Search

The emergence of SARS-CoV-2 variants raised questions regarding the durability of immune responses after homologous or heterologous boosters after Ad26.COV2.S-priming. We found that SARS-CoV-2-specific binding antibodies, neutralizing antibodies, and T cells are detectable 5 months after boosting, although waning of antibodies and limited cross-reactivity with Omicron BA.1 was observed., Competing Interests: Potential conflicts of interest. L. G. V. reports research grants from U Needle, MyLife Technologies, and Bavarian Nordic, all outside of the submitted work; consulting fees from Emergent for expert meeting travel vaccines; participation on a scientific advisory board for Geosentinel; and serving as committee member for the National Board Guideline Development Travel Medicine. A. G. reports participation on a data and safety monitoring board (DSMB) IDSCOVA (Establishing the tolerability, safety and immunogenicity of intradermal delivery of mRNA SARS-CoV-2 vaccine in healthy adults) study on intradermal COVID vaccinations and serving as member of national advisory board on coronavirus disease vaccinations for immunocompromised patients. A. L. W. H. reports support for the present research from the Dutch Research Council (ZonMw) to their organization. D. F. P. reports participation on the DSMB of the COBRA-KAI trial (COVID-19 vaccination in patients with reduced B-cell and T-cell immunity: response after vaccination in a kaleidoscopic group of hematologic patients: what's the impact?). V. A. S. H. D. reports research funding outside of the submitted work from ZonMw and EU Horizon 2020, consulting fees for an advisory board meeting from GSK, and honoraria for lectures from Pharming, Takeda. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives A 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. Methods The 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. Results In 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. Conclusions Patients 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.

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.

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., (© The European Society of Cardiology 2016.)

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.

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.

Atherosclerotic cardiovascular diseases remain the leading cause of morbidity and mortality in both developed and developing countries. Adequate treatment of vascular risk factors, such as low-density lipoprotein cholesterol and systolic blood pressure are known to reduce the future risk of cardiovascular disease in these patients. However currently, large treatment gaps exist among high-risk individuals, in whom the guidelines recommend concomitant treatment with aspirin, statin, and blood-pressure lowering agents. Combining aspirin, cholesterol, and blood-pressure lowering agents into a single pill called the cardiovascular polypill has been proposed as complementary care in the prevention of cardiovascular diseases in both intermediate- and high-risk patient populations. It is now a decade since the first recommendations to develop and trial cardiovascular polypills. The major scientific debate has been about the appropriate initial target population. This review article focuses on the potential role of fixed-dose combination therapy in different patient populations, outlines the pros and cons of combination therapy, and emphasizes the rationale for trialing their use. Current and planned future cardiovascular polypill trials are summarized and the pre-requisites for implementation of the polypill strategy in both primary and secondary prevention are described. The recent development of combination pills containing off-patent medications holds promise for highly affordable and effective treatment and evidence is emerging on the use of this strategy in high-risk populations.