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Polypill for secondary CVD prevention 'likely to be cost-effective'

Giving heart attack patients a three-in-one pill instead of individual drugs to prevent further heart attacks and strokes would be worth the extra cost, according to a modelling study based on UK general practice data.

The study in BMJ Open estimated that if 10% of the 450,000 adults in the UK at risk of a recurrent CVD event took the polypill – combining aspirin, atorvastatin and ramipril – it would improve their adherence to the medications by around 20% and prevent an extra 3,000 heart attacks or strokes, and 600 CVD deaths, over a decade, when compared with using the drugs as monotherapies.

At a cost of £8,200 for each quality-adjust life-year (QALY) gained, the study’s authors said the polypill ‘appears to be a cost-effective strategy to prevent fatal and non-fatal events in the UK’ and that ‘it could therefore become the mainstay of secondary cardiovascular prevention’.

However, they added that ‘future research is needed from long-term, randomised controlled trials to confirm whether this approach offers advantages over multiple monotherapy in preventing CV events in patients who have experienced an MI’.

BMJ Open 2015; available online 9 May

 

 

Readers' comments (7)

  • They couldn't get the original polypill with simvastatin and atenolol off the ground and I don't see anything changing here. Using last century's medications to treat to out-of-date targets is never going to take off. Best stick to the flexibility of individual agents.

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  • Vinci Ho

    This is an quite complex economic model developed with quite a few assumptions: that is why at the end , the authors concluded RCTs are necessary to provide the actual evidence.
    My question is simple : how much is this three in one Polypill going to cost?( the previous ones were four in one):-

    Discussion

    We developed an economic model to investigate the public health benefit and cost-effectiveness that could be expected from the improved adherence achieved with a three-in-one polypill compared with multiple monotherapy for secondary prevention of cardiovascular disease. Based on inputs derived from systematic literature reviews, the model has shown that 47 CV events and 10 CV deaths could be prevented in the UK with the polypill compared with multiple monotherapy per 1000 patients over 10 years, at an ICER of £8200 per QALY gained. In the context of persistent inadequate prescribing despite robust evidence-based guidelines, and poor adherence in those receiving multiple monotherapy, our data suggest that the polypill offers a cost-effective approach to improving outcomes for a substantial proportion of the UK population.
    In considering our results, it is important to note that multiple patient-related factors affect adherence to medication, and while many of these (such as age, gender, ethnicity and previous medication compliance history) cannot be changed, others, such as disease knowledge, social support and tobacco and alcohol consumption, can be altered over time. Crucially, there is also evidence that medication complexity has an adverse effect on adherence in chronic disease,27 ,28 such that products requiring a simpler regimen are likely to be associated with greater patient adherence than are more complicated regimens. Moreover, it is plausible (although unproven) that the simplified prescribing offered by a polypill could also help to improve current suboptimal adherence to prescribing guidelines among healthcare providers, which may occur, for example, due to physicians’ beliefs that dosing schedules associated with multiple monotherapy are overcomplicated.
    There are, however, various limitations in simplifying such a complex clinical pathway, including data uncertainties, within a model as we have done. These include the assumption that adherence rates for each of the monotherapy components will be consistently either good or poor in any one individual and that there is no clinical benefit with individual medication adherence rates below 80%. In practice, adherence may vary by drug in any one individual and there is likely to be a continuous reduction in efficacy with falling adherence. However, the cost-effectiveness of the polypill was £21 400 per QALY in sensitivity analyses that allowed a proportion of patients in the monocomponents arm to be adherent to just one or two monocomponents. We took baseline CV disease risk from that reported in clinical trials, which may underestimate true CV event rates, but this assumption is conservative since higher rates would make the polypill more cost-effective. We assumed relative-risk reductions to be constant over time and, in the absence of data, we assumed no benefit for aspirin in reducing CHF with hospitalisation. It is important to note, however, that the inputs and effect sizes used in our model compare well with those used previously by Gaziano et al.29 We also made assumptions about resource use for monitoring patients receiving secondary prevention, which were supported by recommendations from NICE and the Quality and Outcomes Framework, as well as expert opinion.4 Of significance, the polypill modelled prices for the combination therapy of aspirin, atorvastatin and ramipril, which are widely used in the UK for secondary prevention, although simvastatin is a more widely prescribed statin overall.30 As atorvastatin becomes more widely available as a generic drug in the UK, any cost differences and related variation in cost-effectiveness from the use of different statins will be minimised. Importantly, we used adherence data from the UMPIRE trial,24 which assessed a four-in-one polypill, rather than the three-in-one polypill used in our model. Although adherence to the polypill should be similar, adherence to four monocomponents may be lower than adherence to three, so our model may have overestimated the difference in adherence in the two groups. However, we assumed that all patients would also be taking β-blockers and second antiplatelets as appropriate, so the effects of these were assumed to cancel out when the two groups were compared. This exclusion may have had only a slight impact on our conclusions, given that inclusion of a β-blocker monocomponent taken concomitantly with the polypill or the other three monocomponents with the same adherence in both arms will not produce additional cost differences and may produce only marginal advantages in effectiveness compared with a triple-therapy regimen. The EURO-ASPIRE III study found that patients with a previous MI, seen in routine clinical practice, do not achieve targets as set by established guidelines.31 These include therapeutic, lifestyle and risk factors. Our model, however, only captured the benefits associated with therapeutic compliance and adherence because we assumed that effects on lifestyle changes would be similar in both treatment groups. Accordingly, we did not estimate the incremental effects of attaining additional modifiable lifestyle and risk factor goals in the patients we evaluated. We also did not consider individualisation of therapeutic dosing adjustments or treatment switching due to adverse events. The results of the analysis should, therefore, be interpreted in the context of patients for whom the polypill is suitable as a replacement therapy versus the monocomponents and well tolerated, in the absence of other preventive interventions.
    Although a number of other economic models for secondary prevention have been developed, many of these assessed effectiveness of individual drugs or combinations of drugs compared with no therapy or with different doses or therapeutic combinations, implying different clinical efficacies between interventions.29 ,32–36 Our analysis differs from others in assuming that the therapies are identical in terms of clinical efficacy among adherent patients, but allowing adherence rates to determine differences in CV events and economic outcomes. Our model was consistent with previous ones in terms of time horizon, which ranged from 2 years to a lifetime, with 7 of the 15 models using a lifetime horizon and another 4 using a 10-year horizon. However, we also conducted a lifetime analysis in a sensitivity analysis to reflect the lifelong nature of CV disease and treatment. Our model structure was generally consistent with other models since health states usually included stable disease, recurrent CV events and death. Under the base-case and sensitivity analyses, which varied costs of treatment, the efficacy of interventions, adherence, utility and population characteristics, secondary prevention with the polypill in adult patients with a recent or non-recent diagnosis of MI and eligible for secondary prevention with aspirin, statins and ACEI is a cost-effective strategy at acceptable willingness-to-pay thresholds in the UK, given that ICERs were below or near the £20 000 per QALY threshold.
    The public health benefit suggested by our model depends on an assumed marked increase in adherence to secondary prevention therapy through use of the polypill, based on the UMPIRE study, which demonstrated that a 20% increase in adherence is possible. Our assumption about increased adherence is also in line with the very recent results from the IMPACT trial, part of the ‘Single Pill Against Cardiovascular Events (SPACE)’ collaboration, which demonstrated a significant difference in adherence in patients taking a four-in-one polypill (81%) versus the usual care group (46%), at 12 months.37
    Our model estimates that for each 10% increase in adherence, an additional 6.7% fatal and non-fatal CV events can be prevented. The potential of this result for the eligible UK population is striking: specifically, 3260 CV events and 590 deaths could be prevented in the next decade. This is based on a modified version of our model that assumes that the prevalence of MI survivors aged 25 years and older is 1.4% (as inferred from the British Heart Foundation data);38 the incidence of MI is 0.112% (as derived from Smolina);39 there are 45 271 000 in this age group among the UK population;40 and that 10% of eligible patients switch from monotherapy to the polypill and achieve a 20% improvement in adherence. If uptake of the polypill is more than 10% in those eligible or patients at high risk of a first MI also receive the polypill, the public health benefit would be even greater.
    In summary, our evaluation provides key evidence on an important issue in clinical management: the fact that, while the efficacy of secondary prevention in CV disease is well established in patients adherent to medication, adherence is generally low, and this has a negative impact on clinical outcomes. Despite its analytic limitations, our study suggests that a three-in-one polypill that improves adherence and outcomes in patients with existing CV disease would have a positive public health impact in the UK especially in the context of inadequacies in physician prescribing and patient adherence. It could therefore become the mainstay of secondary cardiovascular prevention for patients in whom such triple therapy is suitable. Future research is needed from long-term RCTs to confirm whether this approach offers advantages over multiple monotherapy in preventing CV events in patients who have experienced an MI.

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  • Vinci Ho

    This Polypill was
    100 mg aspirin, 20 mg atorvastatin and 2.5, 5, or 10 mg ramipril.

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  • Do no harm? Pack citalopram with a cocp too.

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  • ha ha

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  • Alan Shortt

    I used to be sceptical about the polypill approach to polypharmacy - drug A will reduce your mortality by 25% drugs B & C ditto - put them all together & add in drug D your mortality will be reduced by 100%
    (Ok thats a simplification but not too far removed from what seems to have been sold at times)
    I now think its a neat idea and am surprised it still hasn't yet taken off
    Quite a few patients don't take their meds - unless forced to by well meaning carers. The meds, the Webster packs are hidden away in a cupboard under the sink or wherever (over here they end up on the dump) but they are still dutifully collected / accepted by someone. The scripts get cashed but the meds don't get taken. I think we could save the NHS and the national debt if we addressed that - never mind, God forbid, Grandma Grumps one day decides to comply and actually swallows her escalated pharmamentorium.

    I do agree with Dr Steven Martin. Best evidenced based current therapy tailored to motivated ahem health-literate patients' individual clinical circumstances is the Gold Standard ...but a decent polypill might be a reasonable option for many others?

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  • Alan Shortt

    @ Vince Ho
    yes very complex economic arguments
    one thing I don't understand is why the polypill would be dearer - it should surely be cheap as chips to make?

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