Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups Protocol for Past BP: a randomised controlled trial of different blood pressure targets for people with a history of stroke of transient ischaemic attack (TIA) in primary care Ten-year legacy effects of baseline blood pressure ‘treatment naivety’ in the Second Australian National Blood Pressure study Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension. The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS): Protocol, Patient Characteristics, and Blood Pressure during the First 12 Months Substituting Lifestyle Management for Pharmacological Control of Blood Pressure: A Pilot Study in Australian General Practice Treatment of mild hypertension: a five year controlled drug trial. The Oslo study. Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial. Randomized Pilot Study of a Behavioral Feedback Intervention to Improve Medication Adherence in Older Adults With Hypertension On-treatment diastolic blood pressure and prognosis in systolic hypertension. Principal Results of the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) A cluster randomized trial to evaluate physician/pharmacist collaboration to improve blood pressure control. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: The Systolic Blood Pressure Intervention Trial (SPRINT) Non-pharmacological treatment of hypertension in primary health care: a 2-year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study
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 Evidence on long term effectiveness of public health strategies for lowering blood pressure ( BP ) is scarce . In the Control of Blood Pressure and Risk Attenuation ( COBRA ) Trial , a 2 x 2 factorial , cluster r and omized controlled trial , the combined home health education ( HHE ) and trained general practitioner ( GP ) intervention delivered over 2 years was more effective than no intervention ( usual care ) in lowering systolic BP among adults with hypertension in urban Pakistan . However , it was not clear whether the effect would be sustained after the cessation of intervention . We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up . Methods A total of 1341 individuals 40 years or older with hypertension ( systolic BP 140 mm Hg or greater , diastolic BP 90 mm Hg or greater , or already receiving treatment ) were followed by trained research staff masked to r and omization status .  BP was measured thrice with a calibrated automated device ( Omron HEM-737 IntelliSense ) in the sitting position after 5 minutes of rest . BP measurements were repeated after two weeks . Generalized estimating equations ( GEE ) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up . The multivariable model was adjusted for clustering , age at baseline , sex , baseline systolic and diastolic BP , and presence of diabetes . Findings After 7 years of follow-up , systolic BP levels among those r and omised to combined HHE plus trained GP intervention were significantly lower ( 2.1 [ 4.1–0.1 ] mm Hg ) compared to those r and omised to usual care , ( P = 0.04 ) . Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol ( 2.7 [ 4.8 to 0.6 ] mg/dl . Conclusions The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up . These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries . Trial Registration Clinical Trials.gov Background Blood pressure ( BP ) lowering in people who have had a stroke or transient ischaemic attack ( TIA ) leads to reduced risk of further stroke . However , it is not clear what the target BP should be , since intensification of therapy may lead to additional adverse effects . PAST BP will determine whether more intensive BP targets can be achieved in a primary care setting , and whether more intensive therapy is associated with adverse effects on quality of life . Methods / Design This is a r and omised controlled trial ( RCT ) in patients with a past history of stroke or TIA . Patients will be r and omised to two groups and will either have their blood pressure ( BP ) lowered intensively to a target of 130 mmHg systolic , ( or by 10 mmHg if the baseline systolic pressure is between 125 and 140 mmHg ) compared to a st and ard group where the BP will be reduced to a target of 140 mmHg systolic . Patients will be managed by their practice at 1 - 3 month intervals depending on level of BP and followed-up by the research team at six monthly intervals for 12 months.610 patients will be recruited from approximately 50 general practice s. The following exclusion criteria will be applied : systolic BP < 125 mmHg at baseline , 3 or more anti-hypertensive agents , orthostatic hypotension , diabetes mellitus with microalbuminuria or other condition requiring a lower treatment target or terminal illness . The primary outcome will be change in systolic BP over twelve months . Secondary outcomes include quality of life , adverse events and cardiovascular events . In-depth interviews with 30 patients and 20 health care practitioners will be undertaken to investigate patient and healthcare professionals underst and ing and views of BP management . Discussion The results of this trial will inform whether intensive blood pressure targets can be achieved in people who have had a stroke or TIA in primary care , and help determine whether or not further research is required before recommending such targets for this population .Trial Registration IS RCT 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 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 Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults , surprisingly little data exist to confirm the efficacy of these interventions in older persons . METHODS We conducted a r and omized , controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg . The experimental arm was a nonpharmacologic intervention combining weight reduction , sodium restriction , and increased physical activity . The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase , followed by four monthly group sessions during the maintenance phase . The control group received no treatment during the study .  Blood pressure was assessed by certified technicians ( blinded to group assignment ) using r and om zero sphygmomanometers . RESULTS Of 56 participants r and omized , 47 completed the entire 6-month trial ( 21 in the intervention group and 26 in the control group ) . Attendance at the intervention sessions was excellent . The intervention group lost more weight ( -2.1 kg ) over 6 months than the control group ( + 0.3 kg ) . Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups , with greater trend in the intervention group , were not statistically significant . The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group ( mean differences between groups at 6 months , 4.2/4.9 mm Hg , respectively ) . CONCLUSIONS Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure The benefits of a systolic blood pressure ( BP ) below 150–160 mmHg are well established ; whether a systolic BP of less than 140 mmHg provides additional benefits remains controversial . This study was design ed to compare the 2-year effect of a strict treatment to maintain systolic BP below 140 mmHg ( group A ) and that of a mild treatment to maintain systolic BP at between 140 and below 160 mmHg ( group B ) . The study design followed the Prospect i ve R and omized Open Blinded End-point ( PROBE ) study . The subjects were elderly patients ( 65–85 years old ) who consistently had a systolic BP of 160 mmHg or higher . The baseline drug was efonidipine hydrochloride ( efonidipine ) , a long-acting dihydropiridine calcium antagonist . The primary endpoints were stroke , cardiac disease , vascular disease , and renal failure . After a run-in period of 2 to 4 weeks , 2,165 patients were assigned to group A and 2,155 patients to group B. There were no significant differences between the groups in sex , age , baseline BP , or other cardiovascular risk factors . The systolic BP was 7.2 mmHg lower ( p<0.0001 ) and the diastolic BP 2.4 mmHg lower ( p<0.0001 ) in group A than in group B after 12 months of treatment . As of this interim analysis , primary endpoints have occurred in 87 patients ( stroke in 58 patients , cardiac disease in 27 patients , occlusive arterial disease in 1 patient , and renal failure in 1 patient ) . Five patients have died of stroke and 2 patients of myocardial infa rct ion . The primary -endpoint-related morbidity rate was 20.9/1,000 patient-years , and the mortality rate was 1.7/1,000 patient-years . Currently available results indicate that this study , one of the largest r and omized trials of antihypertensive therapy in elderly patients in Japan , was conducted safely . The final results are expected to provide important and practical information for the management of hypertension in elderly patients The HEART project was conducted in general practice to determine whether lifestyle strategies , aim ed at increasing physical activity and dietary modification , can be substituted for drug therapy in patients who have been well controlled on antihypertensive medication . In addition to blood pressure ( BP ) and risk factor outcomes , lifestyle behaviours , quality of life of patients , and the acceptability of the approach to both general practitioners ( GPs ) and patients involved in the trial were assessed . Patients ( n = 45 ) with a history of hypertension and who had been well controlled for at least the past 6 months ( BP < 160/95 mmHg ) were r and omised to a continued medication ( C ) group ( n = 24 ) or a withdrawal ( W ) group ( n = 21 ) . Subjects had received antihypertensive therapy for an average of 7.8 years ( range 1 - 28 years ) .  Drug therapy in the W group was recommenced if BP exceeded 160/95 mmHg on two consecutive visits . Both groups were counselled regarding lifestyle behaviour change by their GP throughout the study and were provided with specifically developed self-help material s. Subjects were review ed at least monthly over a 9-month period . Following r and omisation , there were no significant differences between the two groups for BP , heart rate , age , duration of therapy , total cholesterol or body mass index . All but three subjects ( one from the W and two from the C group ) completed 9 months of monitoring following r and omisation and there were no cardiovascular events ; 71 % of subjects remained off drug therapy and were well controlled at the 9-month follow-up ( 15/21 ) with mean BP of 141/85 mmHg ( W ) and 139/86 mmHg ( C ) . Systolic BP tended to increase during the study period in both W and C groups , however , no significant differences were observed in mean systolic or diastolic BP either between the two groups or within each group in comparison to baseline values . Resting heart rate , body mass index and cholesterol levels remained unchanged in both W and C groups after 9 months follow-up . There were no changes attributable to the lifestyle intervention in the subjects continuing drug therapy in BP or lifestyle variables over the study period . However , the group stopping therapy had a 6 % reduction in body mass index after 9 months . These data suggest that a proportion of motivated patients willing to trial a lifestyle approach can cease drug therapy and be adequately maintained by the prescription of lifestyle advice via their GP for at least a 9-month period . Cessation of drug therapy may be an important motivating factor to achieve weight loss in this group In 1972 - -1973 , 785 symptom-free men , aged 40 to 49 years , without target organ damage , with systolic blood pressures between 150 and 179 mm Hg and diastolic blood pressure below 110 mm Hg , were assigned at r and om to one of two groups : ( 406 to a drug treatment group and 379 to a control group ) for a five-year controlled drug treatment trial to evaluate the effect of therapy on cardiovascular complications . Drug treatment started with hydrochlorothiazide . If systolic blood pressure remained above 140 mm Hg and /or diastolic blood pressure above 90 mm Hg , alphamethyldopa was added . If there were side effects , methyldopa was replaced with propranolol . The control group was not given a placebo . The mean observation time was 66 months ( range 60 to 78 months ) . A difference in blood pressure between groups of about 17 mm Hg systolic and 10 mm Hg diastolic was maintained throughout the study . The study protocol had a rather low " ethical " blood pressure roof , 180 mm Hg systolic and /or 110 mm Hg diastolic . Seventeen percent of the control group had an increase in blood pressure above this level during the trial , and drug treatment was started . There was no effect on major cardiovascular morbidity comparing groups as established by r and omization , with 18 events in the treatment group and 20 events in the control group . There was no difference between the groups in total mortality and mortality from cardiovascular events . However , in the subgroups with diastolic blood pressure greater than or equal to 100 mm Hg before r and omization , there was a probable reduction in total morbidity from cardiovascular events in favor or the group receiving drug therapy , 7.6 and 16.4 percent events in the treated and control groups , respectively . Cerebrovascular events occurred only in the control group , 7 versus 0 . Two cases of fatal aortic aneurysms also occurred in the control group . Other " pressure " complications , such as marked left ventricular hypertrophy in the electrocardiogram and left ventricular failure , occurred only in the control group . However , regarding coronary heart disease , including sudden death , the incidence tended to be higher in the treated group , although it was not statistically significant . Only 13 men ( 1.7 percent ) failed to meet for regular examinations . At the end of the study these men were also followed up with regard to possible cardiovascular events National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure ( BP ) . However , data to support such recommendations in older persons are virtually nonexistent . The Trials of Nonpharmacologic Intervention in the Elderly ( TONE ) is a r and omized , controlled trial that will test whether weight loss or a reduced sodium ( Na ) intake or both can maintain satisfactory BP control , without unacceptable side effects , after withdrawal of antihypertensive drug therapy . Medication-treated hypertensives ( aged 60 to 80 years ) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are r and omly assigned to one of four groups : ( 1 ) weight loss alone , ( 2 ) reduced Na intake alone , ( 3 ) combined weight loss and reduced Na intake , or ( 4 ) usual life-style ( control group ) .  Overweight participants are r and omized to one of these four groups , while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group . The interventions , tailored to the needs of older persons , use behavioral approaches to accomplish intervention-specific goals ( weight loss > or = 10 lb , daily Na intake < or = 80 mEqa ) . Three months after the start of intervention , antihypertensive drug therapy is withdrawn . The primary trial end point is a BP of 150/90 mm Hg or higher , resumption of antihypertensive drug therapy , or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up . It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy Background and Objectives : Older adults ' adherence to antihypertensive medications is far lower than what is considered necessary for clinical effectiveness , despite the risks for adverse cardiovascular events from uncontrolled blood pressure ( BP ) in the elderly . This pilot study tested a novel 8-week behavioral feedback intervention to improve antihypertensive medication adherence ( MA ) and BP control among older adults on existing treatment for hypertension . Methods : Adults 60 years old , or older taking at least 1 antihypertensive medication were r and omized to receive the nurse-delivered adherence intervention or usual care . Medication adherence was monitored continuously using electronic monitoring for 20 weeks . Intervention-group participants received biweekly MA and BP feedback , habit counseling , medication and disease education , a medication instruction card , and were given an electronic medication bottle cap with a digital display that provided daily adherence feedback during the 8-week intervention . Blood pressure was measured by a nurse at 12 and 20 weeks after r and omization . Adherence and BP outcomes were described using descriptive statistics and analyzed for between- and within-group differences using Mann-Whitney U tests . Results : Fifteen participants ( median age , 71 years ; 73 % female ) were eligible for r and omization . Participants took an average of 5.8 prescription medications and 2.93 over-the-counter medications per day . A nonsignificant difference was noted in baseline MA between groups . At the end of the intervention , the treatment group had better antihypertensive MA than did the control group ( median MA : 100 % vs 27.3 % , U = 5.00 , P = .013 ) . Systolic BP improved slightly in the intervention group during the study and was significantly different at week 12 ( median systolic BP : 130 vs 152 mm Hg ; U = 4.50 , P = .008 ) . Diastolic BP was largely unchanged over the course of the study . Conclusion : The results indicate that the intervention had a positive effect on MA . Additional testing is needed to further evaluate the intervention and its effect on adherence behavior and BP control 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 The benefits of lowering a systolic blood pressure below 140 mmHg in elderly hypertension remain controversial . This study is a prospect i ve , r and omized , open-label study with blinded assessment of endpoints to compare the 2-year effect of strict treatment to maintain systolic blood pressure below 140 mmHg with that of mild treatment to maintain systolic blood pressure below 160 but at or above 140 mmHg in elderly hypertensive patients . Patients with essential hypertension ( 65–85 years old , with a pretreatment systolic blood pressure of above 160 mmHg ) were r and omly assigned to receive strict treatment ( n=2,212 ) or mild treatment ( n=2,206 ) . The baseline drug was efonidipine hydrochloride , a long-acting calcium antagonist . The primary endpoint was the combined incidence of cardiovascular disease and renal failure , and the secondary endpoints were total deaths and any safety problems . Although final blood pressures ( systolic/diastolic ) were significantly lower in the strict-treatment group compared with the mild-treatment group ( 135.9/74.8 vs. 145.6/78.1 mmHg ; p<0.001 ) , the incidence of the primary endpoint was similar in the two groups ( 86 patients in each group ; p=0.99 ) . Total deaths were 54 in the strict-treatment group vs. 42 in the mild-treatment group ( p=0.22 ) , and treatment was withdrawn because of adverse events in 36 patients in each group ( p=0.99 ) . An interaction between age and treatment for the primary endpoints ( p=0.03 ) was seen . Complex clinical features associated with aging seem to have obscured the difference in effect between the two treatments . Further studies are needed to assess the optimal treatment strategy for hypertension in the elderly This was a prospect i ve , cluster r and omized controlled trial in patients with uncontrolled hypertension aged 21 to 85 years ( mean , 61 years ) .  Pharmacists made recommendations to physicians for patients in the intervention clinics ( n=101 ) but not patients in the control clinics ( n=78 ) . The mean adjusted difference in systolic blood pressure ( BP ) between the control and intervention groups was 8.7 mm Hg ( 95 % confidence interval [ CI ] , 4.4 - 12.9 ) , while the difference in diastolic BP was 5.4 mm Hg ( CI , 2.8 - 8.0 ) at 9 months . The 24-hour BP levels showed similar effects , with a mean systolic BP level that was 8.8 mm Hg lower ( CI , 5.0 - 12.6 ) and a mean diastolic BP level that was 4.6 mm Hg ( CI , 2.4 - 6.8 ) lower in the intervention group . BP was controlled in 89.1 % of patients in the intervention group and 52.9 % in the control group ( adjusted odds ratio , 8.9 ; CI , 3.8 - 20.7 ; P<.001 ) . Physician/pharmacist collaboration achieved significantly better mean BP values and overall BP control rates , primarily by intensification of medication therapy and improving patient adherence Background : High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes , including coronary heart disease , stroke , decompensated heart failure , chronic kidney disease , and decline in cognitive function . Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg . Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease . However , the optimal systolic blood pressure to reduce blood pressure – related adverse outcomes is unclear , and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large , definitive clinical trial . Purpose : To describe the design considerations of the Systolic Blood Pressure Intervention Trial ( SPRINT ) and the baseline characteristics of trial participants . Methods : The Systolic Blood Pressure Intervention Trial is a multicenter , r and omized , controlled trial that compares two strategies for treating systolic blood pressure : one targets the st and ard target of < 140 mm Hg , and the other targets a more intensive target of < 120 mm Hg . Enrollment focused on volunteers of age ≥50 years ( no upper limit ) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease , chronic kidney disease , 10-year Framingham cardiovascular disease risk score ≥15 % , or age ≥75 years . The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups : participants with chronic kidney disease ( estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) , participants with a history of cardiovascular disease , and participants 75 years of age or older . The primary outcome is first the occurrence of a myocardial infa rct ion ( MI ) , acute coronary syndrome , stroke , heart failure , or cardiovascular disease death . Secondary outcomes include all-cause mortality , decline in kidney function or development of end-stage renal disease , incident dementia , decline in cognitive function , and small-vessel cerebral ischemic disease . Results : Between 8 November 2010 and 15 March 2013 , Systolic Blood Pressure Intervention Trial recruited and r and omized 9361 people at 102 clinics , including 3331 women , 2648 with chronic kidney disease , 1877 with a history of cardiovascular disease , 3962 minorities , and 2636 ≥75 years of age . Limitations : Although the overall recruitment target was met , the numbers recruited in the high-risk subgroups were lower than planned . Conclusions : The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants , including those with prior cardiovascular disease , chronic kidney disease , and those aged ≥75 years Objective To assess whether lifestyle counselling is effective in non-pharmacological treatment of hypertension in primary health care . Design Open r and omized controlled trial . Setting Ten municipal primary health care centres in eastern Finl and . Patients Seven hundred and fifteen subjects aged 25–74 years with systolic blood pressure 140–179 mmHg and /or diastolic blood pressure 90–109 mmHg or antihypertensive drug treatment . Interventions Systematic health counselling given by local public health nurses for 2 years . Main outcome measures Blood pressure , lipids and lifestyle data were collected annually . Results Among participants with no antihypertensive drug treatment , the net reductions after 1 year both in systolic blood pressure [ −2.6 mmHg ; 95 % confidence interval ( CI ) , −4.7 to −0.5 mmHg ] and in diastolic blood pressure ( −2.7 mmHg ; 95 % CI , −4.0 to −1.4 mmHg ) were significant in favour of the intervention group . This difference in blood pressure change was maintained during the second year . In participants with antihypertensive drug treatment , no significant difference in blood pressure reduction was seen between the groups during the study . Conclusions A relatively modest , but systematic counselling in primary health care can , at least among untreated hypertensive subjects , produce reductions in blood pressure levels that are modest for the individual , but very important from the public health point of view 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
The effects of delayed BP lowering treatment on long-term all-cause and CVD mortality did not vary with baseline risk of CVD .
The review showed no clinical ly adverse ‘ legacy effect ’ on mortality or major CVD event from not treating middle-aged adults at a systolic BP threshold of 140 mmHg or over .
Although these studies are non-r and omised post-hoc analyses , they may allay concerns that early treatment of elevated systolic BP is necessary to prevent CVD events in primary prevention population
To investigate if there is evidence for a ‘ legacy effect ’ for blood pressure ( BP ) lowering treatment , that is , worse health outcomes from not initiating drug treatment at a systolic BP threshold of 140 mmHg in middle-age adults .