Blood pressure 1 year after stroke: the need to optimize secondary prevention. The stroke preventive effect in elderly hypertensives cannot fully be explained by the reduction in office blood pressure--insights from the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Apparent effect on blood pressure is only partly responsible for the risk reduction due to antihypertensive treatments. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack Post-stroke antihypertensive treatment study. A preliminary result. Reductions in the risks of recurrent stroke in patients with and without diabetes: The PROGRESS Trial Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): Practical Implications Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous? Results of the pilot study for the Hypertension in the Very Elderly Trial Effects of antihypertensive treatment after acute stroke in the Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial Blood pressure declines and less favorable outcomes in the NINDS tPA stroke study Case management for blood pressure and lipid level control after minor stroke: PREVENTION randomized controlled trial
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 OBJECTIVE To study whether the cardiovascular preventive effect of antihypertensive therapy can be explained solely by the reduction in office blood pressure , and to what extent the risk of stroke and cardiac events is associated with in- study diastolic blood pressure ( DBP ) and systolic blood pressure ( SBP ) . DESIGN The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omized , double-blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70 - 84 years . The study group comprised 1,627 elderly patients ( mean blood pressure 195/102 mm Hg ; mean age 75.7 , SD 3.7 ; 63 % females ) . The average follow-up was 25 months ( range 6 - 65 months ) . No patient was lost to follow-up . METHOD We applied a Poisson model taking current age , sex , treatment , DBP and SBP into account for all patients in the study . The constants of the model were estimated by the maximum likelihood method . RESULTS The risk of stroke was significantly lower ( 42 % , p = 0.0402 ) for a patient on active therapy than for a patient on placebo having the same blood pressure level , age , and sex . There was a corresponding , non-significant , reduction in cardiac events of 21 % . In the whole study group the risk of stroke increased by 3 % per mmHg ( p = 0.0247 ) with increasing diastolic blood pressure for a given systolic pressure . The corresponding value for cardiac events was 2 % per mmHg ( p = 0.0376 ) . CONCLUSION In STOP-Hypertension we found a substantial risk reduction in stroke in actively treated patients , which was not solely explained by the blood pressure reduction obtained by treatment with beta-blockers and a potassium-sparing diuretic combination The mechanism of risk reduction obtained by blood pressure-lowering pharmacological treatment remains unclear . We explored the amount of risk reduction attributable to the apparent effect of antihypertensive medicines on blood pressure by using the capture approach . Five r and omized , placebo or nil controlled trials with a total of 28,997 subjects and 1,935 cardiovascular fatal or non-fatal events from the INDANA data base met the eligibility criteria . Computations were performed on the original individual records using multiple Cox 's proportional hazard regression models design ed for meeting the assumed treatment mode of action and comparing relevant assumptions . For coronary event , the results are inconclusive essentially because the risk reduction is mild . However , for stroke the risk reduction adjusted for baseline risk factors is 34 % ( P<0.0001 ) . The part explained by the effect of treatment on systolic blood pressure is 49 % of this reduction , with 95 % confidence interval not including 100 % . This result suggests that the apparent effect on blood pressure is not the only cause of stroke risk reduction in hypertensive subjects su bmi tted to an antihypertensive medicine OBJECTIVE To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal ( total ) stroke in isolated systolic hypertension . DESIGN Multicenter , r and omized , double-blind , placebo-controlled . SETTING Community-based ambulatory population in tertiary care centers . PARTICIPANTS 4736 persons ( 1.06 % ) from 447,921 screenees aged 60 years and above were r and omized ( 2365 to active treatment , 2371 to placebo ) . Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg . Of the participants , 3161 were not receiving antihypertensive medication at initial contact , and 1575 were . The average systolic blood pressure was 170 mm Hg ; average diastolic blood pressure , 77 mm Hg . The mean age was 72 years , 57 % were women , and 14 % were black . INTERVENTIONS -- Participants were stratified by clinical center and by antihypertensive medication status at initial contact . For step 1 of the trial , dose 1 was chlorthalidone , 12.5 mg/d , or matching placebo ; dose 2 was 25 mg/d . For step 2 , dose 1 was atenolol , 25 mg/d , or matching placebo ; dose 2 was 50 mg/d . MAIN OUTCOME MEASURES Primary . Nonfatal and fatal ( total ) stroke . Secondary . Cardiovascular and coronary morbidity and mortality , all-cause mortality , and quality of life measures . RESULTS Average follow-up was 4.5 years . The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group , and the 5-year average diastolic blood pressure was 72 and 68 mm Hg , respectively . The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo . The relative risk by proportional hazards regression analysis was 0.64 ( P = .0003 ) . For the secondary end point of clinical nonfatal myocardial infa rct ion plus coronary death , the relative risk was 0.73 . Major cardiovascular events were reduced ( relative risk , 0.68 ) . For deaths from all causes , the relative risk was 0.87 . CONCLUSION In persons aged 60 years and over with isolated systolic hypertension , antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36 % , with 5-year absolute benefit of 30 events per 1000 participants . Major cardiovascular events were reduced , with 5-year absolute benefit of 55 events per 1000 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 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 BACKGROUND Blood pressure is a determinant of the risk of stroke among both hypertensive and non-hypertensive individuals with cerebrovascular disease . However , there is uncertainty about the efficacy and safety of blood-pressure-lowering treatments for many such patients . The perindopril protection against recurrent stroke study ( PROGRESS ) was design ed to determine the effects of a blood-pressure-lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack . METHODS 6105 individuals from 172 centres in Asia , Australasia , and Europe were r and omly assigned active treatment ( n=3051 ) or placebo ( n=3054 ) . Active treatment comprised a flexible regimen based on the angiotensin- converting-enzyme inhibitor perindopril ( 4 mg daily ) , with the addition of the diuretic indapamide at the discretion of treating physicians . The primary outcome was total stroke ( fatal or non-fatal ) . Analysis was by intention to treat . FINDINGS Over 4 years of follow up , active treatment reduced blood pressure by 9/4 mm Hg . 307 ( 10 % ) individuals assigned active treatment suffered a stroke , compared with 420 ( 14 % ) assigned placebo ( relative risk reduction 28 % [ 95 % CI 17 - 38 ] , p<0.0001 ) . Active treatment also reduced the risk of total major vascular events ( 26 % [ 16 - 34 ] ) . There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups ( all p<0.01 ) . Combination therapy with perindopril plus indapamide reduced blood pressure by 12/5 mm Hg and stroke risk by 43 % ( 30 - 54 ) . Single-drug therapy reduced blood pressure by 5/3 mm Hg and produced no discernable reduction in the risk of stroke . INTERPRETATION This blood-pressure-lowering regimen reduced the risk of stroke among both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack . Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with perindopril alone . Treatment with these two agents should now be considered routinely for patients with a history of stroke or transient ischaemic attack , irrespective of their blood pressure Post-stroke Antihypertensive Treatment Study ( PATS ) was a r and omized , double-blind and placebo-controlled trial , which aim ed at determining whether antihypertensive treatment could reduce the risk of fatal and nonfatal stroke incidence in patients with a history of stroke or transient ischemic attack ( TIA ) . 5,665 patients were r and omized by a sealed envelope system . Systolic blood pressure ( SBP ) ranged from 80 to 280 mm Hg and diastolic ( DBP ) from 50 to 150 mmHg . The average SBP was 154 mmHg and average DBP 93 mmHg . The mean age was 60 years . Among the patients , women accounted for 28 % . In 71 % the latest stroke was ischemic . Average follow-up approximated to 2 years . The three-year average SBP was 149 mmHg for the placebo group and 144 mmHg for the indapamide treatment group , and the three-year DBP was 89 mmHg and 87 mmHg respectively . The three-year first incidence of fatal and nonfatal stroke was 12.3 per 100 patients placebo treatment and 9.4 per 100 with indapamide . The relative risk by proportional hazards regression analysis was 0.71 ( P = 0.0009 ) . For deaths from all causes , the relative risk was 0.91 . ( P > 0.05 ) . The findings of this trial indicate that in patients with a history of stroke or TIA , blood pressure reduction of 5/2 mmHg with 2.5 mg indapamide reduced the first incidence of fatal and nonfatal stroke by 29 % , with three-year absolute benefit of 29 events per 1000 participants Background : Analyses of the risks of stroke were conducted for subjects with and without diabetes , participating in a r and omized , double‐blind , placebo‐controlled  trial of a perindopril‐based blood pressure lowering regimen in 6105 people with prior stroke or transient ischaemic attack ( TIA ) , followed for a median of 3.9 years . Findings : Seven hundred and sixty‐one patients had diabetes at baseline . Diabetes increased the risk of recurrent stroke by 35 % ( 95 % CI 10–65 % ) principally through an effect on ischaemic stroke ( 1.53 , 95 % CI 1.23–1.90 ) . Active treatment reduced blood pressure by 9.5/4.6 mmHg in patients with diabetes and by 8.9/3.9 mmHg in patients without diabetes . The proportional risk reductions achieved for stroke in patients with diabetes , 38 % ( 95 % CI 8–58 % ) , and patients without diabetes , 28 % ( 95 % CI 16–39 % ) , were not significantly different ( p homogeneity = 0.5 ) . The absolute reduction in the risk of recurrent stroke in the patients with diabetes was equivalent to one stroke avoided among every 16 ( 95 % CI 9–111 ) patients treated for 5 years . Conclusions : Diabetes is an important risk factor for stroke in patients with established cerebrovascular disease . Treatment with the ACE inhibitor perindopril with discretionary use of the diuretic indapamide produced reductions in the risk of recurrent stroke in patients with diabetes that were at least as great as those achieved in patients without diabetes Background To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension  , we extended the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) trial by an open-label follow-up study lasting 4 years . Methods The Syst-Eur trial included 4695 r and omized patients with minimum age of 60 years and an untreated blood pressure of 160–219 mmHg systolic and below 95 mmHg diastolic . The double-blind trial ended after a median follow-up of 2.0 years ( range 1–97 months ) . Of 4409 patients still alive , 3517 received open-label treatment consisting of nitrendipine ( 10–40 mg daily ) with the possible addition of enalapril ( 5–20 mg daily ) , hydrochlorothiazide ( 12.5–25 mg daily ) , or both add-on drugs .  Non- participants ( n = 892 ) were also followed up . Results Median follow-up increased to 6.1 years . Systolic pressure decreased to below 150 mmHg ( target level ) in 2628 participants ( 75.0 % ) . During the 4-year open-label follow-up , stroke and cardiovascular complications occurred at similar frequencies in patients formerly r and omized to placebo and those continuing active treatment . These rates were similar to those previously observed in the active-treatment group during the double-blind trial . Considering the total follow-up of 4695 r and omized patients , immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28 % ( P = 0.01 ) and 15 % ( P = 0.03 ) , respectively , with a similar tendency for total mortality ( 13 % , P = 0.09 ) . In 492 diabetic patients , the corresponding estimates of long-term benefit ( P < 0.02 ) were 60 , 51 and 38 % , respectively . Conclusions Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension . Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years . These findings underscore the necessity of early treatment of isolated systolic hypertension Summary Background High blood pressure is associated with poor outcome after stroke . Whether blood pressure should be lowered early after stroke , and whether to continue or temporarily withdraw existing antihypertensive drugs , is not known . We assessed outcomes after stroke in patients given drugs to lower their blood pressure . Methods In our multicentre , partial-factorial trial , we r and omly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure ( systolic 140–220 mm Hg ) to 7 days of transdermal glyceryl trinitrate ( 5 mg per day ) , started within 48 h of stroke onset , or to  no glyceryl trinitrate ( control group ) . A subset of patients who were taking antihypertensive drugs before their stroke were also r and omly assigned to continue or stop taking these drugs . The primary outcome was function , assessed with the modified Rankin Scale at 90 days by observers masked to treatment assignment . This study is registered , number IS RCT N99414122 . Findings Between July 20 , 2001 , and Oct 14 , 2013 , we enrolled 4011 patients .  Mean blood pressure was 167 ( SD 19 ) mm Hg/90 ( 13 ) mm Hg at baseline ( median 26 h [ 16–37 ] after stroke onset ) , and was significantly reduced on day 1 in 2000 patients allocated to glyceryl trinitrate compared with 2011 controls ( difference −7·0 [ 95 % CI −8·5 to −5·6 ] mm Hg/–3·5 [ –4·4 to −2·6 ] mm Hg ; both p<0·0001 ) , and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients r and omised to stop them ( difference −9·5 [ 95 % CI −11·8 to −7·2 ] mm Hg/–5·0 [ –6·4 to −3·7 ] mm Hg ; both p<0·0001 ) . Functional outcome at day 90 did not differ in either treatment comparison — the adjusted common odds ratio ( OR ) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1·01 ( 95 % CI 0·91–1·13 ; p=0·83 ) , and with continue versus stop antihypertensive drugs OR was 1·05 ( 0·90–1·22 ; p=0·55 ) . Interpretation In patients with acute stroke and high blood pressure , transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome . We show no evidence to support continuing prestroke antihypertensive drugs in patients in the first few days after acute stroke . Funding UK Medical Research Council The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , sponsored by the National Heart , Lung , and Blood Institute ( NHLBI ) , is the largest outcome trial of antihypertensive treatment ever carried out and the only large blood pressure ( BP ) trial to be carried out in a US population in the past decade.1 The rationale for ALLHAT , which was design ed in the early 1990s , was the urgent need to determine which of the several classes of antihypertensive drugs that had been developed and released for clinical use was most effective in preventing coronary heart disease ( CHD ) , defined as fatal CHD and nonfatal myocardial infa rct ion.2 The only r and omized trials that had previously compared representatives of the antihypertensive drug classes , the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents3 and the Treatment of Mild Hypertension Study (TOMHS),4 showed BP reductions with all classes but were not powered to evaluate CHD outcomes . Further , prior outcome trials had shown that the reduction in CHD event rates with antihypertensive treatment was less than expected based on epidemiologic data .5 Adverse effects of study drugs , particularly diuretics , including hypokalemia , hypomagnesemia , hyperuricemia , hyperlipidemia , insulin resistance , and ventricular ectopic activity , had been adduced to account for the disappointing outcomes of earlier trials by off setting the beneficial effects of BP reduction.6,7 To further complicate the picture , benefits beyond BP reduction had been attributed to some antihypertensive drug classes , ie , improved survival and reduced morbidity in persons with heart failure or left ventricular dysfunction treated with angiotensin-converting enzyme ( ACE ) inhibitors8–10 and improved insulin sensitivity and lipid profiles with α-blocker treatment.11 In contrast , another antihypertensive drug class , the dihydropyridine calcium channel blockers ( CCBs ) , had been associated with unfavorable outcomes in patients with acute myocardial infa rct ion or unstable angina.12 There were no data Context Experts debate the consequences of excessive lowering of diastolic pressure in patients with hypertension and coronary artery disease . Contribution This report is a secondary analysis of data from a large trial of 2 antihypertensive drug regimens in patients with known coronary artery disease . The authors found a J-shaped relationship between diastolic blood pressure and all-cause death and myocardial infa rct ion , with the increased risk occurring at diastolic blood pressures below 70 to 80 mm Hg , that is , the lower the diastolic pressure , the higher the risk . Caution s The study examined associations between blood pressure and outcomes ; it could not prove that the antihypertensive therapy that lowered diastolic pressure too much caused the adverse outcomes . The Editors For 2 decades , the hypertension literature has been haunted by the phenomenon of a paradoxical increase in morbidity and mortality with an excessive decrease in blood pressure ( J-curve ) . Indeed , several reports have shown that low diastolic pressure is associated with an increased risk for coronary heart disease and related mortality in older adults and in patients taking antihypertensive medications ( 1 - 13 ) . After doing a review and meta- analysis of pertinent studies , Farnett and colleagues ( 14 ) concluded that although there was no consistent J-shaped relationship between stroke and systolic or diastolic pressure , there was a consistent J-shaped relationship for cardiac events and diastolic pressure . These authors stated that this dichotomy in the relationship between diastolic pressure and target organ disease may leave a clinician with the uncomfortable choice of whether to prevent stroke or renal disease at the expense of coronary heart disease . These findings were at variance with the generally accepted dogma formulated by the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) ( 15 ) , which stated that the relationship between pressure and risk was strong , continuous , independent , predictive and etiologically significant . Within the past decade , the phenomenon of a J-curve has been studied in several large trials of normotensive and hypertensive patients ( 16 - 30 ) . Not surprisingly , arguments regarding whether a J-curve could be clinical ly significant have become somewhat contentious . That is , some rely on evidence that on-treatment diastolic pressure below 70 mm Hg does not increase risk for cardiovascular disease and thus deny an impairment of vital organ perfusion within the usual values achievable by antihypertensive treatment . Others , however , consider the J-curve a more real possibility , particularly for the heart . In contrast to other organs , the heart is perfused mostly during diastole and thus could be more vulnerable to diastolic pressure reduction . If a J-curve did exist , it should be most evident in patients with limited coronary perfusion , in other words , in those with manifest coronary artery disease ( CAD ) . Optimal blood pressure in patients with hypertension and CAD remains controversial because few r and omized clinical trials have been done in this population ( 31 , 32 ) . The International Verapamil-Tr and olapril Study ( INVEST ) ( 33 ) , a r and omized trial , evaluated more than 22000 patients with CAD and hypertension . This patient profile , together with unprecedented levels of blood pressure control , provided a unique opportunity to critically investigate the hypothesis that the risk for CAD would increase with an excessive decrease in diastolic pressure . Methods Study Design and Intervention The INVEST design , methods , and principal results have been previously published ( 33 ) . The trial used an open design with blinded end point assessment . In brief , clinical ly stable patients with CAD and hypertension were r and omly assigned to a verapamil sustained-releasebased or atenolol-based strategy .  Patients with previous myocardial infa rct ion ( MI ) within 3 months of enrollment or class IV or V congestive heart failure were excluded .  Blood pressure goals were based on JNC VI ( systolic pressure < 140 mm Hg and diastolic pressure < 90 mm Hg or systolic pressure < 130 mm Hg and diastolic pressure < 85 mm Hg in patients with diabetes or renal impairment ) ( 15 ) . The addition of tr and olapril or hydrochlorothiazide was recommended when necessary to achieve blood pressure goals . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . Documented CAD was defined as any of the following : remote ( 3 months before enrollment ) confirmed MI , coronary angiography showing more than 50 % narrowing of at least 1 major coronary artery , diagnosis of classic angina pectoris , or concordant abnormalities on 2 different signals ( electrocardiography , echocardiography , or radionuclide scans ) from stress test findings concordant for ischemia ( for example , ST-segment depression or perfusion defects on radionuclide scanning or wall-motion abnormalities on echocardiography or radionuclide scanning ) . Patient Monitoring and Follow-up Protocol visits were scheduled every 6 weeks for the first 6 months and then biannually until 2 years after the last patient was enrolled . Patients were assessed for response to treatment , symptoms , treatment adherence , and adverse effects at each visit and at the end of the study as detailed elsewhere ( 33 ) . Patient follow-up was complete when we received a final assessment form through the online data system or a death report . The Internet-based electronic data collection method used in INVEST did not accept the entry until all required fields were complete . Blood pressure  was measured by using a st and ard mercury sphygmomanometer with an appropriately sized cuff applied to the upper nondominant arm at heart level . By auscultation at the brachial artery , systolic pressure was recorded at the first Korotkoff sound and diastolic pressure was recorded at the disappearance of the fifth Korotkoff sound . Blood pressure was measured twice , at least 2 minutes apart , and the measurements were averaged . Study Outcomes The primary outcome was the first occurrence of all-cause death , nonfatal MI , or nonfatal stroke by intention-to-treat analysis . The MI and stroke definitions are detailed elsewhere ( 34 ) . These 3 components individually were the main secondary outcomes . For this analysis , additional outcomes included fatal and nonfatal MI , fatal and nonfatal stroke , and average on-treatment blood pressure before outcome or censoring . Ascertainment and blinded adjudication of outcomes were described previously ( 32 ) . Follow-up data were available for 22008 ( 97.5 % ) patients . Statistical Analysis The main conclusions of INVEST were that the 2 treatment strategies were equivalent with respect to the primary outcome , main secondary outcomes , and on-treatment systolic and diastolic pressures . Thus , data for all enrolled patients were combined and included in these analyses following the intention-to-treat principle . A P value of 0.05 or less was considered statistically significant . Patients without a primary outcome event were censored at their latest follow-up visit . Average follow-up systolic and diastolic pressures were calculated for each patient by using all post-baseline results , up to the date of primary outcome or censoring . The baseline value was substituted for patients with no post-baseline data ( n= 1154 ) . In this exploratory analysis , the proportions of patients were pooled by 10 mm Hg strata of average follow-up systolic pressure , and the distribution of primary outcome event rate was evaluated to determine whether the relationship was linear . A similar presentation was prepared for diastolic pressure . Because the frequency distributions seemed consistent with a quadratic curve , a quadratic Cox proportional hazards model was formed for the time to primary outcome for each blood pressure variable , with factors for blood pressure and blood pressure squared . Similarly , the relationship between each 10 mm Hg stratum of average systolic pressure and diastolic pressure and all-cause death , fatal and nonfatal MI , and fatal and nonfatal stroke was evaluated . For the time to primary outcome , a second model was fitted , adjusting for the following baseline covariates : age ( 10-year increments ) , sex , race and ethnicity ( white , Asian , black , Hispanic , multiracial , or other ) , previous MI , heart failure ( classes I to III ) , body mass index in increments of 5 kg/m2 , U.S. residency , renal impairment , peripheral vascular disease , left ventricular hypertrophy , smoking history , coronary revascularization , dyslipidemia , stroke or transient ischemic attack , angina pectoris , arrhythmia , diabetes , cancer , aspirin use , and average systolic pressure or diastolic pressure and systolic pressure squared or diastolic pressure squared . To identify clinical ly relevant interactions between the J-shaped curve and baseline diastolic pressure , demographic characteristics , and comorbid conditions for the primary outcome , a 2-step procedure was used . First , baseline covariates were tested individually by adding the variable and 2 interaction terms ( variablediastolic pressure and variable[diastolic pressure squared ] ) to the Cox proportional hazards model . Variables included were age older than 70 years , sex , previous MI , heart failure ( classes I to III ) , previous stroke or transient ischemic attack , diabetes , cancer , renal impairment , hypercholesterolemia , peripheral vascular disease , smoking history , U.S. residency , body mass index greater than 29 kg/m2 ( mean baseline body mass index ) , and diastolic pressure greater than 86 mm Hg ( mean baseline diastolic pressure ) . The change in log likelihood was used to assess the significance of simultaneously adding the 2 interaction terms . The second step in identifying clinical ly relevant interactions between the J-shaped curve and baseline covariates was to plot the hazard ratios for the primary outcome versus diastolic pressure in the Background The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months . Results In the combined actively treated groups , the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths BACKGROUND Up to 50 % of patients with acute stroke are taking antihypertensive drugs on hospital admission . However , whether such treatment should be continued during the immediate post-stroke period is unclear . We therefore aim ed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke . METHODS The Continue or Stop Post-Stroke Antihypertensives Collaborative Study ( COSSACS ) was a UK multicentre , prospect i ve , r and omised , open , blinded-endpoint trial . Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1 , 2003 , to March 31 , 2009 . Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug . Patients were r and omly assigned ( 1:1 ) by secure internet central r and omisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks . Patients and clinicians who r and omly assigned patients were unmasked to group allocation . Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation . The primary endpoint was death or dependency at 2 weeks , with dependency defined as a modified Rankin scale score greater than 3 points . Analysis was by intention to treat . This trial is registered with the International St and ard R and omised Controlled Trial Register , number IS RCT N89712435 . FINDINGS 763 patients were assigned to continue ( n=379 ) or stop ( n=384 ) pre-existing antihypertensive drugs . 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint ( relative risk 0.86 , 95 % CI 0.65 - 1.14 ; p=0.3 ) . The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg ( 95 % CI 10 - 17 ) and the difference in diastolic blood pressure was 8 mm Hg ( 6 - 10 ; difference between groups p<0.0001 ) . No substantial differences were observed between groups in rates of serious adverse events , 6-month mortality , or major cardiovascular events . INTERPRETATION Continuation of antihypertensive drugs did not reduce 2-week death or dependency , cardiovascular event rate , or mortality at 6 months . Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events . These neutral results might be because COSSACS was underpowered owing to early termination of the trial , and support the continuation of ongoing research trials . FUNDING The Health Foundation and The Stroke Association BACKGROUND AND PURPOSE Hypertension is the most important modifiable risk factor for secondary stroke prevention but the immediate management of blood pressure after stroke is uncertain . We evaluated outcomes in the NINDS tPA stroke study in relation to blood pressure declines during the first 24 h after r and omization . METHODS Declines in blood pressure compared to baseline and preceding time points were analyzed in relationship to favorable outcomes ( by a global test ) , poor outcomes ( Rankin scale > 3 ) and death at 3 months . RESULTS 551 patients did not receive immediate pre-r and omization anti-hypertensive treatment and had available blood pressures . Multivariate analysis showed significantly and progressively reducing likelihoods of a favorable outcome with each 10 mmHg decline in systolic blood pressure ( SBP ) > 50 mmHg compared to any preceding measurement . Poor outcomes were significantly more likely in patients with > 50 mmHg SBP reduction ( or > 30 mmHg compared to any immediately preceding measurement ) . There was an increased risk of death with blood pressure declines > 60 mmHg . tPA treatment still produced favorable outcomes compared with placebo even with blood pressure declines . The median largest SBP reduction from baseline in patients treated with tPA was 35 mmHg compared to 30 mmHg in placebo-treated patients ( p<0.01 ) . CONCLUSIONS In this post hoc analysis , progressively reducing likelihoods of a favorable outcome were seen with increasing declines in SBP . Despite a greater likelihood of favorable outcomes , tPA treatment was associated with a greater reduction in blood pressure than placebo . R and omized trials of blood pressure management are needed Background : Optimization of systolic blood pressure and lipid levels are essential for secondary prevention after ischemic stroke , but there are substantial gaps in care , which could be addressed by nurse- or pharmacist-led care . We compared 2 types of case management ( active prescribing by pharmacists or nurse-led screening and feedback to primary care physicians ) in addition to usual care . Methods : We performed a prospect i ve r and omized controlled trial involving adults with recent minor ischemic stroke or transient ischemic attack whose systolic blood pressure or lipid levels were above guideline targets . Participants in both groups had a monthly visit for 6 months with either a nurse or pharmacist . Nurses measured cardiovascular risk factors , counselled patients and faxed results to primary care physicians ( active control ) . Pharmacists did all of the above as well as prescribed according to treatment algorithms ( intervention ) . Results : Most of the 279 study participants ( mean age 67.6 yr , mean systolic blood pressure 134 mm Hg , mean low-density lipoprotein [ LDL ] cholesterol 3.23 mmol/L ) were already receiving treatment at baseline ( antihypertensives : 78.1 % ; statins : 84.6 % ) , but none met guideline targets ( systolic blood pressure ≤ 140 mm Hg , fasting LDL cholesterol ≤ 2.0 mmol/L ) . Substantial improvements were observed in both groups after 6 months : 43.4 % of participants in the pharmacist case manager group met both systolic blood pressure and LDL guideline targets compared with 30.9 % in the nurse-led group ( 12.5 % absolute difference ; number needed to treat = 8 , p = 0.03 ) . Interpretation : Compared with nurse-led case management ( risk factor evaluation , counselling and feedback to primary care providers ) , active case management by pharmacists substantially improved risk factor control at 6 months among patients who had experienced a stroke . Trial registration : Clinical Trials.gov , no.
CONCLUSION Despite recent large trials showing no significant effect , in patients that have experienced a TIA or stroke , blood pressure lowering agents reduced the occurrence of subsequent stroke and cardiovascular events .
The rate of myocardial infa rct ion and all-cause mortality was unchanged
BACKGROUND While hypertension is a leading risk factor for an initial stroke , the role of blood pressure lowering to prevent subsequent stroke is less clear .
The results of recent large clinical trials investigating effects of antihypertensive agents in patients with a history of stroke have not shown a significant benefit ; findings that are at odds with previous data .
Our meta- analysis systematic ally evaluates the available , relevant trials to examine the role of antihypertensive drugs in preventing recurrent stroke .