Effectiveness and safety of a cardiovascular polypill containing aspirin

Abstract

Background: A polypill is a fixed-dose combination of cardiovascular preventive medications with the potential to enhance medication use among people with indications. There is consensus across guidelines internationally about the use of aspirin in secondary prevention but not in primary prevention. Aim: To investigate the effectiveness and safety of a cardiovascular polypill containing aspirin. Methods: Meta-analyses of trials assessing aspirin for the primary prevention of cardiovascular disease were systematically reviewed. The number of cardiovascular events averted and additional major bleeds with aspirin in primary prevention were modelled for different sex, age and cardiovascular risk subgroups. A New Zealand open-label trial (IMProving Adherence using Combination Therapy, IMPACT) randomised 513 patients (50% Māori) at high risk of cardiovascular disease (established disease or at high risk) to polypill-based care or usual care. The polypill contained aspirin 75mg, simvastatin 40mg, lisinopril 10mg and either atenolol 50mg or hydrochlorothiazide 12.5mg. All medications were prescribed by the usual general practitioner and dispensed by local community pharmacists. Results: For men aged 70 to 79 years, at high risk of their first cardiovascular event, it was estimated from meta-analyses that the numbers of cardiovascular events averted and additional major bleeds would be similar when adding aspirin to statin and blood pressure lowering therapy. This age group of men were therefore excluded from the IMPACT trial. At 12 months, the trial found a 75% proportional improvement in self-reported current use of the combination of an antiplatelet, statin and two or more blood pressure lowering agents with polypill-based compared with usual care (95% CI 1.52 to 2.03, p<0.001). Differences in blood pressure and low density lipoprotein cholesterol between groups did not reach statistical significance, but medication use was high in both treatment arms. There was no statistically significant difference between groups in the incidence of serious adverse events during the trial; however 37% in the intervention group discontinued the polypill during the study period (median trial duration 23 months). Conclusions: Benefits of aspirin outweigh harms for some groups at high risk of their first cardiovascular event. A cardiovascular polypill improved adherence but not risk factor levels when compared with usual care in a New Zealand trial of well treated primary care patients with indications for polypill components. A polypill-based treatment strategy could have a significant impact on the burden of cardiovascular disease, with the most potential in settings with low use of cardiovascular preventive medications.