Novel approaches in primary cardiovascular disease prevention: the HOPE-3 trial rationale, design, and participants' baseline characteristics

AbstractBACKGROUND:Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.METHODS:A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization.RESULTS:Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women.CONCLUSIONS:The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.govNCT00468923).

A new model to evaluate the long-term cost effectiveness of orphan and highly specialised drugs following listing on the Australian Pharmaceutical Benefits Scheme: the Bosentan Patient Registry.

BACKGROUND: Pharmaceutical subsidy schemes are under increasing pressure to evaluate the cost effectiveness of new highly specialised and orphan drugs for universal subsidy. In the absence of longer-term outcome data, drug sponsors often present modelled data, which can carry a significant level of uncertainty over longer-term projections. Risk-sharing schemes between drug sponsor and government may provide an acceptable method of balancing the uncertainty of longer-term cost effectiveness with the public demand for equitable and timely access to new drugs. METHODS: The Bosentan Patient Registry (BPR) is an example of a unique risk-sharing model utilised in Australia aiming to provide clinical evidence to support the modelled predictions, with the registry survival outcomes linked to future price. Concomitant medication, health and vital status data was collected from clinicians, government health departments and death registries. RESULTS: The BPR has identified a number of issues surrounding registry governance, ethics and patient privacy, and the collection of timely and accurate data, which need to be addressed for the development of a generic registry model for systematic evaluation. CONCLUSION: The success of a generic drug registry model based on the BPR will be enhanced by addressing a number of operational issues identified during the implementation of this project.