Lowering blood pressure to normal levels - below currently recommended levels - did not significantly reduce the combined risk of fatal or nonfatal cardiovascular disease events in adults with type 2 diabetes who were at especially high risk for cardiovascular disease events, according to new results from the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial.
Similarly, treating multiple blood lipids with combination drug therapy of a fibrate and a statin did not reduce the combined risk of cardiovascular disease events more than treatment with statin alone. The study of more than 10,000 participants is sponsored by the National Institutes of Health.
ACCORD is one of the largest studies ever conducted in adults with type 2 diabetes who were at especially high risk of cardiovascular events, such as heart attacks, stroke, or death from cardiovascular disease. The multicenter clinical trial tested three potential strategies to lower the risk of major cardiovascular events: intensive control of blood sugar, intensive control of blood pressure, and treatment of multiple blood lipids. The lipids targeted for intensive treatment were high density lipoprotein (HDL) cholesterol and triglycerides, in addition to standard therapy of lowering low density lipoprotein (LDL) cholesterol.
The results of the ACCORD blood pressure and lipid clinical trials appear online in the New England Journal of Medicine (NEJM) today and will be in the April 29, 2010, NEJM print edition. The results are also being presented today at the American College of Cardiology's 59th annual scientific session in Atlanta. Results of the ACCORD blood sugar clinical trial were reported in 2008.
"ACCORD provides important evidence to help guide treatment recommendations for adults with type 2 diabetes who have had a heart attack or stroke or who are otherwise at especially high risk for cardiovascular disease," said Susan B. Shurin, M.D., acting director of the NIH's National Heart, Lung, and Blood Institute (NHLBI), the primary sponsor of ACCORD. "This information provides guidance to avoid unnecessarily increasing treatment that provides limited benefit and potentially increases the risk of adverse effects."
ACCORD researchers from 77 medical centers in the United States and Canada studied 10,251 participants between the ages of 40 and 79 who had type 2 diabetes for an average of 10 years. When they joined the study, all participants were at especially high risk of cardiovascular events because they had pre-existing cardiovascular disease, evidence of subclinical cardiovascular disease, or at least two cardiovascular disease risk factors in addition to diabetes.
All participants were enrolled in the ACCORD blood sugar treatment clinical trial and maintained good control of blood sugar levels during the study. In addition, participants were enrolled in either the blood pressure trial or the lipid trial and were treated and followed for an average of about five years.
The ACCORD blood pressure trial is the largest clinical trial to test the effect on cardiovascular disease of systolic blood pressure (the top number in a blood pressure reading) below 120 mmHg, which is considered normal. Current blood pressure guidelines recommend that adults with type 2 diabetes maintain systolic blood pressure at less than 130 mm Hg. Previous clinical trials have only proven benefits to less than 140 mm Hg; however, observational studies have linked systolic blood pressure levels of 120 mmHg or below to lower cardiovascular disease rates in adults with type 2 diabetes. A clinical trial was needed to determine the effects of treatment to reach this normal systolic blood pressure level in these patients.
Researchers randomly assigned 4,733 participants with elevated blood pressure to a target systolic blood pressure of either less than 120 mmHg (the intensive group) or to less than 140 mmHg (the standard group). A variety of FDA-approved blood pressure medications was used to reach blood pressure goals. After an average follow-up of about five years, researchers found no significant differences between the intensive group and the standard group in rates of a combined endpoint including nonfatal heart attack, nonfatal stroke, or cardiovascular death. There were 208 cardiovascular events in the intensive group and 237 events in the standard group.
Lowering blood pressure to below the standard level significantly cut the risk of stroke by about 40 percent. The intensive blood pressure group had 36 strokes, compared to 62 strokes in the standard group. The researchers caution, however, that participants in the intensive blood pressure group were more likely to have complications such as abnormally low blood pressure or high levels of blood potassium. They noted 77 events in the intensive groups compared to 30 in the standard group. In addition, some laboratory measures of kidney function were worse in the intensive therapy group, but there was no difference in the rates of kidney failure.
"Our results provide no conclusive evidence that targeting a normal systolic blood pressure compared with targeting a systolic blood pressure of less than 140 mmHg lowers the overall risk of major cardiovascular events in high risk adults with type 2 diabetes," said William C. Cushman, M.D., chief of the Preventive Medicine Section, Veterans Affairs Medical Center, Memphis, Tenn., and lead author. "However, the study suggests that lower blood pressure levels in patients like those in ACCORD may reduce the risk of stroke. This finding is consistent with other blood pressure trials."
"Our results also showed a higher risk of serious adverse events with more intensive blood pressure control," Cushman added. "Diabetic patients should discuss their systolic blood pressure goal with their health care provider and, as with any treatment, weigh the risks and benefits of various treatments to lower blood pressure."
The ACCORD lipid trial studied whether adding a fibrate to a statin to improve multiple blood lipids is more effective at lowering the risk of cardiovascular events than treatment with a statin alone. Both statins and fibrates are commonly used medications to treat abnormal levels of blood lipids. Statins lower LDL, or bad cholesterol, and are proven to lower cardiovascular disease risk in people with diabetes. Fibrates primarily lower fats in the blood known as triglycerides and raise HDL or good cholesterol. Fibrates are sometimes used in combination with statins. High triglycerides and low HDL levels are common in diabetes patients.