A Polypill Strategy to Improve Adherence Castellano, José M., MD, PhD; Sanz, Ginés, MD, PhD; Peñalvo, José L., PhD ...
Journal of the American College of Cardiology,
11/2014, Letnik:
64, Številka:
20
Journal Article
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Abstract Background Adherence to evidence-based cardiovascular (CV) medications after an acute myocardial infarction (MI) is low after the first 6 months. The use of fixed-dose combinations (FDC) has ...been shown to improve treatment adherence and risk factor control. However, no previous randomized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients. Objectives The cross-sectional FOCUS (Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention) study (Phase 1) aimed to elucidate factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI. Additionally, 695 patients from Phase 1 were randomized into a controlled trial (Phase 2) to test the effect of a polypill (containing aspirin 100 mg, simvastatin 40 mg, and ramipril 2.5, 5, or 10 mg) compared with the 3 drugs given separately on adherence, blood pressure, and low-density lipoprotein cholesterol, as well as safety and tolerability over a period of 9 months of follow-up. Methods In Phase 1, a 5-country cohort of 2,118 patients was analyzed. Patients were randomized to either the polypill or 3 drugs separately for Phase 2. Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green questionnaire (MAQ) and pill count (patients had to meet both criteria for adherence at the in-person visit to be considered adherent). Results In Phase 1, overall CV medication adherence, defined as an MAQ score of 20, was 45.5%. In a multivariable regression model, the risk of being nonadherent (MAQ <20) was associated with younger age, depression, being on a complex medication regimen, poorer health insurance coverage, and a lower level of social support, with consistent findings across countries. In Phase 2, the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up: 50.8% versus 41% (p = 0.019; intention-to-treat population) and 65.7% versus 55.7% (p = 0.012; per protocol population) when using the primary endpoint, attending the final visit with MAQ = 20 and high pill count (80% to 110%) combined, to assess adherence. Adherence also was higher in the FDC group when measured by MAQ alone (68% vs. 59%, p = 0.049). No treatment difference was found at follow-up in mean systolic blood pressure (129.6 mm Hg vs. 128.6 mm Hg), mean low-density lipoprotein cholesterol levels (89.9 mg/dl vs. 91.7 mg/dl), serious adverse events (23 vs. 21), or death (1, 0.3% in each group). Conclusions For secondary prevention following acute MI, younger age, depression, and a complex drug treatment plan are associated with lower medication adherence. Meanwhile, adherence is increased in patients with higher insurance coverage levels and social support. Compared with the 3 drugs given separately, the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI. (Fixed Dose Combination Drug Polypill for Secondary Cardiovascular Prevention FOCUS; NCT01321255 )
Background The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly ...defined. Objective The PESA study examines the presence of subclinical atherosclerosis by means of noninvasive imaging and prospectively analyzes the determinants associated with its development and progression in a middle-aged population. Methods The PESA study is an observational, longitudinal and prospective cohort study in a target population of 4000 healthy subjects (40-54 years old, 35% women) based in Madrid (Spain). Recruitment began in June 2010 and will be completed by the end of 2013. Baseline examination consists of (1) assessment for cardiovascular risk factors (including lifestyle and psychosocial factors); (2) screening for subclinical atherosclerosis using 2D/3D ultrasound in carotid, abdominal aorta and iliofemoral arteries, and coronary artery calcium score (CACS) by computed tomography; and (3) blood sampling for determination of traditional risk factors, advanced “omics” and biobanking. In addition, a subgroup of 1300 participants with evidence of atherosclerosis on 2D/3D ultrasound or CACS will undergo a combined18 F-fluorodeoxyglucose–positron emission tomography/magnetic resonance imaging (18 FDG PET/MRI) study of carotid and iliofemoral arteries. Follow-up at 3 and 6 years will include a repetition of baseline measurements, except for the18 FDG PET/MRI study, which will be repeated at 6 years. Conclusions The PESA study is expected to identify new imaging and biological factors associated with the presence and progression of atherosclerosis in asymptomatic people and will help to establish a more personalized management of medical care.
Abstract Background The importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would ...contribute greatly to inform effective primary prevention strategies. Objectives This study sought to quantify the association between specific dietary patterns and presence and extent of subclinical atherosclerosis in a population of asymptomatic middle-aged adults. Methods The PESA (Progression of Early Subclinical Atherosclerosis) study enrolled 4,082 asymptomatic participants 40 to 54 years of age (mean age 45.8 years; 63% male) to evaluate the presence of subclinical atherosclerosis in multiple vascular territories. A fundamental objective of this cohort study was to evaluate the life-style–related determinants, including diet, on atherosclerosis onset and development. We conducted a cross-sectional analysis of baseline data, including detailed information on dietary habits obtained as part of the overall life-style and risk factor assessment, as well as a complete vascular imaging study that was performed blinded to the clinical information. Results Most PESA participants follow a Mediterranean (40% of participants) or a Western (41%) dietary pattern. A new pattern, identified among 19% of participants, was labeled as a social-business eating pattern, characterized by a high consumption of red meat, pre-made foods, snacks, alcohol, and sugar-sweetened beverages and frequent eating-out behavior. Participants following this pattern presented a significantly worse cardiovascular risk profile and, after adjustment for risk factors, increased odds of presenting subclinical atherosclerosis (odds ratio: 1.31; 95% confidence interval: 1.06 to 1.63) compared with participants following a Mediterranean diet. Conclusions A new social-business eating pattern, characterized by high consumption of red and processed meat, alcohol, and sugar-sweetened beverages, and by frequent snacking and eating out as part of an overall unhealthy life-style, is associated with an increased prevalence, burden, and multisite presence of subclinical atherosclerosis. (Progression of Early Subclinical Atherosclerosis PESA; NCT01410318 )
Abstract Background Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to ...analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. Methods and Results ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 0.19-1.97 versus 2 1-2 labeled cells/cm2 , respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the number of small vessels than transendocardial administration (223 ± 40 versus 168 ± 35 vessels/mm2 ; P < .05). Ejection fraction was not modified by stem cell therapy. Conclusions This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.
In spite of advances in prevention and treatment, the burden of cardiovascular diseases is increasing. A fixed-dose combination (FDC) pill, or “polypill,” composed of evidence-based drugs has been ...proposed as a means of improving cardiovascular prevention by reducing cost and increasing patient adherence to treatment. The aim of the FOCUS project, funded by the 7th Framework Programme of the European Commission, is to characterize the factors that underlie inadequate secondary prevention and to test a new FDC. To achieve these goals, a 9-member consortium has been constituted, including institutions from Argentina, France, Italy, Spain, and Switzerland. FOCUS Phase-1 will examine factors potentially related to lack of adequate secondary prevention in 4,000 post–myocardial infarction (MI) patients and analyze the relationship between these factors and patient treatment adherence. Primary end points will be (1) the percentage of patients receiving aspirin, angiotensin-converting enzyme inhibitors, and statins and (2) adherence to treatment measured by the Morisky-Green test. FOCUS Phase-2 is a randomized trial that will compare adherence to treatment in 1,340 post–myocardial infarction patients either receiving an FDC comprising aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and simvastatin (40 mg) or receiving the same 3 drugs separately.
Abstract Background Assessment of myocardial deformation in Chagas disease may help us to better understand the disease pathophysiology and to detect early myocardial involvement. We aimed to ...characterize myocardial deformation in patients in different forms of Chagas disease and, specifically, assess differences between patients in the indeterminate form and controls. Methods and Results Speckle tracking echocardiography was performed in 98 subjects (22 with Chagas cardiomyopathy, 32 in the indeterminate form, and 44 control subjects) to quantify global and segmental left ventricular (LV) radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). In a subset of patients from the indeterminate and control groups (n = 25), LV peak systolic twist and untwisting velocities were additionally assessed. Global RS, CS, and LS showed a significant decreasing trend across groups. Patients in the indeterminate form had significantly lower global RS and RS in the midinferior segment (median 39.8% vs 49.3% P = .046 and 44.0% vs 56.0% P = .038, respectively) and lower twist and untwisting velocity ( P < .05 for both) compared with control subjects. Conclusion Evaluation of myocardial deformation, particularly of RS, appears to be a sensitive technique for detection of myocardial involvement in patients in the indeterminate form and provides insights into the still unrevealed pathophysiology of Chagas heart involvement.
Abstract The prevention of cardiovascular disease (CVD) by using a polypill has gained increasing momentum as a strategy to contain progression of the disease. Since its initial conception just over ...a decade ago, only a handful of trials have been completed assessing the efficacy and safety of this innovative concept. The results of these trials have supported the viability of the polypill in CVD prevention and management, albeit with a few caveats, essentially related to the lack of evidence on the effect of the polypill to effectively reduce cardiovascular events. The polypill has the potential to control the global health epidemic of CVD by effectively reaching underdeveloped regions of the world, simplifying healthcare delivery, improving cost-effectiveness, increasing medication adherence, and supporting a comprehensive prescription of evidence-based cardioprotective drugs. Major trials underway will provide definitive evidence on the efficacy of the polypill in reducing cardiovascular events in a cost-effective manner. The results of these studies will determine whether a polypill strategy can quell the burgeoning public health challenge of CVD and will potentially provide the evidence to implement an effective, simple, and innovative solution to restrain the global CVD pandemic.
Background Infarct size predicts post-infarction mortality. Oral β-blockade within 24 hours of a ST-segment elevation acute myocardial infarction (STEMI) is a class-IA indication, however early ...intravenous (IV) β-blockers initiation is not encouraged. In recent magnetic resonance imaging (MRI)–based experimental studies, the β1 -blocker metoprolol has been shown to reduce infarct size only when administered before coronary reperfusion. To date, there is not a single trial comparing the pre- vs. post-reperfusion β-blocker initiation in STEMI. Objective The METOCARD-CNIC trial is testing whether the early initiation of IV metoprolol before primary percutaneous coronary intervention (pPCI) could reduce infarct size and improve outcomes when compared to oral post-pPCI metoprolol initiation. Design The METOCARD-CNIC trial is a randomized parallel-group single-blind (to outcome evaluators) clinical effectiveness trial conducted in 5 Counties across Spain that will enroll 220 participants. Eligible are 18- to 80-year-old patients with anterior STEMI revascularized by pPCI ≤6 hours from symptom onset. Exclusion criteria are Killip-class ≥III, atrioventricular block or active treatment with β-blockers/bronchodilators. Primary end point is infarct size evaluated by MRI 5 to 7 days post-STEMI. Prespecified major secondary end points are salvage-index, left ventricular ejection fraction recovery (day 5-7 to 6 months), the composite of (death/malignant ventricular arrhythmias/reinfarction/admission due to heart failure), and myocardial perfusion. Conclusions The METOCARD-CNIC trial is testing the hypothesis that the early initiation of IV metoprolol pre-reperfusion reduces infarct size in comparison to initiation of oral metoprolol post-reperfusion. Given the implications of infarct size reduction in STEMI, if positive, this trial might evidence that a refined use of an approved inexpensive drug can improve outcomes of patients with STEMI.
Despite the use of newer immunosuppressors such as sirolimus (SRL) and tacrolimus (TRL) in heart transplantation, the rate of humoral rejection has remained unchanged. The aim of this study was to ...analyze the immunologic and histologic effects of cyclosporine (CsA), SRL, and TRL in a porcine model of arterial transplantation.
Each transplant recipient animal (n = 49) received an autograft and an allograft and was then allocated to one of four treatment groups and a 7- or 30-day follow-up period, as follows: a WOT group (without immunosuppressor treatment), 7 days (n = 6) and 30 days (n = 5); a CsA group, 7 days (n = 5) and 30 days (n = 6); an SRL group, 7 days (n = 7) and 30 days (n = 8); and a TRL group, 7 days (n = 6) and 30 days (n = 6). The presence of donor-specific antibodies (DSA) was tested at the end of the follow-up period. Morphometric parameters and inflammatory infiltration were analyzed in the explanted grafts.
At 30-day follow-up, SRL was the only treatment capable of suppressing DSA formation (0 of 7 vs 4 of 5 in the WOT group; p < 0.05). SRL completely prevented aneurismal dilation and reduced the number of macrophages in the allografts. TRL treatment achieved a greater reduction of T lymphocytes. CsA did not prevent the reduction in total vascular area at 7 days that was achieved with the SRL and TRL groups. Animals treated with CsA had the largest number of T lymphocytes and macrophages in both follow-up periods.
SRL prevented DSA formation and reduced the number of macrophages as compared with TRL and CsA.
Abstract Ischemic heart disease and stroke are the leading causes of death worldwide. What was once thought to be an endemic disease of high income countries has become a global epidemic, as low and ...middle income countries have adopted Western lifestyles, to the point that noncommunicable diseases are now the main cause of death in these regions, above and beyond communicable diseases, malnutrition, and injury. As a result, a large proportion of individuals at high 10-year risk of a cardiovascular event live in low- and middle-income countries, and the most of all cardiovascular events occur in developing countries. A large amount of evidence supports the use of pharmacological treatment for the prevention of cardiovascular death in this population, including antiplatelet drugs, β-blockers, lipid-lowering agents, and angiotensin-converting enzyme inhibitors, however, the efficacy of cardiovascular event prevention is hampered by several problems, including inadequate prescription of medication, poor adherence to treatment, limited availability of medications, and unaffordable cost of treatment. Here we examine the use of fixed-dose combination therapy, and how this therapy could improve adherence to treatment, reduce the cost, and improve treatment affordability in low-income countries.
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