Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.
Comparing Two High-Intensity Statin Regimens: Atorvastatin and Rosuvastatin
Source: Nicholls SJ, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011;365:2078-2087.
Between statin head-to-head trials are uncommon. The PROVE-IT trial convincingly demonstrated that intensive LDL reduction with atorvastatin (achieved LDL = 62 mg/dL) vs pravastatin (achieved LDL = 95 mg/dL) improved outcomes in persons with acute coronary syndromes. In persons with stable atherosclerotic disease, however, it remains controversial whether high-dose statin treatment reduces mortality when compared with "standard" dosages, even though it has been shown to reduce cardiovascular (CV) events.
Results from clinical trials are sometimes hampered by the limitations of time: In a 5-year window of opportunity, are the long-term effects of intervention adequately represented? Such time limitations have prompted consideration of surrogate markers, which might more promptly reflect the anticipated long-term effects of intervention. Accordingly, Nicholls et al performed a controlled trial (n = 1039) to compare, by means of intravascular ultrasound, the effects of high-dose atorvastatin (80 mg/d) vs rosuvastatin (40 mg/d) on coronary atherosclerosis.
At 2 years, atheroma regression was similar between the two agents, despite the superior performance of rosuvastatin for attained LDL (62.6 mg/dL vs 70.2 mg/dL) and HDL (50.4 mg/dL vs 48.6 mg/dL). Maximal doses of these statins appear to perform similarly for the endpoint of regression of atherosclerosis.
The Effect of Adiposity on Insulin Pharmacodynamics
Source: Porcellati F, et al. Differential effects of adiposity on pharmacodynamics of basal insulins NPH, glargine, and detemir in type 2 diabetes mellitus. Diabetes Care 2011;34:2521-2523.
It is probably not a surprise to clinicians that adiposity and efficacy of therapeutic insulins are related. We are accustomed to seeing type 2 diabetes (DM2) associated with being overweight and obesity, and watching control of diabetes become more difficult if obesity worsens. The question addressed by Porcellati et al is not whether insulin requirements are affected by obesity, but rather are various insulins differently affected by obesity.
To that end, DM2 subjects (n = 18) were studied using infusions of glucose to maintain constant plasma levels. Three different insulins NPH, insulin glargine, and detemir were compared. The threshold at which glucose infusion rates were meaningfully different was a body mass index (BMI) > 29 kg/m2, at which point all three insulins demonstrated less efficacy to control glucose. That is, as BMI goes up, insulin sensitivity goes down.
Within this study group, however, there was a statistically significantly greater reduction in insulin sensitivity with detemir than with either NPH or insulin glargine. Ultimately, this means that in patients with progressively greater BMI, a higher dose of detemir may be required to achieve glucose control than the other two forms of basal insulin. Some clinical trials have also reflected this requirement for greater doses of detemir than comparators in patients with obesity. Nonetheless, because the amount of data addressing this issue remains small, whether there are meaningful differences that need to be considered when addressing insulin needs of obese DM2 patients in reference to choice of basal insulin is still considered a matter of controversy.
Psoriasis Predisposes to Serious Infections
Source: Wakkee M, et al. Increased risk of infectious disease requiring hospitalization among patients with psoriasis: a population-based cohort. J Am Acad Dermatol 2011;65:1135-1144.
As the use of systemic immune-modulating treatments for rheumatoid arthritis (RA) has evolved, the risk for serious infectious disease complications related to their use has become more evident. Since many of the drugs used to treat RA are now used for patients with psoriasis (PSR), it is logical to evaluate PSR patients for risk of serious infectious diseases.
Wakkee et al looked at a database comprised of PSR patients (n = 25,742) and controls (n = 128,710) from a Dutch registry compiled from 1997-2008. They examined the incidence of infectious disease events resulting in hospitalization during this interval.
Overall, persons with PSR were more than twice as likely to be hospitalized for a serious infectious disease than controls; multivariate analysis (adjustment for confounding issues like age, diabetes, COPD) modified this hazard ratio slightly (down from 2.08 to 1.54).
Perhaps the greatest surprise from this trial was that the use of systemic antipsoriatic medications was not associated with risk for infectious disease. Apparently then, it is PSR itself which imposes an increased risk of infectious diseases, not the immunosuppressive agents increasingly used to treat it.
Between statin head-to-head trials are uncommon.Subscribe Now for Access
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