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The high-performance liquid chromatography method was only reported for simultaneous estimation of aspirin, simvastatin, ramipril, atenolol and hydrochlorothiazide in polycap capsule. High-performance thin-layer chromatography (HPTLC) method is now accepted as a method of analysis by many pharmaceutical industries and included as an official method in monographs of pharmacopeias of many countries. Hence, HPTLC method was developed and validated for the estimation of polycap capsule using enhanced analytical quality by design based on principles of quality risk management and design of experiment (DOE). Quality risk management was performed by the identification and assessment of risky method parameters. DoE was carried out by Placket–Burman screening design and Box–Behnken response surface methodology using resolution and tailing factor as critical method attributes. Method operable design region was navigated for optimization and development of the method. The developed method was validated as per ICH Q2 (R1) guideline. The method was found accurate, specific, precise and sensitive for the said estimation. The developed method was applied for the assay of polycap capsule and results were found in good agreement with the labeled claim. The developed method can be used as an alternative to reported HPLC methods for quality control of polycap capsule.

Background Cardiovascular (CV) polypills have been defined as scalable strategies for CV prevention. Nonetheless, their impact on health systems from an economic perspective has been questioned. The NEPTUNO study has evaluated the effectiveness, the healthcare resources utilization (HRU) and the economic impact of the CNIC-polypill - aspirin (ASA) 100mg, atorvastatin (A) 20/40mg and ramipril (R) 2,5/5/10mg – compared to usual care in a real-life clinical setting in Spain. Methods The NEPTUNO study is a retrospective, non-interventional analysis of an anonymized medical history dataset covering patients contained in the BIG-PAC administrative database in the years 2015–2018. Patients at age ≥18 years with medical history of previous CV disease were allocated in 4 different cohorts according to their therapy: (1) CNIC-polypill (case cohort), (2) identical mono-components (ASA,R,A), (3) equipotent medication and (4) usual care (control cohorts) and were followed for 2 years. To ensure comparability the cohorts a propensity score matching was performed. Direct all-cause HRU, including inpatient stay, outpatient visits, emergency room visits, rehabilitation, testing and medical treatment, were registered. Total direct medical costs were computed based on unit costs (€, 2020) assigned to each HRU item and were expressed on a per patient (PP) basis. Indirect costs where estimated based on registered productivity loss and the interprofessional average salary. Results 8,946 patients were recruited. After PSM, each of the four study cohorts consisted of 1,614 patients. There was acceptable comparability between the study cohorts (balance). The mean age was 63.3 years and 60.4% were men. Cohort 1 compared with the control cohorts 2, 3 and 4 showed a significant reduction in HRU on a per patient average for all items (table), specifically in visits to primary care (16.6 vs. 18.7, 18.9 and 21.0; p Conclusion(s) The results of our analysis demonstrate that the use of the CNIC-polypill results in a significantly lower HRU compared to control cohorts as well as a significantly lower total cost and direct medical costs. This data could support the sustainability and scalability of the polypill strategy. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Unrestricted grant from Ferrer Lab, Spain

8 p., 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 randomized controlled trial. METHODS: TIPS-3 is a 2x2x2 factorial randomized 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 randomized 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.

There has been an unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA), which when compared to stroke profiles in high-income countries (HIC) is characterized by a younger age of onset, higher case fatality rates, and more severe disability among survivors. Stroke survivors in SSA (vs. HIC) are especially at high risk for recurrent vascular events or death due to undiagnosed or under-controlled vascular risk factors, logistical challenges, low health literacy, and lack of care affordability. While international expert consensus secondary prevention guidelines recommend that antihypertensive, statin and anti-platelet therapy, be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular risk reduction, these goals are seldom realized in routine clinical care settings in SSA. A relatively simple, low-cost, evidence-based strategy that could be largely applied in a uniform manner to stroke survivors in low-to-middle income countries (LMICs), including the nations of SSA, is sorely needed. Fixed-dose combination pills, also known "polypills", containing generic drugs, i.e. Aspirin, a statin, and blood pressure (BP) lowering medication(s) may be a viable avenue to improve medication adherence and consequently reduce risk of further disability or death on a large scale among stroke survivors encountered in resource-constrained regions. In this conceptual article, we review the data supporting the rationale for a polypill to improve stroke outcomes in SSA and propose the conduct of a Stroke Minimization through Additive Anti-atherosclerotic Agent in Routine Treatment (SMAART) pilot study to determine the impact of a polypill such as the Polycap DS® in reducing future vascular risk compared to usual care in recent stroke in SSA. A preliminarily feasible and efficacy-suggesting SMAART trial could inform the future design of a multi-center, double-blinded, placebo-controlled, randomized trial comparing the clinical efficacy of the polypill strategy for vascular risk moderation among stroke survivors in LMICs.

Aims Cardiovascular fixed-dose combination pills, or polypills, may help address the widespread lack of access and adherence to proven medicines. Initiation of polypill-based care typically entails switching from current separately taken medications. Given the heterogeneity in usual care, there is interest in the impact of polypill treatment across different patterns of prior medication regimen. Methods A total of 2004 participants with established cardiovascular disease or estimated 5-year cardiovascular risk of over 15% were randomised to polypill-based treatment (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg) or usual care. Baseline medications were classified by potency relative to polypill components. Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous randomised trials. Results For cholesterol reduction conferred by polypills, there was a dose response across baseline statin groups, with mean low-density lipoprotein (LDL)-cholesterol differences of 0.37, 0.22, 0.14 and 0.07 mmol/L among patients taking no statin, less potent, equipotent and more potent statin at baseline, respectively. Similarly there were differences in mean systolic BP of 5.4, 6.2, 3.3 and 1.8 mmHg among patients taking 0, 1, 2 or 3 BP-lowering agents. Among patients taking more potent statins at baseline, there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence. Similar results were seen among patients taking 3 BP-lowering agents at baseline. Switching to a polypill-based strategy resulted in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet, statin and BP-lowering therapy prescribing. Conclusion Adherence benefits from switching to a polypill resulted in risk factor changes that were at least as good as usual care across a wide variety of treatment patterns, including equally potent or more potent regimens. The benefits of switching to polypill-based care were greatest among those stepped up from partial treatment or less potent treatment.

Aim The aim of this study was to investigate whether polypill-based care for the prevention of cardiovascular disease (CVD) is associated with a change in lifestyle risk factors when compared with usual care, among patients with CVD or high calculated cardiovascular risk. Methods We conducted an individual participant data meta-analysis of three trials including patients from Australia, England, India, Ireland, the Netherlands and New Zealand that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior CVD event or who were at high risk of their first event. Analyses investigated any differential effect on anthropometric measures and self-reported lifestyle behaviours. Results Among 3140 patients (75% male, mean age 62 years and 76% with a prior CVD event) there was no difference in lifestyle risk factors in those randomised to polypill-based care compared with usual care over a median of 15 months, either across all participants combined, or in a range of subgroups. Furthermore, narrow confidence intervals (CIs) excluded any major effect; for example differences between the groups in body mass index was -0.1 (95% CI -0.2 to 0.1) kg/m2, in weekly duration of moderate intensity physical activity was -2 (-26 to 23) minutes and the proportion of smokers was 16% vs 17% (RR 0.98, 0.84 to 1.15) at the end of trial. Discussion This analysis allays concern that polypill-based care may lead to neglect of lifestyle risk factors, at least among high-risk patients. Maximally effective preventive approaches should address lifestyle factors alongside pharmaceutical interventions, as recommended by major international guidelines.

IMPORTANCE: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. OBJECTIVE: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. INTERVENTIONS: A once-daily fixed-dose triple combination pill (20 mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone) therapy (n = 349) or usual care (n = 351). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion achieving target systolic/diastolic BP (

6 p., The simplification of fixed dose medications by using a single ‘polypill’ is an attractive strategy to improve adherence to medications which has shown benefit to cardiovascular risk factor control and cardiovascular disease prevention or delay in the progression of these diseases. We review the evidence obtained from a series of clinical trials demonstrating an improvement in adherence to the polypill compared to the use of each compound separately, and found similar or better control of the classical cardiovascular risk factors and a similar safety profile. These results suggest that the use of the polypill could have a beneficial impact in cardiovascular morbidity and mortality. Furthermore, the polypill has the potential to improve cost effectiveness and is simple to use. However, before recommending the implementation of the polypill in programs aimed at primary and secondary cardiovascular prevention, we are awaiting the results of several current clinical trials aimed at measuring the impact on the frequency of major cardiovascular outcomes, particularly in low–medium-income countries.

Background There is an unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA). Secondary prevention guidelines recommend that antihypertensive, statin and antiplatelet therapy be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular-risk reduction. However, these goals are seldom realized in routine clinical care settings in SSA due to logistical challenges. We seek to assess whether a polypill containing fixed doses of three antihypertensive agents, a statin and antiplatelet therapy taken once daily per os for 12 months among recent stroke survivors would result in carotid intimal thickness regression compared with usual care (UC). Methods The Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART) trial is a phase 2, open-label, evaluator-blinded trial involving 120 Ghanaian recent-ischemic-stroke survivors. Using a computer-generated sequence, patients will be randomly allocated 1:1 into either the intervention arm or UC. Patients in the intervention arm will receive Polycap DS® (containing aspirin, 100 mg; atenolol, 50 mg; ramipril, 5 mg; thiazide, 12.5 mg; simvastatin, 20 mg) taken as two capsules once daily. Patients in the UC will receive separate, individual secondary preventive medications prescribed at the physician’s discretion. Both groups will be followed for 12 months to assess changes in carotid intimal thickness regression – a surrogate marker of atherosclerosis – as primary outcome measure. Secondary outcome measures include adherence to therapy, safety and tolerability, health-related quality of life, patient satisfaction, functional status, depression and cognitive dysfunction. Discussion An efficacy-suggesting SMAART trial could inform the future design of a multi-center, double-blinded, placebo-controlled, parallel-group, randomized controlled trial comparing the clinical efficacy of the polypill strategy for vascular risk moderation among stroke survivors in SSA. Trial registration ClinicalTrials.gov, ID: NCT03329599. Registered on 11 February 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-2564-0) contains supplementary material, which is available to authorized users.

The purpose of this study was to develop a novel dabigatran etexilate hemisuccinate (DEH) salt-loaded polycap with bioequivalence to the dabigatran etexilate mesylate (DEM)-loaded commercial product. DEH prepared with dabigatran etexilate base (DE) and succinic acid was less hygroscopic but less soluble than DEM. Numerous micronized DEHs and DEH-loaded solid dispersions were prepared employing the spiral jet-milling and spray-drying techniques, respectively. Among the formulations prepared, a micronized DEH prepared with the injection air at 1.5bar and the grinding air at 2bar, and a DEH-loaded solid dispersion prepared with 6g HPMC most improved the drug solubility, respectively. Moreover, the micronized DEH provided more increased drug solubility and dissolution compared with the solid dispersion, even though its drug solubility was still lower than that of DEM. Unlike the situation in other studies, the enhanced solubility and dissolution of DEH was more due to particle size reduction than to a change to the amorphous form. The micronized DEH prepared with Myrj 52S had greater drug solubility than preparations with other surfactants. Among the organic acids investigated, only fumaric acid (128.8mg) showed a similar pattern in pH changes to the DEM-loaded commercial product. Furthermore, in order to make the environment acidic while preventing the direct contact of the drug with fumaric acid, the polycap was composed of a tablet containing the micronized DEH, Myrj 52S and other ingredients, and separate fumaric acid. This micronized DEH-loaded polycap was dissolution- and bio-equivalent to the DEM-loaded commercial product in beagle dogs. Thus, the novel micronized DEH-loaded polycap would be a promising alternative to the DEM-loaded commercial product.

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).The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized 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 infarction, unstable angina, sudden death, heart failure, coronary artery revascularization procedures, and non-fatal and fatal stroke.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.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.

Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs ('polypills') would promote use of such medications.We conducted a randomized, open-label trial involving 623 participants from Australian general practices. 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 randomized 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 randomized 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.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.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 This study examines whether the coronary artery calcium (CAC) score can be used to define the target population to treat with a polypill. Background Prior studies have suggested a single polypill to reduce cardiovascular disease (CVD) at the population level. Methods 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. Results 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. Conclusions 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.

Background Despite a wide range of medications being available for the prevention of cardiovascular events such as stroke, myocardial infarction and mortality in both a primary and secondary setting, patient adherence to complex therapy regimens involving different drug classes remains low worldwide. Combining antiplatelet, antihypertensive, lipid-lowering and potentially further drugs into one 'polypill' has the potential to increase adherence, thereby reducing risk factors to a greater extent and for a longer duration. The World Health Organization has recently highlighted increased adherence as a key development need for reducing cardiovascular disease. Methods Recent clinical trial data regarding adherence, reductions in cardiovascular risk and outcomes, safety and tolerability and the cost-effectiveness of the polypill approach are summarised and reviewed. In addition, ongoing trials and the questions they intend to answer are considered. References were retrieved from a PubMed literature search (date range 1990-2016) using the terms 'polypill', 'cardiovascular events' and 'adherence', and selected based on relevance. The website www.clinicaltrials.gov was also consulted for the identification of ongoing trials. Conclusions To date, the polypill approach has been conclusively shown to increase adherence relative to usual care in all patients, with those in a primary care setting or with poor baseline adherence potentially standing to benefit most. Concomitant risk factor reductions have also been suggested. However, whether this translates into a reduction in cardiovascular events and generates good cost-effectiveness in a given healthcare environment is currently under further investigation.

Background— A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol. We examined the incremental effects of 2 (full dose) plus K + supplementation versus single polycap (low dose) on risk factors and tolerability. Methods and Results— After a run-in period, 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were randomly assigned to a single-dose polycap or to 2 capsules of the polycap plus K + supplementation for 8 weeks. The effects on BP, heart rate (HR), serum lipids, serum and urinary K + , and tolerability were assessed using an intention-to-treat analysis. The full-dose polycap (plus K + supplementation) reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic, compared with that observed with the low-dose polycap ( P =0.003; P =0.001), but there were no differences in HR (0.1 bpm). The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL ( P =0.014) and 6.6 mg/dL ( P =0.006), respectively, but there were no differences in high-density lipoprotein cholesterol or triglycerides. The rates of discontinuation of the study drug after randomization were similar in the 2 groups (6.9% low dose versus 7.8% full dose). Conclusions— The full-dose polycap (plus K + supplementation) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose, with similar tolerability. Therefore, the full-dose polycap should potentially lead to larger benefits. Clinical Trial Registration— URL: http://www.ctri.nic.in . Unique identifier: CTRI/2010/091/000054.

AIM: Based on guidelines, patients with established cardiovascular disease are likely to already receive a combination of aspirin, a statin, and blood pressure (BP)-lowering agents. Combining these pharmacological agents into a cardiovascular polypill could be considered in these patients to reduce prescription gaps and non-adherence. We aimed to assess the prevalence of the combined use of aspirin, statin, and BP-lowering agents in patients with established cardiovascular diseases or type 2 diabetes mellitus (DM2) in the period 1996-2009.METHODS: In total, 5702 patients with coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral arterial occlusive disease (PAOD), abdominal aortic aneurysm (AAA) or, DM2 were included in the period 1996-2009.RESULTS: The overall use of combination therapy with aspirin, statin, and ≥ 1 BP-lowering agent increased substantially from 9% in 1996 to 66% in 2009 and ≥ 2 BP-lowering agents increased from 1% to 47%. In 2009, combination therapy with ≥ 1 BP-lowering agent was used by 83% of those with CAD, 48% of those with CVD, 43% of those with PAOD, 36% of the patients with AAA, and 19% of the patients with DM2. In most patient groups, obesity, metabolic syndrome, hypertension concomitant CAD, CVD, or DM2 were related to the use of combination therapy in models adjusted for age and gender.CONCLUSION: A high proportion of patients with established cardiovascular diseases already uses a combination of pharmacological agents. Introduction of a polypill in high-risk patients might be feasible to reduce prescription gaps and increase adherence to indicated therapy.

Objective: To evaluate the efficacy and safety of the polypill for prevention of cardiovascular disease (CVD) and stroke and to present literature related to the polypill components (statin, aspirin, antihypertensive) for primary prevention of CVD and stroke. Data Sources: A literature search was conducted in MEDLINE (1948-January 2011) and EMBASE (1974-January 2011) using the terms polypill and Polycap. When limited to clinical trials, systematic reviews, or meta-analyses, 7 studies were identified. Bibliographies of pertinent review articles and studies were scanned for additional references. A similar search was conducted to identify literature related to the use of polypill components for primary prevention of CVD and stroke. Study Selection and Data Extraction: Studies that evaluated the hypothetical benefits of a polypill and controlled trials that assessed a formulation of the polypill related to prevention of CVD and stroke were included. Studies were assessed for efficacy, safety, drug interactions, and clinical pharmacokinetics. Data Synthesis: An initial study to predict benefit estimated that a hypothetical polypill would reduce diastolic blood pressure by 11 mm Hg and low-density lipoprotein cholesterol (LDL-C) by 70 mg/dL, thus reducing the relative risks of CVD and stroke by 68% and 80%, respectively. One clinical trial in patients at low risk for CVD and stroke found that diastolic Wood pressure was reduced by 1.6 mm Hg and LDL-C was reduced by 17.7 mg/dL, correlating with 44% and 21% reduction in the relative risks of CVD and stroke, respectively. Studies in higher risk patients reported reductions in systolic blood pressure of up to 28.8 mm Hg and in LDL-C of up to 54 mg/dL, correlating with 62% and 60% relative reduction in risks of CVD and stroke, respectively. Conclusions: Polypill study results have been more modest than originally theorized. However, results show promise in patients at higher risk for CVD and stroke.

Polypill is a fixed dose combination, used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. In the present study, gradient LC method was developed for simultaneous determination of the Polycap, that is, Atenolol, Hydrochlorothiazide, Aspirin, Ramipril, and Simvastatin, in presence of their major interaction/degradation products. The individual drug components and their major interaction/degradation products were well separated using reverse phase C18 column and a mobile phase containing Acetonitrile:Phosphate buffer (pH 2.3). Other instrumental parameters were flow rate, 1 mL min−1; detection wavelength, 230 nm; column oven temperature, 40°C; and injection volume, 5 µL. The combined drugs were subjected to stress conditions such as hydrolysis, oxidation, photolysis, and thermal decomposition. The method was validated for linearity, precision, accuracy, specificity, and robustness.

ObjectivesA polypill containing aspirin, a statin and blood pressure (BP)-lowering agents has been proposed for the prevention of cardiovascular disease. To increase adherence and reduce the gaps between indicated and used therapy, a polypill might be of interest for patients with type 2 diabetes (T2DM). Our aim was to assess the prevalence of the combined use of polypill components in patients with T2DM over time.MethodsThe combined use of polypill components was assessed between 1996 and 2015 in patients with T2DM in the prospective SMART cohort ( n = 1828). The results were dichotomized into patients without ( n = 568) and with ( n = 1260) vascular disease. The patient characteristics associated with the use of polypill components were evaluated.ResultsIn total, 19% of patients with T2DM without vascular disease received a statin and ≥2 BP-lowering agents (‘cardiovascular polypill’) and 13% received additional oral glucose-lowering therapy (‘diabetic polypill’). Of the patients with T2DM with vascular disease, 42% received the combination of an antiplatelet agent, a statin and ≥2 BP-lowering agents (‘cardiovascular polypill’) and 30% received additional glucose-lowering therapy (‘diabetic polypill’). The prevalence of the use of the cardiovascular and diabetic polypill combination has substantially increased between 1996 and 2015 to 36 and 32% in patients without vascular disease and to 67 and 57% in patients with vascular disease.ConclusionsPatients with T2DM frequently use polypill components, often together with oral glucose-lowering agents, and this rate of use has increased steadily between 1996 and 2015. Introducing a cardiovascular or diabetic polypill for patients with T2DM seems to be highly relevant.

Cardiovascular disease (CVD) is the leading cause ofdeath and disability worldwide and is presently lead-ing cause of death and disability in low and middle-income countries including Iran (1–3). Treatment ofCVD is expensive, with more than 98% of healthcare expenditure on CVD devoted to treatmentrather than prevention, (1,3), and such costs areincreasing as new therapies emerge (4). There istherefore a need for coherent strategies for CVDprevention in low- and middle-income countries.It has been established that there is a continuousrelationship between cardiovascular risk and bothblood pressures and cholesterol levels (5–8). As low-ering elevated cholesterol or blood pressure reducescardiovascular risk, it is therefore plausible that low-ering these risk factors from average levels wouldalso reduce cardiovascular risk (9,10). There isevidence that aspirin is effective in primary preven-tion of cardiovascular disease in individuals at highrisk (11). Incidence of cardiovascular diseaseincreases with age, therefore it has been arguedthat fixed-dose combination therapy (dubbed the‘polypill’) including antiplatelet agents, blood pres-sure-lowering and lipid-lowering drugs could reduceincidence of cardiovascular disease in middle-agedand older adults (12). The most novel aspect of thisproposal has been to offer treatment to individualswhose risk factors are below usual treatment levels,but who are nevertheless at high risk of cardiovascu-lar disease because of their age and gender. Thereare a number of issues to consider in choosing theexact formulation of a polypill, and a greater numberof active components promises greater effectiveness,but poses greater technical problems in develop-ing the polypill (13). As a result of this, a numberof variations of the polypill are currently under

Summary Background The combination of three blood-pressure-lowering drugs at low doses, with a statin, aspirin, and folic acid (the polypill), could reduce cardiovascular events by more than 80% in healthy individuals. W e examined the eff ect of the Polycap on blood pressure, lipids, heart rate, and urinary thromboxane B2, and assessed its tolerability. Methods In a double-blind trial in 50 centres in India, 2053 individuals without cardiovascular disease, aged 45–80 years, and with one risk factor were randomly assigned, by a central secure website, to the P olycap (n=412) consisting of low doses of thiazide (12·5 mg), atenolol (50 mg), ramipril (5 mg), simvastatin (20 mg), and aspirin (100 mg) per day, or to eight other groups, each with about 200 individuals, of aspirin alone, simvastatin alone, hydrochlorthiazide alone, three combinations of the two blood-pressure-lowering drugs, three blood-pressure-lowering drugs alone, or three blood-pressure-lowering drugs plus aspirin. The primary outcomes were LDL for the eff ect of lipids, blood pressure for antihypertensive drugs, heart rate for the eff ects of atenolol, urinary 11-dehydrothromboxane B2 for the antiplatelet eff ects of aspirin, and rates of discontinuation of drugs for safety. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00443794. Findings Compared with groups not receiving blood-pressure-lowering drugs, the Polycap reduced systolic blood pressure by 7·4 mm Hg (95% CI 6·1–8·1) and diastolic blood pressure by 5·6 mm Hg (4·7–6·4), which was similar when three blood-pressure-lowering drugs were used, with or without aspirin. R eductions in blood pressure increased with the number of drugs used (2·2/1·3 mm Hg with one drug, 4·7/3·6 mm Hg with two drugs, and 6·3/4·5 mm Hg with three drugs). Polycap reduced LDL cholesterol by 0·70 mmol/L (95% CI 0·62–0·78), which was less than that with simvastatin alone (0·83 mmol/L, 0·72–0·93; p=0·04); both reductions were greater than for groups without simvastatin (p

Aims Recent data indicate that fixed-dose combination (FDC) pills, polypills, can produce sizeable risk factor reductions. There are very few published data on the consistency of the effects of a polypill in different patient populations. It is unclear for example whether the effects of the polypill are mainly driven by the individuals with high individual risk factor levels. The aim of the present study is to examine whether baseline risk factor levels modify the effect of polypill treatment on low-density lipoprotein (LDL)-cholesterol, blood pressure (BP), calculated cardiovascular relative risk reduction and adverse events. Methods This paper describes a post-hoc analysis of a randomised, placebo-controlled trial of a polypill (containing aspirin 75 mg, simvastatin 20 mg, lisinopril 10 mg and hydrochlorothiazide 12.5 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated five-year risk for cardiovascular disease ≥7.5%. The outcomes considered were effect modification by baseline risk factor levels on change in LDL-cholesterol, systolic BP, calculated cardiovascular relative risk reduction and adverse events. Results The mean LDL-cholesterol in the polypill group was 0.9 mmol/l (95% confidence interval (CI): 0.8-1.0) lower compared with the placebo group during follow-up. Those with a baseline LDL-cholesterol >3.6 mmol/l achieved a greater absolute LDL-cholesterol reduction with the polypill compared with placebo, than patients with an LDL-cholesterol ≤3.6 mmol/l ('1.1 versus '0.6 mmol/l, respectively). The mean systolic BP was 10 mm Hg (95% CI: 8-12) lower in the polypill group. In participants with a baseline systolic BP >135 mm Hg the polypill resulted in a greater absolute systolic BP reduction with the polypill compared with placebo, than participants with a systolic BP ≤ 135 mm Hg ('12 versus '7 mm Hg, respectively). Calculated from individual risk factor reductions, the mean cardiovascular relative risk reduction was 48% (95% CI: 43-52) in the polypill group. Both baseline LDL-cholesterol and estimated cardiovascular risk were significant modifiers of the estimated cardiovascular relative risk reduction caused by the polypill. Adverse events did not appear to be related to baseline risk factor levels or the estimated cardiovascular risk. Conclusion This study demonstrated that the effect of a cardiovascular polypill on risk factor levels is modified by the level of these risk factors. Groups defined by baseline LDL-cholesterol or systolic BP had large differences in risk factor reductions but only moderate differences in estimated cardiovascular relative risk reduction, suggesting also that patients with mildly increased risk factor levels but an overall raised cardiovascular risk benefit from being treated with a polypill.

Background Cardiovascular disease (CVD) is a global epidemic and the largest cause of noncommunicable disease–related death worldwide. The concept of a combination pill, or “polypill,” composed of aspirin, antihypertensives, and a statin has been suggested to simplify and improve the prevention and treatment of CVD. Individually, these medications have been shown to effectively modify risk factors of CVD, and a single pill composed of these medications has the potential to conveniently and cost effectively provide additive benefits in relative risk reduction. In particular, the polypill concept presents significant potential for reducing the impact of cardiovascular disease in low- and middle-income countries where populations account for >80% of all CVD-related deaths worldwide. Using a polypill as the primary way to prevent CVD has been proposed as a broad “vaccination” strategy to treat asymptomatic individuals based solely on age or the presence of risk factors. Findings Several clinical trials have shown that combination pills are well tolerated and have lower relative risk by as much as 60–70% by moderately reducing blood pressure and LDL-cholesterol. However, uncertainty remains in regards to long-term adherence, cost effectiveness, and “medicalization” of asymptomatic individuals, who account for a large percentage of the world's population. Furthermore, more data regarding CVD outcomes is required to evaluate the widespread use of a polypill in primary prevention. Conclusion The use of a combination pill in individuals with overt CVD provides the potential to reduce the “treatment gap” that exists in the secondary prevention of CVD by simplifying treatment algorithms, reducing nonadherence, and improving access to medications in countries lacking adequate healthcare infrastructure. The promising results of completed clinical trials have lead to the approval of polypill formulations (e.g., Polycap, Trinomia®, or Zycad) and several large clinical trials are posed to present new data regarding outcomes and adherence.

Background: It has not been fully elucidated whether antihypertensive medication adherence affects blood pressure (BP) control in hypertension cases. Aim: To investigate the association of adherence to antihypertensive drug regimens and BP control using data from the Combination Pill of Losartan Potassium and Hydrochlorothiazide for Improvement of Medication Compliance Trial (COMFORT) study. Design: An observational analysis from a randomized controlled trial. Methods: A total of 203 hypertensive subjects were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or two pills, an angiotensin II receptor blocker and a thiazide diuretic. Medication adherence calculated based on pill counts and BPs was evaluated at 1, 3 and 6 months after randomization. Results: The subjects were divided into three groups according to their adherence, i.e. relatively low-adherence (

BACKGROUND AND RATIONALE: In clinical practice, blood pressure (BP)-lowering agents are generally prescribed for use in the morning, whereas (short-acting) statins are recommended for use in the evening. There is evidence that the reduction in LDL cholesterol (LDL-c) achieved with short-acting statins is superior when taken in the evening and reported improvement in BP control when aspirin and BP-lowering agents are taken in the evening. However, it is unclear whether the additional reduction in LDL-c and BP is offset by a reduction in adherence, given that taking medication in the evening may be less typical or convenient. There is therefore uncertainty concerning the best timing of administration of a cardiovascular combination pill such as the polypill.AIM: The aim of TEMPUS (NCT01506505), a prospective randomized open blinded endpoint (PROBE) crossover trial, is to evaluate whether there is a difference in LDL-c levels or 24-hour ambulatory BP in individuals at increased risk of cardiovascular disease when the cardiovascular polypill is taken in the evening compared to the morning. An additional aim is to assess the effect of the polypill on LDL-c and BP compared to the administration of separate pills of identically dosed components of the polypill.METHODS: In total 75 participants with established cardiovascular disease or an intermediate to high risk for cardiovascular disease are randomly allocated to the sequence of three different treatments of 6-8 weeks: (1) the cardiovascular polypill (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and hydrochlorothiazide 12.5 mg) in the evening; (2) the polypill in the morning; and (3) the use of the identically dosed agents in separate pills taken at different time points during the day. The primary endpoint is the difference in LDL-c and mean 24-hour ambulatory systolic BP. Secondary outcomes are the difference in relative risk reduction, biochemistry, platelet function and pulse wave analysis, participants' adherence, and acceptability.CONCLUSIONS: TEMPUS will evaluate the effect of timing of the administration of a cardiovascular polypill on LDL-c and BP measurements in patients with an intermediate or high risk for cardiovascular disease.

Despite groundbreaking advances in health care, cardiovascular disease (CVD) remains the leading cause of death and disability worldwide, making it one of the most pressing global health issues to face the modern world. In 2002, Wald and Law proposed the concept of the polypill as a potential solution to this global health epidemic. The polypill represents a powerhouse pill that would consist of a combination of several key medications commonly prescribed for CVD prevention, such as a statin, diuretic, beta blocker, or angiotensin converting enzyme inhibitor, in one pill. It was suggested that it could be a novel, tactical measure in the approach to CVD prevention in that it greatly simplifies the healthcare delivery system. Not only does it increase medication compliance for those currently receiving health care, but it also has the potential to access those in underserved healthcare sectors of the world, primarily low- and middle-income countries, which have been identified as areas of highest CVD risk. A major drawback of the polypill is that there are limited data demonstrating its safety and efficacy in the prevention of cardiovascular morbidity and mortality. Thus far, research shows that the polypill has promise but needs to be approached with a few considerations, such as desired target patient population and formulation. This article will examine the published and ongoing studies associated with the polypill, outline the advantages and disadvantages of using the polypill as a global CVD prevention strategy, and discuss the design and availability of the polypill in the United States.

BackgroundThere has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability.MethodsWe conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up.FindingsAt baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment.ConclusionsThis polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12607000099426.

Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials.To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD.Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B6, and vitamin B12 or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005.Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12.A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality.Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10,000 person-years vs 39.5/10,000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10,000 person-years vs 36.8/10,000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10,000 person-years vs 49.6/10,000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P.001) in the active group (n = 150) over that observed in the placebo group (n = 150), for a difference of 2.27 micromol/L (95% CI, 1.54-2.96 micromol/L).After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.clinicaltrials.gov Identifier: NCT00000541.

Guidelines for the management of cardiovascular disease (CVD) stress the importance of treating global risk, rather than individual risk, factors. Patients at high cardiovascular (CV) risk, for example, benefit from a combination of aspirin, antihypertensive agents, lipid-lowering drugs, and possibly folic acid. As the number of medications that a patient requires increases, adherence and compliance to therapy are likely to decrease. The use of affordable, multiple-target, fixed-combination 'polypills', which concomitantly reduce multiple risk factors without increasing the pill burden or the risk of adverse effects, has the potential to improve CV risk factor management, thereby reducing the incidence of CVD. This review discusses the benefits of the polypill and the challenges and requirements for its success and registerability. Discussions with regulatory bodies are required in order to obtain some 'balance' between an overcautious registration approach and the potentially large public health benefits that are likely to arise from the use of polypills.

In this Viewpoint, Dr Xavier and colleagues discuss the rationale behind their choice to perform a study on a cardiovascular Polypill in the setting of primary prevention, and behind the drug combinations used in The Indian Polycap study. Results of The Indian Polycap study will be available in April 2009.

The prevalence and disease burden of cardiovascular disease (CVD) and thewidespread use ofmedications for its preventionand treatmenthave led to the concept that a singlepill containing several cardiovascular medications, a “polypill,” might be useful inmore effectively delivering pharmacologic interventions than the samemedicationsprescribedand taken separately. For about a decade and a half there have been active discussions of combination pills for primary or secondary prevention of CVD.1 The discussion is consistent with the widespread interest in the importance of noncommunicable diseases, particularly in lowandmiddle-income countries. The logic for the polypill seems sound. CVD is commonas are its major risk factors, and effective pharmacologic treatmentsareoftentakentogether.Combiningsomeof thesemedications into a single pill most likely will improve adherence, whichdeclineswith increasing numbers of medications, and a polypill might improvedistributionofmedication. It is alsopossible that costs could be lower because generic medications with a long history of use could be combined; for instance, several available blood pressure pills combine 2 antihypertensive medications.With this simple logic, the concept of providing combination therapy in a single pill has been embraced by prominent researchers andorganizations including theWorldHealth Organization. Yet for all the discussion, movement toward implementation has been slow. Why has what seems to be such a good idea still not been widely studied and implemented? There are several challenges tomake a successful combination pill. Technically the agents must be stable when combined. There must be no adverse interaction when the medications are taken together. Medications have to be able to be taken at the same time of the day. The combination pill might require regulatory approval. Itneeds tobeproduced,marketed,anddistributed;and itmustbeeconomically viable. This all requires substantial investment to ensure widespread uptake. Factors that could further complicate theuse of combination pills include the issue of adverse effects to one drug and theneed toproducemultiple pills if a numberof possibledose combinations are necessary. Adverse effects to one medication could result in cessation of all agents in a given polypill. Cliniciansmay not knowwhich polypill ingredient is causing the adverse effects. If just 2 doses each of 4 medications are used, 2 x 2 x 2 x 2 or 16 different dose combinationswould be needed to make all dose combinations available. Another consideration is identifying good candidates for the polypill. There are 3 settings in which this combination medication approach could beuseful. First, thepolypill could beusedbypatientswith knownCVDor those at high riskwho are already taking severalmedications, oftenat the same time. In this setting a polypill could improve medication adherence. Second, in lower-incomecountries a singlepill for either primary or secondary CVD prevention might lower cost and increase efficiencyby simultaneouslydeliveringmultiplepreventive interventions to appropriate higher-risk patientswho are not receiving these interventions. Third, the combination pill could be used to increase the number of people receiving preventive interventions if this approachwere promoted as a simpleway for those at risk for CVD to adopt an effective preventive intervention.WaldandLaw2havesuggested thatusing a polypill in everyone older than about 55 years for primary prevention could reduce CVD bymore than 80%. Many formulations for a CVD polypill have been proposed. Because hypertension and dyslipidemia are common and often coexist, most combinations contain at least 1 blood pressuremedicationand1 statin. Somecombinationagents include aspirin, andothers have suggested including certain vitamins and minerals. While there have been many proposed polypill combinations andseveral settings inwhich theycould be used, randomized trial data of specific polypills in specific settings are limited. Several short-term, randomized trials3-7 have evaluated variouspolypills containing from1to3antihypertensiveagents and a statin and some contained aspirin. These trialswere designed to determine the magnitude of change in blood pressure or lipid levels and whether this magnitude was consistent with what would be expected based on trials of single agents. When compared with placebo, the combination pills resulted in meaningful reductions in systolic and diastolic bloodpressure, and in total and low-density lipoprotein (LDL) cholesterol, but these reductions were less than what would have been expected from the component medications based on trials of these agents taken as single medications.8 In this issue of JAMA, Thom and colleagues,9 representing a group of international investigators, evaluated the utility of a polypill strategy in 3 European countries and India for deliveringmedication to patients with CVD or at high risk for CVDevents by presence ofmultiple risk factors. The 2004patientswere takingmultiplemedications for hypertension and dyslipidemiaprior to enrollment. In this randomized trial, the polypill group was given a combination of 2 blood pressure medications (lisinopril 10 mg, atenolol 50 mg), 1 lipidloweringmedication (simvastatin40mg), andaspirin (75mg), while the usual care group continued individual medication intake as per usual. Comparedwith patients in the usual care group, those in thecombinationpill grouphad improvedmedicationadherenceandmodest reductions inbloodpressure (2.6 Related article page 918 Opinion

Background A Polypill is proposed for the primary prevention of cardiovascular disease in people judged to be at risk on account of their age alone. Its efficacy in reducing cholesterol and blood pressure is uncertain. Methods We conducted a randomized double-blind placebo-controlled crossover trial of a Polypill among individuals aged 50+ without a history of cardiovascular disease and compared the reductions with those predicted from published estimates of the effects of the individual drugs. Participants took the Polypill (amlodipine 2.5 mg, losartan 25 mg, hydrochlorothiazide 12.5 mg and simvastatin 40 mg) each evening for 12 weeks and a placebo each evening for 12 weeks in random sequence. The mean within-person differences in blood pressure and low density lipoprotein (LDL) cholesterol at the end of each 12 week period were determined. Results 84 out of 86 participants completed both treatment periods. The mean systolic blood pressure was reduced by 17.9 mmHg (95% CI, 15.7–20.1) on the Polypill, diastolic blood pressure by 9.8 mmHg (8.1–11.5), and LDL cholesterol by 1.4 mmol/L (1.2–1.6), reductions of 12%, 11%, and 39% respectively. The results were almost identical to those predicted; 18.4 mmHg, 9.7 mmHg, and 1.4 mmol/L respectively. Conclusion The Polypill resulted in the predicted reductions in blood pressure and LDL cholesterol. Long term reductions of this magnitude would have a substantial effect in preventing heart attacks and strokes. Trial Registration Controlled-Trials.com ISRCTN36672232

In less than a decade since it was proposed, the polypill has been the subject of many studies and remains “the only panacea we can see” for the toll taken by cardiovascular disease, delegates were told at a seminar in London on 13 July. Denis Xavier is project director and coauthor of the TIPS trial (The Indian Polycap Study) and head of the department of pharmacology at St John’s Medical College in Bangalore. He argued at a seminar organised by C3 Collaborating for Health—an international charity aimed at controlling non-communicable diseases worldwide—that the polypill had demonstrated its safety and efficacy. But several barriers still stood in the way of its wider adoption. Since Nicholas Wald and Malcolm Law first suggested the idea of combining a statin, three blood pressure lowering drugs, …

Researchers have proposed that physicians should advise all of their patients over age 55 to take a polypill containing treatments for many cardiovascular risk factors rather than testing them for ...