Cost-effectiveness analysis of use of a polypill versus usual care or best practice for primary prevention in people at high risk of cardiovascular disease.

BACKGROUND: Clinical trials suggest that use of fixed-dose combination therapy ('polypills') can improve adherence to medication and control of risk factors of people at high risk of cardiovascular disease (CVD) compared to usual care, but cost-effectiveness is unknown. OBJECTIVE: To determine whether a polypill is cost-effective compared to usual care and optimal guideline-recommended treatment for primary prevention in people already on statins and/or blood pressure lowering therapy. METHODS: A Markov model was developed to perform a cost-utility analysis with a one year time cycle and a 10 year time horizon to compare the polypill with usual care and optimal implementation of NICE Guidelines, using patient level data from a retrospective cross-sectional study. The model was run for ten age (40 years+) and gender-specific sub-groups on treatment for raised CVD risk with no history of CVD. Published sources were used to estimate impact of different treatment strategies on risk of CVD events. RESULTS: A polypill strategy was potentially cost-effective compared to other strategies for most sub-groups ranging from dominance to up to £18,811 per QALY depending on patient sub-group. Optimal implementation of guidelines was most cost-effective for women aged 40-49 and men aged 75+. Results were sensitive to polypill cost, and if the annual cost was less than £150, this approach was cost-effective compared to the other strategies. CONCLUSIONS: For most people already on treatment to modify CVD risk, a polypill strategy may be cost-effective compared with optimising treatment as per guidelines or their current care, as long as the polypill cost is sufficiently low.

A feasibility study to inform the design of a randomised controlled trial to identify the most clinically effective and cost-effective length of Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT).

BACKGROUND: Venous thromboembolism is common in cancer patients and requires anticoagulation with low-molecular-weight heparin (LMWH). Current data recommend LMWH for anticoagulation as far as 6 months, yet guidelines recommend LMWH beyond 6 months in patients who have ongoing or active cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. OBJECTIVES: (1) To identify the most clinically and cost-effective length of anticoagulation with LMWH in the treatment of cancer-associated thrombosis (CAT); (2) to identify practicalities of conducting a full randomised controlled trial (RCT) with regard to recruitment, retention and outcome measurement; and (3) to explore the barriers for progressing to a full RCT. DESIGN: The Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT) trial is a randomised, multicentre, feasibility mixed-methods study with three components: (1) a RCT comparing ongoing LMWH treatment for CAT with cessation of LMWH at 6 months' treatment (current licensed practice) in patients with locally advanced or metastatic cancer, consulted in three clinical settings (haematology outpatients, oncology outpatients and primary care); (2) a nested qualitative study, including focus groups with clinicians to investigate attitudes for recruiting to the study and identify the challenges of progressing to a full RCT, and semistructured interviews with patients and relatives to explore their attitudes towards participating in the study, and potential barriers and concerns to participation; and (3) a UK-wide survey exercise to develop a classification and enumeration system for the CAT models and pathways of care. SETTING: A haematology outpatients department, an oncology outpatients department and primary care. PARTICIPANTS: Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT. INTERVENTIONS: Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months' treatment in patients with locally advanced or metastatic cancer. MAIN OUTCOME MEASURES: (i) The number of eligible patients over 12 months; (ii) the number of recruited patients over 12 months (target recruitment rate of 30% of eligible patients); and (iii) the proportion of randomised participants with recurrent venous thromboembolisms (VTEs) during follow-up. RESULTS: Following several delays in setting up the RCT component of the study, 5 out of 32 eligible patients consented to be randomised to the RCT suggesting progression to a full RCT was not feasible. Reasons for non-consenting were primarily based on a fixed preference for continuing or discontinuing treatment after 6 months of anticoagulation, and a fear of randomisation to their non-preferred option. Views were largely influenced by patients' initial experience of CAT. Focus groups with clinicians revealed that they would be reticent to recruit to such a study as they had fixed views of best management despite the lack of evidence. Patient pathway modelling suggested that there is a broad heterogeneity of practice with respect to CAT management and co-ordination, with no consensus on which specialty should best manage such cases. CONCLUSIONS: The results of the RCT reflect recruitment from the oncology site only and provide no recruitment data from haematology centres. However, it is unlikely that these other sites would have access to more eligible patients. The management of cancer-associated thrombosis beyond 6 months will remain a clinical challenge. As it is unlikely that a prospective study will successfully recruit, other strategies to accrue relevant data are necessary. Currently the LONGHEVA (Long-term treatment for cancer patients with deep-venous thrombosis or pulmonary embolism) registry is in development to prospectively evaluate this important and common clinical scenario. STUDY REGISTRATION: This study is registered as clinical trials.gov number NCT01817257 and International Standard Randomised Controlled Trial Number (ISRCTN) 37913976. FUNDING DETAILS: Funding for the ALICAT trial was provided by the Health Technology Assessment programme (10/145/01) in response to a themed funding call. The study was designed in accordance with the initial funding brief and feedback from the review process.

Patients' views about taking a polypill to manage cardiovascular risk: a qualitative study in primary care.

BACKGROUND: A 'polypill' containing a combination of antihypertensives and statins could prevent up to 80% of cardiovascular disease (CVD) events. AIM: To investigate patients' opinions about the use of a polypill for CVD prevention. DESIGN AND SETTING: Qualitative study of 17 patients from seven primary care practices in Birmingham, UK. METHOD: Patients were recruited through purposive sampling to maximise variation of characteristics. Semi-structured interviews were conducted with responders. Results were analysed and reported using a qualitative description approach. RESULTS: Patients expressed concerns that polypill prescription for primary prevention simply on the basis of age was unnecessary and would lead to side effects, despite recognising potential benefits. For high-risk patients, or for secondary prevention, a polypill was deemed more acceptable, but was still felt to require regular monitoring of blood pressure and cholesterol. CONCLUSION: Patients were sceptical about the role of a polypill as a 'blanket' approach. If a population strategy offering a polypill to all people over a certain age was to be implemented, it would need to be supported by patient education.

Would primary healthcare professionals prescribe a polypill to manage cardiovascular risk? A qualitative interview study.

OBJECTIVES: A 'polypill' containing both blood pressure-lowering and cholesterol-lowering drugs could prevent up to 80% of cardiovascular disease events. Since little is known about the attitudes of primary healthcare professionals to use of such a pill for cardiovascular disease prevention, this study aimed to investigate opinions. DESIGN: Semistructured interviews were conducted with participants. A qualitative description approach was used to analyse and report the results. SETTING: Participants were recruited from nine primary care practices in Birmingham. PARTICIPANTS: Sixteen healthcare professionals (11 primary care physicians and 5 practice nurses) were selected through purposive sampling to maximise variation of characteristics. OUTCOME MEASURES: Outcome measures for this study were: the attitude of healthcare professionals towards the use of a polypill for primary and secondary cardiovascular disease prevention; their views on monitoring the drug; and the factors influencing their willingness to prescribe the medication. RESULTS: Healthcare professionals expressed considerable concern over using a polypill for primary prevention for all people over a specific age, although there was greater acceptance of its use for secondary prevention. Regularly monitoring patients taking the polypill was deemed essential. Evidence of effectiveness, patient risk level and potential medicalisation were key determinants in willingness to prescribe such a pill. CONCLUSIONS: Primary healthcare professionals have significant concerns about the use of a polypill, particularly in the prevention of cardiovascular disease in people who are not regarded as being at 'high risk'. If a population-based polypill strategy is to be successfully implemented, healthcare professionals will need to be convinced of the potential benefits of a drug-based population approach to prevention.

A cross-sectional study of quality of life in an elderly population (75 years and over) with atrial fibrillation: secondary analysis of data from the Birmingham Atrial Fibrillation Treatment of the Aged study.

AIMS: To compare the quality of life (QoL) of those in atrial fibrillation (AF) aged 75 years and over with that of the general population, to explore what factors affect the QoL of those with AF, and to assess the sensitivity of the EuroQol (EQ-5D) and Short-Form 12 (SF-12) generic health questionnaires in detecting differences in health status in those with AF in this age group. METHODS AND RESULTS: The study population was 1762 men and women aged 75 years and over with confirmed AF who attended a randomization clinic for the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study, a primary care based trial of stroke prevention. Patients self-completed the EQ-5D and SF-12 questionnaires, and a simple measure of disability (Rankin). Cardiovascular co-morbidities were collected and number of drugs used as an additional proxy for co-morbidity. Quality-of-life outcomes were compared with general population samples of the same age. On multiple regression, female gender, greater medication use, and disability were independently associated with lower QoL scores in AF. Those in AF with a Rankin score ≥2 had lower QoL scores, while those with a Rankin score <2 had higher scores than the general population. Increasing co-morbidity was associated with reduced QoL scores, with the EQ-5D and SF-12 Physical Component Score showing similar sensitivity to these associations, and the SF-12 Mental Component Score showing less sensitivity. CONCLUSION: In the absence of co-morbidity, chronic AF has little impact on generic QoL in an elderly non-acutely ill population.

A cross-sectional study of hypertension in an elderly population (75 years and over) with atrial fibrillation: secondary analysis of data from the Birmingham Atrial Fibrillation in the Aged (BAFTA) randomised controlled trial.

BACKGROUND: Atrial fibrillation and hypertension are two common conditions in the elderly, associated with significant morbidity and mortality. Little information is available regarding the epidemiology of hypertension in elderly patients with atrial fibrillation. SUBJECTS AND METHODS: A secondary analysis of data from the Birmingham Atrial Fibrillation Treatment of the Aged study, a randomised controlled trial of thrombo-prophylaxis in atrial fibrillation in a primary care population. The study population comprised patients aged 75 and over with electrocardiogram (ECG) confirmed atrial fibrillation. Blood pressure was recorded in the general practice surgery on two occasions using standardised methods. History of hypertension was sought from the medical records and from asking the patient. RESULTS: 3059 subjects had ECG confirmed atrial fibrillation. The prevalence of a history of hypertension in this group was 57.5%. The mean systolic blood pressure was 141 mmHg (standard deviation: 21 mmHg) in men and 144 mmHg (22 mmHg) in women. The mean diastolic blood pressure was 79 mmHg (12 mmHg) in men and 80 mmHg in women (12 mmHg). The mean systolic blood pressure was slightly lower than that of the general population aged 75 and over, but the mean diastolic blood pressure was significantly higher in patients in atrial fibrillation (by 8 mmHg). Among the patients with a diagnosis of hypertension, 86.5% were on blood pressure lowering medications. CONCLUSIONS: Hypertension is more commonly diagnosed in older patients with atrial fibrillation than in the general population. The mean systolic blood pressure is slightly lower, but the mean diastolic blood pressure substantially higher in older patients in atrial fibrillation, compared to the general population.

Lentiviral vector expression of tumour antigens in dendritic cells as an immunotherapeutic strategy.

Therapeutic cancer vaccines need to stimulate a refractory immune system to make an effective anti-tumour response. We have explored the use of lentiviral vectors to deliver tumour antigen genes to dendritic cells (DC) as a possible mechanism of immune stimulation. Direct injection of a lentiviral vector encoding the melanoma antigen NY-ESO-1 in HLA-A2 transgenic mice primed NY-ESO-1-specific CD8+ cells that could be expanded by boosting with an NY-ESO-1 vaccinia virus. The expanded cells could kill NY-ESO-1(157-165) peptide-pulsed targets in vivo. In order to examine the priming step directly, we constructed another lentiviral vector expressing the melanoma antigen Melan-A (MART-1). Here we show that Melan-A protein is also efficiently expressed after transduction of human DC cultured from peripheral blood mononuclear cells. When these transduced DC are co-cultured with autologous naïve T cells, they cause the expansion of cells that recognise the HLA-A2 restricted Melan-A(27-35) epitope. The expanded cells are functional in that they release IFN-gamma upon antigen stimulation. Melan-A lentiviral vector transduced DC caused a similar level of naïve T-cell expansion to Melan-A(27-35) peptide-pulsed DC in four experiments using different HLA-A2 positive donors. These data suggest that a vaccine based either on DC transduced with a lentiviral vector ex vivo, or on direct lentiviral vector injection, should be assessed in a phase I clinical trial.