Evidence for the efficacy of ARBs across the cardiovascular continuum.

INTRODUCTION: Angiotensin II receptor blockers (ARBs) are antihypertensive agents with considerable evidence of efficacy and safety for the reduction of cardiovascular (CV) disease risk in numerous patient populations from one end of the CV continuum (i.e., primary prevention among patients with CV risk factors) to the other (i.e., secondary prevention in the post-MI setting). There are several agents within the ARB class, all of which have contributed to various degrees to this evidence base. SCOPE: This review presents the design and main results of large, well designed studies examining the CV risk-reducing properties of ARBs. The authors searched major literature databases (Embase, Medline, PubMed) for randomized, controlled studies published between January, 1995 and October, 2009 that compared ARBs with placebo or active controls and reported major CV outcomes (e.g., myocardial infarction, stroke) and/or mortality as the primary study endpoint(s). LIMITATIONS: Although many trials evaluating similar agents are presented, between-trial comparisons are inappropriate. The results of each study stand on their own merits and weaknesses, but do not provide any additional insight into the results of the other studies. RESULTS: Agents in the ARB class have demonstrated efficacy in reducing CV events and/or mortality in a number of different patient populations, from primary prevention studies in patients with pre-specified risk factors (e.g., hypertension and left-ventricular hypertrophy in the LIFE study) to secondary prevention (i.e., post-MI patients in the VALIANT study). Some studies have also demonstrated the statistical equivalence of ARBs to ACE inhibitors in certain populations (e.g., among post-MI patients in VALIANT and among a broad population of patients with vascular disease or diabetes in the ONTARGET). There are several major studies currently underway that will provide further information on the risk-reducing properties of ARBs in additional populations (e.g., patients with impaired glucose tolerance in the NAVIGATOR study). CONCLUSIONS: ARBs have demonstrated efficacy in reducing CV morbidity and mortality in a broad spectrum of CV disease states across the CV continuum. Ongoing research continues to provide additional evidence, with ongoing trials investigating their role in additional patient populations.

Clinical outcome and echocardiographic predictors of aortic valve replacement in patients with bicuspid aortic valve.

BACKGROUND: Clinical outcomes and echocardiographic parameters associated with aortic valve replacement (AVR) for bicuspid aortic valve are scarce. METHODS: We conducted retrospective analysis of 208 adults with bicuspid aortic valve referred for transthoracic echocardiograms. RESULTS: The Kaplan-Meier survival free of death or need for cardiac surgery was 72% at 5 years. Cardiac surgery was performed in 19%, the majority (68%) for symptomatic aortic stenosis. Peak gradient 80 mm Hg or greater (hazard ratio 11.8, 95% confidence interval 3.7-37.8, P < .0001) and aortic valve area less than or equal to 0.75 cm(2) (hazard ratio 2.9, 95% confidence interval 1.0-8.5, P = .05) predicted the need for AVR. Patients with a large (54%) versus normal left ventricular outflow tract dimension underwent AVR for symptomatic aortic stenosis at a larger calculated aortic valve area (1.07 +/- 0.21 vs 0.75 +/- 0.18 cm(2), P < .0001) but at a similar peak gradient and velocity ratio (76 +/- 19 vs 76 +/- 22 mm Hg, P = not significant; 0.23 +/- 0.06 vs 0.26 +/- 0.12, P = not significant, respectively). CONCLUSIONS: Clinical events are common among patients with bicuspid aortic valve. Peak gradient 80 mm Hg or more and aortic valve area less than or equal to 0.75 cm(2) predicts the need for AVR. Gradients and velocity ratio better reflect the hemodynamic burden of aortic stenosis in patients with a large left ventricular outflow tract.

How does the prognosis of diabetes compare with that of established vascular disease? Insights from the Canadian Vascular Protection (VP) Registry.

BACKGROUND: Diabetes mellitus is a major risk factor for atherosclerotic cardiovascular disease. In a large, prospective, practice-based registry (the Vascular Protection Registry), we enrolled patients with vascular disease and/or diabetes, and compared the following features between diabetic and non-diabetic participants: (1) risk factor profiles, (2) utilization of cardioprotective medications, and (3) cardiovascular outcomes in short-term follow-up. METHODS: Patients were enrolled by participating physicians practicing in family medicine or specialty practices across Canada. The primary outcome was a composite of the first occurrence of any of the following vascular events: myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, or death. Patients were stratified according to the presence or absence of cardiovascular disease and diabetes. RESULTS: In all, 3297 patients were available for analysis (972 [30%] with diabetes but no cardiovascular disease; 899 [27%] with both diabetes and cardiovascular disease; and 1425 [43%] with cardiovascular disease but no diabetes). Most of the measured risk factors were worse for patients with diabetes. Compared to non-diabetic patients, diabetes was associated with substantial undertreatment with cardioprotective medications, including antiplatelet agents, beta blockers, and statins. During a mean follow-up of 10 (SD 3.3) months, patients with both diabetes and cardiovascular disease had the worst prognosis, with the primary outcome occurring at a rate of 16.3 per 100 person-years of follow-up. CONCLUSIONS: Patient registries provide a powerful tool for examining treatment patterns, risk factors, and outcomes. Patients with both cardiovascular disease and diabetes had the highest rates of adverse vascular outcomes. Possible reasons include relatively worse risk factor profiles and undertreatment with proven cardiovascular medications.