ShortCuts-This Week in the Journals

June 9, 2008

sunset.jpgCommentary by Neil Shapiro MD, Editor-in-Chief, Clinical Correlations

Spiking oil prices, unemployment at 5.5%, Israel considering bombing Iran, 95 degree heat in early June, the White House exaggerating the case to go to war…the news was just tremendously uplifting this week. At least the democrats seem to be getting their act together. Sorry to start ShortCuts on a downer, but I thought maybe what follows could be seen as a reprieve from the news, where you can spend a moment not cursing the $60 it just cost to fill up your car and thinking about the price it costs you to fill your brain here at Clinical Correlations…absolutely free.

The focus this week was clearly on primary care, specifically diabetes and hypertension. Let’s start with 2 important articles released this week discussing hypertension. The United States Preventive Services Task Force (USPSTF) stated in the Annals that they were of moderate certainty (you wonder why the surgeons laugh at medicine people) that there was substantial benefit to screen asymptomatic patients with hypertension for diabetes. However they are no longer recommending that adults with hyperlipidemia get screened for diabetes. The task force recommends using fasting glucose<126, 2 hour postprandial >200 and hemoglobin A1c as the screening tests. Although intuitively one would think the focus on newly diagnosed diabetics should be on glucose control, the USPSTF focused rather on the benefit of tighter blood pressure control in patients with diabetes. As we shall see below, there is no evidence that tight glucose control decreases cardiovascular events.

The other important article related to hypertension released this week in the Lancet looks at the prevalence of primary hyperaldosteronism in refractory hypertension. It’s always been controversial when to initiate a workup for secondary causes of hypertension. Generally, for most practitioners, it’s an arbitrary point when you’re getting frustrated with the lack of control despite 3 or 4 drugs. This study was a 20 year retrospective look at 1600 patients with “resistant hypertension” (>140/90 despite 3 drugs with a diuretic). Only 10% of these patients were found to have primary hyperaldosteronism. Of patients with true primary hyperaldosteronism, <50% had hypokalemia and 50% with + aldosterone/renin ratios did not end up having hyperaldosteronism. Where does that leave us? A bit confused.

Lots of news was released at this year’s meeting of the American Diabetes Association. Most of it focuses on tight control of type 2 diabetics and the news is profoundly disappointing. The official data from the ACCORD trial was released this week in the New England Journal of Medicine to coincide with the ADA meetings. We already knew that the ACCORD trial was stopped early because of the increase in deaths in the intensive therapy group, and now that data is being reviewed. This trial studied 10,251 patients with a hemoglobin A1c of 8.1 were assigned to standard treatment (goal A1c 7-7.9) vs. intensive treatment (goal A1c<6.0). Primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke or death from cardiovascular causes. Hazard ratio for death in the intensive treatment group was 1.22. In addition there were more episodes of serious hypoglycemia and weight gain in the intensive therapy group.

Confirming this negative finding are the results of the ADVANCE study. Here 11,140 patients with type 2 diabetes were assigned to standard vs. intensive control (A1c<6.5). Primary end points were the composite of major macrovascular events (cardiovascular death, nonfatal mi, nonfatal stroke) and major microvascular events (new worsening nephropathy or retinopathy). After 5 years of follow-up there was no significant effect in any of the above endpoints except the incidence of nephropathy (4.1% vs. 5.2 % hr 0.79), driving the combined endpoint to have a significant difference. This study clearly highlights the problem with combined endpoints, a favorite pastime of the pharmaceutical industry. You should always always make sure that a significant difference in the incidence of a combined endpoint is not being driven solely by a single outcome. Taken together, these studies are clearly disappointing to those of us who thought that with tight control we were making dramatic changes in our patients overall prognosis.

The second theme of the week is our vices and how they help and hurt our patients. Three important items made the news this week and each was picked up by the mass media.

1. Tobacco
Heralded as the next great thing in smoking cessation, Chantix (varenicline) has now been under fire as associations and case reports of suicidal ideation have come to light. In recent weeks, The FDA has sent a warning to providers and the drug has been banned by the FAA for use in pilots and flight controllers. The drug is the only one in its class which blocks the nicotinic acetylcholine receptor that releases dopamine when nicotine binds to it. Much less dopamine is released when varenciline binds to the receptor than when nicotine binds. As reported in medpagetoday.com, Pfizer this week sponsored a roundtable discussion for journalists to espouse the benefit risk/profile as more favorable than the recent publicity has led us to believe. By their report, further studies will be released in the coming weeks to. But until then, I would stress prescribing with caution, as we always should when any new drug hits the market.

2. Alcohol
Maybe I should put red wine in my daughter’s bottle…drinking the equivalent of 35 bottles a day of red wine (focusing on Resveratrol as the active ingredient), inhibits mice heart, skeletal muscle and brain gene expression that is associated with aging.

3. Marijuana
Hardcore marijuana smokers were found to have reduced hippocampal and amygdala volumes in comparison to normal controls. Somehow I know the response I will probably get when I tell my stoner patients that their brain will get smaller-a giggle and then uproarious laughter. This gives new meaning to Steve Martin’s first ever comedy routine, “Let’s get small…”

One Response to ShortCuts-This Week in the Journals

  1. david zimmerman on June 11, 2008 at 11:04 am

    With an ever-increasing list of benefits from imbibing reasonable amounts of alcohol, I would no longer classify it as a vice. Doing so inhibits patients from drinking the requisite 2 glasses of red wine with dinner, one of the few things I have been able to recommend in a long career in Internal Medicine that adds, rather than subtracts from the quality of life. I say vive le vin rouge, no vice is it.

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