5 research outputs found
Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes
BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events
Thrombin-receptor antagonist vorapaxar in acute coronary syndromes
BACKGROUND
Vorapaxar is a new oral protease-activated–receptor 1 (PAR-1) antagonist that inhibits
thrombin-induced platelet activation.
METHODS
In this multinational, double-blind, randomized trial, we compared vorapaxar with
placebo in 12,944 patients who had acute coronary syndromes without ST-segment
elevation. The primary end point was a composite of death from cardiovascular causes,
myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent
coronary revascularization.
RESULTS
Follow-up in the trial was terminated early after a safety review. After a median follow-up
of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031
of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo
(Kaplan–Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval
[CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes,
myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group
versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89;
95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the
vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58;
P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard
ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events
were similar in the two groups.
CONCLUSIONS
In patients with acute coronary syndromes, the addition of vorapaxar to standard
therapy did not significantly reduce the primary composite end point but significantly
increased the risk of major bleeding, including intracranial hemorrhage
Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes
BACKGROUND
Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin,
a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2
diabetes and cardiovascular disease.
METHODS
In this randomized, double-blind study, we assigned 14,671 patients to add either
sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic
therapy was encouraged as required, aimed at reaching individually appropriate
glycemic targets in all patients. To determine whether sitagliptin was noninferior
to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The
primary cardiovascular outcome was a composite of cardiovascular death, nonfatal
myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.
RESULTS
During a median follow-up of 3.0 years, there was a small difference in glycated
hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo,
120.29 percentage points; 95% confidence interval [CI], 120.32 to 120.27). Overall,
the primary outcome occurred in 839 patients in the sitagliptin group (11.4%;
4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per
100 person-years). Sitagliptin was noninferior to placebo for the primary composite
cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001).
Rates of hospitalization for heart failure did not differ between the two groups
(hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). There were no significant
between-group differences in rates of acute pancreatitis (P=0.07) or pancreatic
cancer (P=0.32).
CONCLUSIONS
Among patients with type 2 diabetes and established cardiovascular disease, adding
sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular
events, hospitalization for heart failure, or other adverse events.
(Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke