2 research outputs found
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
BACKGROUND
Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent
ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data
are needed to determine its effects on ischemic events.
METHODS
We performed a multicenter, randomized, double-blind, placebo-controlled trial involving
patients with established cardiovascular disease or with diabetes and other risk factors, who
had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg
per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of
41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned
to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary
end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal
stroke, coronary revascularization, or unstable angina. The key secondary end point was a
composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
RESULTS
A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular
events) and were followed for a median of 4.9 years. A primary end-point event occurred in
17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients
in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001);
the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio,
0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed
according to a prespecified hierarchical schema, were significantly lower in the icosapent
ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs.
5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in
the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation
or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients
in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06).
CONCLUSIONS
Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded
by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361
Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD
BACKGROUND
Treatment guidelines recommend the use of inhaled long-acting bronchodilators to
alleviate symptoms and reduce the risk of exacerbations in patients with moderate-tovery-severe chronic obstructive pulmonary disease (COPD) but do not specify whether
a long-acting anticholinergic drug or a β2-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β2-agonist
salmeterol in preventing exacerbations of COPD.
METHODS
In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg
of salmeterol twice daily on the incidence of moderate or severe exacerbations in
patients with moderate-to-very-severe COPD and a history of exacerbations in the
preceding year.
RESULTS
A total of 7376 patients were randomly assigned to and treated with tiotropium
(3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17%
reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90;
P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96;
P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13;
rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious
adverse events and of adverse events leading to the discontinuation of treatment was
similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group
and 78 (2.1%) in the salmeterol group.
CONCLUSIONS
These results show that, in patients with moderate-to-very-severe COPD, tiotropium
is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer
Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.