Evaluation of the Glycometabolic Effects of Ranolazine in Patients With and Without Diabetes Mellitus in the MERLIN-TIMI 36 Randomized Controlled Trial

被引:129
作者
Morrow, David A. [1 ,2 ]
Scirica, Benjamin M. [1 ,2 ]
Chaitman, Bernard R. [3 ]
McGuire, Darren K. [4 ]
Murphy, Sabina A. [1 ,2 ]
Karwatowska-Prokopczuk, Ewa [5 ]
McCabe, Carolyn H. [1 ,2 ]
Braunwald, Eugene [1 ,2 ]
机构
[1] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TMI Study Grp, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] St Louis Univ, Sch Med, St Louis, MO USA
[4] Univ Texas Southwestern Med Sch, Dallas, TX USA
[5] CV Therapeut, Palo Alto, CA USA
关键词
angina; coronary disease; diabetes mellitus; hemoglobin A(1c); ACUTE CORONARY SYNDROMES; CHRONIC ANGINA; MYOCARDIAL-INFARCTION; EXERCISE TOLERANCE; ANTIANGINAL AGENT; RISK; ROSIGLITAZONE; ASSOCIATION; DISEASE; GLUCOSE;
D O I
10.1161/CIRCULATIONAHA.107.763912
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Ranolazine is a novel antianginal shown in an exploratory analysis in patients with diabetes mellitus and chronic angina to be associated with a decline in hemoglobin A(1c) (HbA(1c)). We designed a prospective evaluation of the effect of ranolazine on hyperglycemia as part of a randomized, double-blind, placebo-controlled outcomes trial. Methods and Results-We compared HbA(1c) (percentage) and the time to onset of a >= 1% increase in HbA(1c) among 4918 patients with acute coronary syndrome randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. Ranolazine significantly reduced HbA(1c) at 4 months compared with placebo (5.9% versus 6.2%; change from baseline, -0.30 versus -0.04; P<0.001). In patients with diabetes mellitus treated with ranolazine, HbA(1c) declined from 7.5 to 6.9 (change from baseline, -0.64; P<0.001). Diabetic patients were more likely to achieve an HbA(1c) <7% at 4 months with ranolazine compared with placebo (59% versus 49%; P<0.001) and were less likely to have a >= 1% increase in HbA(1c) (14.2% versus 20.6% at 1 year; hazard ratio, 0.63; 95% confidence interval, 0.51 to 0.77; P<0.001). Moreover, ranolazine reduced recurrent ischemia in diabetic patients (hazard ratio, 0.75; 95% confidence interval, 0.61 to 0.93; P=0.008). Notably, in patients without diabetes mellitus at baseline, the incidence of new fasting glucose >110 mg/dL or HbA(1c) >= 6% was reduced by ranolazine (31.8% versus 41.2%; hazard ratio, 0.68; 95% confidence interval, 0.53 to 0.88; P=0.003). Reported hypoglycemia did not increase with ranolazine (P=NS). Conclusions-Ranolazine significantly improved HbA(1c) and recurrent ischemia in patients with diabetes mellitus and reduced the incidence of increased HbA(1c) in those without evidence of previous hyperglycemia. The mechanism of this effect is under investigation. (Circulation. 2009; 119: 2032-2039.)
引用
收藏
页码:2032 / 2039
页数:8
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