Relation between weight loss and causes of death in patients with cardiovascular disease: finding from the SCOUT trial.

AIMS: Obesity is associated with an increased incidence of mortality. The Sibutramine Cardiovascular Outcomes (SCOUT) trial can provide the first evidence of the effect of intentional weight loss on mortality in an obese population at high risk. METHODS: SCOUT was a randomized, double-blind, placebo-controlled trial testing sibutramine vs. placebo. Eligibility for the trial required both men and women aged at least 55 years, with BMI of at least 27 kg/m and 45 kg/m or less. Study participants with type 2 diabetes mellitus (T2DM) only should have at least one other risk factor defined as hypertension, dyslipidaemia, smoking, or diabetic nephropathy, and/or they had a history of cardiovascular disease. Study participants were stratified in three groups: patients with T2DM, patients with a prior cardiovascular event but without diabetes, and patients with both T2DM and a prior cardiovascular event.The relationship between weight loss and mortality (all-cause, cardiovascular, and noncardiovascular) was investigated with Cox regression models. RESULTS: The main study showed that all-cause mortality was not different in patients allocated to sibutramine or placebo. This ancillary analysis demonstrates that there is a general trend showing higher mortality in patients with the greatest weight loss (weight reduction >10 kg) and in those with increasing weight (>1 kg). If integrated weight loss (area under the curve from baseline to 12 months) is used, these observations are confirmed. The impact of substantial weight loss on mortality is marked in those dying of noncardiovascular causes, specifically cancer. CONCLUSION: The relationship between weight change and mortality differs for cardiovascular and noncardiovascular mortality.

INVEST revisited: review of findings from the International Verapamil SR-Trandolapril Study.

The International Verapamil SR-Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus trandolapril) with a beta-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of the PO. Overall, there was no difference in the PO comparing the strategies; however, new-onset diabetes occurred more frequently in those assigned the atenolol strategy. This report summarizes findings from INVEST and puts them in perspective with our current state of knowledge derived from other large hypertension treatment trials. INVEST findings support that BP reduction is important for prevention of adverse cardiovascular morbidity and mortality, and selection of antihypertensive agents should be based on patient comorbidities and other risk factors (e.g., risk for diabetes) and not necessarily that any one drug be given to all.

Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST).

AIM: To determine the relationship between resting heart rate (RHR) and adverse outcomes in coronary artery disease (CAD) patients treated for hypertension with different RHR-lowering strategies. METHODS AND RESULTS: Time to adverse outcomes (death, non-fatal myocardial infarction, or non-fatal-stroke) and predictive values of baseline and follow-up RHR were assessed in INternational VErapamil-SR/trandolapril STudy (INVEST) patients randomized to either a verapamil-SR (Ve) or atenolol (At)-based strategy. Higher baseline and follow-up RHR were associated with increased adverse outcome risks, with a linear relationship for baseline RHR and J-shaped relationship for follow-up RHR. Although follow-up RHR was independently associated with adverse outcomes, it added less excess risk than baseline conditions such as heart failure and diabetes. The At strategy reduced RHR more than Ve (at 24 months, 69.2 vs. 72.8 beats/min; P < 0.001), yet adverse outcomes were similar [Ve 9.67% (rate 35/1000 patient-years) vs. At 9.88% (rate 36/1000 patient-years, confidence interval 0.90-1.06, P = 0.62)]. For the same RHR, men had a higher risk than women. CONCLUSION: Among CAD patients with hypertension, RHR predicts adverse outcomes, and on-treatment RHR is more predictive than baseline RHR. A Ve strategy is less effective than an At strategy for lowering RHR but has a similar effect on adverse outcomes.