Looking at CAD through the PERISCOPE
Source: Nissen SE, et al. JAMA. 2008;299(13):1561-1573.
Coronary artery disease (CAD) is the most common cause of death in America, and diabetics suffer a disproportionate burden of risk from cardiovascular disease. Although glucose control has consistently demonstrated a favorable impact upon microvascular diabetic consequences (retinopathy, nephropathy, neuropathy), clinical trials have not been able to convincingly prove favorable effects upon macrovascular endpoints, most importantly CAD.
The PERISCOPE Trial (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) prospectively compared the impact of a sulfonylurea (glimepiride) with a thiazolidinedione (pioglitazone) upon coronary atherosclerosis as measured by intravascular ultrasound (IVUS). To that end, adult type 2 diabetics were randomized to glimepiride or pioglitazone and followed for 18 months.
Percent atheroma volume progressed modestly with glimepiride, and regressed modestly with pioglitazone (p=.002). During the trial, the pioglitazone subjects had a slightly more favorable A1c and HDL than the glimepiride group.
For the first time, it has been demonstrated that a thiazolidinedione has more favorable effects on coronary atherosclerosis than a sulfonylurea. These promising findings about surrogate markers are encouraging, but do not satisfy the remaining uncertainty about whether either class of agent can reduce macrovascular endpoints.
Addressing Agitation and Aggression in Persons with Advanced Dementia
Source: Wilcock GK, et al. Clin Psych. 2008;69:341-348.
Agitation, aggression, and psychosis are predictably problematic in persons with progressive dementia—over 90% of dementia patients will experience one or more of these during the course of their illness. Indeed, such affective changes are quite often the "straw that breaks the camel's back," resulting in institutionalization because of the unmanageability of such problems in the home setting. Agitation and aggression (A&A) are more commonplace than psychosis, but treatment interventions to prevent or modulate A&A are limited. In addition, the presence of A&A is predictive of a more rapid progression of dementia.
The Neuropsychiatry Inventory (NPI) is a scoring system which contains subitems addressing agitation and psychosis. Study subjects with moderately-severe to severe Alzheimer's disease (n=983) were randomized to memantine (MEM) or placebo and a post-hoc analysis assessed the impact among dementia patients with prevalent A&A.
Memantine was associated with a statistically significant reduction in risk for agitation and aggression. This was not at the expense of functionality, since the Alzheimer Disease Cooperative Study Activities of Daily Living Inventory also showed improvements with memantine compared to placebo. Memantine is promising as a tool for management of aggression and agitation in persons with advanced dementia.
It Used To Be Easier To Treat Sinusitis
Source: Young J, et al Lancet 2008;371:908-914.
In the last decade, advice from consensus groups on management of acute sinusitis ranges from exhortation to wisely choose among antibiotics and/or nasal steroids all the way through admonitions against utilization of either. This literature inconsistency helps little to balance the requests of patients who supplicatingly report a history of protracted sinusitis surrendering only to well-chosen antibiotics.
In the United States, more than three-fourths of patients with a clinical diagnosis of sinusitis are prescribed an antibiotic. Young, et al obtained individual patient data from numerous clinical trial databases, including the Cochrane Central Register of Controlled Trials. All trials compared antibiotic to placebo, and reported the percentage of patients cured at trial end. (n=2,547).
The odds ratio for attaining cure by trial end favored antibiotics, but the margin was not large. The number needed to treat (NNT) with antibiotics to be beneficial was 15. The authors suggest that because the benefit of antibiotics is small, a watch-and-wait posture is appropriate for most patients with sinusitis.
CAC: A kinder, Gentler Way to Predict Cardiovascular Risk
Source: Detrano R, et al. N Engl J Med. 2008;358:1336-1345.
In 2007, the ACCF/AHA published a consensus statement in the Journal of the American College of Cardiology endorsing a role for coronary artery calcium scoring (CAC) in cardiovascular risk stratification. Because the CAC process is relatively inexpensive, brief, highly reproducibly, non-invasive and supported by multiple large data sets, it holds great appeal.
Detrano, et al studied an ethnically diverse population (n=6,722) comprised of white (38.6%), black (27.6%), Hispanic (21.9%) and Chinese (11.9%) adults over the age of 45. Subjects, who had no known cardiovascular disease at study enrollment, underwent CAC at baseline and were followed for a median of 3.8 years.
During the followup period, 162 major coronary events occurred. Compared to persons without increased CAC scores, the relative risk for coronary events was more than 7-fold higher in persons with elevated CAC scores. There was no discernible difference in the association of CAC score with coronary events between the different ethnic groups. The authors note that the predictive capacity of CAC goes beyond that of traditional risk factors. CAC is not yet universally available, but merits consideration by clinicians. Experts suggest that the greatest utility of CAC is in individuals calculated to be at intermediate coronary risk by traditional scoring, such as Framingham.
Was Mae West Right? CV Risk Reduction: Too Much of A Good Thing is Wonderful
Source: Howard BV, et al. JAMA. 2008;299(14):1678-1689.
The concept that global cardiovascular risk reduction (ie, concomitant lipid, BP, glucose, diet, and exercise interventions) is the most sensible path for success in persons identified as vasculopaths has few detractors. On the other hand, how much of a good thing gets to be too much of a good thing? Despite the counsel of Mae West, increasing intensity of pharmacotherapy is typically associated with increased cost, risk, and complexity, and should be documented to provide meaningful incremental benefit because of the associated increased burdens.
The SANDS trial (Stop Atherosclerosis in Native Diabetics Study) enrolled American Indian type 2 diabetics (n=499) and randomized them to aggressive LDL control (<70 mg/dL) and BP control (<115 mmHG SBP) vs standard therapy (LDL<100, SBP <130). The primary endpoint was progression of carotid artery intimal medial thickness. Clinical events were a secondary endpoint. Carotid IMT was measured at baseline, 18, and 36 months.
There was a statistically significant difference in carotid IMT favoring the intensive intervention group. Left ventricular mass also decreased more with aggressive intervention. Although there was a trend towards fewer CVD events, this difference did not achieve statistical significance, perhaps attributed to the unusually low number of events in the trial as a whole. These data are supportive of aggressive risk factor reduction in diabetics.
Midlife Contraception
Source: Kaunitz AM. N Engl J Med. 2008;358:12:1262-1270.
The mean age of attainment of menopause in American women—51 years— has not meaningfully changed over more than a century. During late reproductive life, pregnancy has more adverse consequences than in younger women. The therapeutic abortion rate of post-40 women is higher than any other age group except adolescents. Hence, midlife contraceptive decisions might be weighed differently than at other periods of reproductive life.
Kaunitz reviews multiple factors that impact contraceptive decisions after age 40. DVT risk after age 39 is more than 4-fold greater than in adolescent women, exaggerated further in obese women, in whom progestin-only oral contraceptives might logically be preferred. Older women who smoke should not be prescribed oral contraceptives, and Kaunitz recommends similar restrictions for midlife women with hypertension or diabetes.
Data on risk for breast cancer in association with oral contraceptives is largely reassuring, although data sets usually contain few women over age 45 to study. Oral contraceptives improve bone mineral density, and are associated with reduced risk for ovarian, endometrial, and colon cancer.
No method of discontinuation of contraception has proven ideal in all women. Kaunitz suggests continuing oral contraceptives, if well tolerated, into the early-mid 50s, after which pregnancy risk upon discontinuation is very low. Women who continue to menstruate after that point may use barrier methods. The ideal candidate for midlife oral contraceptives is the lean, slender, nonsmoker.
Looking at CAD through the PERISCOPE; Addressing Agitation and Aggression in Persons with Advanced Dementia; It Used To Be Easier To Treat Sinusitis; CAC: A kinder, Gentler Way to Predict Cardiovascular Risk; Was Mae West Right? CV Risk Reduction: Too Much of A Good Thing is Wonderful; Midlife ContraceptionYou have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content