Polypill Therapy Research Articles

Dynamics of structural and functional characteristics of arteries during polypill therapy in high and low high risk patients

Dynamics of structural and functional characteristics of arteries during polypill therapy in high and low high risk patients

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Polypill Therapy for Cardiovascular Disease Prevention and Combination Medication Therapy for Hypertension Management

Although various guidelines for cardiovascular disease prevention have been established, the optimal drug therapy is often not implemented due to poor medication adherence and the clinical inertia of healthcare practitioners. Polypill strategies are one solution to this problem. Previous studies have established the usefulness of polypills, i.e., combination tablets including three or more medications, for the prevention of cardiovascular disease. For this purpose, the polypills generally contain an antiplatelet medication, an antihypertensive medication, and a statin. For the specific management of hypertension, combination therapy including more than two classes of antihypertensive medications is recommended by most international guidelines. Combination tablets including two classes of antihypertensive medications, such as renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) and Ca-channel blockers or thiazide diuretics, have been reported to be useful for cardiovascular disease prevention and lowering blood pressure (BP) levels. The use of RAS inhibitors is recommended for a wide range of complications, including diabetes, chronic heart failure, and chronic kidney disease. The combination of an RAS inhibitor and diuretic or Ca-channel blocker is thus recommended for the management of hypertension. Finally, we expect that novel medications such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2i), which have a more diverse range of effects in hypertension, heart failure, or diabetes, may be a solution to the problem of polypharmacy. Evidence is accumulating on the benefits of polypill strategies in cardiovascular disease prevention. Combination tablets are also effective for the treatment of hypertension.

Effect of polypill therapy on lipid profile and arterial stiffness in patients with dyslipidemia, arterial hypertension and COVID-19 in different age groups

Effect of polypill therapy on lipid profile and arterial stiffness in patients with dyslipidemia, arterial hypertension and COVID-19 in different age groups

Examining the Use of a Polypill in Cardiovascular Disease Prevention.

Cardiovascular disease (CVD) is a significant cause of death worldwide. To address the global burden of CVD and its risk factors, the polypill, an all-in-one therapy that combines multiple existing medications for preventing CVD and reducing CVD events (such as angiotensin-converting enzyme inhibitor, beta-blocker, statin, or aspirin) into a single combination pill, has emerged as a potential strategy to improve CVD prevention. Clinical trials on the polypill have found that polypill use is associated with significant reductions in CVD events and risk factors in both patients with established CVD and at risk of developing CVD, suggesting a potential benefit in primary and secondary CVD prevention. The polypill has also been demonstrated to be a cost-effective therapy that may potentially increase treatment accessibility, affordability, and availability particularly in low- and middle-income countries. Further, patients on polypill therapy have shown high rates of treatment compliance, with significant improvements in medication adherence for patients with low baseline compliance. Given its potential advantages and benefits, the polypill may become a promising therapy for the prevention of CVD.

Meta-Analysis on the Clinical Outcomes With Polypills for Cardiovascular Disease Prevention

Randomized controlled trials (RCTs) examining the outcomes of "polypill" therapy in cardiovascular disease prevention have yielded mixed results. We performed an electronic search through January 2023 for RCTs that examined the use of polypills for cardiovascular disease primary or secondary prevention. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The final analysis included 11 RCTs with 25,389 patients; 12,791 patients were in the polypill arm, and 12,598 patients were in the control arm. The follow-up period ranged from 1 to 5.6 years. Polypill therapy was associated with a lower risk of MACCE (5.8% vs 7.7%; risk ratio [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.91). The reduction of MACCE risk was consistent in both primary and secondary prevention. Polypill therapy was associated with a lower incidence of cardiovascular mortality (2.1% vs 3%; RR 0.69, 95% CI 0.55 to 0.87), myocardial infarction (2.3% vs 3.2%; RR 0.72, 95% CI 0.61 to 0.84) and stroke (0.9% vs 1.6%; RR 0.62, 95% CI 0.42 to 0.90). Polypill therapy was associated with a higher degree of adherence. There was no difference between both groups in the incidence of serious adverse events (16.1% vs 15.9%; RR 1.12, 95% CI 0.93 to 1.36). In conclusion, we found that a polypill strategy was associated with a lower incidence of cardiac events and higher adherence, without an increased incidence of adverse events. This benefit was consistent for both primary and secondary prevention.

Оценка эффективности полипилл-терапии у пациентов с артериальной гипертензией и дислипидемией, перенесших новую коронавирусную инфекцию

Оценка эффективности полипилл-терапии у пациентов с артериальной гипертензией и дислипидемией, перенесших новую коронавирусную инфекцию

Polypill for atherosclerotic cardiovascular disease prevention in Haiti: Eligibility estimates in a low-income country.

Multidrug therapy is a World Health Organization "best buy" for the prevention and control of noncommunicable diseases. CVD polypills, including ≥2 blood pressure medications, and a statin with or without aspirin, are an effective, scalable strategy to close the treatment gap that exists in many low- and middle-income countries, including Haiti. We estimated the number of Haitian adults eligible for an atherosclerotic CVD (ASCVD) polypill, and the number of potentially preventable CVD events if polypills were implemented nationally. We used cross-sectional data from the Haiti CVD Cohort, a population-based cohort of 3,005 adults ≥18 years in Port-au-Prince, to compare two polypill implementation strategies: high-risk primary prevention and secondary prevention. High-risk primary prevention included three scenarios: (a) age ≥40 years, (b) hypertension, or (c) predicted 10-year ASCVD risk ≥7.5%. Secondary prevention eligibility included history of stroke or myocardial infarction. We then used the 2019 Global Burden of Disease database and published polypill trials to estimate preventable CVD events, defined as nonfatal MI, nonfatal stroke, and cardiovascular death over a 5-year timeline. Among 2,880 participants, the proportion of eligible adults for primary prevention were: 51.6% for age, 32.5% for hypertension, 19.3% for high ASCVD risk, and 5.8% for secondary prevention. Based on current trends, an estimated 462,509 CVD events (95% CI: 369,089-578,475) would occur among adults ≥40 years in Haiti from 2019-2024. Compared with no polypill therapy, we found 32% or 148,003 CVD events (95% CI: 70,126-248,744) could be prevented by a combined primary and secondary prevention approach in Haiti if polypills were fully implemented over 5 years. These modeling estimates underscore the potential magnitude of preventable CVD events in low-income settings like Haiti. Model calibration using observed CVD events, costs, and implementation assumptions are future directions. clinicaltrials.gov, identifier: NCT03892265.

Association of polypill therapy with cardiovascular outcomes, mortality, and adherence: A systematic review and meta-analysis of randomized controlled trials

Prior studies have reported improvements in population-level risk factor burden and cardiovascular disease (CVD) outcomes using polypills for CVD risk reduction. However, a comprehensive assessment of the impact of polypills on CVD outcomes, mortality, adherence, and side effects across different settings has not previously been reported. We performed a systematic review and meta-analysis of randomized controlled trials examining the association between polypill therapy and CVD outcomes published before February 2021. The primary outcome of interest was the risk of major adverse CVD events (MACE). Risk ratios for dichotomous outcomes were converted to log RR and pooled using a generic inverse variance weighted random-effects model. Data for continuous outcomes were pooled using random-effects modeling and presented as mean differences with 95% CIs. Eight studies representing 25,584 patients were included for analysis. In the overall pooled analysis, the use of polypills was associated with a non-significant reduction in the risk of MACE (RR: 0.85; 95% CI: 0.70–1.02) and significant reductions in the risk of all-cause mortality (RR: 0.90; 95% CI: 0.81–1.00). The reductions in the risk of MACE with polypill use varied by baseline risk and nature of the study population (primary prevention vs. secondary prevention), with the most significant risk reduction among lower-risk cohorts, including within primary prevention populations [RR 0.70 (0.62, 0.79)]. Among measures of CVD risk factors, modest but significant reductions were observed for systolic and diastolic blood pressure [systolic: mean difference 1.99 mmHg (95% CI: −3.07 to −0.91); diastolic: mean difference 1.30 mmHg (95% CI: −2.42 to −0.19), but not for levels of total or low-density lipoprotein-cholesterol. Use of the polypill strategy significantly improved drug adherence (RR: 1.31; 95% CI: 1.11–1.55) with no association between polypill use and rates of adverse events or drug discontinuation. The use of polypill formulations is associated with significant reductions in CVD risk factors and the risk of all-cause mortality and MACE, particularly in the low-risk and primary prevention population.

Abstract 14379: Polypill Therapy and Risk of Adverse Cardiovascular Events and Mortality: A Systematic Review and Meta-Analysis

Introduction: Prior studies have reported improvements in population-level risk factor burden and cardiovascular outcomes using polypill strategy. We aimed to provide an updated meta-analysis of RCTs evaluating the efficacy of polypill-based strategy in reducing the risk of adverse cardiovascular outcomes. Methods: RCTs examining the association between polypill therapy and cardiovascular outcomes published before 2/1/2021 were included. The outcomes of interest were major adverse cardiovascular events (MACE) and all-cause mortality. Risk ratios for dichotomous outcomes were converted to log RR and pooled using a generic inverse variance weighted random-effects model. Data for continuous outcomes were pooled using random-effects modeling and presented as mean differences with 95% CIs. Results: Eight studies representing 25,584 patients were included for analysis. In pooled analysis, the use of polypills was associated with a non-significant reduction in the risk of MACE [RR(95% CI): 0.85(0.70-1.02)] and significant reductions in the risk of all-cause mortality [RR(95% CI): 0.90(0.81-1.00)]. The reductions in the risk of MACE with polypill use varied by baseline risk and nature of the study population [primary prevention (polypill, 476/10503; control, 684/10509) vs. secondary prevention (polypill, 170/2307; control, 153/2265)], with the most significant risk reduction among lower-risk cohorts, including within primary prevention populations [RR 0.70 (0.62, 0.79)]. Among CV risk factors, modest but significant reductions were observed for systolic and diastolic blood pressure, but not for levels of total or LDL-cholesterol. Polypill strategy was also associated with significantly improved drug adherence [RR(95% CI): 1.31(1.11-1.55)]. Conclusions: . Polypill strategy is associated with significant reductions in cardiovascular risk factors and the risk of all-cause mortality and MACE, particularly in the primary prevention population.

The Attitude towards Polypills Questionnaire (APPQ): a phase I-III development and validation study in patients with cerebrovascular disease.

Background and purposeThe polypill approach has been proposed to reduce patients’ pill burden, increase medication adherence and lower stroke incidence. However, little is known about patients’ attitudes towards polypills for cerebrovascular medication.MethodsBased on the European Organization for Research and Treatment of Cancer Quality of Life Group questionnaire development guidelines, a questionnaire to measure patients’ attitudes towards polypills for the secondary prevention of stroke (phase I–III) was developed. In phase I, issues were generated via literature review and interviews with patients and healthcare professionals. The issues were operationalized into items in phase II. In phase III the questionnaire was validated in a large single‐centre sample, and test–retest and internal validity were evaluated.ResultsIn phase I, 34 relevant issues were identified through literature search and interviews. Pre‐testing the questionnaire indicated high applicability and comprehensibility. The final Attitudes towards Polypills Questionnaire was tested in N = 260 patients and showed a two‐factor structure. The factors were labelled ‘concerns’ and ‘benefits’. The scales showed acceptable and good internal validity (concerns, Cronbach's α = 0.85; benefits, α = 0.93), but the scales’ test–retest validity was ambiguous. On a 0 to 3 rating scale, concerns were rated lower than benefits (mean 1.07, SD 0.69 vs. mean 1.87, SD 0.89).ConclusionsThe Attitudes towards Polypills Questionnaire showed high comprehensibility and content validity to assess German language patients’ attitudes towards a polypill medication. Our data and questionnaire may aid the implementation of polypill treatments in clinical practice and can be used in the design of future clinical trials on polypill therapy. Further validation of the questionnaire is advised.

Polypill therapy and frailty in elderly: Time to stop treating everything

Background: Frailty is a reversible age-related condition of increased vulnerability and risk of death or unplanned hospitalization. Frailty and polypill therapy are common in elderly, although little is known about the impact, they may have on each other.
 Aims and Objective: The study was a prospective observational study, designed with an aim to observe the six-month and one-year outcomes of elderly patients on polypill therapy.
 Material and Methods: Three hundred forty-two patients aged more than 60 years on polypill treatment were enrolled in this study, which were on regular follow up in our rural hospital at geriatric units of medicine department.
 Results: At the end of one year, 38.1% were in severe frailty (FIRE >0.7) category, out of which death happened at the end of one year were 41.6%. 47.6% required repeated hospitalisations that were on polypill therapy.
 Conclusions: A reduction of polypill therapy could be a cautious strategy to prevent and manage frailty. Further research is needed to confirm the possible benefits of reducing polypill in the development, reversion or delay of frailty.

Polypill for Cardiovascular Disease Prevention in an Underserved Population

BackgroundPersons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called “polypills”) containing low doses of medications with proven benefits for the prevention of cardiovascular disease may be beneficial in such persons. However, few data are available regarding the use of polypill therapy in underserved communities in the United States, in which adherence to guideline-based care is generally low.MethodsWe conducted a randomized, controlled trial involving adults without cardiovascular disease. Participants were assigned to the polypill group or the usual-care group at a federally qualified community health center in Alabama. Components of the polypill were atorvastatin (at a dose of 10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The two primary outcomes were the changes from baseline in systolic blood pressure and low-density lipoprotein (LDL) cholesterol level at 12 months.ResultsThe trial enrolled 303 adults, of whom 96% were black. Three quarters of the participants had an annual income below $15,000. The mean estimated 10-year cardiovascular risk was 12.7%, the baseline blood pressure was 140/83 mm Hg, and the baseline LDL cholesterol level was 113 mg per deciliter. The monthly cost of the polypill was $26. At 12 months, adherence to the polypill regimen, as assessed on the basis of pill counts, was 86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill group, as compared with 2 mm Hg in the usual-care group (difference, −7 mm Hg; 95% confidence interval [CI], −12 to −2; P=0.003). The mean LDL cholesterol level decreased by 15 mg per deciliter in the polypill group, as compared with 4 mg per deciliter in the usual-care group (difference, −11 mg per deciliter; 95% CI, −18 to −5; P<0.001).ConclusionsA polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population. (Funded by the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health; ClinicalTrials.gov number, NCT02278471.)

Six Month Polypill Therapy Improves Lipid Profile in Patients with Previous Acute Myocardial Infarction: The Heart-Mex Study

Acute myocardial infarction (AMI) is a leading cause of death in Mexico. Atherogenic lipid profile is a key component in AMI. Thus, it is imperative to find drug therapies able to reduce atherogenic lipids in AMI patients and prevent subsequent myocardial infarctions. To investigate the effect of polypill (Sincronium®) alone or combined with beta blockers (BB) and/or thiazide diuretics (TD) on total cholesterol, triglycerides, low-density lipoproteins (LDL), high-density lipoproteins (HDL), and cardiovascular risk markers in a Mexican population with AMI. Secondary AMI-prevention patients (n=256) were included in the study and categorized into three groups depending on the drug scheme, as follows: polypill (n=150), polypill+BB (n=91), and polypill+ BB+ TD (n=15). Lipid profile and cardiovascular risk markers were evaluated in each patient before and 6months after drug therapy. The Wilcoxon-matched pairs signed rank test showed significant ∼25-30% reductions in total cholesterol, triglycerides, and LDL in the polypill group as compared to polypill+ BB and polypill+ BB+ TD groups. On the contrary, HDL was significantly increased in polypill and polypill+ BB groups. Polypill therapy showed more marked reductions in blood pressure, atherogenic index, Framingham risk score, and vascular age with respect to polypill+ BB and polypill+ BB+ TD groups. This study demonstrates for the first time that polypill therapy without being combined with BB and TD is effective to improve the atherogenic lipid profile and cardiovascular risk markers in AMI patients. Further studies are needed to examine the efficacy of polypill in reducing the occurrence of a second AMI in the Mexican population.

Clinical Effectiveness of the Cardiovascular Polypill in a Real-Life Setting in Patients with Cardiovascular Risk: The SORS Study

The cardiovascular disease pandemic has promoted the cardiovascular polypill as one of the most scalable public health strategies to improve cardiovascular risk by increasing accessibility and adherence to treatments. Data from randomized clinical trials has shown that the polypill strategy significantly improves adherence as well as risk factor control (cholesterol and blood pressure), however, to date, no information from phase IV registries has been available. We conducted a multicentre, observational and prospective registry of a polypill-based treatment strategy. A total of 1193 patients in Mexico were included. Patient demographics, clinical history, blood pressure, analysis of blood lipids and the Framingham risk score were measured at baseline and after 12months of treatment with the CNIC-Ferrer polypill. At one year with the polypill, systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels changed from mean 146.9mmHg to 128mmHg (p<0.001), and from 89.1mmHg to 80.4mmHg (p<0.001) respectively. LDLc levels were significantly reduced 132.5-107.6mg/dL (p<0.001). The 10year Framingham cardiovascular disease risk was also reduced in the high-risk group (33.7+ 22.0 vs. 21.2+ 14.8; p<0.001) and in the intermediate risk group (23.7+ 14.8 vs. 12.7+ 11.4; p<0.001). To our knowledge, the results of the current study constitute the first real life data on the impact of a polypill therapy on cardiovascular risk factor control. The results show major improvements on the primary outcome, above and beyond those presented previously in the setting of randomized clinical trials.

Medication adherence in cardiovascular diseases.

Nonadherence to medications is common in cardiovascular diseases because of their long duration, the patient age and the complexity of therapy. Its prevalence depends on the population, the types of drugs and the disease under study. Adherence decreases from the initial prescription and it is usually under 80%, a value defined as satisfactory. Adverse outcomes of nonadherence consist of an increase in ambulatory visits and hospitalization and death rates. The causes of nonadherence are multiple and depend on the patient, the type of medication, the healthcare professional, and the health system. Methods adopted to reduce nonadherence include sanitary education, direct patient-doctor-pharmacist interactions and the use of electronic devices of alert. "Deprescribing", a mechanism proposed to reduce unnecessary or redundant medications, may improve the situation of long-term drug use in patients with cardiovascular disease, thus increasing adherence. Recommendations from the guidelines are sometimes confounding and the role of polypill therapy is still controversial.

The Effect of a Cardiovascular Polypill Strategy on Pill Burden.

Recent trials of cardiovascular polypills in high-risk populations show improvements in the use of cardiovascular preventive treatments, compared to usual care. We describe patterns of pill burden in Australian practice, define the impact of polypill therapy on pill burden, and explore how physicians add medication to polypill therapy. The Kanyini Guidelines Adherence with the Polypill Study was an open-label trial involving 623 participants in Australia which randomized participants to a polypill strategy (containing a statin, antiplatelet agent, and two blood-pressure-lowering medications) or usual care. Participants either had established cardiovascular disease or were at high calculated risk (≥15% over 5 years). Current medications, daily pill burden, and self-reported use of combination treatment were recorded prior to randomization and at study end. Median pill burden at baseline and study end was compared in both arms. Subgroup analysis of the polypill strategy on trial primary outcomes was conducted by pill burden at baseline. Median total and cardiovascular pill burdens of the polypill group decreased from 7 to 5 and from 4 to 2, respectively (median change -2; IQR -3, 0), with no change in the usual care group (comparison of change; P < 0.001). No change was seen for noncardiovascular medications. Of those still using the polypill at study end, 43.8% were prescribed additional medications; 84.5% of these additional medications were blood-pressure-lowering medications. Within the polypill group, lower pill burden at baseline was associated with greater increases in the use of indicated cardiovascular preventive medications at study end compared to those with higher pill burdens. No trend was observed between the level of baseline pill burden and the effect of poylpill treatment on systolic blood pressure or total cholesterol. A cardiovascular polypill in contemporary Australian practice reduces cardiovascular and total pill burdens, despite frequent prescription of additional medications.

Adherence to cardiovascular medications in the South Asian population: A systematic review of current evidence and future directions.

To review methods of assessing adherence and strategies to improve adherence to cardiovascular disease (CVD) medications, among South Asian CVD patients. We conducted a systematic review of English language studies that examined CVD medication adherence in South Asian populations from 1966 to April 1, 2015 in SCOPUS and PubMed. Working in duplicate, we identified 61 studies. After exclusions, 26 studies were selected for full text review. Of these, 17 studies were included in the final review. We abstracted data on several factors including study design, study population, method of assessing adherence and adherence rate. These studies were conducted in India (n = 11), Pakistan (n = 3), Bangladesh (n = 1), Nepal (n = 1) and Sri Lanka (n = 1). Adherence rates ranged from 32%-95% across studies. Of the 17 total publications included, 10 focused on assessing adherence to CVD medications and 7 focused on assessing the impact of interventions on medication adherence. The validated Morisky Medication Adherence Scale (MMAS) was used as the primary method of assessing adherence in five studies. Three studies used validated questionnaires similar to the MMAS, and one study utilized Medication Event Monitoring System caps, with the remainder of the studies utilizing pill count and self-report measures. As expected, studies using non-validated self-report measures described higher rates of adherence than studies using validated scale measurements and pill count. The included intervention studies examined the use of polypill therapy, provider education and patient counseling to improve medication adherence. The overall medication adherence rates were low in the region, which suggest a growing need for future interventions to improve adherence.

Coronary artery calcium and polypill therapy

Controversy surrounds the use of polypills in the primary prevention of cardiovascular disease, particularly in relation to which individuals should be targeted for treatment. Coronary artery calcium imaging has been presented as being of potential benefit in excluding those who are least likely to benefit from such treatment.

Polypill Therapy, Subclinical Atherosclerosis, and Cardiovascular Events—Implications for the Use of Preventive Pharmacotherapy: MESA (Multi-Ethnic Study of Atherosclerosis)

This study examines whether the coronary artery calcium (CAC) score can be used to define the target population to treat with a polypill. Prior studies have suggested a single polypill to reduce cardiovascular disease (CVD) at the population level. Participants from MESA (Multi-Ethnic Study of Atherosclerosis) were stratified using the criteria of 4 polypill studies (TIPS [The Indian Polycap Study], Poly-Iran, Wald, and the PILL [Program to Improve Life and Longevity] Collaboration). We compared coronary heart disease (CHD) and CVD event rates and calculated the 5-year number needed to treat (NNT) after stratification based on the CAC score. Among MESA participants eligible for TIPS, Poly-Iran, Wald, and the PILL Collaboration, CAC= 0 was observed in 58.6%, 54.5%, 38.9%, and 40.8%, respectively. The rate of CHD events among those with CAC= 0 varied from 1.2 to 1.9 events per 1,000 person-years, those with CAC scores from 1 to 100 had event rates ranging from 4.1 to 5.5, and in those with CAC scores >100 the event rate ranged from 11.6 to 13.3. The estimated 5-year NNT to prevent 1 CVD event ranged from 81-130 for patients with CAC= 0, 38-54 for those with CAC scores from 1 to 100, and 18-20 for those with CAC scores >100. In MESA, among individuals eligible for treatment with the polypill, the majority of CHD and CVD events occurred in those with CAC scores >100. The group with CAC= 0 had a very low event rate and a high projected NNT. The avoidance of treatment in individuals with CAC= 0 could allow for significant reductions in the population considered for treatment, with a more selective use of the polypill and, as a result, avoidance of treatment in those who are unlikely to benefit.