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Acarbose fails to lower risk for major adverse CV events in CHD
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The risk for major adverse cardiovascular events was not reduced in Chinese adults with coronary heart disease treated with acarbose, but the therapy was effective in reducing the incidence of diabetes, according to findings from the Acarbose Cardiovascular Evaluation study, or ACE, presented at the European Association for the Study of Diabetes Annual Meeting and published simultaneously in The Lancet Diabetes & Endocrinology.
Rury R. Holman, MD, FRCP, of the diabetes trials unit at Churchill Hospital in Oxford, United Kingdom, and colleagues evaluated data on 6,522 adults with CHD and impaired glucose tolerance from 176 hospitals in China. Participants were randomly assigned the alpha-glucosidase inhibitor acarbose (Glucobay, Bayer AG; n = 3,272) or placebo (n = 3,250) and followed for a median 5 years to determine whether acarbose can reduce the frequency of CV events and the incidence of type 2 diabetes.
The primary composite outcome included a 5-point composite of CV death, nonfatal myocardial infarction, nonfatal stroke, hospital admission for unstable angina and hospital admission for heart failure. Secondary outcomes included a 3-point composite outcome of CV death, nonfatal MI and nonfatal stroke; death from any cause; CV death; fatal or nonfatal MI; fatal or nonfatal stroke; hospital admission for unstable angina; hospital admission for heart failure; development of diabetes; and development of impaired renal function.
The acarbose group had lower HbA1c, 2-hour plasma glucose, triglycerides and body weight (P < .0001 for all) at 1 year compared with the placebo group. No significant differences were observed between the groups for systolic blood pressure, diastolic BP or LDL cholesterol.
The primary 5-point major adverse CV event outcome occurred in 14.4% of the acarbose group compared with 14.7% of the placebo group. No significant differences were observed between the groups for the secondary outcomes.
The acarbose group had an 18% lower incidence of new-onset diabetes compared with the placebo group during a median 4.4 years of follow-up.
No significant differences were observed between the groups for mild and severe hypoglycemic episodes or the incidence of events of clinical interest, serious adverse events or adverse events other than gastrointestinal disorders.
“ACE provides reassurance that acarbose may be used safely to improve blood glucose levels in people with coronary heart disease and impaired glucose regulation with no impact on rate of cardiovascular complications or heart failure,” Holman said in a press release. “The reduced incidence of diabetes seen with acarbose in the ACE trial may, however, help reduce cardiovascular risk in the longer term by delaying the onset of diabetes in the high-risk population studied.”
In an accompanying editorial, Michael A. Nauck, MD, and Juris J. Meier, MD, both of the Diabetes Center Bochum-Hattingen, Medical Department I, St. Josef-Hospital, Ruhr University Bochum in Germany, wrote that the study “is an important milestone in the debate about whether or not postprandial glucose rises are a specific risk factor predictive of cardiovascular events.”
“The new state-of-the-art answer, at least for people with impaired glucose tolerance, seems to be no,” they wrote. “But this might not be the ultimate conclusion for all populations, including patients with advanced stages of diabetes, for whom treatment with acarbose or drugs with a preferential postprandial mechanism of action might still provide some cardiovascular benefit.” – by Amber Cox
References:
Holman RR. Acarbose Cardiovascular Evaluation (ACE): primary results. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 11-15, 2017; Lisbon, Portugal.
Holman RR, et al. Lancet Diabetes Endocrinol. 2017;doi:10.1016/S2213-8587(17)30309-1.
Nauck MA, et al. Lancet Diabetes Endocrinol. 2017;doi:10.1016/S2213-8587(17)30318-2.
Disclosures: Holman reports he receives grants from AstraZeneca, Bayer AG, personal fees from Amgen, Bayer AG and Servier, grants and personal fees from Boehringer Ingelheim and Merck Sharp & Dohme and chairs or participates in independent data monitoring committees for Elcelyx, GlaxoSmithKline, Janssen and Takeda. Nauck reports he receives compensation for lectures or advisory board membership from AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Fractyl, GlaxoSmithKline, Intarcia/Servier, Menarini/Berlin-Chemie, Merck Sharpe & Dohme and Novo Nordisk and receives grant support form AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Menarini/Berlin-Chemie, Merck, Sharp & Dohme and Novartis. Meier reports he receives compensation for lectures or advisory board membership from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly & Co., Merck Sharp & Dohme, Novo Nordisk, Servier and Sanofi and receives research support from Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk and Sanofi. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Alan J. Garber, MD, PhD, FACE
The ACE trial is essentially a randomized, placebo-controlled, multicenter, follow-on study of an earlier observation from the STOP NIDDM trial in which there was an unexpected 49% reduction in CV events. However, ACE was performed in a much larger group (6,522 subjects) than STOP NIDDM (1,429 subjects) and was performed exclusively in China rather than a multinational trial. Overall, ACE was more highly powered than STOP NIDDM. It showed 470 patients on acarbose had a primary expanded MACE endpoint vs. 479 on placebo. This outcome calls into question the generalizability of the finding from STOP NIDDM; it is certainly generalizable to a population living in China, but may not be relevant to other counties and populations.
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