Wilkinson Michael S. Garshick Pam R. Discusses proper diet and nutrition for preventing dyslipidemia, cardiometabolic disease, and obesity Clearly delineates between diet and lifestyle interventions that are evidence-based and those which should be considered experimental Provides an up-to-date review of the many current diet and lifestyle trends and controversies Examines dietary approaches to inflammation and the role of the microbiome in CVD. Front Matter Pages i-x.
Pages Impact of Nutrition on Biomarkers of Cardiovascular Health. Cameron K. Ormiston, Rebecca Ocher, Pam R. The Mediterranean Dietary Pattern. Jessica K. Bjorklund, Carol F. Kirkpatrick, Eugenia Gianos. Keith C.
Ferdinand, Samar A. Nasser, Daphne P. Ferdinand, Rachel M. Dylan Lowe, Kevin C. Corbit, Ethan J. Rajiv S. The rationale behind using polypill for primary or secondary prevention of CVDs is not quite the same. One of the main aims for using polypill in secondary prevention is to increase adherence to multi-drug regimens in patients with established CVD. The individual level approach, participants are screened for risk factors of CVD and the polypill is administered to individuals whose risk score is over a threshold.
But, this approach has major limitations including high screening costs and difficulties in developing prediction models for different type of risk factors and different population. It has been suggested that population level strategies using polypill for primary prevention of CVD may have a larger impact than focusing only on high- risk individuals.
Compared with the use of aspirin in secondary prevention among patients at high baseline risk of further MCVE, aspirin use for primary prevention of CVDs remain controversial due to its side effects mostly bleeding. Based on these rationales and specific considerations, a low-cost fixed-dose combination pill production fee: 5 US cents per pill including known medications for prevention of CVDs7,10,17,27,33,34 was produced and delivered free of charge for both primary and secondary prevention groups.
These results could be due to the insufficient dosing of antihypertensive drugs. Our participants were almost healthy with normal BP, so we did not expect considerable decrease in blood pressure in our study.
Likewise, in the HOPE-3 study, using candesartan and hydrochlorothiazide 16 and It also showed that there were no significant differences in the risk of outcomes between minimal care arm and usual care group. This may partly be explained by implementation of cardiovascular diseases surveillance program in public health network in Iran during the last decade which is being conducted more rigorously during recent years as part of the national action plan for prevention and control of non-communicable diseases.
These programs are almost similar to the minimal care intervention of the minimal care arm of the PolyIran study. These national preventive services were routinely provided to all individuals in our study area including the participants of the polypill arm, minimal care arm as well as usual care arm. Therefore, this point should be taken into account during interpretation of the PolyIran results. This study has some limitations. First, we used only one fixed-dose combination pill for all participants, including primary and secondary prevention individuals.
It seems that using flexible possibilities i. It could have affected the behaviors of the enrolling physicians, e. Thereafter, enrolment team were blinded to cluster allocation. A subgroup analysis did not show a significant difference between participants with or without allocation concealment. Third, healthy lifestyle education e. Forth, the PolyIran study was conducted only on rural population and this point may affect the generalizability of our findings and should be considered in interpretation of our results.
In conclusion, the PolyIran study, using fixed-dose combination of aspirin, atorvastatin, and two blood pressure lowering drugs was associated with a significant lower risk of major cardiovascular events in year-old individuals. This pragmatic trial showed for the first time that using a low-cost polypill in a real-life setting could significantly reduce cardiovascular events and should now be considered an important step in applying the cardiovascular polypill strategy to eligible adults, broadly, especially in LMICs.
Table 1. Eligibility criteria in PolyIran study. All subjects in the polypill arm, minimal care arm and those receiving usual care were assessed for inclusion criteria but the exclusion criteria were only applied to the minimal care and polypill arms. Daily symptoms b. History of nasal polyposis d.
Major depression disorder, dementia, schizophrenia, manic-depressive bipolar disorder and other disorders with presentation of psychosis b. Cognitive impairments c. Blindness d.
Inability to do diurnal activities independently, e. For subgroup analyses, the subgroup variable was not entered into the model. Cumulative Hazard function for major cardiovascular events MCVE in the two arms The clustering effects were adjusted using frailty model. Month Month 60 Polypill arm Smoking, No. Cholesterol level, No. Ethnicity, No. Gender Male Polypill arm Female Polypill arm Cumulative Hazard function for major cardiovascular events MCVE in polypill arm, minimal care arm and usual care group of the PolyIran study additional comparison.
GBD collabortaors. Burden of cardiovascular diseases in the Eastern Mediterranean Region, — findings from the Global Burden of Disease study.
Sustainable Development Goals SDGs , and their implementation: A national global framework for health, development and equity needs a systems approach at every level. United Nations Development Program. Sustainable Developement Goals. Causes of premature death and their associated risk factors in the Golestan Cohort Study, Iran. BMJ Open ; 8 7 : e Iran in transition. The polypill: An effective approach to increasing adherence and reducing cardiovascular event risk.
Bmj ; : Uses of polypills for cardiovascular disease and evidence to date. Use of the cardiovascular polypill 40mg in secondary cardiovascular prevention. A Polypill for primary prevention of cardiovascular disease: a feasibility study of the World Health Organization. Trials ; 3. PLoS One ; 6 5 : e Polypill for the prevention of cardiovascular disease PolyIran : study design and rationale for a pragmatic cluster randomized controlled trial.
Curr Cardiol Rep ; 19 5 : The polypill in the prevention of cardiovascular diseases: key concepts, current status, challenges, and future directions. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Rose G. Sick individuals and sick populations. If a participant could not be accessed in a follow up visit and no further information was available, adherence for that follow-up was coded as missing. For time to certain occurrence of secondary outcomes e.
For continuous secondary outcomes changes in blood pressure and LDL-cholesterol , data were analyzed using mixed effects linear regression models. Log transformations were considered for variables with non-normal distribution. Analysis of adverse events: Data on adverse events were collected for all participants who attended the follow up visits. If a participant reported similar adverse events in more than one follow-up visit, the earliest date was taken into account.
At the end of study month 60 follow up visit , the study participants were asked about the occurrence of physician-confirmed diagnosis of selected conditions including peptic ulcer diseases and upper gastrointestinal bleeding.
Additional comparison: The aim of additional comparison was to compare the HRs of MCVE in usual care group with those of polypill and minimal care arms. Usual care group participants were not assessed for eligibility criteria; hence it was not possible to determine eligible subjects in this group. Since outcome ascertainment in all 20, would have been burdensome and expensive, a random sample of 4, participants was selected from the usual care group using cluster randomization method, for whom complete outcome ascertainment was performed similar to study arms.
Cox regression models were used to compare the HR of MCVE in usual care group with those of polypill and minimal care arms.
As the usual care group members did not attend the eligibility check, there was no enrollment time for these participants. Therefore, we considered a fixed date the date of enrollment of the first participant in the polypill or minimal care arms as enrollment date for all usual care participants.
As with previous analyses, Cox regression results were adjusted for clustering effects using shared frailty models. Further details are shown in the study flow chart Figure 1 and in Supplementary Figure 1. Figure 2 shows the time sequence of steps and blinding status in the PolyIran study.
The allocation status was concealed to the enrolment team in the first 48 clusters 1, participants and the remaining clusters 5, participants were enrolled with allocation concealment Table 2. Analysis of primary outcomes: The two study arms are reasonably balanced with respect to gender, history of pre-existing cardiovascular disease, hypertension, diabetes mellitus, smoking, age group, and other potential confounders.
Table 2 Table 3 shows the results of the primary and subgroup analyses. There were MCVE during the 60 months in the polypill arms and in the minimal care arm. The corresponding Kapan-Meier curve is shown in Figure 3. The results using shared frailty models were very similar to those without frailty models, as were those using the VCE option in Stata Supplementary Table 1. When stratified by age, gender, pre-existing MCVE, hypertension, diabetes mellitus, baseline cholesterol levels and smoking, there was no statistically significant difference in effect among the subgroups Table 3.
See Table 3 and Figure 4. Analysis of secondary outcomes: The median interquartile range of adherence was The adherence levels were high, medium and low in 2, Figure 5 shows adherence levels in polypill participants by follow up month.
We found no significant differences in the risk of overall mortality, non-MCVE mortality, sudden death and heart failure between the study arms Table 6. Adverse events Figures 6 shows the frequencies of adverse events in polypill and minimal care arms. We found decreasing trends in the frequencies of dyspepsia, cough and dizziness during the study period. The frequencies of adverse events and their trends were almost similar in polypill and minimal care arms.
A total number of 21 cases of intracranial hemorrhages were ascertained during the 5 years follow up, including 10 participants 0. The frequencies of physician-confirmed diagnosis of peptic ulcer disease were 34 1. The frequencies of physician-confirmed diagnosis of upper GI bleeding were 13 0. During 60 months of follow-up 1, new MCVEs occurred among all 12, participants included in the additional comparison analysis, including , and in the polypill arm, minimal care arm, and usual care group, respectively.
Table 8 and Figure 7 presents the results of Cox regression models. Our results showed no difference in the risk of MCVE between minimal care arm and usual care group. Discussion: The main aim of the PolyIran study was to assess the effect of a polypill a fixed-dose combination pill comprising aspirin 81 mg, atorvastatin 20 mg, hydrochlorothiazide To our knowledge, this is the first large-scale pragmatic trial with long term follow up to investigate the effects of a fixed-dose combination therapy on primary and secondary prevention of CVDs.
The most striking difference was seen by adherence to treatment. These significant results were consistent among men and women, younger and older individuals, and those with or without preexisting hypertension or a high blood cholesterol level.
The risk of both fatal and non-fatal ischemic heart disease and both fatal and non-fatal stroke decreased significantly in the polypill arm. Adverse events were comparable between the polypill arm and the minimal care arm, suggesting that polypill tablet could reduce cardiovascular outcomes without additional adverse events. Several similar trials were conducted on fixed-dose combination pills in different population, but most of them were focused on adherence to polypill intake and its effects on CVD risk factors not hard outcomes as in this study major cardiovascular events and most studies also had a shorter follow up than the 60 months of the PolyIran study.
Therefore, polypill strategy could be used for both primary and secondary prevention in such high-risk settings. The rationale behind using polypill for primary or secondary prevention of CVDs is not quite the same.
One of the main aims for using polypill in secondary prevention is to increase adherence to multi-drug regimens in patients with established CVD. The individual level approach, participants are screened for risk factors of CVD and the polypill is administered to individuals whose risk score is over a threshold.
But, this approach has major limitations including high screening costs and difficulties in developing prediction models for different type of risk factors and different population. It has been suggested that population level strategies using polypill for primary prevention of CVD may have a larger impact than focusing only on high- risk individuals.
Compared with the use of aspirin in secondary prevention among patients at high baseline risk of further MCVE, aspirin use for primary prevention of CVDs remain controversial due to its side effects mostly bleeding.
Based on these rationales and specific considerations, a low-cost fixed-dose combination pill production fee: 5 US cents per pill including known medications for prevention of CVDs7,10,17,27,33,34 was produced and delivered free of charge for both primary and secondary prevention groups. These results could be due to the insufficient dosing of antihypertensive drugs. Our participants were almost healthy with normal BP, so we did not expect considerable decrease in blood pressure in our study.
Likewise, in the HOPE-3 study, using candesartan and hydrochlorothiazide 16 and It also showed that there were no significant differences in the risk of outcomes between minimal care arm and usual care group. This may partly be explained by implementation of cardiovascular diseases surveillance program in public health network in Iran during the last decade which is being conducted more rigorously during recent years as part of the national action plan for prevention and control of non-communicable diseases.
These programs are almost similar to the minimal care intervention of the minimal care arm of the PolyIran study. These national preventive services were routinely provided to all individuals in our study area including the participants of the polypill arm, minimal care arm as well as usual care arm. Therefore, this point should be taken into account during interpretation of the PolyIran results.
This study has some limitations. First, we used only one fixed-dose combination pill for all participants, including primary and secondary prevention individuals. It seems that using flexible possibilities i. It could have affected the behaviors of the enrolling physicians, e.
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