Three aggressive treatment strategies doctors had expected would prevent heart attacks among people with Type 2 diabetes and some who are on the verge of developing it have proved to be ineffective or even harmful, studies released Sunday show.
The results are surprising and disappointing, heart and diabetes experts say. An estimated 21 million Americans have Type 2 diabetes, the kind once known as adult-onset, and they are at enormous risk for heart disease. The only measures proved to reduce their risk — avoiding cigarettes and taking medication to lower bad cholesterol and blood pressure — still leave diabetics with a heart attack risk equivalent to that of a nondiabetic who has already had a heart attack.
So doctors began trying other strategies they hoped would help: getting blood pressure to a normal range; raising levels of good cholesterol and lowering levels of dangerous triglycerides; or modulating sharp upswings in blood sugar after a meal.
It is not known how many doctors have been encouraging patients to take these measures, but medical specialists say it seemed reasonable.
"Doctors always want to improve the lives of their patients," said Dr. Henry Ginsberg, director of the Irving Institute for Clinical and Translational Research at Columbia University. Now, the new studies could save people from taking drugs that will not help, he said.
The papers were presented at an American College of Cardiology meeting in Atlanta and were published online by the New England Journal of Medicine.
In Type 2 diabetes, the body is resistant to the hormone insulin, leading to abnormally high blood sugar levels that can cause eye, kidney and nerve disease. But heart disease is what kills most patients. A quarter to a third of heart attack patients have diabetes, even though diabetics are just 9 percent of the population. And 25 percent of heart attack patients are on the verge of diabetes, with abnormally high blood sugar levels.
High blood sugar levels themselves increase the risk of heart disease, but researchers found two years ago that rigorously controlling blood sugar did not prevent heart disease or deaths in people with Type 2 diabetes. Researchers said that failure was probably because most of those patients also have other problems that make their odds of heart disease soar, like high levels of LDL cholesterol, low levels of HDL cholesterol, high levels of triglycerides and high blood pressure. And most are older and overweight.
One large federal study asked if getting blood pressure down to a level considered normal, a systolic pressure of no more than 120, would help protect diabetics from heart disease. This hypothesis was promising because studies have found that heart disease and stroke risk increase continuously as systolic blood pressure rises from 115 on up, said Dr. William Cushman, a study investigator and chief of the preventive medicine section at the Veterans Affairs Medical Center in Memphis.
To put the idea of a normal blood pressure to the test, half of the study's 4,773 participants took drugs to get their systolic blood pressure to 120 or below. The rest had a blood pressure goal of less than 140.
But lower blood pressure did not prevent heart attacks or cardiovascular deaths, and those with lower blood pressure were more likely to suffer severe side effects from the drugs, like high potassium levels or dangerously low blood pressures.
A second, less rigorous study, involving 6,400 patients with Type 2 diabetes and heart disease, asked whether getting systolic blood pressure lower than 130 was any better than getting it to 130 to 140. It found that patients actually were worse off: Those with the lower blood pressure ended up with a 50 percent greater risk of strokes, heart attacks or deaths.
People with diabetes also tend to have low levels of HDL cholesterol and high levels of triglycerides, a combination known to increase the risk of heart disease. And in some studies, treating that combination with a type of drug called a fibrate reduced risk in diabetics and nondiabetics who were not taking statins. So it made sense to see if fibrates also helped Type 2 diabetics who were taking statins.
It did not, concluded another arm of the study involving 5,518 people with Type 2 diabetes.
It means, said Dr. Denise Simons-Morton of the National Heart, Lung and Blood Institute, the project officer for the federal study, that "doctors and patients now know that the inclination to do intensive treatment that people seemed to think would be better for cardiovascular risk reduction wasn't better."
A final study investigated the hypothesis that rapid rises in blood glucose after a meal were dangerous and could lead to heart disease. The study, which involved 9,300 patients at high risk for diabetes because their blood sugar was high, tested the drug nateglinide, which enhances insulin secretion. It also tested a blood pressure drug. Neither decreased heart disease risk.