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Evidence-Based Diabetes Management May 2014

To Treat or Not to Treat? Questions, Controversies in Prevention

Mary K. Caffrey
American College of Cardiology 2014
Should patients with moderately elevated levels of triglycerides be treated, even while cardiologists await the results of a trial that may provide a definitive answer?

What are “real-world” blood pressure (BP) goals for patients with type 2 diabetes mellitus (T2DM), despite what guidelines say? What about BP management for patients with chronic kidney disease (CKD)?

Finally, what is the right level of glycemic control for patients with T2DM? Should “control” mean the same thing for everyone, or does the line move depending on the patient’s cardiovascular (CV) profile?

A panel of leading physicians took on these questions at the 63rd Scientific Sessions of the American College of Cardiology, held in Washington, DC, March 29-31, 2014, with the debate proving lively at times. Sanjay Kaul, MD, best characterized the spirit of the exchange when he said of Michael Miller, MD, his partner in the triglyceride debate, “Mike and I look at the same data set and come to different conclusions; it doesn’t mean that Mike is right or I am right—it speaks to the weakness of the data.”

Triglycerides. First, Miller, of the University of Maryland School of Medicine, Baltimore, and Kaul, of Cedars-Sinai Medical Center, Los Angeles, discussed whether medications should be routinely used to treat patients with triglyceride levels between 200 mg/dL and 500 mg/dL, with Miller asserting that there are epidemiologic, mechanistic, post hoc clinical data to support treatment.

A randomized, double-blind trial called REDUCE-IT is under way, with a primary end point of the prevention of the first major CV event. The trial involves men and women at least 45 years of age who have medical histories that include coronary heart disease or T2DM, and triglyceride levels ranging from 200 mg/dL to 500 mg/dL. The trial will compare groups taking icosapent ethyl (Vascepa) or placebo. Results are expected in 2016.1

With the trial under way, Miller said, “Why wait?”

There’s reason to wait, Kaul said. Non-statin therapies for hyperlipidemia do not provide acceptable risk reduction benefits compared with adverse effects (this includes fish oil–based treatment). He said these should be avoided, with a few exceptions. In looking at Lovaza and Vascepa, 2 approved omega-3 fatty acids, Kaul said they were approved for patients with severely high triglyceride levels (at least 500 mg/dL) on the presumption of increased risk of pancreatitis; Kaul said there are no data to support using these agents for triglycerides at lower levels.

Blood pressure, diabetes, and CKD.Both William C. Cushman, MD, who discussed BP goals for patients with diabetes, and George L. Bakris, MD, who outlined goals for those with CKD, offered insights into how guidelines are developed. Bakris went so far as to ask whether the now-updated Joint National Committee 7 (JNC 7) goal of having a BP at, or lower than, 130/80 mm Hg was “defensible.”

But Bakris, who noted that both he and Cushman served on the panel that developed the JNC 7 guidelines, knows that in a real-world setting, primary care physicians use some latitude in applying a guideline and will move up to 140/80 mm Hg, and so that knowledge is taken into account.

What’s known now is that the patient population suffering from these diseases is aging, and these realities must now be weighed as physicians push patients toward certain goals. As Cushman noted, “strict interpretation” of randomized controlled trials would call for a goal of 150 mm Hg for the systolic BP in hypertensive patients with T2DM, but based on the more recent ACCORD trial, 140 mm Hg might be reasonable. However, it is important not to overlook the diastolic number just to push the systolic.

Glycemic control. Darren K. McGuire, MD, MHSc, of the University of Texas Southwestern Medical Center in Dallas, led off his case, “No Need for Tight Glycemic Control,” with a product label for tolbutamide, which reads in part that the drug is “associated with increased cardiovascular mortality.” As if that weren’t enough to get everyone’s attention, McGuire showed results from a series of studies, including the ACCORD trial,2 that displayed what he called “discordance” between control of glycated hemoglobin (A1C) and outcomes. He acknowledged that control of A1C early on in younger patients did have favorable outcomes down the road, but older, sicker patients need flexibility in control of glycemic levels.

McGuire’s comments dovetailed with comments he and others made the previous day at a session on pharmacotherapy and diabetes, where it was observed that, for all the advances in diabetes care, the field still lacks a bulletproof treatment that poses no CV risks.

Stuart Zarich, MD, FACC, FAHA, FASE, of Bridgeport Hospital and Yale School of Medicine, took the opposite position in observing the “glucose paradox.” He said that although base glycemia predicts both future microvascular and macrovascular events, “Tight glucose control has only been linked to a reduction in microvascular events, while its role in reducing macrovascular events has been controversial.”

Meanwhile, control of BP and use of statins to reduce lipid levels have been shown to limit macrovascular events for those with T2DM. Part of the problem is that reducing BP will have immediate positive benefits, while the other steps can take several years to show benefits, Zarich said. Conversely, some effects of intense medication therapy include weight gain or even use of additional antidiabetic drugs.

Zarich read the ACCORD results somewhat differently, observing that the lowest risk of death was seen when A1C was well controlled at 6% to 7%, with excess mortality above 7%. Mortality increased for every 1% increase in A1C above 6%, he said.

In a sense, Zarich agreed with McGuire—early treatment may work; it just takes years for the evidence to appear. This “legacy” effect, or memory, requires patience on the part of physicians and patients—not to mention those reviewing the literature. EBDM
References

1. Bradberry JC, Hillman D. Overview of omega-3 fatty acid therapies. PT. 2013;38(11):681-691.

2. The Accord to Control Cardiovascular Risk in Diabetes Study Group (ACCORD). Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559.
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