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).

Cardiovascular disease in South America: current status and opportunities for prevention

South America comprises widely different environments consisting of many complex and heterogeneous ethnicities, societies and cultures. During recent decades conspicuous advances in human and societal development have been made. South America now faces three major demographic shifts: population growth; urbanisation (almost 90% of the population live in urban areas) and ageing.

Recently, an epidemiological transition has been seen. Urbanisation has brought unfavourable and prominent changes, such as increased smoking rates, stress, lack of physical activity and poor diets (more fat and calories).

Consequently, owing to the interaction between environment and genetic susceptibility, the modifications induced by

urbanisation have resulted in enhancement of the cardiovascular risk factors and cardiovascular disease (CVD). This situation is responsible for the burden of CVD in

South America, requiring effective action towards better detection and control of cardiovascular risk factors aimed

at reducing the burden of disease in the region, which tends to be higher and increasingly serious.

Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both

Angiotensin-converting–enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients.methods Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. results During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartanand-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group.conclusions Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival...

INTER-HEART: a global study of risk factors for acute myocardial infarction

Background Although declines in mortality rates have occurred in most developed countries, increases are being seen in developing countries. Our knowledge of risk factors for acute myocardial infarction (AMI) is largely derived from studies in the former. Applicability of these results to other populations is unknown. The objectives of INTER-HEART are to

determine the association between risk factors and AMI within populations defined by ethnicity and/or geographic region and to assess the relative importance of risk factors across these populations. Methods INTER-HEART is a study of 14,000 cases of AMI and 16,000 matched control patients from 46 countries, which was conducted with a standardized protocol. Questionnaires were translated into 11 languages; physical measurements

were obtained, and 20 mL of blood was drawn and shipped frozen to a central laboratory in Canada. The study will evaluate the importance of conventional and emerging risk factors within each geographic region and whether their impact

varies by region. Results INTER-HEART is sponsored by the World Health Organization and the World Heart Federation and has received funding from several peer-reviewed agencies and many different pharmaceutical companies. A vanguard phase

(February 1999 to 2000) enrolled 4000 subjects from 41 countries. Full data collection started in April 2000 and is expected to be completed by October 2002. Conclusions Several years of targeted work have allowed the development of the concepts that were tested in the

pilot studies. This has ensured the feasibility of INTER-HEART. This study has the potential to have a major impact in developing a worldwide strategy for cardiovascular disease prevention, especially in developing countries and nonwhite populations.