Valsartan

van der Bom, Teun, et al. Circulation 127.3 (2013): 322-330.

Patients with a systemic right ventricle due to congenitally or surgically corrected transposition of the great arteries face progressive right ventricular dysfunction and heart failure in adulthood. The role of renin-angiotensin-aldosterone system blockade in this population had not been previously established. This double-blind, randomized, placebo-controlled trial investigates the effect of the angiotensin II receptor blocker valsartan on systemic right ventricular function in these patients over a three-year follow-up period.
Experimental Protocol: The multicenter trial enrolled 88 adult patients with a systemic right ventricle, who were randomized in a 1:1 ratio to receive valsartan 160 mg twice daily or matching placebo. The primary endpoint was the change in right ventricular ejection fraction over a 3-year follow-up period, assessed by cardiovascular magnetic resonance imaging or, in patients with contraindications, multirow detector computed tomography. Secondary endpoints included changes in right ventricular volumes and mass, maximal exercise capacity measured by cardiopulmonary exercise testing, and quality of life assessed by standardized questionnaires. All analyses were performed on an intention-to-treat basis.
Performance Evaluation: After 3 years of follow-up, no significant treatment effect of valsartan on systemic right ventricular ejection fraction was observed (treatment effect, 1.3%; 95% confidence interval, -1.3% to 3.9%; P=0.34). Similarly, valsartan did not significantly improve maximal exercise capacity or quality of life compared to placebo. However, the placebo group showed a significantly larger increase in right ventricular end-diastolic volume and mass compared to the valsartan group, suggesting that valsartan may attenuate adverse right ventricular remodeling over time. The incidence of clinical events was similar between groups and no serious adverse effects were attributable to valsartan.

McMurray, John J., et al. New England Journal of Medicine 362.16 (2010): 1477-1490.

Patients with impaired glucose tolerance are at elevated risk for developing type 2 diabetes mellitus and cardiovascular disease. The NAVIGATOR trial was a large-scale, international, double-blind, randomized clinical trial designed to evaluate whether valsartan, an angiotensin receptor blocker, could reduce the incidence of diabetes and cardiovascular events in patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, when added to a standardized lifestyle modification program.
Experimental Protocol: The trial employed a 2-by-2 factorial design, randomizing 9,306 patients with impaired glucose tolerance to receive valsartan (up to 160 mg daily) or placebo, and nateglinide or placebo, in addition to a structured lifestyle modification program targeting weight loss, dietary fat reduction, and increased physical activity. Patients were followed for a median of 5.0 years for the development of diabetes and 6.5 years for vital status. The three coprimary outcomes were the development of diabetes (confirmed by fasting plasma glucose and oral glucose tolerance testing), an extended composite cardiovascular outcome, and a core composite cardiovascular outcome.
Performance Evaluation: The cumulative incidence of diabetes was 33.1% in the valsartan group compared to 36.8% in the placebo group, representing a significant 14% relative reduction in the risk of developing diabetes (hazard ratio, 0.86; 95% confidence interval, 0.80 to 0.92; P<0.001). However, valsartan did not significantly reduce either the extended cardiovascular composite outcome (14.5% vs. 14.8%; hazard ratio, 0.96; P=0.43) or the core cardiovascular composite outcome (8.1% vs. 8.1%; hazard ratio, 0.99; P=0.85). Blood pressure reductions were modestly greater in the valsartan group. The study demonstrates that valsartan can reduce the incidence of diabetes in high-risk patients, though this did not translate into a reduction in cardiovascular events during the follow-up period.