypertensive agent . The proportion of patients treated to target blood pressure ( systolic blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg for patients without diabetes mellitus or systolic blood pressure < 130 mm Hg and diastolic blood pressure < 80 mm Hg for diabetic patients ) at 6 months was analyzed at the practice level . The proportion of patients achieving target was significantly higher in the intervention group ( 64.7 % versus 52.7 % ; absolute difference : 12.0 % ; 95 % CI : 1.5 % to 22.4 % ; P=0.026 ) . Multivariate analysis of patient-level data showed that assignment to the intervention arm increased the chance of reaching the target by 20 % ( P=0.028 ) , when adjusted for other covariates . In conclusion , the Simplified Treatment Intervention to Control Hypertension Study indicates that a simplified antihypertensive algorithm using initial low-dose fixed-dose combination therapy is superior to guideline -based practice for the management of hypertension Rationale Controversy exists over the optimal dose of intravenous ( iv ) recombinant tissue plasminogen activator ( rt-PA ) and degree of blood pressure ( BP ) control in acute ischaemic stroke ( AIS ) . Asian studies suggest low-dose ( 0·6 mg/kg ) is more efficacious than st and ard-dose ( 0·9 mg/kg ) iv rt-PA , and guidelines recommend reducing systolic BP to < 185 mmHg before and < 180 mmHg after use of iv rt-PA , despite observational studies indicating better outcomes at much lower ( < 140 mmHg ) systolic BP levels in this patient group . Aims The study aims to assess in thrombolysis-eligible AIS patients whether : ( i ) low-dose ( 0·6 mg/kg body weight ; maximum 60 mg ) iv rt-PA has non-inferior efficacy and lower risk of symptomatic intracerebral haemorrhage ( sICH ) compared to st and ard-dose ( 0·9 mg/kg body weight ; maximum 90 mg ) iv rt-PA ; and ( ii ) early intensive BP lowering ( systolic target 130–140 mmHg ) has superior efficacy and lower risk of any ICH compared to guideline -recommended BP control ( systolic target < 180 mmHg ) . Design The ENhanced Control of Hypertension And Thrombolysis strokE stuDy ( ENCHANTED ) trial is an independent , 2 × 2 quasi-factorial , active-comparison , prospect i ve , r and omized , open blinded endpoint ( PROBE ) , clinical trial that is evaluating Arm [ A ] ‘ rt-PA dose ’ and /or Arm [ B ] ‘ BP control ’ , using central Internet r and omization and data collection in patients fulfilling local criteria for thrombolysis and clinician uncertainty over the study treatments . The treatment arms will be analyzed separately . Study outcomes The primary study outcome in both trial Arms is death or disability according to the modified Rankin scale ( mRS , scores 2–6 ) assessed at 90 days . Secondary outcomes include sICH , any ICH , a shift ( ‘ improvement ’ ) in function across mRS scores , separately on death and disability , early neurological deterioration , recurrent major vascular events , health-related quality of life , length of hospital stay , need for permanent residential care , and health care costs . Results Following launch of the trial in February 2012 , the study has recruited more than 2500 patients across a global network of approximately 100 sites in 15 countries . The required sample sizes are 3300 for Arm [ A ] and 2300 for Arm [ B ] , which will provide > 90 % power to detect non-inferiority of low-dose iv rt-PA and superiority of intensive BP lowering on the primary clinical outcome , respectively . Conclusions Low-dose iv rt-PA and early intensive BP lowering could provide more affordable and safer use of thrombolysis treatment for patients with AIS worldwide
Acetylsalicylic acid ( ASA ) did not reduce stroke or ‘ all cardiovascular events ’ compared to placebo in primary prevention patients with elevated BP and no prior cardiovascular disease .
To conclude for primary prevention in patients with elevated BP , antiplatelet therapy with ASA can not be recommended since the magnitude of benefit , a reduction in myocardial infa rct ion , is negated by a harm of similar magnitude , an increase in major haemorrhage .
Although elevated systemic blood pressure ( BP ) results in high intravascular pressure , the main complications of hypertension are related to thrombosis rather than haemorrhage .
It therefore seemed plausible that use of antithrombotic therapy may be useful in preventing thrombosis-related complications of elevated BP .
The objectives were to conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with BP , to address the following hypotheses : ( i ) antiplatelet agents reduce total deaths and /or major thrombotic events when compared to placebo or other active treatment ; and ( ii ) oral anticoagulants reduce total deaths and /or major thromboembolic events when compared to placebo or other active treatment .