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- Holman, Rury R, et al.
(författare)
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Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 377:13, s. 1228-1239
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups.CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).
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| 2. |
- Pagidipati, Neha J., et al.
(författare)
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An examination of the relationship between serum uric acid level, a clinical history of gout, and cardiovascular outcomes among patients with acute coronary syndrome
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 187, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- Background Studies have suggested a relationship between higher baseline serum uric acid (sUA) levels and an elevated risk of subsequent ischemic cardiovascular outcomes among acute coronary syndrome (ACS) patients; this relationship may be modified by a clinical history of gout and has not been studied in large patient cohorts. We sought to understand the effect of sUA and gout on ACS outcomes. Methods Using PLATO and TRACER data on 27,959 ACS patients, we evaluated baseline sUA levels in relation to a composite of cardiovascular death, myocardial infarction (MI), or stroke. We assessed interaction terms to determine if a baseline clinical diagnosis of gout modified this putative relationship; 46% (n = 12,882) had sUA levels elevated >6.0 mg/dL. Results Patients with elevated levels were more often male with a history of prior MI, diabetes, and heart failure compared with those with sUA <6.0 mg/dL. The unadjusted risk of the composite endpoint increased with corresponding elevations in sUA levels (per 1 mg/dL increase) (HR = 1.23 [95% CI: 1.20-1.26]) above the statistical inflection point of 5.0 mg/dL. After adjustment, the association between sUA level and the composite outcome remained significant (HR = 1.07 [95% CI: 1.04-1.10]), and baseline gout did not modify this relationship. ' Conclusions In patients with ACS, increasing levels of sUA are associated with an elevated risk of cardiovascular events, regardless of a clinical diagnosis of gout. Further investigation is warranted to determine the mechanism behind this relationship and to delineate whether sUA is an appropriate therapeutic target to reduce cardiovascular risk.
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