REDUCE-IT: outcomes by baseline statin type

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Bhatt ◽  
M Miller ◽  
P.G Steg ◽  
E.A Brinton ◽  
T.A Jacobson ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Risk Reduction ◽  
Coronary Revascularization ◽  
Secondary Endpoint ◽  
Nonfatal Stroke ◽  
Funding Source ◽  
Icosapent Ethyl ◽  
Prescription Form ◽  
One Year ◽  
The Impact

Abstract Background REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) randomized 8,179 statin-treated patients with elevated triglycerides and increased cardiovascular (CV) risk to either icosapent ethyl (IPE), a pure, stable prescription form of eicosapentaenoic acid, 4g/day or placebo. IPE significantly reduced time to first occurrence of the primary composite endpoint of major adverse CV events (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) (HR 0.75, CI 0.68–0.83) and key secondary endpoint events (composite of CV death, nonfatal MI, or nonfatal stroke) (HR 0.74, CI 0.65–0.83) versus placebo (all p<0.0001). A modest reduction in placebo-corrected LDL-C was observed (−6.6%; p<0.0001). The mechanisms for the CV benefit of icosapent ethyl are not fully understood. Purpose Explore the impact of statin type and lipophilic/lipophobic category on outcomes, and on LDL-C, to further consider the possible relevance of LDL-C pathways to the observed CV benefit of icosapent ethyl. Methods Primary and key secondary endpoint analyses and LDL-C changes from baseline were explored by individual statin type (atorvastatin, simvastatin, rosuvastatin, or pravastatin) at baseline, and then by categorizing these statins into lipophilic (i.e., hydrophobic: atorvastatin, simvastatin) and lipophobic (i.e., hydrophilic: rosuvastatin, pravastatin) statin groups; 96.1% of patients fell within these individual statin groups. Results CV outcomes were similar across statin types (interaction p=0.61) and lipophilic/lipophobic categories (interaction p=0.51) (Figure). Statin type and category had a similar lack of meaningful impact on the modest placebo-corrected median LDL-C changes from baseline to one year, which ranged from −5.8 to −8.4% (all p≤0.0003). Conclusion No meaningful treatment differences in the primary or key secondary endpoints across statin type or lipophilic/lipophobic category were observed. A similar lack of treatment difference was observed in LDL-C changes from baseline to one year. Therefore, the LDL-C changes and CV risk reduction in REDUCE-IT appear independent of the type of concomitant statin therapy. These data provide clinicians with additional insight regarding concomitant statin therapy considerations when prescribing icosapent ethyl and suggest there are important mechanisms of action for the substantial CV risk reduction observed with icosapent ethyl that are distinct from the LDL receptor pathway. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The study was funded by Amarin Pharma, Inc.

REDUCE-IT: total ischemic events reduced across the full range of baseline LDL cholesterol and other key subgroups

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Bhatt ◽  
M Miller ◽  
P.G Steg ◽  
E.A Brinton ◽  
T.A Jacobson ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Negative Binomial ◽  
Absolute Risk ◽  
Full Range ◽  
Secondary Endpoint ◽  
Nonfatal Stroke ◽  
Funding Source ◽  
Icosapent Ethyl ◽  
Prescription Form ◽  
Ischemic Events

Abstract Background REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), a study of 8,179 randomized statin-treated patients with elevated triglycerides (TG) and increased cardiovascular (CV) risk followed for a median of 4.9 years, demonstrated robust results. Icosapent ethyl (IPE), a pure and stable prescription form of eicosapentaenoic acid, 4g/day reduced both time-to-first and total primary endpoint ischemic events (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) by 25% (HR 0.75; 95% CI 0.68–0.83; p<0.0001) and 30% (rate ratio 0.70; 95% CI 0.62–0.78; p<0.0001), respectively. Similar substantial reductions in first and total key secondary endpoint ischemic events (composite of CV death, nonfatal MI, or nonfatal stroke) were also observed. Demographic and baseline disease characteristics were generally balanced across treatment groups. Time-to-first event analyses showed robust and generally consistent benefit across subgroups. Previous total event analyses by baseline TG demonstrated large, consistent, statistically significant reductions across tertiles, suggesting the CV benefit of IPE is tied primarily to non-TG factors. Purpose Further explore the extent to which IPE reduced total primary and key secondary events across prespecified baseline demographic, disease, treatment, and lipid/lipoprotein/inflammatory biomarker subgroups. Methods Total events across subgroups were assessed with the prespecified negative binomial regression method. Main outcomes were total (first and subsequent) primary and key secondary composite endpoint events. Results Median baseline LDL-C levels in ascending tertiles were 58, 76, and 96 mg/dL; there were large, significant relative reductions in total primary endpoint events with IPE across tertiles (35%, 28%, and 27%, respectively; interaction p=0.62), with parallel substantial absolute risk reductions. Similar, significant relative reductions of 33%, 28%, and 24% in total key secondary endpoint events were observed, along with substantial absolute risk reductions. Total events analyses of prespecified subgroups also demonstrated robust and generally consistent findings for the primary and key secondary composite endpoints. Conclusion REDUCE-IT demonstrated substantial reductions in first and total primary and key secondary endpoint ischemic events, with robust and generally consistent results across baseline TG and LDL-C levels, as well as other prespecified baseline biomarker, demographic, disease, and treatment subgroups. These analyses provide useful insights for clinicians considering the range of patients who may benefit from IPE therapy and suggest that mechanisms beyond the lipid/lipoprotein/inflammatory pathways tested, including mechanisms beyond the LDL receptor pathways, may contribute to the observed substantial reductions in total ischemic burden with IPE therapy. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The study was funded by Amarin Pharma, Inc.

scholarly journals REDUCE-IT: accumulation of data across prespecified interim analyses to final results

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Olshansky ◽  
D Bhatt ◽  
M Miller ◽  
P.G Steg ◽  
E.A Brinton ◽  
...  
Keyword(s):  
Risk Reduction ◽  
Primary Endpoint ◽  
Statistical Significance ◽  
Composite Endpoint ◽  
Nonfatal Stroke ◽  
Funding Source ◽  
Efficacy And Safety ◽  
Interim Analyses ◽  
Icosapent Ethyl

Abstract Background REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), an event-driven trial, randomized 8,179 statin-treated patients with elevated triglycerides (TGs) and increased cardiovascular (CV) risk to icosapent ethyl (IPE); pure, stable prescription eicosapentaenoic acid, 4g/day or placebo. 1,612 primary endpoint events (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) projected 90% power to detect 15% relative risk reduction (5% 2-sided alpha). The key secondary composite endpoint was CV death, nonfatal MI, or nonfatal stroke. An independent data and safety monitoring committee (DMC) performed prespecified interim analyses (IAs) at ∼60% (IA1 31 May 2016 data cutoff; 2.9 y median primary endpoint follow-up) and ∼80% (IA2 01 May 2017; 3.7 y) of events; final analysis included 1,606 events (06 Sep 2018; 4.9 y median study follow-up). Purpose Explore REDUCE-IT efficacy and safety across prespecified IAs for insight into progression of robustness and consistency of conclusions. Methods The interim statistical analysis plan guided study continuation decisions by a prespecified decision-making process, including assessment of safety, treatment arm performance, primary composite endpoint formal analyses, and informal robustness analyses, with no futility or efficacy stopping requirements. Prior to DMC IA study continuation decisions, the need for a mature dataset to support the robustness of final efficacy and safety findings was discussed. Sponsor, Steering Committee, and Clinical Endpoint Committee were blinded throughout. Results Primary and key secondary endpoints achieved statistical significance at IA1 and IA2 that persisted at final analyses (p-value below final adjusted 2-sided alpha of 0.0437); hazard ratios also remained consistent and similar robustness was observed across individual endpoint components; clarity of findings across endpoints and subgroups improved with more events. Stopping for overwhelming efficacy was discussed at each IA; prior to IA study continuation recommendations, the DMC considered historical examples of failed CV outcome studies for TG-lowering and mixed omega-3 therapies, reflected on the potential for overestimating final demonstrated benefit using incomplete data, and weighed societal impacts of fuller datasets relative to patient therapy access. Conclusions Consistent, potent efficacy emerged early and persisted across the two prespecified interim and final analyses. The mature dataset demonstrated highly statistically significant reductions in the primary (25%; p=0.00000001) and key secondary (26%; p=0.0000006) endpoints and allowed robust analyses to support overall efficacy and safety conclusions. Allowing the REDUCE-IT dataset to fully mature provided clinicians with robust, consistent, and reliable data upon which to base clinical decisions for IPE in CV risk reduction. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The study was funded by Amarin Pharma, Inc.

Abstract 15091: Significant Reductions in Both Adjudicated and Investigator-Reported Ischemic Events in REDUCE-IT

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Deepak L Bhatt ◽  
Robert Giugliano ◽  
Philippe G Steg ◽  
Michael Miller ◽  
Eliot A Brinton ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Coronary Revascularization ◽  
Hazard Ratio ◽  
Secondary Endpoint ◽  
Icosapent Ethyl ◽  
Clinical Events ◽  
High Degree ◽  
Ischemic Events ◽  
Fatal Myocardial Infarction

Introduction: REDUCE-IT was an event-driven trial that randomized 8,179 statin-treated patients with controlled LDL-C and moderately elevated triglycerides to icosapent ethyl (IPE) 4g daily or placebo, with a median of 4.9 years of follow-up. There was a significant reduction in the prespecified adjudicated rates of the primary endpoint (cardiovascular [CV] death, non-fatal myocardial infarction [MI], non-fatal stroke, coronary revascularization, and unstable angina requiring hospitalization) and of the key secondary endpoint (CV death, MI, stroke), as well as in all the primary endpoint components. We sought to determine the effect of IPE on investigator-reported events. Methods: The Clinical Endpoint Committee (CEC) blindly adjudicated investigator-reported events according to a prespecified charter. Medical records and reports were also reviewed to assess for clinical events not reported by investigators. An endpoint management team compiled and electronically provided event packets to the CEC via an adjudication database. The CEC Chair provided final adjudication if the two primary adjudicators could not reach consensus. Results: IPE significantly reduced the rate of the primary endpoint (hazard ratio 0.74, p=0.0000000002) and the key secondary endpoint (hazard ratio 0.75, p=0.000007) as reported by the site investigators, with consistent benefits in each component of the primary endpoint (Table). There was a high degree of concordance between investigator-reported and adjudicated endpoints. Conclusions: Icosapent ethyl significantly reduced multiple types of ischemic events, both by independent, blinded adjudication as well as by investigator-reported assessment. These results underscore the robustness of the benefits of icosapent ethyl seen in REDUCE-IT.

Lack of statin therapy is associated with plaque instability in non-culprit non-ischemic lesions of diabetic patients – data from the COMBINE OCT-FFR study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Berta ◽  
T Roleder ◽  
R.S Hermanides ◽  
A.J.J Ijsselmuiden ◽  
F Alfonso ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Plaque Rupture ◽  
Plaque Morphology ◽  
Diabetic Patients ◽  
Funding Source ◽  
Fractional Flow ◽  
Jude Medical ◽  
Flow Reserve ◽  
Pre Treatment ◽  
The Impact

Abstract Background Effect of statin therapy on coronary plaque stabilisation and reducing adverse cardiovascular events is well known both in primary and secondary prevention. Nevertheless, there is a paucity of data presenting the impact of statins on plaque morphology as assessed by optical coherence tomography (OCT). Purpose The goal of this analysis was to evaluate the plaque morphology using OCT within non-culprit, non-ischaemic coronary lesions in diabetes mellitus (DM) patients with or without statin pre-treatment. Methods All patients of the COMBINE (FFR-OCT) trial underwent fractional flow reserve (FFR) measurement followed by OCT in FFR negative lesions. OCT recorded the presence of thin-cap fibroatheroma (TCFA), plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN). Results From the 391 patients, 82 (21%) had no statin at baseline. OCT was performed in 463 lesions of which 96 lesions assessed in statin naive and 367 lesions in statin treated group. The median angiographic diameter stenosis was 50% and the median FFR value was 0.88 in both groups (p=0.953 and p=0.448, respectively). Myocardial infarction (MI) at presentation was 16.6% and did not differ between groups (p=0.380). Patients without statin pre-treatment were characterized by lower rate of known hypercholesterolemia (47.6% vs. 63.0%; p=0.011), male gender (52.4% vs. 65.7%; p=0.027), active smokers (8.5% vs. 22.3%; p=0.004) and previous MI (22.0% vs. 35.3%; p=0.022) as compared to patients with statin pre-treatment, respectively. The results of the qualitative OCT findings see in Table 1. Conclusions Non-ischemic lesions of DM patients without statin pre-treatment showed more vulnerable and instable plaque features like wider lipid arc, thinner fibrotic cap and a higher prevalence of lipid-rich plaque, TCFA and PR suggesting a stabilizing effect of statins on non-ischemic atherosclerotic lesions. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The trial is founded from the Department of Cardiology Zwolle Heart-centrum with support from a non-restricted grant from St Jude Medical (now Abbott)

Ten years of high-sensitivity cardiac troponin testing in the Netherlands: impact on the diagnosis of myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.M Kimenai ◽  
Y Appelman ◽  
H.M Den Ruijter ◽  
N.L Mills ◽  
S.J.R Meex
Keyword(s):  
Myocardial Infarction ◽  
The Netherlands ◽  
Cardiac Troponin ◽  
High Sensitivity ◽  
Funding Source ◽  
Private Company ◽  
Absolute Change ◽  
Before And After ◽  
One Year ◽  
The Impact

Abstract Introduction High-sensitivity cardiac troponin (hs-cTn) assays have enhanced sensitivity for myocardial injury and may lead to an increase in the diagnosis of myocardial infarction. Few real-world studies have investigated the transition from conventional cardiac troponin (cTn) to hs-cTn. We evaluated the impact of implementing hs-cTn assays and sex-specific thresholds in the Netherlands on the diagnosis of myocardial infarction in women and men. Methods Twelve Dutch hospitals were included (hs-cTnI assay [sex-specific thresholds], n=4; hs-cTnT assay [uniform threshold], n=8). Data from the health insurance claims of consecutive patients with anginal symptoms were collected before (cTn period) and after (hs-cTn period) implementation from January 2008 to December 2017. The proportion of patients with a diagnosis of myocardial infarction overall, and in men and women separately, and one-year mortality was compared before and after implementation of the hs-cTn assay. Results Across twelve hospitals, a total number of 77,464 patients presenting with anginal symptoms were included (cTn period: 35,409 [36.6% women]; hs-cTn period: 42,055 [34.6% women]). Following implementation of hs-cTn testing the proportion of patients with anginal symptoms diagnosed with myocardial infarction doubled from 24% (3,111/12,970) to 48% (7,014/14,560) in women, and from 25% (5,712/22,439) to 51% (13,912/27,495) in men, with similar increases in sites implementing hs-cTnI and hs-cTnT. The proportion of patients diagnosed with myocardial infarction who were women increased in sites implementing sex-specific thresholds (from 36.4% [1,435/3,941] to 37.5% [1,700/4,532], absolute change 1.1%), but did not increase in sites using a uniform threshold (from 34.3% [1,676/4,882] to 32.4% [5,314/16,394], absolute change −1.9%). In patients with a diagnosis of myocardial infarction, one-year mortality was 15.6% (485/3,111) and 11.6% (814/7,014) in women, and was 11.8% (673/5,712) and 9.4% (1,303/13,912) in men, before and after implementation of hs-cTn. Conclusions In patients presenting with anginal symptoms, the diagnosis of acute myocardial infarction doubled after implementation of hs-cTn testing in both women and men. Use of sex-specific thresholds increased the proportion of patients with myocardial infarction who were women compared to use of a uniform threshold. Implementation was associated with a reduction in one-year mortality, but further research is needed to understand whether this is due to differences in the risk profile of patients with myocardial infarction or improvements in treatment. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was supported by a grant from Abbott Laboratories to S.J.R.M.

Abstract 3544: One year follow-up after acute Coronary Artery Disease (CAD) - Immediate hospital discharge vs. cardiac rehabilitation

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Bernhard Schwaab ◽  
Annika Waldmann ◽  
Alexander Katalinic ◽  
Britta Poppe ◽  
Abdolhamid Sheikhzadeh ◽  
...  
Keyword(s):  
Risk Reduction ◽  
Absolute Risk ◽  
Controlled Trial ◽  
Absolute Risk Reduction ◽  
Number Needed To Treat ◽  
Preventive Medication ◽  
All Cause Mortality ◽  
Artery Disease ◽  
One Year ◽  
The Impact

Background: The evidence of cardiac Rehab is not fully settled as meta-analysis mostly included studies without acute revascularisation and modern preventive medication. Method: In a multicentre randomised controlled trial, 1.474 patients (pts.) with acute CAD were included to investigate the impact of telemedicine on chronic CAD: 679 pts. were included immediately at discharge from the hospital (Hosp), 795 pts. after three week in-patient Rehab. All pts. had acute coronary angiography and were followed for one year. As Hosp pts. were included 11,3 ± 3 days (median 11) earlier than Rehab pts., events in the Hosp group were counted from day 12. Results: Rehab pts. were older (64 ±10 vs. 62 ±10 years; p<.001), had more congestive heart failure (64 vs. 40%, p<.001), renal insufficiency (10 vs. 7%, p=.036), hypercholesterolemia (79 vs. 74%, p=.023), and carotid stenosis (8 vs. 4%, p=.004). Telemedicine device prescription, gender, atrial fibrillation, peripheral artery disease, diabetes, hypertension, education and social status were similar in groups. After one year, Rehab pts. had more β-blockers (88 vs. 75%, p<.001), ACE-inhibitors (81 vs. 70%, p<.001), lower LDL-C (102 ±35 vs. 121 ±47 mg/dl, p<.001) and a higher proportion of non-smokers (62 vs. 56%, p=.024). There was no difference in platelet inhibition, anticoagulation and statin therapy (81 vs. 79%). The primary combined endpoint of all-cause mortality, acute myocardial infarction (AMI), coronary revascularisation and hospitalisation occurred in 32.6% of Rehab pts. and in 38.7% of Hosp pts. (p=.014; absolute risk reduction (ARR) 0.0615, relative risk reduction (RRR) 16%, number needed to treat (NNT) 17). AMI (1.8 vs. 3.8%, p=.015; ARR 0.0207, RRR 54%, NNT 49) was reduced. Revascularisation (4.2 vs. 5.4%), hospitalisation (33.6 vs. 38.0%) and all-cause mortality (2.1 vs. 2.4%) were similar between groups. After multivariate analysis, the primary endpoint was still significant: OR 0.716 (95% CI 0.575–0.892; p=0.003) giving a RRR of 28% in favour of Rehab therapy. Conclusion: Although Rehab pts. were sicker at entry, cardiac Rehab substantially reduced relevant clinical endpoints within one year. With a very low NNT, Rehab is highly effective and should be advised to all suitable patients with acute CAD.

The impact of hyperuricemia on all patients and low-BMI patients after endovascular treatments: from I-PAD registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Nagae ◽  
T Kato ◽  
S Ebisawa ◽  
T Saigusa ◽  
A Okada ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Overall Survival ◽  
Secondary Prevention ◽  
Endovascular Treatment ◽  
Secondary Endpoint ◽  
Funding Source ◽  
Long Time ◽  
Low Bmi ◽  
The Impact ◽  
High Bmi

Abstract Background Hyperuricemia (≥7.0 mg / dl) is known to be one of the risks of arteriosclerosis. For a long time, it has been said that metabolic syndrome and high-BMI has been implicated to hyperuricemia and also that it's a consequence of those patient background, not a cause of arteriosclerosis. Now, the accumulation of data about hyperurisemia is still not enough. Also the importance of secondary prevention for patients after endovascular treatment (EVT) is still unclear too. Purpose To investigate the impact of hyperuricemia on prognosis of all patients and low-BMI patients after EVT. Methods From July 2015 to July 2016, 335 consecutive PAD patients who performed EVT were enrolled in I-PAD registry. And we divided them into 2 groups; with hyperuricemia or not, and analyzed them. In addition to that, among them, we selected 245 low-BMI patients (&lt;25) and divided them into 2 groups; with hyperuricemia or not, and analyzed them. The primary end point was all-cause-death and the secondary endpoint was MACLE (Major Adverse Cardiovascular and limbs Events) at 3-years. Result At 3 years in the patients group with hyperuricemia, overall survival and freedom from MACLE were significantly lower (57.7% vs 83.4% P=0.0012; 30.3% vs 68.6% P=0.0095) than the group without hyperuricemia. Even among the low-BMI patients, in the patients with hyperuricemia, overall survival and freedom from MACLE were significantly lower (55.2% vs 77.1% P=0.003; 48.2% vs 69.9% P=0.002) than the patients without hyperuricemia at 3 years. Conclusion In this study, the prognosis of patients after EVT with hyperuricemia was worse than the patient without. And even among the low-BMI patients, The prognosis after EVT with hyperuricemia was worse than the patient without. Funding Acknowledgement Type of funding source: None

Abstract P456: Examining Framingham Coronary Heart Disease 10-year Risk Reduction in Individuals Treated With Lorcaserin, a Selective 5HT 2C Receptor Agonist for Weight Management

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Russell Knoth ◽  
Xuan Li ◽  
Debanjana Chatterjee ◽  
Ken Fujioka
Keyword(s):  
Weight Loss ◽  
Risk Reduction ◽  
Weight Management ◽  
Receptor Agonist ◽  
Low Risk ◽  
Baseline Risk ◽  
Diabetic Patients ◽  
Cvd Risk ◽  
One Year ◽  
The Impact

Introduction: Obesity contributes significantly to cardiovascular disease (CVD) risk and weight management is associated with CVD risk reduction. Lorcaserin, a selective 5HT 2C receptor agonist, is indicated as an adjunct to a reduced-calorie diet and increase physical activity for weight management in adults with obesity (BMI≥30) and overweight (BMI 27-29.9 and ≥1 weight-related comorbidity). This analysis used the Framingham 10-year CVD risk to examine the impact of lorcaserin treatment on CVD risk and risk reduction. Method: Pooled data from two randomized, double-blind studies (BLOOM & BLOSSOM) investigating the efficacy of lorcaserin vs. placebo among non-diabetic patients with overweight or obesity, were used in this analysis. Framingham CVD risk was calculated for those whose lipid values were available at baseline and at one year. A Framingham CVD risk of <5% was classified as low risk. Patients were stratified by cohort, lorcaserin (LOR) vs. placebo (PBO) and response at week 12 (≥5% weight loss vs. < 5%) for calculating the 10-year CVD risk at one year. Logistic regression was used to adjust for baseline risk and determine if proportional differences in risk reduction were significant. Results: A total of 5,658 patients were evaluated, 51% treated with LOR. Among the LOR-treated patients, 43% achieved ≥5% weight loss at week 12 (compared to 19% treated with PBO). At one year, more patients in the LOR cohort had reduced CVD risk (from high to low risk, 21% vs. 15%, respectively). The regression analysis showed LOR-treated patients were 34% more likely to have low CVD risk (p<0.001). Similarly, for patients who lost ≥5% baseline body weight at 12 weeks, more patients in the LOR cohort had reduced CVD risk (from high to low risk, 26% vs. 16% respectively) at one year. The regression showed LOR-treated patients were 23% more likely to have low CVD risk (p<0.05). Conclusion: The analysis suggests that patients treated with LOR are more likely to have low CVD risk at one year than those treated with PBO. The effect is magnified if patients have ≥5% weight loss at 12 weeks.

Abstract 57: Reduction in Ischemic Stroke With Icosapent Ethyl - Insights From REDUCE-IT

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Deepak L Bhatt ◽  
Philippe G Steg ◽  
Michael Miller ◽  
Eliot A Brinton ◽  
Terry A Jacobson ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Risk Reduction ◽  
Hemorrhagic Stroke ◽  
Absolute Risk ◽  
Coronary Revascularization ◽  
Composite Endpoint ◽  
Number Needed To Treat ◽  
Icosapent Ethyl ◽  
Significant Difference ◽  
Event Rates

Background: In patients at elevated cardiovascular risk, statins reduce the occurrence of ischemic stroke. However, residual stroke risk persists. Methods: REDUCE-IT, a multinational, double-blind trial, randomized 8179 statin-treated patients with controlled low-density lipoprotein cholesterol, elevated triglycerides, and risk for, or evidence of, atherosclerosis to icosapent ethyl (IPE), a purified, stable ethyl ester of eicosapentaenoic acid (4 grams/day), or placebo. IPE reduced the primary composite endpoint (CV death, myocardial infarction (MI), stroke, coronary revascularization, hospitalization for unstable angina) and the key secondary composite endpoint (CV death, MI, stroke) by 25% and 26%, respectively, (each p<0.000001). Total (first and recurrent) ischemic events were reduced by 32% (p<0.000001). We examined additional prespecified and post hoc stroke endpoints. Results: Event rates for time to first fatal or nonfatal stroke were 2.4% vs. 3.3% for IPE vs. placebo; hazard ratio (HR) (95% CI) = 0.72 (0.55-0.93); P=0.01; the relative risk reduction (RRR) was 28%, absolute risk reduction (ARR) 0.9%, and number needed to treat (NNT) 114. For every 1,000 patients treated for 5 years with IPE, approximately 14 strokes (fatal or nonfatal) were averted; rate ratio (RR) (95%CI) = 0.68 (0.52-0.91); P=0.008 (Figure). Ischemic stroke time to first event rates were 2.0% vs 3.0% for IPE vs placebo a 36% reduction [HR=0.64 (0.49-0.85); P=0.002]. Hemorrhagic stroke occurred at low rates with no significant difference for IPE vs. placebo (0.3% vs 0.2%; P=0.55). Conclusions: In REDUCE-IT, icosapent ethyl significantly reduced the risk of ischemic stroke, with no excess in hemorrhagic stroke, in statin-treated patients with elevated triglycerides and atherosclerosis or diabetes.

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