A Survey of Availability and Affordability of Polypills for Cardiovascular Disease in Selected Countries.

Background: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally. Methods: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised for marketing and/or included in EMLs and clinical guidelines. In each country, we collected retail and price data for polypills from at least one public-sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable if the lowest-paid worker spent more than a day's wage to purchase a monthly supply. Results: Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. In the four countries, no surveyed public pharmacies stocked polypills. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Private sector availability was 100% in Argentina and Spain. Most combinations (n = 5) identified were in India. Combinations found in India and Spain were affordable in the local context. A lowest-paid government worker would spend between 0.2 (India) and 2.8 (Mauritius) days' wages to pay the price for one month's supply of the polypills. Polypills were likely to be affordable if they were manufactured in the same country. Conclusion: Low availability and affordability of polypills in the public sector suggest that implementation remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

Polypill versus medication monotherapy in the prevention of cardiovascular diseases in Iran: An economic evaluation study.

Background and Aims: Cardiovascular diseases (CVDs) are one of the major diseases in developing and developed countries and have high prevalence and mortality rates. Pharmacological interventions, especially the use of combination medications, can have preventive effects in patients with CVDs. Recently, in the PolyIran trial, a combination of atorvastatin, hydrochlorothiazide, aspirin, and valsartan or enalapril (Polypill) was shown to be effective in providing survival benefits as a primary prevention strategy. In the present study, we examine the cost-effectiveness of the use of polypill compared to its individual components (named as medication monotherapy) in the prevention of CVDs in Iran. Methods: This was an economic evaluation study conducted to compare the cost-utility of polypill with that of medication monotherapy for 10,000 hypothetical cohorts of people over 35 years of age using the Markov model and with a lifetime horizon. The study perspective was patient perspective and direct medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio were estimated. To deal with uncertaintysensitivity analyses were used. Results: The results showed that polypill, with the lowest costs (871 USD) and highest QALYs (14.55), had the most cost-utility than medication monotherapy. Also, the results showed that the highest sensitivities were related to the utilities of angina and stroke states. At the 21,768 USD threshold, polypill had a 92% probability of being cost-effective versus other medications. Conclusion: Considering that polypill had the most cost-utility, it is suggested that health system policymakers pay special attention to polypill in designing clinical guidelines. Also, through covering this medication by health insurance organizations, it is possible to complete the country's medicine pharmacopeia in preventing CVDs.

The Polypill: A New Alternative in the Prevention and Treatment of Cardiovascular Disease.

Cardiovascular disease (CVD) is the primary cause of death and disability worldwide. Although age-standardized CVD mortality rates decreased globally by 14.5% between 2006 and 2016, the burden of CVD remains disproportionately higher in low- and middle-income countries compared to high-income countries. Even though proven, effective approaches based on multiple-drug intake aimed at the prevention and treatment of CVD are currently available, poor adherence, early discontinuation of treatment, and suboptimal daily execution of the prescribed therapeutic regimes give rise to shortfalls in drug exposure, leading to high variability in the responses to the prescribed medications. Wald and Law, in their landmark paper published in BMJ 2003, hypothesized that the use of a fixed-dose combination of statins, ß-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and aspirin (classic Polypill composition) may increase adherence and decrease CVD by up to 80% when prescribed as primary prevention or in substitution of traditional protocols. Since then, many clinical trials have tested this hypothesis, with comparable results. This review aims to describe the available clinical trials performed to assess the impact of fixed-dose combinations on adherence, cost-effectiveness, and the risk factors critical to the onset of CVD.

Cost effectiveness analysis of a fixed dose combination pill for primary prevention of cardiovascular disease from an individual participant data meta-analysis.

Background: Cardiovascular disease (CVD) continues to impart a large burden on the global population, especially in lower income countries where affordability limits the use of cardiovascular medicines. A fixed dose combination strategy of at least 2 blood pressure lowering medications and a statin with aspirin in a single pill has been shown to reduce the risk of incident CVD by 38% in primary prevention in a recent meta-analysis. We report the in-trial (median follow-up: 5 years) cost-effectiveness of a fixed dose combination (FDC) pill in different income groups based on data from that meta-analysis. Methods: Countries were categorized using World Bank economic groups: Lower Middle Income Countries (LMIC), Upper Middle Income Countries (UMIC) and High Income Countries (HIC). Country specific costs were obtained for hospitalized events, procedures, and non-study medications (2020 USD). FDC price was based on the cheapest equivalent substitute (CES) for each component. Findings: For the CES-FDC pill versus control the difference in cost was $346 (95% CI: $294-$398) per participant in Lower Middle Income Countries, $838 (95% CI: $781-$895) in Upper Middle Income Countries and $42 (95% CI: -$155 to $239) (cost-neutral) in High Income Countries. During the study period the CES-FDC pill was associated with incremental gain in quality-adjusted life years of 0.06 (95% CI: 0.04-0.08) resulting in an incremental cost-effectiveness ratio (ICER) of $5767 (95% CI: 5735-$5799), $13,937 (95% CI: $13,893-$14,041) and $700 (95% CI: $662-$738) respectively. In subgroups analyses, the highest 10 years CVD risk subgroup had ICERs of $2033, $7322 and -$6000/QALY. Interpretation: A FDC pill produced at CES costs is cost-neutral in HIC. Governments of LMI and UMI countries should assess these results based on the ICER threshold accepted in their own country and own specific health care priorities but should consider prioritizing this strategy for patients with high 10 years CVD risk as a first step. Funding: Population Health Research Institute.

[Effectiveness of the CNIC polypill in secondary cardiovascular prevention in the subgroup of patients of the NEPTUNO study using atorvastatin doses of 20 mg]. / Efectividad de la polipíldora CNIC en prevención cardiovascular secundaria en el subgrupo de pacientes del estudio NEPTUNO con dosis de atorvastatina de 20 mg.

Objective: To analyse the incidence and risk of recurrent major adverse cardiovascular events (MACE), level of risk factor control, treatment persistence and cost of the CNIC polypill version containing acetylsalicylic acid (ASA) 100 mg, atorvastatin 20 mg (A20), and ramipril 2.5, 5.0 or 10 mg in secondary cardiovascular prevention patients. Method: Subanalysis of the observational, retrospective, multicentre, NEPTUNO study in patients treated for two years with the CNIC polypill A20, the same monocomponents as single drugs, equipotent drugs, and other therapies. Results: 922 patients were included in each group. The risk of recurrent MACE was lower among CNIC A20 polypill users than all others (21%, 23% and 26% increased risk among the monocomponents, equipotent or other therapy cohorts, respectively; p < 0.05). The magnitude of the mean change in low-density lipoprotein cholesterol and blood pressure, as well as the increase in the proportion of patients achieving target goals, was also greater among patients treated with the CNIC A20 polypill than in any of the other cohorts (all p < 0.001). Treatment persistence was significantly higher in patients treated with the CNIC A20 polypill (p < 0.001) and was a less costly strategy than any other therapeutic option. Conclusions: In patients in secondary cardiovascular prevention, the CNIC A20 polypill (ASA 100 mg, atorvastatin 20 mg, and ramipril 2.5, 5.0 or 10 mg) constitutes a valid therapeutic option with similar benefits and outcomes to the version of the polypill with atorvastatin 40 mg.

Objetivo: Analizar la incidencia y el riesgo de eventos adversos cardiovasculares mayores (MACE) recurrentes, el nivel de control de factores de riesgo, la persistencia al tratamiento y el coste de la versión de la polipíldora CNIC que contiene 100 mg de ácido acetilsalicílico (AAS), 20 mg de atorvastatina (A20) y 2.5/5.0 ó 10 mg de ramipril en pacientes en prevención cardiovascular secundaria. Método: Subanálisis del estudio observacional, retrospectivo y multicéntrico NEPTUNO en pacientes tratados durante 2 años con la polipíldora CNIC A20, los mismos monocomponentes por separado, medicamentos equipotentes uotras terapias. Resultados: Se incluyeron 922 pacientes en cada grupo. El riesgo de sufrir un MACE recurrente en el grupode polipíldora CNIC A20 fue menor que en todas las demás cohortes (21%, 23% y 26% de aumento del riesgo en las cohortesde monocomponentes, equipotentes u otras terapias, respectivamente; p < 0.05). La magnitud del cambio en el colesterol unidoa lipoproteínas de baja densidad y la presión arterial, así como el incremento en la proporción de pacientes que alcanzaron losobjetivos establecidos, fueron mayores en los pacientes tratados con la polipíldora CNIC A20 que en cualquiera de las otrascohortes (p < 0.001). La persistencia al tratamiento fue mayor en los pacientes tratados con la polipíldora CNIC A20 (p < 0.001)y esta estrategia resultó ser menos costosa que cualquier otra opción terapéutica. Conclusiones: En pacientes en prevencióncardiovascular secundaria, la polipíldora CNIC A20 (AAS 100 mg; atorvastatina 20 mg; ramipril 2.5/5.0 ó 10 mg) constituye unaopción terapéutica válida con beneficios y resultados similares a la versión de la polipíldora con 40 mg de atorvastatina.

Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on the simplification of the drug regimen for secondary cardiovascular prevention.

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socio-economic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence.

Cholesterol-Lowering Strategies for Cardiovascular Disease Prevention: The Importance of Intensive Treatment and the Simplification of Medical Therapy.

Cardiovascular diseases (CVDs) are a leading global cause of mortality and are primarily driven by atherosclerotic coronary artery disease. Their pathogenesis involves multi-factorial mechanisms, among which low-density lipoprotein (LDL) plays a causative role. Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases. Intensive lipid-lowering therapy has been shown to be pivotal, especially in post-acute coronary events. Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes.

Single-pill combination for treatment of hypertension: Just a matter of practicality or is there a real clinical benefit?

Elevated blood pressure (BP) is the largest contributor to the incident cardiovascular disease worldwide. Despite explicit guideline recommendations for the diagnosis and management of hypertension, a large proportion of patients remain undiagnosed, untreated, or treated but uncontrolled. Inadequate BP control is associated with many complex factors including patient preference, physician's inertia, health systems disparities, and poor adherence to prescribed antihypertensive drug treatment. The primary driver for reduced cardiovascular morbidity and mortality is lowering of BP ''per se'' and not class effects of specific pharmacotherapies. The recent ESH guidelines recommend the use of four major classes of drugs including renin-angiotensin-aldosterone system (RAS) blockers (angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEi)), calcium channel blockers (CCB), thiazide and thiazide-like diuretics, and betablockers. Initiation of treatment for hypertension with a two-drug regimen, preferably in a single pill combination (SPC), is recommended for most patients. Preferred combinations should comprise a RAS blocker (either an ACEi or an ARB) with a CCB or thiazide/thiazide-like diuretic. These strategies are supported by robust evidence that combination therapy produces greater BP reductions than monotherapy, reduces side effects of the individual components, improves therapeutic adherence and long-term persistence on treatment, and permits achievement of earlier BP control.

The Evolving Field of Acute Coronary Syndrome Management: A Critical Appraisal of the 2023 European Society of Cardiology Guidelines for the Management of Acute Coronary Syndrome.

Acute coronary syndromes (ACS), encompassing conditions like ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndromes (NSTE-ACS), represent a significant challenge in cardiovascular care due to their complex pathophysiology and substantial impact on morbidity and mortality. The 2023 European Society of Cardiology (ESC) guidelines for ACS management introduce several updates in key areas such as invasive treatment timing in NSTE-ACS, pre-treatment strategies, approaches to multivessel disease, and the use of imaging modalities including computed tomography (CT) coronary angiography, magnetic resonance imaging (MRI), and intracoronary imaging techniques, such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS). They also address a modulation of antiplatelet therapy, taking into consideration different patient risk profiles, and introduce new recommendations for low-dose colchicine. These guidelines provide important evidence-based updates in practice, reflecting an evolution in the understanding and management of ACS, yet some potentially missed opportunities for more personalized care and technology adoption are discussed.

The CNIC-polypill (acetylsalicylic acid, atorvastatin, and ramipril), an effective and cost-saving secondary prevention strategy compared with other therapeutic options in patients with ischaemic heart disease.

Aims: The retrospective NEPTUNO study evaluated the effectiveness of the Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (including acetylsalicylic acid, ramipril, and atorvastatin) vs. other therapeutic approaches in secondary prevention for cardiovascular (CV) disease. In this substudy, the focus was on the subgroup of patients with ischaemic heart disease (IHD). Methods and results: Patients on four strategies: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. The primary endpoint was the incidence of recurrent major adverse CV events (MACEs) after 2 years. After matching, 1080 patients were included in each cohort. The CNIC-polypill cohort had a significantly lower incidence of recurrent MACE compared with monocomponents, equipotent drugs, and other therapies cohorts (16.1 vs. 24, 24.4, and 24.3%, respectively; P < 0.001). The hazard ratios (HRs) for recurrent MACE were higher in monocomponents (HR = 1.12; P = 0.042), equipotent drugs (HR = 1.14; P = 0.031), and other therapies cohorts (HR = 1.17; P = 0.016) compared with the CNIC-polypill, with a number needed to treat of 12 patients to prevent a MACE. The CNIC-polypill demonstrated a greater reduction in LDL cholesterol (LDL-c; -56.1 vs. -43.6, -33.3, and -33.2% in the monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) and systolic blood pressure (-13.7 vs. -11.5, -10.6, and -9.1% in the CNIC-polypill, monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) compared with other cohorts. The CNIC-polypill intervention was less costly and more effective than any other therapeutic option, with €2317-€2407 cost savings per event prevented. Conclusion: In IHD, the CNIC-polypill exemplifies a guideline-recommended secondary prevention treatment linked to better outcomes and cost saving compared with other therapeutic options.

Fixed-dose combination therapy in pulmonary arterial hypertension: Pros & cons.

Quality of life of patients suffering from chronic diseases is inevitably conditioned by the number of pills taken during the day. To improve patients' tolerability, compliance and quality of life and reduce healthcare costs, pharmaceutical companies are focusing on the commercialization of fixed-dose combination (FDC) therapies. The last ESC/ERS guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend initial dual combination therapy for newly diagnosed patients at low or intermediate mortality risk. In this regard, polypills including an endothelin receptor antagonist (ERA) and a phosphodiesterase 5 inhibitor (PDE5-i) could represent an useful therapeutic strategy, although with some limitations. To date, evidence about the use of FDCs in PAH is limited but future studies evaluating their safety and efficacy are welcome.

Polypill Strategy in Secondary Cardiovascular Prevention.

PURPOSE OF REVIEW: The polypill strategy, originally developed to improve medication adherence, has demonstrated efficacy in improving baseline systolic blood pressures and cholesterol levels in multiple clinical trials. However, the long-term clinical impact of improved major cardiovascular events (MACE) outcomes by the polypill remains uncertain. RECENT FINDINGS: Recent trials with long-term follow-up, which included minority groups and people with low socioeconomic status, have shown non-inferiority with no difference in adverse effects rates for the secondary prevention of MACE. Although the polypill strategy was initially introduced to improve adherence to guideline-directed medical therapy (GDMT) for cardiovascular complications, the strategy has surpassed standard medical treatment for secondary prevention of MACE outcomes. Studies also showed improved medication compliance in underserved populations.

Comparing screening based on the NHS Health Check and Polypill Prevention Programmes in the primary prevention of heart attacks and strokes.

OBJECTIVE: To compare the NHS Health Check Programme with the Polypill Prevention Programme in the primary prevention of heart attacks and strokes. DESIGN: Use of published data and methodology to produce flow charts of the two programmes to determine screening performance and heart attacks and strokes prevented. SETTING: The UK population. INTERVENTION: The NHS Health Check Programme using a QRISK score on people aged 40-74 to select those eligible for a statin is compared with the Polypill Prevention Programme in people aged 50 or more to select people for a combination of a statin and three low-dose blood pressure lowering agents. In both programmes, people had no history of heart attack or stroke. MAIN OUTCOME MEASURES: In 1000 people, the number of heart attacks and strokes prevented in the two programmes. RESULTS: In the hypothetical perfect situation with 100% uptake and adherence to the screening protocol, in every 1000 persons, the NHS Health Check would prevent 287 cases of a heart attack or stroke in individuals who would gain on average about 4 years of life without a heart attack or stroke amounting to 1148 years in total, the precise gain depending on the extent of treatment for those with raised blood pressure, and 136 would be prescribed statins with no benefit. The corresponding figures for the Polypill Prevention Programme are 316 individuals who would, on average, gain 8 years of life without a heart attack or stroke, amounting to 2528 years in total, and 260 prescribed the polypill with no benefit. Based on published estimates of uptake and adherence in the NHS Health Check Programme, in practice only 24 cases per 1000 are currently benefitting instead of 287, amounting to 96 years gained without a heart attack or stroke. CONCLUSIONS: The Polypill Prevention Programme is by design simpler with the potential of preventing many more heart attacks and strokes than the NHS Health Check Programme.

The polypill in the primary prevention of heart attacks and strokes: Overcoming barriers to implementation.

This commentary, linked to our paper in the same issue of the Journal of Medical Screening, discusses the reluctance to consider and adopt the polypill in the primary prevention of heart attacks and strokes, access to the polypill as a public health service, the formulation of the polypill in current use, its prescription as an unlicensed medicine, and what can be done to facilitate the adoption of the polypill approach as a routine public health service.

Rationale for a New Low-Dose Triple Single Pill Combination for the Treatment of Hypertension.

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

Tailoring drug release in bilayer tablets through droplet deposition modeling and injection molding.

This study explores the innovative production of personalized bilayer tablets, integrating two advanced manufacturing techniques: Droplet Deposition Modeling (DDM) and Injection Molding (IM). Unlike traditional methods limited to customizing dense bilayer medicines, our approach uses Additive Manufacturing (AM) to effectively adjust drug release profiles. Focusing on Caffeine and Paracetamol, we found successful processing for both DDM and IM using Caffeine formulation. The high viscosity of Paracetamol formulation posed challenges during DDM processing. Integrating Paracetamol formulation for the over-molding process proved effective, demonstrating IM's versatility in handling complex formulations. Varying infill percentages in DDM tablets led to distinct porosities affecting diverse drug release profiles in DDM-fabricated tablets. In contrast, tablets with high-density structures formed through the over-molding process displayed slower and more uniform release patterns. Combining DDM and IM techniques allows for overcoming the inherent limitations of each technique independently, enabling the production of bilayer tablets with customizable drug release profiles. The study's results offer promising insights into the future of personalized medicine, suggesting new pathways for the development of customized oral dosage forms.

Single-Pill, Triple Antihypertensive Therapy in Rural Sub-Saharan Africa: Preliminary Experience.

INTRODUCTION: Worldwide, arterial hypertension is the foremost preventable and modifiable cardiovascular risk factor. In addition to lifestyle changes, recent international guidelines recommend single-pill, low-dose combinations as initial treatment strategy. We investigated whether this approach is feasible in a rural sub-Saharan Africa setting. METHODS: Diagnosis of hypertension was established over three sets of blood pressure measurements, performed according to the European Society of Hypertension recommendations by trained personnel, using a validated, automated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals with arterial hypertension, a once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at an appropriate dose. Patients were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. The treatment regimen was adjusted, if needed, at each outpatient clinic scheduled after 4, 8, 12, and 16 weeks. RESULTS: Seventy-nine patients (aged 61 [53-70] years; median and interquartile range) strictly adhered to the treatment schedule, while 19 individuals (70 [65-80] years) dropped out. Blood pressure was < 140/90 mmHg after 4 weeks in 44 (56%), after 8 weeks in 62 (78%), after 12 weeks in 69 (87%), and after 16 weeks in 74 (94%) participants. Excellent tolerance was reported. CONCLUSIONS: These results provide real-life evidence that hypertension management with a once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide as initial treatment is feasible and effective also in a rural sub-Saharan setting. Single-pill combinations should be made available also in rural and remote areas in low- and middle-income countries as a reliable first-line treatment strategy.

World Heart Federation Roadmap for Secondary Prevention of Cardiovascular Disease: 2023 Update.

Background: Secondary prevention lifestyle and pharmacological treatment of atherosclerotic cardiovascular disease (ASCVD) reduce a high proportion of recurrent events and mortality. However, significant gaps exist between guideline recommendations and usual clinical practice. Objectives: Describe the state of the art, the roadblocks, and successful strategies to overcome them in ASCVD secondary prevention management. Methods: A writing group reviewed guidelines and research papers and received inputs from an international committee composed of cardiovascular prevention and health systems experts about the article's structure, content, and draft. Finally, an external expert group reviewed the paper. Results: Smoking cessation, physical activity, diet and weight management, antiplatelets, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors, and cardiac rehabilitation reduce events and mortality. Potential roadblocks may occur at the individual, healthcare provider, and health system levels and include lack of access to healthcare and medicines, clinical inertia, lack of primary care infrastructure or built environments that support preventive cardiovascular health behaviours. Possible solutions include improving health literacy, self-management strategies, national policies to improve lifestyle and access to secondary prevention medication (including fix-dose combination therapy), implementing rehabilitation programs, and incorporating digital health interventions. Digital tools are being examined in a range of settings from enhancing self-management, risk factor control, and cardiac rehab. Conclusions: Effective strategies for secondary prevention management exist, but there are barriers to their implementation. WHF roadmaps can facilitate the development of a strategic plan to identify and implement local and national level approaches for improving secondary prevention.

The Impact of Polypill on Adherence and Cardiovascular Outcomes: A Comprehensive Systematic Review with Meta-Analysis.

BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. Polypills, containing various combinations of medications for primary and secondary CVD prevention, have been developed to enhance medication adherence and reduce the healthcare burden of CVD. However, their effectiveness compared to usual care remains uncertain. OBJECTIVE: This meta-analysis aimed to evaluate the effects of polypills on cardiovascular risk factors, major adverse cardiovascular events (MACE), and medication adherence. METHODS: We conducted a comprehensive search for large-scale randomized controlled trials and observational studies comparing the effects of polypills versus usual care on CVD risk factors and events. Outcomes included changes in systolic and diastolic blood pressure (SBP, DBP), lipid profiles, occurrence of MACE, and medication adherence. RESULTS: The use of polypills led to a statistically significant yet clinically modest reduction in SBP (mean difference -1.47 mmHg, 95% CI: -2.50 to -0.44, p<0.01) and DBP (mean difference- 1.10 mmHg, 95% CI: -1.68 to -0.51, p< 0.01) compared to usual care. Polypills also showed a significant reduction in the risk of MACE (RR: 0.86, 95% CI: 0.77 -0.95, p<0.01). There was a non-significant reduction in LDL and HDL levels. Adherence to medication improved by up to 17% in polypill users compared to those on usual care (p < 0.01). A multivariable metaregression analysis suggested that adherence may be the underlying factor responsible for the observed effect of the polypills on blood pressure. CONCLUSION: Polypills were found to significantly reduce SBP, DBP and MACE. An improvement in medication adherence was also observed among polypill users, which might be responsible for the significant reduction in SBP observed users. Future research might benefit from exploring a more personalized approach to the composition of polypills, which could reveal a more clinically significant impact of increased adherence on CVD outcomes.