IMProving Adherence using Combination Therapy (IMPACT): design and protocol of a randomised controlled trial in primary care. 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 Estimating the benefits of modifying risk factors of cardiovascular disease: a comparison of primary vs secondary prevention. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. 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 A Polypill for primary prevention of cardiovascular disease: A feasibility study of the World Health Organization Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. Global Risk Assessment to Guide Blood Pressure Management in Cardiovascular Disease Prevention 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. A cardiovascular disease policy model that predicts life expectancy taking into account socioeconomic deprivation A polypill strategy to improve adherence: results from the FOCUS project. Evaluating the impact of population and high-risk strategies for the primary prevention of cardiovascular disease. Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Cardiovascular complications of HIV: an overview of risk and a novel approach to prevention – the HIV polypill study World Salt Awareness Week. Cardiovascular disease risk reduction in rural China: a clustered randomized controlled trial in Zhejiang 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 The effects of Hartcoach, a life style intervention provided by telephone on the reduction of coronary risk factors: a randomised trial Using mobile technology to support lower-salt food choices for people with cardiovascular disease: protocol for the SaltSwitch randomized controlled trial Polypill for the prevention of cardiovascular disease (PolyIran): study design and rationale for a pragmatic cluster randomized controlled trial The Cholesterol, Hypertension, and Glucose Education (CHANGE) study for African Americans with diabetes: study design and methodology. Leisure time physical activity and long-term cardiovascular and cancer outcomes: the Busselton Health Study
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 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 OBJECTIVES To compare the potential years of life saved ( YOLS ) associated with risk factor modification in the primary and secondary prevention of cardiovascular disease ( CVD ) . METHODS The CVD life expectancy model estimates the risk of death due to coronary disease , stroke , and other causes based on the levels of independent risk factors ( such as age , blood pressure , and blood lipid levels ) found in the cohort of the Lipid Research Clinics . The model was vali date d by comparing its predictions with the observed fatal outcomes of 9 r and omized clinical trials . We then estimated the YOLS associated with treating hyperlipidemia or hypertension among hypothetical patient groups with and without CVD at baseline . We defined high-risk patients as those with 3 risk factors ( hyperlipidemia , cigarette smoking , and hypertension ) and low-risk patients as those with isolated hypertension or hyperlipidemia . RESULTS The fatal events predicted by the model were consistent with the clinical trial results . Among men and women with hyperlipidemia without CVD , the forecasted benefits of lipid therapy  were substantially greater among high-risk groups vs low-risk groups ( 4.74 - 0.78 YOLS vs 2.50 - 0.25 YOLS , respectively ) . Among those with CVD , the forecasted benefits of treatment were similar for both high-risk and low-risk groups ( 4.65 - 0.65 YOLS vs 3.84 - 0.58 YOLS , respectively ) . The results for  hypertension  therapy also demonstrated greater benefits for high-risk vs low-risk patients undergoing primary prevention therapy ( 1.34 - 0.29 YOLS vs 0.85 - 0.13 YOLS , respectively ) , and the forecasted benefits in secondary prevention were similar ( 1.26 - 0.23 YOLS vs 1.00 - 0.23 YOLS , respectively ) . CONCLUSIONS The clinical approach to risk factor modification in primary prevention should be different from that in secondary prevention . The forecasted benefits of therapy among patients without CVD are greatest in the presence of other risk factors . Among those with CVD , the benefits of therapy are equivalent , thereby obviating the need to target high-risk patients 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 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 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 : IMPORTANCE Most patients with cardiovascular disease ( CVD ) do not take recommended medications long-term . The use of fixed-dose combinations ( FDCs ) improves adherence in several clinical areas . Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment . OBJECTIVE To assess whether FDC delivery of aspirin , statin , and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors , systolic blood pressure ( SBP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PARTICIPANTS The UMPIRE trial , a r and omized , open-label , blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe . The trial follow-up concluded in July 2012 . INTERVENTIONS Participants were r and omly assigned ( 1:1 ) to an FDC-based strategy  ( n=1002 ) containing either ( 1 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 50 mg atenolol or ( 2 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 12.5 mg hydrochlorothiazide or to usual care ( n=1002 ) . MAIN OUTCOMES AND MEASURES Adherence to medication ( defined as self-reported use of antiplatelet , statin , and ≥2 BP-lowering medications ) and changes in SBP and LDL-C from baseline . RESULTS At baseline , mean BP was 137/78 mm Hg , LDL-C was 91.5 mg/dL , and 1233 ( 61.5 % ) of 2004 participants reported use of antiplatelet , statin , and 2 or more BP-lowering medications . Median follow-up was 15 months ( interquartile range , 12 - 18 months ) . The FDC group had improved adherence vs usual care ( 86 % vs 65 % ; relative risk [ RR ] of being adherent , 1.33 ; 95 % CI , 1.26 - 1.41 ; P < .001 ) with concurrent reductions in SBP ( -2.6 mm Hg ; 95 % CI , -4.0 to -1.1 mm Hg ; P < .001 ) and LDL-C ( -4.2 mg/dL ; 95 % CI , -6.6 to -1.9 mg/dL ; P < .001 ) at the end of the study . Although there was consistency of effects across predefined subgroups , evidence existed of larger benefits in patients with lower adherence at baseline . In this subgroup of 727 participants ( 36 % ) , adherence at the end of study was 77 % vs 23 % ( RR , 3.35 ; 95 % CI , 2.74 - 4.09 ; P < .001 for interaction ) , SBP was reduced by 4.9 mm Hg ( 95 % CI 7.3 - 2.6 mm Hg ; P = .01 for interaction ) , and LDL-C was reduced by 6.7 mg/dL ( 95 % CI , 10.5 - 2.8 mg/dL ; P = .11 for interaction ) . There were no significant differences in serious adverse events or cardiovascular events ( 50 [ 5 % ] in the FDC group and 35 [ 3.5 % ] in the usual care group ; RR , 1.45 ; 95 % CI , 0.94 - 2.24 ; P=.09 ) between the groups . CONCLUSIONS AND RELEVANCE Among patients with or at high risk of CVD , use of an FDC strategy for blood pressure , cholesterol , and platelet control vs usual care result ed in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION clinical trials.gov Identifier : NCT01057537 Elevated blood pressure ( BP ) is a causal risk factor for cardiovascular disease ( CVD ) . Epidemiological analyses have established the grade d and continuous association between higher BP and CVD . Moreover , r and omized clinical trials among individuals with hypertension have demonstrated , in aggregate , a reduction in CVD events by 20 % , coronary heart disease ( CHD ) by 17 % , stroke by 27 % , and heart failure by 28 % for every 10 mm Hg systolic BP ( SBP ) lowering with medical therapy.1 Therefore , prevention , detection , treatment , and control of elevated BP , and its clinical correlate hypertension , is an important public health priority and a primary target for CVD prevention . Although national health surveys have demonstrated improvements in hypertension awareness and treatment , strategic opportunities to improve the efficiency and efficacy of applying BP-lowering therapy in patients most likely to benefit remain.2 Global CVD risk assessment , using multivariable prediction models that estimate absolute CVD risk from routinely measured clinical variables , has been promulgated in several CVD prevention guidelines for cholesterol management to target the most intensive preventive therapies to those at highest absolute CVD risk.3–5 Hypertension guidelines , however , have instead relied solely on isolated BP thresholds and BP goals to guide treatment initiation and intensity . In this review , we provide a rationale for incorporating global CVD risk assessment in BP treatment decision-making and propose a framework to guide its implementation in future CVD prevention guidelines . Epidemiological analyses have firmly established that CVD is a multifactorial condition and that modest increases of several CVD risk factors can often lead to greater overall risk than a severe elevation of a 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 ) Objectives A policy model is a model that can evaluate the effectiveness and cost-effectiveness of interventions and inform policy decisions . In this study , we introduce a cardiovascular disease ( CVD ) policy model which can be used to model remaining life expectancy including a measure of socioeconomic deprivation as an independent risk factor for CVD . Design A state transition model was developed using the Scottish Heart Health Extended Cohort ( SHHEC ) linked to Scottish morbidity and death records . Individuals start in a CVD-free state and can transit to three CVD event states plus a non-CVD death state . Individuals who have a non-fatal first event are then followed up until death . Taking a competing risk approach , the cause-specific hazards of a first event are modelled using parametric survival analysis . Survival following a first non-fatal event is also modelled parametrically . We assessed discrimination , validation and calibration of our model . Results Our model achieved a good level of discrimination in each component ( c-statistics for men (women)—non-fatal coronary heart disease ( CHD ) : 0.70 ( 0.74 ) , non-fatal cerebrovascular disease ( CBVD ) : 0.73 ( 0.76 ) , fatal CVD : 0.77 ( 0.80 ) , fatal non-CVD : 0.74 ( 0.72 ) , survival after non-fatal CHD : 0.68 ( 0.67 ) and survival after non-fatal CBVD : 0.65 ( 0.66 ) ) . In general , our model predictions were comparable with observed event rates for a Scottish r and omised statin trial population which has an overlapping follow-up period with SHHEC . After applying a calibration factor , our predictions of life expectancy closely match those published in recent national life tables . Conclusions Our model can be used to estimate the impact of primary prevention interventions on life expectancy and can assess the impact of interventions on inequalities BACKGROUND Adherence to evidence -based cardiovascular ( CV ) medications after an acute myocardial infa rct ion ( MI ) is low after the first 6 months . The use of fixed-dose combinations ( FDC ) has been shown to improve treatment adherence and risk factor control . However , no previous r and omized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients . OBJECTIVES The cross-sectional FOCUS ( Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention ) study ( Phase 1 ) aim ed to eluci date factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI . Additionally , 695 patients from Phase 1 were r and omized into a controlled trial ( Phase 2 ) to test the effect of a polypill ( containing aspirin 100 mg , simvastatin 40 mg , and ramipril 2.5 , 5 , or 10 mg ) compared with the 3 drugs given separately on adherence , blood pressure , and low-density lipoprotein cholesterol , as well as safety and tolerability over a period of 9 months of follow-up . METHODS In Phase 1 , a 5-country cohort of 2,118 patients was analyzed . Patients were r and omized to either the polypill or 3 drugs separately for Phase 2 . Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green question naire ( MAQ ) and pill count ( patients had to meet both criteria for adherence at the in-person visit to be considered adherent ) . RESULTS In Phase 1 , overall CV medication adherence , defined as an MAQ score of 20 , was 45.5 % . In a multivariable regression model , the risk of being nonadherent ( MAQ < 20 ) was associated with younger age , depression , being on a complex medication regimen , poorer health insurance coverage , and a lower level of social support , with consistent findings across countries . In Phase 2 , the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up : 50.8 % versus 41 % ( p = 0.019 ; intention-to-treat population ) and 65.7 % versus 55.7 % ( p = 0.012 ; per protocol population ) when using the primary endpoint , attending the final visit with MAQ = 20 and high pill count ( 80 % to 110 % ) combined , to assess adherence . Adherence also was higher in the FDC group when measured by MAQ alone ( 68 % vs. 59 % , p = 0.049 ) . No treatment difference was found at follow-up in mean systolic blood pressure ( 129.6 mm Hg vs. 128.6 mm Hg ) , mean low-density lipoprotein cholesterol levels ( 89.9 mg/dl vs. 91.7 mg/dl ) , serious adverse events ( 23 vs. 21 ) , or death ( 1 , 0.3 % in each group ) . CONCLUSIONS For secondary prevention following acute MI , younger age , depression , and a complex drug treatment plan are associated with lower medication adherence . Meanwhile , adherence is increased in patients with higher insurance coverage levels and social support . Compared with the 3 drugs given separately , the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI . ( Fixed Dose Combination Drug [ Polypill ] for Secondary Cardiovascular Prevention [ FOCUS ] ; NCT01321255 ) 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 The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) was a r and omized , double-blind , active , controlled clinical trial conducted to determine whether newer antihypertensive agents , including doxazosin , an alpha-blocker , differ from chlorthalidone , a diuretic , with respect to coronary heart disease ( CHD ) and other cardiovascular disease ( CVD ) events in hypertensive patients at high risk of CHD . In February 2000 , the doxazosin treatment arm was discontinued , and findings through December 1999 were reported . This report includes an additional 9232 participant-years and 939 CVD events . At 623 clinical centers , patients ( aged > or=55 years ) with hypertension and at least 1 other CHD risk factor were r and omly assigned to either chlorthalidone or doxazosin . The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infa rct ion ( MI ) , analyzed by intent to treat ; prespecified secondary outcome measures included all-cause mortality , stroke , combined CHD ( fatal CHD , nonfatal MI , hospitalized angina , and coronary revascularization ) , and combined CVD ( combined CHD , stroke , angina treated outside the hospital , heart failure , and peripheral arterial disease ) . Mean follow-up was 3.2 years . There was no difference in primary outcome between the arms ( relative risk [ RR ] , 1.02 ; 95 % confidence interval [ CI ] , 0.92 to 1.15 ) . All-cause mortality also did not differ ( RR , 1.03 ; 95 % CI , 0.94 to 1.13 ) . However , the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke ( RR , 1.26 ; 95 % CI , 1.10 to 1.46 ) and combined CVD ( RR 1.20 ; 95 % CI , 1.13 to 1.27 ) . These findings confirm the superiority of diuretic-based over alpha-blocker-based antihypertensive treatment for the prevention of CVD 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 Cardiovascular disease ( CVD ) , including stroke , heart attack and heart failure , is the leading cause of death and disability worldwide . Raised blood pressure ( BP ) is a major cause of CVD , responsible for 62 % of stroke and 49 % of coronary heart disease cases . There is much evidence for a causal relationship between salt intake and BP . The current salt intake in many countries around the world is between 9 g ⁄d and 12 g ⁄d ( ie , 3.6–4.8 g of sodium ) . R and omized trials have demonstrated that a modest reduction in salt intake lowers BP in individuals with raised BP and also in those with ‘ ‘ normal ’ ’ BP . Furthermore , there is a dose-response relationship . Within the range of 12 g ⁄d to 3 g ⁄d , the lower the salt intake , the lower the BP . Because raised BP throughout its range is a major cause of CVD , salt reduction would reduce cardiovascular risk . It was estimated that a reduction of 6 g ⁄d in salt intake would reduce stroke by 24 % and coronary heart disease by 18 % . This would prevent approximately 35,000 stroke and coronary heart disease deaths a year in the United Kingdom and approximately 2.5 million deaths worldwide . Both prospect i ve studies and outcome trials have demonstrated that a lower salt intake is related to a reduced risk of CVD .  Salt reduction is one of the most cost-effective interventions to reduce CVD in both developed and developing countries . For example , the UK salt reduction campaign , which result ed in a fall in salt intake by approximately 10 % ( ie , from 9.5 g ⁄d in 2003 to 8.6 g ⁄d by May 2008 ) , cost just £ 15 million and led to approximately 6000 fewer CVD deaths per year , saving the UK economy approximately £ 1.5 billion per annum according to the recent report by the UK government ’s health advisory agency , the National Institute for Health and Clinical Excellence . In most developed countries , approximately 80 % of salt consumed is added to foods at the stage of manufacturing , and the consumers have no say over how much salt is added . Therefore , to achieve a reduction in population salt intake , it is imperative that the food industry make a gradual and sustained reduction in the amount of salt that is added to all foods . This approach has been successful in the United Kingdom and is now being exp and ed worldwide . World Salt Awareness Week was introduced by the salt reduction action group World Action on Salt and Health ( WASH ) in 2008 . The event serves as a platform for international experts in the fields of hypertension and nephrology to raise the profile of the importance of salt reduction to both the public and health professionals worldwide 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 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 Background Cardiovascular disease ( CVD ) is the leading cause of death worldwide . Secondary prevention is essential , but participation rates for cardiac rehabilitation are low . Furthermore , current programmes do not accomplish that patients with CVD change their lifestyle in a way that their individual risk factors for recurrent events decrease , therefore more effective interventions are needed . In this study , the effectiveness of the Hartcoach-programme , a telephonic secondary prevention program focussing on self management , is studied . Methods / design A multicenter , r and omised parallel-group study is being conducted . Participants are 400 patients with acute myocardial infa rct ion ( STEMI , NSTEMI , ) and patients with chronic or unstable angina pectoris ( IAP ) . Patients are recruited through the participating hospitals and r and omly assigned to the experimental group ( Hartcoach-programme plus usual care ) or the control group ( usual care).The Hartcoach-programme consists of a period of six months during which the coach contacts the patient every four to six weeks by telephone . Coaches train patients to take responsibility for the achievement and maintenance of the defined target levels for their particular individual modifiable risk factors . Target levels and treatment goals are agreed by the nurse and patient together . Data collection is blinded and occurs at baseline and after 26 weeks ( post-intervention ) . Primary outcome is change in cardiovascular risk factors ( cholesterol , body mass index , waist circumference , blood pressure , physical activity and diet ) . Secondary outcomes include chances in glucose , HbA1c , medication adherence , self-management and quality of life . Discussion This study evaluates the effects of the Hartcoach-programme on the reduction of individual risk factors of patients with CVDs . Patients who are not invited to follow a hospital based rehabilitation programme or patients who are unable to adhere to such a programme , may be reached by this home based Hartcoach-programme . If positive results are found , the implementation of the Hartcoach-programme will be extended , having implication s for the management of many people with CVD.Trial registration Background Cardiovascular disease ( CVD ) is the leading cause of early death worldwide , responsible for an estimated 29 % of all global deaths . Reducing salt intake lowers blood pressure and risk of secondary cardiac events . However , identifying low salt foods can be challenging . SaltSwitch is a simple smartphone application ( app ) that enables shoppers to scan the barcode of packaged foods and receive an immediate , interpretive , traffic light nutrition label on the screen , along with suggestions for healthier lower-salt alternatives . A growing body of evidence suggests mobile technologies can support healthy behaviour change . However , robust evidence for the impact of smartphone interventions is lacking . This manuscript outlines the rationale and methods for a r and omized controlled trial design ed to determine the effectiveness of SaltSwitch in supporting people with CVD to make lower-salt food choices . Design / Methods A 6-week , two-arm , parallel , r and omized controlled trial is being undertaken in New Zeal and ( 2 weeks baseline and 4 weeks intervention ) . Three hundred adults aged 40 years and older with CVD and their main household shoppers are recruited from research lists , cardiac rehabilitation clinics , and communities in Auckl and . Participants are r and omized to receive either the SaltSwitch smartphone app or no intervention ( control ) . R and omisation is stratified by ethnicity and age . The primary outcome is the salt content of household food purchases . Secondary outcomes are the saturated fat and energy content of household food purchases , household food expenditure , use and acceptability of the SaltSwitch app by shoppers , and urinary sodium and blood pressure of participants with CVD . Ambulatory blood pressure and potential longer-term impact ( 12 weeks ) of SaltSwitch will be assessed in sub- studies ( n ~ 40 and n ~ 20 , respectively ) . Household purchases of salt and other nutrients will be assessed using till receipt data electronically linked with br and ed food composition data . Discussion The results of the SaltSwitch trial will determine the effectiveness , use and acceptability of a smartphone application to support lower salt food choices and secondary prevention of CVD.Trial registration ACTRN12614000206628 . Registered 30 March 2014 Background The complexity of treatment regimens , costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage . The polypill , a fixed dose combination pill of established drugs , is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events ( MCVE ) . Design and methods The PolyIran trial is a pragmatic cluster r and omized trial nested within the Golestan Cohort Study ( GCS ) . Subjects were r and omized to either non-pharmacological preventive interventions alone ( minimal care arm ) or together with a polypill ( polypill arm ) comprising hydrochlorothiazide , aspirin , atorvastatin and either enalapril or valsartan . This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers ( Behvarz ) to the participants . The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infa rct ion , unstable angina , sudden death , heart failure , coronary artery revascularization procedures , and non-fatal and fatal stroke . Trial status From February 2011 to April 2013 , 8410 individuals ( 236 clusters ) attended the eligibility assessment . Of those , 3421 in the polypill arm and 3417 in the minimal care arm were eligible . The study is ongoing . Conclusion The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial . If the polypill strategy proves effective , it may be implemented to prevent cardiovascular disease in developing countries BACKGROUND Cardiovascular disease ( CVD ) and diabetes account for over one third of the mortality difference between African Americans and white patients . The increased CVD risk in African Americans is due in large part to the clustering of multiple CVD risk factors . OBJECTIVES The current study is aim ed at improving CVD outcomes in African-American adults with diabetes by addressing the modifiable risk factors of systolic blood pressure , glycosylated hemoglobin , and low-density lipoprotein cholesterol . METHODS A sample of African American patients with diabetes ( N = 400 ) will receive written education material at baseline and be r and omized to one of 2 arms : ( 1 ) usual primary care or ( 2 ) nurse-administered disease-management intervention combining patient self-management support and provider medication management . The nurse administered intervention is delivered monthly over the telephone . The nurses also interacts with the primary care providers at 3 , 6 , and 9 months to provide concise patient up date s and facilitate changes in medical management . All patients are followed for 12 months after enrollment . The primary outcomes are change in glycosylated hemoglobin , systolic blood pressure , and low-density lipoprotein cholesterol over 12-months . Secondary outcomes include change in overall cardiovascular risk , aspirin use , and health behaviors . CONCLUSION Given the continued racial disparities in CVD , the proposed study could result in significant contributions to cardiovascular risk reduction in African-American patients Abstract The study aim ed to investigate whether meeting leisure time physical activity recommendations was associated with reduced incident and fatal cancer or cardiovascular disease ( CVD )  in a community-based cohort of middle- to late-aged adults with long-term follow-up . At baseline , 2,320 individuals were assessed on a large number of lifestyle and clinical parameters including their level of physical activity  per week , other risk factors ( e.g. smoking and alcohol use ) various anthropometric measures , blood tests and medical history . Individuals were linked to hospital and mortality registry data to identify future cancer and cardiovascular events ( fatal and non-fatal ) out to 15 years of follow-up . Cox regression analyses adjusted for relevant confounders identified a priori were used to estimate risk for all-cause , cancer-specific and CVD-specific mortality . In the full cohort an estimated 21 % decreased risk for all-cause mortality ( HR 0.79 ; 95 % CI 0.66–0.96 ) and 22 % decreased risk for fatal/non-fatal CVD events ( HR 0.78 ; 95 % CI 0.66–0.92 ) was associated with baseline self-reported physical activity levels of 150 min or more . After exclusion of those with chronic co-morbidities ( CVD , cancer , diabetes , chronic obstructive pulmonary disease , hypertension treatment ) at baseline , lower risk for fatal/non-fatal CVD events remained significantly associated with 150 min or more of physical activity ( HR 0.77 ; 95 % CI 0.62–0.96 ) . Results from this well established prospect i ve community-based cohort study support the role of leisure time physical activity in reducing all-cause mortality and CVD events ( fatal/nonfatal ) in the broader population studied . The data also suggest that physical activity associated reductions in risk for CVD events ( fatal/nonfatal ) were not overly impacted by prevalent key non-communicable diseases
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 .