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By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.
Cardioprotective effects of ACE inhibitors in African American men
Source: Papademetriou V, et al. Protective effects of angiotensin-converting enzyme inhibitors in high-risk African American men with coronary heart disease. J Clin Hypertens 2009;11: 621-626.
The HOPE trial convinced many experts that midlife adults (age ≥ 55 years) with existing vasculopathy (history of CAD, CVD, diabetes and CV risk factors) will have improved outcomes on an ACE inhibitor (ramipril, to be specific). There is controversy about whether African Americans achieve similar risk reduction as other ethnicities; for instance, in the SOLVD CHF trial, retrospective analysis suggested less benefit for some endpoints in African Americans.
Papademetriou reviewed electronic records from the Washington, DC, VA Medical Center to study African American study subjects who had CAD documented by catheterization (n = 810). Subjects were parsed into those who had vs had not been treated with an ACE inhibitor.
Over a study period of 3-10 years (mean, 6.8 years), the relative risk reduction for CAD mortality was more than 30% in those treated with ACE inhibitors. All-cause mortality was 80% higher in African American patients who had not been treated with ACE inhibitors. Because many African American patients have relatively low renin levels, some clinicians have doubted whether CV benefits would be readily achieved with ACE inhibitors. This data analysis suggests substantial benefit from ACE inhibitor treatment in African Americans with CAD.
Which insulin regimen for type 2 diabetes
Source: Holman RR, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009; 361:1736-1747.
The most recently published ADA/EASD consensus algorithm for management of type 2 diabetes (DM2) suggests that when the combination of metformin and lifestyle is insufficient to control diabetes, either sulfonylurea (if close to goal) or insulin is the most well-validated next step. Because there are many different insulins to choose from, the clinician may be uncertain whether basal insulin (i.e., detemir, glargine, NPH), prandial insulin (i.e., regular insulin or rapid-acting insulin analog), or biphasic insulin (a combination containing a basal as well as prandial insulin) should be preferred.
Holman et al performed a 3-year trial in DM2 subjects (n = 708) not at A1c goal with the combination of metformin and a sulfonylurea. Subjects were randomized to biphasic insulin aspart (BIA) bid, prandial insulin aspart (PIA) tid, or insulin detemir (DET) qd (some received detemir bid).
At 3 years, there was no statistically significant between-group difference in A1c attained. Hypoglycemia was least frequent in the DET group, and most common in the PIA cohort. Weight gain was least in the DET group, and greatest in the PIA group.
All regimens were successful in attaining goal A1c. Because hypoglycemia and/or weight gain are often deal breakers for our patients, basal insulin regimens may be preferred.
Missed opportunity: Aldosterone antagonists in heart failure
Source: Albert NM, et al. Use of aldosterone antagonists in heart failure. JAMA 2009;302:1658-1665.
The seminal rales trial (randomized Aldactone Evaluation Study), in which patients with NYHA Class III-IV systolic heart failure received either aldactone or placebo in addition to standard-of-care treatment (e.g., ACE inhibitors, beta blockers, digoxin) indicated that the utilization of this well tolerated, inexpensive treatment could reduce mortality by as much as 30%.
One might anticipate that such benefits would result in widespread utilization of aldosterone antagonists in heart failure.
Albert et al reviewed data from more than 200 U.S. hospitals, encompassing 43,625 patient admissions for heart failure over the 2005-2007 time period. By this time, the RALES data were more than 5 years old. Contraindications to this life-saving treatment are few, with hyperkalemia being the most common.
According to their analysis, less than 33% of patients with heart failure who were eligible for treatment with an aldosterone antagonist (i.e., without contraindications) received one. With proper monitoring, aldosterone antagonist therapy reduces risk, is safe, and is well tolerated. Although aldosterone antagonist use improved over time (from a baseline rate of 28% to an end-of-study rate of 34%), much opportunity for reduction of mortality was missed.