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Why Drugs Don’t Help Diabetes Patients’ Hearts

7 minute read
Alice Park

Doctors at the annual meeting of the American College of Cardiology in Atlanta on Sunday got some surprising news on their first day of sessions. Researchers presented three studies revealing that some of the most widely prescribed medications to reduce the risk of heart disease in Type 2 diabetes patients appeared not to provide much benefit at all.

People with diabetes are twice as likely as nondiabetics to suffer a heart attack — most diabetes patients die of heart disease — and for years, physicians have used aggressive drug treatments to lower that risk. To that end, the goal has commonly been to lower blood sugar or control blood-sugar spikes after eating, lower triglycerides and reduce blood pressure in diabetes patients to levels closer to those of healthy, nondiabetic individuals. By using medication to treat these factors, which are linked to a higher risk of heart attack and stroke in other patients, doctors assumed they would also be reducing the risk in people with diabetes.

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Now, in the aftermath of reports concluding that these targets do not cut the risk of heart disease in diabetes patients, and in some cases may even do harm, researchers are struggling to make sense of the seemingly counterintuitive data, and physicians are trying to figure out how to incorporate the findings into their practice.

Already, researchers anticipate that more careful analyses of the trial data over the coming months and years may lead to more nuanced conclusions; it may turn out, for instance, that certain subgroups of patients like younger, newly diagnosed diabetics actually benefit from the medications, even while the larger population of diabetes patients do not.

The data come from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, a three-part federal study launched a decade ago to investigate whether the aggressive lowering of those key risk factors — blood sugar, cholesterol and blood pressure — would reduce heart risks in diabetes and prediabetes patients. Two years ago, the blood-sugar arm of the study was terminated, when people who drastically reduced glucose levels ended up having a higher overall mortality rate than those not receiving such intensive therapy.

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Now, results of the remaining two arms of the trial — one in which patients were treated with blood-pressure-lowering drugs and another in which they received statins to reduce cholesterol and fibrate medications to slice their trigylceride levels — showed the same trend, finding that aggressive drug treatment did little to reduce the volunteers’ risk of developing heart problems.

In the blood-pressure study, involving about 4,700 diabetes patients, researchers lowered the participants’ systolic blood pressure to either below 120 or 140 using a combination of drugs. But lower blood pressure did not lead to fewer heart attacks or heart-related deaths, and patients taking more drugs to keep their blood pressure under the lower target were more likely to suffer severe side effects.

In the statin and fibrate study, about 5,500 patients with diabetes and at least one other health problem were given cholesterol-lowering statins; half were also given a triglyceride-lowering fibrate. There was no difference in heart-attack and stroke rates between the groups.

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The findings were published online in the New England Journal of Medicine (NEJM). The results of two other related studies were also published online: one large trial also looked at the effect of reducing blood pressure in diabetes patients; another trial, involving 9,300 patients who had high blood sugar and were at high risk of developing diabetes, measured the benefit of drugs that blunt the sharp peaks and valleys in blood glucose levels that occur after eating. Neither study showed benefits of these treatments in reducing risk of heart disease.

Although each of these studies included several thousand diabetes patients, which bolsters the reliability of their results, it doesn’t mean they are the final word on the tested treatments. In the blood-fats arm of the ACCORD study, for instance, about 40% of the volunteers had already had a previous heart event and the remainder had risk factors, other than diabetes, that put them at high risk for heart disease, notes Dr. Om Ganda, director of the lipid clinic at Joslin Diabetes Center in Boston. That means the trial was not truly a primary-prevention study designed to test whether aggressive drug treatment could prevent a first heart attack in newly diagnosed diabetes patients.

The researchers had hoped that treated patients would lower their risk of heart events because they were given both statin drugs, which curb the liver’s production of cholesterol, and a fibrate, which mops up harmful triglycerides in the blood and boosts levels of “good” cholesterol. But all of the volunteers either already suffered from heart disease, or had two or more major risk factors for heart problems — including cigarette smoking, family history and high cholesterol — in addition to diabetes. That may have pushed their diabetes too far along to allow them to see any benefit from the drugs. “This may be too late a state to expect major benefits from the medications,” says Ganda.

Another reason these patients showed no significant heart benefits, he says, may be that most of them never needed the fibrate to begin with. About two-thirds of the patients in the trial already had triglyceride levels below those at which doctors would normally prescribe the drug, which skewed the study results toward the negative side.

In fact, when the trial’s investigators looked specifically at diabetics with the highest triglyceride levels, they did see a benefit, with those patients enjoying a lower risk of heart disease than the volunteers with lower triglyceride levels. “Maybe one can say that, at a later stage of the disease, adding a fibrate is not spectacularly beneficial except for this subgroup,” says Ganda.

That’s a pattern that many diabetes experts expect to emerge more robustly as researchers dig deeper into the data. It’s possible, for instance, that younger, newly diagnosed patients with diabetes may actually benefit from aggressively lowering their blood pressure, cholesterol and blood sugar levels — a trend that may have been lost in the noise of the current studies, which included patients who were up to 79 years old. “I tend to be far more tuned in to getting normal targets in my younger patients,” says Dr. Daniel Einhorn, medical director of the Scripps Whittier Diabetes Institute, who is a co-author on one of the NEJM studies. “Without question, now I am more conservative in my treatment of older, sicker patients, because they don’t benefit, and these studies just confirm that.”

But the primary lesson that clinicians can take away from the new findings is that the blind push to lower all risk factors such as blood pressure or cholesterol isn’t necessarily healthy, says Dr. Christopher Saudek, director of the diabetes center at Johns Hopkins University. That may even mean resisting the commonsense urge to reduce these measures to recommended or normal range in diabetics patients. “To me, it’s a matter of having reasonable and patient-oriented individual targets,” he says, “rather than trying to push and push and push just to get lower and lower glucose or blood pressure or lipid levels.”

Given that such aggressive drug treatment does not seem to afford significant benefits to diabetics on the whole, Saudek and his colleagues anticipate that going forward physicians and patients will increasingly reintroduce the importance of lifestyle changes, such as improving diet and getting more physically active, for slowing the progression of diabetes and reducing the risk of heart disease. These are therapies that are, after all, proven to work. “These discussions obviously should be going on the whole time, but these studies are one more reminder that medication therapy has its downsides,” says Einhorn.

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