Lancet
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Randomized Controlled Trial Multicenter Study
Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review.
Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. ⋯ National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.
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Reduction of premature mortality is a UN Sustainable Development Goal. Unlike other high-income countries, age-adjusted mortality in the USA plateaued in 2010 and increased slightly in 2015, possibly because of rising premature mortality. We aimed to analyse trends in mortality in the USA between 1999 and 2014 in people aged 25-64 years by age group, sex, and race and ethnicity, and to identify specific causes of death underlying the temporal trends. ⋯ US National Cancer Institute Intramural Research Program.
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Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. ⋯ None.
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Polypills have been approved in more than 30 countries, but worldwide experience with and availability of polypills remain limited, unlike fixed-dose combinations in other diseases such as HIV, tuberculosis, and malaria. In this Series review, we aim to propose a guide for the use of polypills in future research and clinical activities and to synthesise contemporary evidence supporting the use of polypills for prevention of atherosclerosis. Polypill uses can be categorised by population and indication, both of which influence the balance between benefits and risks. ⋯ Polypills improve adherence, are generally well tolerated, and reduce risk factor levels, although heterogeneity limits the certainty of the effect on risk factors. Trials published to date have not been designed to detect differences in clinical outcomes, and thus no significant differences between polypill and comparator groups have been reported. Polypill therapy could be one of the most scalable strategies to reduce the risk of premature mortality from atherosclerosis by 25% by 2025 by improving medication adherence and access, but further trial data and clinical experience will be useful to determine how polypills can best be implemented to achieve this goal.