IMProving Adherence using Combination Therapy (IMPACT): design and protocol of a randomised controlled trial in primary care. A Polypill for primary prevention of cardiovascular disease: A feasibility study of the World Health Organization Cardiovascular disease risk reduction in rural China: a clustered randomized controlled trial in Zhejiang PolyPill for Prevention of Cardiovascular Disease in an Urban Iranian Population with Special Focus on Nonalcoholic Steatohepatitis: A Pragmatic Randomized Controlled Trial within a Cohort (PolyIran - Liver) - Study Protocol. Evaluating the impact of population and high-risk strategies for the primary prevention of cardiovascular disease. An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk Electronic Health Record-Based Patient Identification and Individualized Mailed Outreach for Primary Cardiovascular Disease Prevention: A Cluster Randomized Trial Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE): rationale and design of a randomised controlled trial of a cardiovascular preventive polypill-based strategy in India and Europe Cardiovascular complications of HIV: an overview of risk and a novel approach to prevention – the HIV polypill study Simultaneous treatment to attain blood pressure and lipid goals and reduced CV risk burden using amlodipine/atorvastatin single-pill therapy in treated hypertensive participants in a randomized controlled trial An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial The preventing recurrent vascular events and neurological worsening through intensive organized case-management (PREVENTION) trial protocol [clinicaltrials.gov identifier: NCT00931788] Estimated cardiovascular relative risk reduction from fixed-dose combination pill (polypill) treatment in a wide range of patients with a moderate risk of cardiovascular disease Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study. HOT Study Group.
BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death , and principal reason for the large difference in life expectancy between indigenous Māori and the non-indigenous population in New Zeal and . CVD guidelines recommend that people who are at high risk or who have had previous CVD should be offered aspirin , blood pressure lowering and lipid lowering therapies . However , prescribing and adherence rates are low and CVD events remain high . AIM To assess whether a medication strategy using a fixed dose combination pill ( ' polypill ' ) could improve prescribing and adherence to recommended medications , lower blood pressure and improve lipids compared with current care over 12 months . METHODS IMProving Adherence using Combination Therapy ( IMPACT ) is an open-label r and omised controlled trial comparing a once-daily polypill containing four preventive medications with usual care .  Six hundred participants who have had previous CVD events or are at high risk of CVD will be enrolled , including 300 Māori . Participants are identified , enrolled and prescribed either the polypill or current medications at their usual primary health care practice , with medications ( including the polypill ) dispensed through local community pharmacies . The polypill contains 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril and either 12.5 mg hydrochlorothiazide or 50 mg atenolol . Primary outcomes are adherence to guidelines -recommended medications and changes in systolic blood pressure and low density lipoprotein at 12 months . Secondary outcomes include other lipids , medication dispensing , barriers to adherence , CVD and other serious adverse events , quality of life and prescriber acceptability . The trial is registered with the Australian New Zeal and Clinical Trial Registry ( ACTRN12606000067572 ) Background The feasibility of conducting a large-scale Polypill clinical trial in developing countries remains unclear . More information is needed regarding the efficacy in reducing the risk factors of cardiovascular disease ( CVD ) , side effects , improvement in adherence and physician/patient " acceptability " of the Polypill . Methods We conducted an open-label , parallel-group , r and omized clinical trial involving three sites in Sri Lanka that enrolled a total of 216 patients without established CVD . The trial compared a Polypill ( 75 mg aspirin , 20 mg simvastatin , 10 mg lisinopril and 12.5 mg hydrochlorothiazide ) to St and ard Practice . After r and omization , patients were followed monthly for three months . Pre-specified primary outcomes included reduction in systolic blood pressure , total cholesterol and estimated 10-year CVD risk . We also evaluated the recruitment process and acceptability of the Polypill by both physicians and patients . Results Patients were recruited in a six-month period as planned . Two hundred three patients ( 94.0 % ) completed the treatment program and returned for their three-month follow-up visits . No safety concerns were reported . These findings suggest a high rate of patient acceptability , a finding that is bolstered by the majority of patients completing the trial ( 90 % ) indicating that they would take the Polypill " for life " if proven to be effective in reducing CVD risk . Approximately 86 % of the physicians surveyed agreed with and supported use of the Polypill for primary prevention and 93 % for secondary prevention of CVD . Both the Polypill and St and ard Practice result ed in marked reductions in systolic blood pressure , total cholesterol and 10-year risk of CVD . However , the differences between the treatment groups were not statistically significant . Conclusions We successfully completed a Polypill feasibility trial in Sri Lanka . We were able to document high acceptability of the Polypill to patients and physicians . We were unable to estimate the risk factor reductions on the Polypill because the control group received similar treatment with individual drugs . The Polypill was however simpler and achieved comparable risk factor reductions , highlighting its potential usefulness in the prevention of CVD.Trial registration number Clinical trials.gov : Background Cardiovascular disease ( CVD ) is a major cause of death in China . Despite government efforts , the majority of hypertensive and diabetic patients in China do not receive proper treatment . Reducing CVD events requires long-term care that is proactive , patient-centred , community-based , and sustainable . We have design ed a package of interventions for patients at high risk of CVD to be implemented by family doctors based in township hospitals ( providers of primary care ) in rural Zhejiang , China . This trial aims to determine whether the systematic CVD risk reduction package results in reduced CVD events among patients at risk of CVD compared with usual care , and whether the package is cost-effective and suitable for routine implementation and scale-up . Methods / Design This is a prospect i ve , open-label , cluster r and omized controlled trial ( RCT ) with blinded data analysis . The trial will r and omize 67 township hospitals with 31,708 participants in three counties in Zhejiang Province . Participants will be identified from existing health records and will comprise adults aged 50 to 74 years , with a calculated 10-year CVD risk of 20 % or higher , or diabetes . In the intervention arm , participants will receive a package of interventions including : 1 ) healthy lifestyle counseling ( smoking cessation , and salt , oil , and alcohol reduction ) ; 2 ) prescription of a combination of drugs ( antihypertensives , aspirin , and statin ) ; and 3 ) adherence support for drug compliance and healthy lifestyle change . In the control arm , participants will receive usual care for hypertension and diabetes management at individual clinicians ’ discretion . The primary outcome is the incidence of severe CVD events over 24 months of follow-up . All CVD events will be defined according to the World Health Organization ( WHO ) monitoring of trends and determinants in cardiovascular disease ( MONICA ) definitions , diagnosed at the county hospital or higher level , and reported by the Zhejiang surveillance system . Secondary outcomes include : mean systolic and diastolic blood pressure , blood glucose , serum total cholesterol ( TC ) , and adherence to appointments , and drugs and lifestyle changes . Discussion This trial focuses on risk reduction of CVD rather than specific diseases . It is not design ed to compare therapeutic and healthy lifestyle interventions , but rather their combined effects in primary care setting s. Through the trial , we intend to underst and the effectiveness of the comprehensive CVD reduction package in routine practice . We also intend to underst and the barriers and facilitators to implementing the package , and thus to advise on policy and practice change . Trial registration Current Controlled Trials : IS RCT BACKGROUND Cardiovascular disease ( CVD ) is among the most common causes of mortality in all population s. Nonalcoholic steatohepatitis is a common finding in patients with CVD . Prevention of CVD in individual patients typically requires periodic clinical evaluation , as well as diagnosis and management of risk factors such as hypertension and hyperlipidemia . However , this is re source consuming and hard to implement , especially in developing countries . We design ed a study to investigate the effects of a simpler strategy : a fixed-dose combination pill consisting of aspirin , valsartan , atorvastatin and hydrochlorthiazide ( PolyPill ) in an unselected group of persons aged over 50 years . DESIGN The PolyIran-Liver study was performed in Gonbad city as an open label pragmatic r and omized controlled trial nested within the Golestan Cohort Study . We r and omly selected 2,400 cohort study participants aged above 50 years , r and omly assigned them to intervention or usual care and invited them to participate in an additional measurement study ( if they met the eligibility criteria ) to measure liver related outcomes . Those agreeing and r and omized to the intervention arm were offered a daily single dose of PolyPill . We will follow participants for 5 years . The primary outcome is major cardiovascular events , secondary outcomes include all-cause mortality and liver related outcomes : liver stiffness and liver enzyme levels . Cardiovascular outcomes and mortality will be determined from the cohort study and liver-related outcomes in those consenting to follow up . Analysis will be by allocated group . TRIAL STATUS Between October and December 2011 , 1,320 intervention and 1,080 control participants were invited to participate in the additional measurement study . For all these participants , the major cardiovascular events will be determined using blind assessment of outcomes through the cohort study . In the intervention and control arms , 875 ( 66 % ) and 721 ( 67 % ) respectively , met the eligibility criteria and agreed to participate in the additional measurement study . Liver related outcomes will be measured in these participants . Of the 1,320 participants r and omized to the intervention , 787 ( 60 % ) accepted the PolyPill . CONCLUSION The PolyIran-liver urban study will provide us with important information on the effectiveness of PolyPill on major cardiovascular events , all-cause mortality and liver related outcomes . ( Clinical Trials.gov ID : NCT01245608 ) AIMS To estimate the potential effectiveness of different " high-risk " and " population " approaches to the primary prevention of  cardiovascular disease ( CVD ) in middle-aged British men , after correction for regression dilution bias . METHODS AND RESULTS We used a combination of cohort and r and omised controlled trial evidence to estimate the effectiveness of high-risk strategies , based on the identification of high-risk factors or high absolute risk , and strategies based on population -wide reductions in cholesterol and blood pressure . High-risk strategies were potentially effective but would need to be used widely to have a substantial effect on CVD in the population . Aggressive pharmacological treatment ( using statins , beta-blockers , ACE-inhibitors and aspirin ) in individuals with a 10-year Framingham event risk of > or=30 % ( 6 % of population ) would have reduced major CVD by at most 11 % . This figure increased to 34 % at a > or=20 % treatment threshold ( 26 % of population ) . In contrast , modest downwards shifts in the population distributions of serum total cholesterol and systolic blood pressure led to marked expected reductions in major CVD . Taking regression dilution bias into account , 10 % reductions in long-term mean blood cholesterol and blood pressure could have reduced major CVD by 45 % . CONCLUSIONS If high-risk strategies are to have a major impact on CVD in the population , they need to be more widely used than previously envisaged . Population -wide reduction of major risk factors is needed if CVD is to be substantially reduced AIMS To examine the unanticipated , excess mortality observed in patients r and omized to clopidogrel and aspirin vs. aspirin alone  in the prespecified ' asymptomatic ' subgroup of CHARISMA , we investigated whether dual-antiplatelet therapy may be associated with adverse  cardiovascular ( CV )  events in a primary prevention population . METHODS AND RESULTS Of 15 603 patients enrolled , 3284 were initially categorized as asymptomatic with CV risk factors , but 995 had a prior CV event , leaving 2289 patients to represent the primary prevention cohort . This subset was compared with 13 148 symptomatic patients with established vascular disease and both were evaluated for CV death and bleeding . A multivariate analysis analysed predictors of CV death in this group . No post mortem data were available . Compared with aspirin alone , a significant increase in CV death ( P = 0.01 ) was observed in patients receiving dual-antiplatelet therapy in the asymptomatic population . Within the primary prevention cohort , this excess CV death was not significant ( P = 0.07 ) . Multivariate analysis of the primary prevention group showed a trend towards excess CV death ( P = 0.054 ; HR 1.72 ; CI 0.99 - 2.97 ) with dual-antiplatelet therapy ( aspirin plus clopidogrel ) . Other independent predictors of CV death included increasing age , hypertension , atrial fibrillation , and a history of heart failure . There was a non-significant increase in moderate or severe bleeding ( P = 0.218 ) with dual-antiplatelet therapy ; thus , bleeding was an unlikely explanation for the excess event rate . CONCLUSION These findings do not support the use of dual-antiplatelet therapy with clopidogrel and aspirin in a primary prevention population . In this subgroup analysis , CV death occurred more frequently than anticipated . The cause of this apparent harm is not eluci date d , may represent play of chance , but requires further prospect i ve evaluation Background It is hypothesized that in individuals without clinical cardiovascular disease ( CVD ) , but at increased CVD risk , a 50 % to 60 % reduction in CVD risk could be achieved using fixed dose combination ( FDC ) therapy ( usually comprised of multiple blood‐pressure agents and a statin [ with or without aspirin ] ) in a single “ polypill ” . However , the impact of a polypill in preventing clinical CV events has not been evaluated in a large r and omized controlled trial . Methods TIPS‐3 is a 2x2x2 factorial r and omized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population . This study aims to determine whether the Polycap ( comprised of atenolol , ramipril , hydrochlorothiazide , and a statin )  reduces CV events in persons without a history of CVD , but who are at least at intermediate CVD risk . Additional interventions in the factorial design of the study will compare the effect of ( 1 ) aspirin versus placebo on CV events ( and cancer ) , ( 2 ) vitamin D versus placebo on the risk of fractures , and ( 3 ) the combined effect of aspirin and the Polycap on CV events . Results The study has r and omized 5713 participants across 9 countries . Mean age of the study population is 63.9 years , and 53 % are female . Mean INTERHEART risk score is 16.8 , which is consistent with a study population at intermediate CVD risk . Conclusion Results of the TIP‐3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD Background Most individuals at high cardiovascular disease ( CVD ) risk worldwide do not receive any or optimal preventive drugs . We aim ed to determine whether fixed dose combinations of generic drugs ( ‘ polypills ’ ) would promote use of such medications . Methods We conducted a r and omized , open-label trial involving 623 participants from Australian general practice s. Participants had established CVD or an estimated five-year CVD risk of ≥15 % , with indications for antiplatelet , statin and ≥2 blood pressure lowering drugs ( ‘ combination treatment ’ ) . Participants r and omized to the ‘ polypill-based strategy ’  received a polypill containing aspirin 75 mg , simvastatin 40 mg , lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg . Participants r and omized to ‘ usual care ’ continued with separate medications and doses as prescribed by their doctor . Primary outcomes were self-reported combination treatment use , systolic blood pressure and total cholesterol . Results After a median of 18 months , the polypill-based strategy was associated with greater use of combination treatment ( 70 % vs. 47 % ; relative risk 1.49 , ( 95 % confidence interval ( CI ) 1.30 to 1.72 ) p < 0.0001 ; number needed to treat = 4.4 ( 3.3 to 6.6 ) ) without differences in systolic blood pressure ( −1.5 mmHg ( 95 % CI −4.0 to 1.0 ) p = 0.24 ) or total cholesterol ( 0.08 mmol/l ( 95 % CI −0.06 to 0.22 ) p = 0.26 ) . At study end , 17 % and 67 % of participants in polypill and usual care groups , respectively , were taking  atorvastatin  or rosuvastatin . Conclusion Provision of a polypill improved self-reported use of indicated preventive treatments . The lack of differences in blood pressure and cholesterol may reflect limited study power , although for cholesterol , improved statin use in the polypill group counter-balanced use of more potent statins with usual care ABSTRACT BACKGROUND Many individuals at higher risk for cardiovascular disease ( CVD ) do not receive recommended treatments . Prior interventions using personalized risk information to promote prevention did not test clinic-wide effectiveness . OBJECTIVE AND DESIGN To perform a 9-month cluster-r and omized trial , comparing a strategy of electronic health record-based identification of patients with increased CVD risk and individualized mailed outreach to usual care . PARTICIPANTS Patients of participating physicians with a Framingham Risk Score of at least 5 % , low-density lipoprotein (LDL)-cholesterol level above guideline threshold for drug treatment , and not prescribed a lipid-lowering medication were included in the intention-to-treat analysis .INTERVENTION Patients of physicians r and omized to the intervention group were mailed individualized CVD risk messages that described benefits of using a statin ( and controlling hypertension or quitting smoking when relevant).MAIN MEASURES The primary outcome was occurrence of a LDL-cholesterol level , repeated in routine practice , that was at least 30 mg/dl lower than prior . A secondary outcome was lipid-lowering drug prescribing . Clinical trials.gov identifier : NCT01286311.KEY RESULTS Fourteen physicians with 218 patients were r and omized to intervention , and 15 physicians with 217 patients to control . The mean patient age was 60.7 years and 77 % were male . There was no difference in the primary outcome ( 11.0 % vs. 11.1 % , OR 0.99 , 95 % CI 0.56–1.74 , P = 0.96 ) , but intervention group patients were twice as likely to receive a prescription for lipid-lowering medication ( 11.9 % , vs. 6.0 % , OR 2.13 , 95 % CI 1.05–4.32 , p = 0.038 ) . In post hoc analysis with extended follow-up to 18 months , the primary outcome occurred more often in the intervention group ( 22.5 % vs. 16.1 % , OR 1.59 , 95 % CI 1.05–2.41 , P = 0.029 ) . CONCLUSIONS In this effectiveness trial , individualized mailed CVD risk messages increased the frequency of new lipid-lowering drug prescriptions , but we observed no difference in proportions lowering LDL-cholesterol after 9 months . With longer follow-up , the intervention ’s effect on LDL-cholesterol levels was apparent Most patients with type 2 diabetes mellitus develop cardiovascular disease ( CVD ) , with substantial loss of life expectancy . Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes . The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge . Despite the importance of this health problem , there is a lack of definitive data on the effects of the intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes . The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial is a r and omized , multicenter , double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors . ACCORD is testing the effects of 3 medical treatment strategies to reduce CVD morbidity and mortality . All participants are in the glycemia trial , which is testing the hypothesis that a therapeutic strategy that targets a glycosylated hemoglobin ( HbA1c ) level of < 6.0 % will reduce the rate of CVD events more than a strategy that targets an HbA1c level of 7.0%-7.9 % . The lipid trial includes 5,518 of the participants , who receive either fenofibrate or placebo in a double-masked fashion to test the hypothesis of whether , in the context of good glycemic control , a therapeutic strategy that uses a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels together with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) to lower low-density lipoprotein cholesterol will reduce the rate of CVD events compared with a strategy that uses a statin plus a placebo . The blood pressure trial includes the remaining 4,733 participants and tests the hypothesis that a therapeutic strategy that targets a systolic blood pressure of < 120 mm Hg in the context of good glycemic control will reduce the rate of CVD events compared with a strategy that targets a systolic blood pressure of < 140 mm Hg . The primary outcome measure for all 3 research questions is the first occurrence of a major CVD event , specifically nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death . Upon the expected completion of participant follow-up in 2009 , the ACCORD trial should document for the first time the benefits and risks of intensive glucose control , intensive blood pressure control , and the combination of fibrate and statin drugs in managing blood lipids in high-risk patients with type 2 diabetes The use of preventive medications in people at high risk of cardiovascular disease is conceptually straightforward , yet in practice the adoption of such measures is disappointingly low , plus there is wide international variation in preventive therapies . Several barriers might explain this shortfall and variation , but the simplicity and economy of a polypill-based strategy might overcome some barriers . The ‘ Use of a Multidrug Pill In Reducing cardiovascular Events ’ ( UMPIRE ) trial assesses whether a polypill strategy ( by combining aspirin , a statin and two blood pressure lowering agents ) would improve adherence to guideline -indicated therapies and would lower both blood pressure and cholesterol , in people with established cardiovascular disease . UMPIRE , running in India and three European countries ( Engl and , Irel and and the Netherl and s ) , is an open , r and omised , controlled trial design ed to include 1000 participants in India and 1000 in Europe , with a followup of 12–24 months . Participants were r and omised to one of two versions of the polypill or relegated to usual care . The primary study outcomes were the self-reported use of aspirin , a statin and at least two blood pressure lowering agents ; as well as changes in blood pressure and cholesterol . Secondary outcomes included : any cardiovascular events , reasons for stopping medications , serious adverse events and perceived changes in quality of life . Interpretation of the study data will be enhanced by health , economic and process-related evaluations . UMPIRE is registered with the European Clinical Trials data base , as EudraCT : 2009 - 016278 - 34 and the Clinical Trials Registry , India as CTRI/2010/091/000250 . The trial was part of the ‘ Single Pill Against Cardiovascular Events ( SPACE ) ’ collaboration , which encompasses the ‘ IMProving Adherence using Combination Therapy ( IMPACT ) ’ and ‘ Kanyini Guidelines Adherence with the Polypill ( Kanyini-GAP ) ’ trials Purpose of review To review the risk of cardiovascular complications in HIV-infected patients receiving combination antiretroviral treatment .  Recent findings Recent data suggest that patients with chronic HIV infection will require continuous lifelong combination antiretroviral treatment , which may increase the risk of cardiovascular disease in all population s by substantial amounts . Simple , safe and effective interventions to reduce cardiovascular complications in HIV-infected patients will be required . Studies in the general population suggest that the primary prevention of cardiovascular disease with a pill combining blood-pressure-lowering , cholesterol-lowering and antiplatelet treatments ( a polypill ) might decrease cardiovascular events . An HIV polypill study with 8000 HIV-infected patients with a moderate risk of cardiovascular disease r and omized to either a polypill of low-dose pravastatin , aspirin , hydrochlorothiazide and lisinopril or to placebo is described . The primary clinical endpoint would be a composite of cardiovascular mortality , non-fatal myocardial infa rct ion and stroke .  A vanguard study of 400 patients could assess changes in cholesterol , blood pressure and other risk factors . The clinical endpoint study described would have 80 % power to detect a 23 % reduction in the rate of cardiovascular events in the polypill arm . Summary A study of a polypill like that proposed for the general population will provide crucial information on the risks and benefits of primary cardiovascular prevention in HIV-infected patients TOGETHER investigated whether targeting multiple cardiovascular ( CV ) risk factors using single-pill amlodipine/atorvastatin ( AML/ATO ) and therapeutic lifestyle changes ( TLC ) results in greater blood pressure (BP)/lipid control and additional reduction in estimated cardiovascular disease ( CVD ) risk compared with blood pressure intervention only using amlodipine ( AML ) + TLC . TOGETHER was a 6-week , r and omized , double-blind , double-dummy trial using hypertensive participants with additional CV risk factors without CVD/diabetes . Participants were r and omized to either AML/ATO ( 5 to 10/20 mg ) + TLC or AML ( 5 to 10 mg ) + TLC . The primary end point was the difference in proportion of participants attaining both BP ( < 140/90 mm Hg ) and low-density lipoprotein cholesterol ( LDL-C ) ( < 100 mg/dL ) goals at week 6 . At week 6 , 67.8 % of participants receiving AML/ATO + TLC attained the combined BP/LDL-C goal versus 9.6 % with AML + TLC ( RD [ A – B ] : 58.2 ; 95 % CI [ 48.1 to 68.4 ] P < 0.001 ; OR : 19.0 ; 95 % CI 9.1 to 39.6 ; P < 0.001 ) . Significant reductions from baseline in LDL-C , total cholesterol and triglycerides and estimated 10-year Framingham risk were also observed . Treatment with AML/ATO was well tolerated . In conclusion , a multifactorial CV management approach is more effective in achieving combined BP/LDL-C targets as well as CV risk reduction compared with BP intervention only in this patient population Background Cardiovascular diseases ( CVD ) are responsible for significant morbidity , premature mortality , and economic burden . Despite established evidence that supports the use of preventive medications among patients at high CVD risk , treatment gaps remain . Building on prior evidence and a theoretical framework , a complex intervention has been design ed to address these gaps among high-risk , under-treated patients in the Australian primary care setting . This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities ; availability of a range of CVD polypills ( fixed-dose combinations of two blood pressure lowering agents , a statin ± aspirin ) for prescription when appropriate ; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification . Methods Following a systematic development process , the intervention will be evaluated in a pragmatic cluster r and omized controlled trial including 70 general practice s for a median period of 18 months . The 35 general practice s in the intervention group  will work with a nominated partner pharmacy , whereas those in the control group will provide usual care without access to the intervention tools . The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) levels at the study end . The outcomes will be analyzed using data from electronic medical records , utilizing a vali date d extraction tool . Detailed process and economic evaluations will also be performed . Discussion The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients , pharmacists , and general practitioners ( GPs ) for CVD prevention . Trial registration Australian New Zeal and Clinical Trials Registry Background Survivors of transient ischemic attack ( TIA ) or stroke are at high risk for recurrent vascular events and aggressive treatment of vascular risk factors can reduce this risk . However , vascular risk factors , especially hypertension and high cholesterol , are not managed optimally even in those patients seen in specialized clinics . This gap between the evidence for secondary prevention of stroke and the clinical reality leads to suboptimal patient outcomes . In this study , we will be testing a pharmacist case manager for delivery of stroke prevention services . We hypothesize this new structure will improve processes of care which in turn should lead to improved outcomes . Methods We will conduct a prospect i ve , r and omized , controlled open-label with blinded ascertainment of outcomes ( PROBE ) trial . Treatment allocation will be concealed from the study personnel , and all outcomes will be collected in an independent and blinded manner by observers who have not been involved in the patient 's clinical care or trial participation and who are masked to baseline measurements . Patients will be  r and omized to control or a pharmacist case manager treating vascular risk factors to guideline -recommended target levels . Eligible patients will include all adult patients seen at stroke prevention clinics in Edmonton , Alberta after an ischemic stroke or TIA who have uncontrolled hypertension ( defined as systolic blood pressure ( BP ) > 140 mm Hg ) or dyslipidemia ( fasting LDL-cholesterol > 2.00 mmol/L ) and who are not cognitively impaired or institutionalized . The primary outcome will be the proportion of subjects who attain ' optimal BP and lipid control'(defined as systolic BP < 140 mm Hg and fasting LDL cholesterol < 2.0 mmol/L ) at six months compared to baseline ; 12-month data will also be collected for analyses of sustainability of any effects . A variety of secondary outcomes related to vascular risk and health-related quality of life will also be collected . Conclusions Nearly one-quarter of those who survive a TIA or minor stroke suffer another vascular event within a year . If our intervention improves the provision of secondary prevention therapies in these patients , the clinical ( and financial ) implication s will be enormous Aims Recent data indicate that fixed-dose combination ( FDC ) pills , polypills , can produce sizeable risk factor reductions . There are very few published data on the consistency of the effects of a polypill in different patient population s. It is unclear for example whether the effects of the polypill are mainly driven by the individuals with high individual risk factor levels . The aim of the present study is to examine whether baseline risk factor levels modify the effect of polypill treatment on low-density lipoprotein (LDL)-cholesterol , blood pressure ( BP ) , calculated cardiovascular relative risk reduction and adverse events . Methods This paper describes a post-hoc analysis of a r and omised , placebo-controlled trial of a polypill ( containing aspirin 75 mg , simvastatin 20 mg , lisinopril 10 mg and hydrochlorothiazide 12.5 mg ) in 378 individuals without an indication for any component of the polypill , but who had an estimated five-year risk for cardiovascular disease ≥7.5 % . The outcomes considered were effect modification by baseline risk factor levels on change in LDL-cholesterol , systolic BP , calculated cardiovascular relative risk reduction and adverse events . Results The mean LDL-cholesterol in the polypill group was 0.9 mmol/l ( 95 % confidence interval ( CI ) : 0.8–1.0 ) lower compared with the placebo group during follow-up . Those with a baseline LDL-cholesterol > 3.6 mmol/l achieved a greater absolute LDL-cholesterol reduction with the polypill compared with placebo , than patients with an LDL-cholesterol ≤3.6 mmol/l ( −1.1 versus −0.6 mmol/l , respectively ) . The mean systolic BP was 10 mm Hg ( 95 % CI : 8–12 ) lower in the polypill group . In participants with a baseline systolic BP > 135 mm Hg the polypill result ed in a greater absolute systolic BP reduction with the polypill compared with placebo , than participants with a systolic BP ≤ 135 mm Hg ( −12 versus −7 mm Hg , respectively ) . Calculated from individual risk factor reductions , the mean cardiovascular relative risk reduction was 48 % ( 95 % CI : 43–52 ) in the polypill group . Both baseline LDL-cholesterol and estimated cardiovascular risk were significant modifiers of the estimated cardiovascular relative risk reduction caused by the polypill . Adverse events did not appear to be related to baseline risk factor levels or the estimated cardiovascular risk . Conclusion This study demonstrated that the effect of a cardiovascular polypill on risk factor levels is modified by the level of these risk factors . Groups defined by baseline LDL-cholesterol or systolic BP had large differences in risk factor reductions but only moderate differences in estimated cardiovascular relative risk reduction , suggesting also that patients with mildly increased risk factor levels but an overall raised cardiovascular risk benefit from being treated with a polypill BACKGROUND The Hypertension Optimal Treatment ( HOT ) Study has provided information about cardiovascular events in 18790 hypertensives , subjected to pronounced blood pressure ( BP ) lowering for a mean of 3.8 years . The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk , and it has been found that , despite intensive blood pressure lowering in all risk strata , morbid event rates increased with increasing risk stratum . OBJECTIVES Previously analysed global risk strata were based on combinations of risk factors . The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk , despite good BP control . METHODS Risk ratios ( RR ) for patients with and those without a risk factor were calculated with 95 % confidence intervals ( CI ) using a Cox proportional hazard model , and adjusted for all variables except the one under examination . RESULTS For all risk factors considered and for all types of event , RR were always greater than 1 , indicating a greater risk in the presence , compared with that in the absence of each factor . The male gender was a statistically significant risk for cardiovascular ( CV ) events , CV and total mortality and particularly for myocardial infa rct ion ( MI ) ; age > or = 65 years for CV events , stroke , CV and particularly total mortality ; smoking for all events analysed , but particularly for total mortality ( twice higher in smokers than in non-smokers ) ; high serum cholesterol ( > 6.8 mmol/l ) for CV events , MI and CV mortality ; high serum creatinine ( > 155 micromol/l ) for CV events , stroke , CV and total mortality ; diabetes for CV events , stroke , total mortality and particularly CV mortality ; and ischaemic heart disease for all events analysed . Adjusted RR were often close to or greater than 2 . CONCLUSIONS Each of the risk factors considered was found to be an important cause of residual risk , despite good BP control . These findings emphasize the importance of addressing other correctable risk factors , e.g. smoking , hypercholesterolaemia and diabetes , as well as rigorous control of blood pressure , and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest
Reductions in blood pressure and lipid parameters are generally lower than those previously projected , though substantial heterogeneity of results exists .
Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo , single drug active component , or usual care but may be associated with improved adherence to a multidrug regimen .
BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death and disability worldwide , yet CVD risk factor control and secondary prevention rates remain low .
A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill , or polypill , has been proposed as one strategy to reduce the global burden of CVD by up to 80 % given its potential for better adherence and lower costs .
OBJECTIVES To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD .
We also aim ed to determine discontinuation rates , adverse events , health-related quality of life , and costs of fixed-dose combination therapy .