Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.
Comprehensive Diabetes Care: The Whole Enchilada
The greatest challenge for any potentially mortal disorder is to prove that therapeutic interventions reduce not only disease-specific mortality, but also all-cause mortality. For instance, PSA screening is associated with reduced prostate-cancer related mortality, but has never been convincingly shown to reduce all-cause mortality, leaving in question whether PSA screening results in some sort of mortality "trade-off," with no net benefit.
The Steno-2 Study enrolled type 2 diabetics with microalbuminuria (n=160) in 1993. Study subjects were randomized to intensive therapy (tight control of glucose, cholesterol, triglycerides, blood pressure, and microalbuminuria) or usual diabetic care. The study concluded after 8 years, at which point both groups and their clinicians were encouraged to employ intensive therapy post-trial.
In 2006 (five years after formal study closure), Gaede et al examined death from any cause comparing the two original study groups. The hazard ratio for all-cause mortality was 0.54 in the intensive treatment group (24 deaths vs 40 deaths), which included a 57% lesser chance of cardiovascular death, and a 59% lesser incidence of cardiovascular events.
Part of the intensive regimen included low-dose ASA and ACE (or ARB) for all, regardless of blood pressure. Although glucocentric focus in diabetes produces microvascular benefits, dealing with the "whole enchilada"-BP, lipids, the renin-angiotensin system, and platelets-increases the payoff for the patient.
Source: Goede P, et al. New Engl J Med. 2008;358:580-591.
The ENDORSE Study: Preventable Hospital Deaths
Pulmonary embolism (PUL-E) is generally accepted as the most common preventable cause of in-hospital deaths in developed countries. As many as 10% of in-hospital deaths are attributable to PUL-E, hence prevention of venous thromboembolism is an epidemiologically compelling mandate. ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) is a chart audit of at-risk hospitalized patients to ascertain the rate of appropriate VTE thromboprophylaxis (TPX). Hospitals from 32 countries (including the US, UK, Germany and France) provided data on 68,183 hospital patients, categorically divided into surgical (45%) and medical (55%). American College of Chest Physicians (ACCP) guidelines were used to assess risk status and appropriateness of TPX.
Considering the entire study population, slightly over half (58.5%) of high-risk surgical patients, and less than half (39.5%) of the high-risk medical patients received appropriate TPX. Germany and Switzerland achieved distinctively higher levels of appropriate overall TPX (85% and 80%, respectively). With a few exceptions, the tendency to effectively prophylax medical patients less often than surgical patients was seen in all nations.
Reduced mortality through TPX for VTE is readily achievable, yet there remains an important gap between our potential to utilize VTE TPX and current practice worldwide.
Source: Cohen AT, et al. Lancet. 2008;371;387-394.
Risks of Stopping Clopidogrel
In addition to aspirin (ASA), clopidogrel (CPG) has demonstrated class 1A level evidence of its efficacy in acute coronary syndromes (ACS), and is typically continued for 1 year post-discharge. In ACS subjects it has been previously observed that at the time of cessation of antiplatelet therapies (ASA and heparin, for example), the risk of adverse cardiovascular (CV) events increases, suggesting a transient hyperthrombotic state, since this signal of increased events is not sustained. The authors sought to determine whether a CPG rebound effect occurs, as would be manifest by a cluster of CV events shortly after CPG discontinuation.
A cohort of VA hospital patients (n=3,137) post-discharge for ACS comprised the subjects for this retrospective cohort study. The study subjects were equally distributed between medically treated ACS and PCI treated patients. The incidence of MI and all-cause mortality was examined in the period 0-90 days, 91-180 days, and 181-270 days post CPG cessation.
Overall, there was a statistically significant increased risk of adverse CV events (1.82 relative risk) when comparing the immediate 0-90 day interval with the rest of the followup period. Both medically treated and PCI patients had similar outcomes.
This is the first study of its kind to specifically examine risk in the immediate CPG-cessation period. If confirmed, clinicians may have to rethink either the duration of CPG therapy, the discontinuation scheme (eg, down-titration, supplementary antiplatelet therapy), or both.
Source: Ho PM, et al. JAMA. 2008;299(5):532-539.
The greatest challenge for any potentially mortal disorder is to prove that therapeutic interventions reduce not only disease-specific mortality, but also all-cause mortality.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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