STOP-NIDDM: New analysis suggests acarbose reduces CVD, hypertension in IGT

Susan Jeffrey

July 22, 2003

Tue, 22 Jul 2003 20:00:00

Chicago, IL - A new report suggests that treatment with the alpha-glucosidase inhibitor acarbose (Precose®, Bayer AG) is associated with a significant reduction in the risk for cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT).

The new report appears in the July 23/30, 2003 issue of the Journal of the American Medical Association.

The main findings of this study, called the STOP-Noninsulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, reported last year in the Lancet, showed treatment of these patients with acarbose delayed progression to type 2 diabetes.

"STOP-NIDDM is the first prospective interventional study showing that treatment with an alpha-glucosidase inhibitor in IGT patients is associated with a significant reduction in the incidence of CVD and hypertension," the researchers, led by Dr Jean-Louis Chiasson (Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu), conclude. "These observations are compatible with the hypothesis that postprandial hyperglycemia is a risk factor for CVD and provide further arguments for screening and treating people with IGT."

IGT: A independent risk factor for CVD

Cardiovascular disease is a major cause of morbidity and mortality among the growing population of patients with type 2 diabetes, the researchers write. Although diabetes is frequently associated with other CVD risk factors, including dyslipidemia and hypertension, it is thought that hyperglycemia itself is an independent risk factor. "More recently, special emphasis has been given not only to fasting but more particularly to postprandial hyperglycemia as a risk factor for CVD in patients that do not have diabetes as well as those who have it," Chiasson et al point out. Macrovascular damage is thought to begin before a diagnosis of diabetes, and studies have now confirmed an increased risk of CVD in patients who are still in the IGT stage.

Acarbose decreases postprandial plasma glucose levels in patients with IGT. Main results of the STOP-NIDDM study demonstrated that this strategy could reduce the risk of diabetes in these patients.

The trial, conducted at hospitals in nine countries, included 1429 patients with IGT, defined as a two-hour plasma glucose concentration of >7.8 mmol/L and <11.1 mmol/L after a 75-g glucose load and a fasting plasma glucose concentration of 5.6 to 7.7 mmol/L, a value associated with a three- to fourfold increase in risk of progression to diabetes.

Patients were randomized to acarbose three times per day or placebo. To keep the known gastrointestinal side effects of acarbose (flatulence, diarrhea, abdominal cramps) to a minimum, the drug was started at 50 mg/day and increased to a maximum of 100 mg three times per day or the maximum tolerated dose. Patients were also encouraged to make lifestyle changes, exercising regularly and following a weight-reduction or weight-maintenance diet. The primary end point of the trial was the development of diabetes. A total of 61 patients (4%) were excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for the modified intention-to-treat analysis.

After 3.3 years of follow-up, 32% of those on acarbose developed diabetes compared with 42% of those on placebo (relative hazard 0.75 [95% CI 0.63-0.90]; p=0.0015). Patients on acarbose were also more likely to have their IGT revert back to normal glucose tolerance than patients on placebo, the investigators reported.

"Another important objective of the study was to test whether decreasing postprandial hyperglycemia would also diminish the risk of CVD and hypertension," Chiasson et al write.

CVD risk

Of the 1368 patients, 341 (24%) discontinued participation in the trial, 211 in the acarbose group and 130 in the placebo group. The most common reason for discontinuation was gastrointestinal symptoms, they note, but all patients were followed for outcome variables. Outcomes of interest for this analysis were the development of major cardiovascular events (CHD, cardiovascular death, congestive heart failure, cerebrovascular event, or peripheral vascular disease) or hypertension (BP >140/90 mm Hg).

After the same 3.3 years of follow-up, decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events and a 2.5% absolute risk reduction. The major difference was seen in the risk of MI, with 12 of 13 cases occurring in the placebo group (hazard ratio 0.09 [0.01-0.72]; p=0.02). "The number needed to treat to prevent one cardiovascular event would be 40 patients with IGT over 3.3 years," they note.

There was also a significant 5.3% absolute risk reduction in new cases of hypertension. Mean systolic and diastolic BPs were lower in the acarbose-treated group throughout the study period. The number needed to treat to prevent one case of hypertension would be 19 patients with IGT treated for 3.3 years.

STOP-NIDDM: CVD, hypertension risk reduction with acarbose vs placebo


End point

Relative risk reduction (%)

Hazard ratio (95% CI)

p

49
0.51 (0.28-0.95)
0.03
34
0.66 (0.49-0.89)
0.006

After adjustment for major cardiovascular risk factors, the reduction in risk of CVD and hypertension remained statistically significant.

STOP-NIDDM: Adjusted CVD, hypertension risk with acarbose vs placebo


End point

Hazard ratio (95% CI)

p

0.47 (0.24-0.90)
0.02
0.62 (0.45-0.86)
0.004
To download tables as slides, click on slide logo below

The authors point out that, despite the limitations of their studyincluding a higher-than-expected level of premature discontinuation by patients in the trialtheir results show a "consistency" in the effect of acarbose on overall cardiovascular events and MI in particular, and they believe these results to be "statistically and clinically significant."

"They are, however, hypothesis generating and will need to be confirmed," Chiasson et al conclude.



Related link

1. [HeartWire > News; June 13, 2002]


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