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
Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial
Auteurs : the PRECISION investigatorsInternational audienceBackground Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. Methods PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12•5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. Findings The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was-15•3 (SE 0•9) mm Hg for aprocitentan 12•5 mg,-15•2 (0•9) mm Hg for aprocitentan 25 mg, and-11•5 (0•9) mm Hg for placebo, for a difference versus placebo of-3•8 (1•3) mm Hg (97•5% CI-6•8 to-0•8, p=0•0042) and-3•7 (1•3) mm Hg (-6•7 to-0•8; p=0•0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was-4•2 mm Hg (95% CI-6•2 to-2•1) and-5•9 mm Hg (-7•9 to-3•8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5•8 mm Hg, 95% CI 3•7 to 7•9, p<0•0001). The most frequent adverse event was mild-to-moderate oedema or fluid retention, occurring in 9%, 18%, and 2% for patients receiving aprocitentan 12•5 mg, 25 mg, and placebo, during the 4-week double-blind part, respectively. This event led to discontinuation in seven patients treated with aprocitentan. During the trial, a total of 11 treatment-emergent deaths occurred, none of which were regarded by the investigators to be related to study treatment. Interpretation In patients with resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4 with a sustained effect at week 40