REWIND Trial Investigators. Called the REWIND trial, McMaster University reports on the results of this international effort involving more than 9,900 participants in 24 countries. A 15% reduction in all-cause mortality (HR 0.85, 95% CI 0.74 to 0.97, p = 0.02) in the liraglutide arm compared to the placebo arm was also observed.3, Unlike the SUSTAIN-6 trial, the LEADER trial demonstrated significant differences in the primary composite outcome for those with established ASCVD compared to those with CV disease risk factors (p for interaction = 0.04), with a greater benefit seen with liraglutide in those with a history of ASCVD.3. The study was a large, well-designed, double-blind randomized control trial that appropriately targeted a population that with good generalizability for many patients with type 2 diabetes. Number needed to treat with rosuvastatin to prevent first cardiovascular events and death among men and women with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER). In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. This was considered a primary trial; however, the outcomes were driven by reduction of nonfatal stroke. Epub 2019 Nov 11. In summary, the results of the REWIND trial indicate that dulaglutide could be a suitable addition to the antihyperglycemic regimen for a patient with type 2 diabetes who is unable to tolerate a SGLT2 inhibitor or in whom greater weight loss is desired for the benefit of primary prevention of CVD. 2019. This allowed for a lower annual risk of CV event at 2.7% than in the LEADER study. The aim of the REWIND trial was to assess whether adding dulaglutide to the treatment of patients with type 2 diabetes with either CV risk factors or established CVD reduced the occurrence of CV events. The patients in the REWIND trial also had significantly better controlled diabetes than those in other CV outcomes trials of GLP-1 receptor agonists and SGLT2 inhibitors, which may also account for the relatively lower cardiovascular benefit. The REWIND trial sought to determine if the GLP-1 receptor agonist dulaglutide demonstrated a CV benefit over a longer period of time in a study population that included patients with T2DM and CV risk factors.7 Individuals with type 2 diabetes (A1c < 9.5%) and age ≥50 years with either known ASCVD or CV risk factors, as pre-specified based on age cut-offs, participated in the study. 7 Individuals with type 2 diabetes (A1c < 9.5%) and age ≥50 years with either known ASCVD or CV risk factors, as pre-specified based on age cut-offs, participated in the study. Sudipa Sarkar, MD, MSCI, is assistant professor of medicine in the division of endocrinology, diabetes and metabolism at Johns Hopkins University School of Medicine. But, numerically speaking, the results made Trulicity look normal against its … Original Date of Publication: April 2005 Study […] The average age of REWIND participants was 66.2 years, 46.3% were women, and they had a mean A1c of 7.3%, reflective of a general population of patients with well-controlled diabetes in a primary care clinic. Two major drug classes have been associated with a reduction in major adverse cardiac events: the SGLT2 inhibitors and the GLP-1 receptor agonists. The primary outcome was driven largely by a reduction in nonfatal stroke (HR 0.76, 95% CI 0.61-0.95), and the benefits were mostly seen in the non-US cohorts. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. It is also useful to know that GLP-1 receptor agonists are contraindicated in patients with a personal or family history of medullary thyroid cancer/ multiple endocrine neoplasia type 2 (MEN2) syndrome. REWIND was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 371 sites in 24 countries. ALLHAT, the largest trial of treatments for high blood pressure, began in 1994 and lasted 8 years. To assess model accuracy, we compared the predicted failure distributions to the observed (empirical) Kaplan–Meier curves. Pfeffer MA, Claggett B, Diaz R, et al. Nearly 20% of people over 60 have diabetes, and most of those are afflicted with type 2 … Marso SP, Bain SC, Consoli A, et al. However, in contrast to the other CV outcomes trials of GLP-1 receptor agonists, the REWIND trial included a substantial proportion of patients without established CV disease (68.5%), which provided more information as to whether GLP-1 receptor agonists may be beneficial in a primary prevention setting. SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) randomized approximately 3,300 adults with type 2 diabetes mellitus (T2DM) and elevated cardiovascular (CV) risk to standard of care and either the GLP-1 receptor agonist, semaglutide or placebo.2 Over a median 2 years of follow-up, the study authors found a 26% reduction in CV death, nonfatal myocardial infarction (MI) and nonfatal stroke in the semaglutide arm compared to the placebo arm (HR 0.74, 95% CI 0.58 to 0.95, p < 0.001 for noninferiority, p = 0.02 for superiority). GoodRx. Strikingly, the number needed-to-treat (NNT) to prevent one cardio-vascular death, non-fatal MI or non-fatal stroke was 45 The study enrolled 9,901 eligible participants aged 50 years and older with type 2 diabetes (HbA1c 9.5%) who were on two or fewer oral glucose-lowering drugs with or without basal insulin therapy. Zinman B, Wanner C, Lachin JM, et al. In December 2008, the U.S. Food and Drug Administration issued guidance to the pharmaceutical industry setting new expectations for the development of antidiabetes drugs for type 2 diabetes. We also discuss how this new data might affect future American College of Cardiology/American Heart Association (ACC/AHA) prevention guidelines, in particular, whether the evidence supports a possible upgrade in the level of recommendation from "Weak/Modest" (IIb)1 to "Moderate" (IIa) on the use of GLP-1 receptors agonists, which would more strongly favor the use of GLP-1 receptor agonist therapy in primary prevention of ASCVD. Although the benefit of dulaglutide for primary prevention in the REWIND trial was mostly in the reduction of nonfatal stroke, the investigators also observed a significant benefit in reducing ASCVD risk factors including HbA1c, weight and systolic BP. The REWIND Trial Centro de Investigación Cardiometabólica de Aguascalientes. Liraglutide and cardiovascular outcomes in type 2 diabetes. The adverse effects of GLP-1 receptor agonists, including gastrointestinal symptoms, should be kept in mind when prescribing these medications. With 9,901 participants, REWIND was a large trial and had a median follow-up time of 5.4 years, compared to 3.8 years in the LEADER study. Arnett DK, Blumenthal RS, Albert MA, et al. Cardiologists should be aware of this class of agents as beneficial, but given their gastrointestinal side effects, cost and being injectable rather than oral should leave the prescribing to diabetologists rather than moving forward themselves. Accessed June 2019. Women with pre-eclampsia randomized to magnesium experienced a greater than 50% reduction in eclampsia compared to women on placebo. The REWIND trial also notably had the longest follow-up of the GLP-1 receptor agonist CV outcome trials to date. One member of this class is dulaglutide (Trulicity, Eli Lilly), a long-acting GLP-1 receptor agonist and the study drug in the recent REWIND trial, which was presented at the American Diabetes Association Scientific Sessions in June and simultaneously published in The Lancet. cular risk factor. Reductions in major adverse CV events were similar in patients with and without established CVD, raising a potential role for dulaglutide in primary prevention of CVD. Importantly, both NNT and NNH should be interpreted alongside the absolute risk of events. This is consistent with known adverse effects of the medication. This equates to a number needed to treat (NNT) of about 72 over 5.4 years to prevent one major adverse cardiac event. © 2021 American College of Cardiology Foundation. A negative NNT, conversely, indicates an increased risk in the negative outcome associated with the active intervention: this number is commonly referred to as the NNH. The number needed to treat (NNT) for study participants without established CVD in the REWIND trial was 60 vs. an NNT of 18 for those with established CVD. 2%), as well as showing efficacy over and above excellent background therapy, which, similar to other GLP-1 receptor agonist studies, was independent of baseline glycaemia, duration of diabetes, and weight. The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial assessed the effect of dulaglutide on MACE when added to the existing anti-hyperglycemic regimen in T2DM subjects with and without a prior CV event . 1999;doi:10.2337/diabetes.48.12.2270. Análisis Independiente Enrique C Morales Villegas. Ultimately, the REWIND trial confirms findings from multiple trials supporting the benefit of GLP-1 receptor agonists for MACE reduction. The recent results of Cardiovascular Outcomes Trials (CVOTs) in type 2 diabetes have clearly established the cardiovascular (CV) safety or even the benefit of two therapeutic classes, Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Co-Transporter-2 inhibitors (SGLT-2i). & ↓ mortality NNT=72/3.8yr LEADER, semaglutide subcut wkly ↓MACE NNT=44/2.1yr SUSTAIN-6vs MF dulaglutide ↓ MACE NNT=72/5.4yr REWIND albiglutide ↓MACE NNT=50/1.6yr (HARMONY) 15 18,19,20empagliflozin ↓ MACE NNT=63/3.1yr, ↓ mortality NNT=39/3.1yr (EMPA-REG) canagliflozin ↓ MACE NNT~220/yr (CANVAS) but mortality NS dapagliflozin MACE 2018 Jan;20(1):42-49. doi: 10.1111/dom.13028. EMPA-REG: CV Outcomes Trial Summary - RxFiles. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Roger S. Blumenthal, MD, is director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease and professor of medicine at Johns Hopkins University School of Medicine. Share. Bolanle Akinyele, MD, is a general cardiology fellow at Johns Hopkins Hospital. This trial, taken together with the other GLP-1 agents tested, shows benefit of primary prevention in a relatively lower-risk group than previous trials; however, it was driven by stroke events. The recent REWIND (Researching Cardiovascular Events with a Weekly Incretin in Diabetes) trial provides ample opportunity to pause and reflect on the recent data on novel glucose-lowering medications and their associated cardiovascular outcomes—a topic of intense interest. Hernandez AF, Green JB, Janmohamed S, et al. For secondary prevention of CV disease, GLP-1 agonists seem unobjectionably beneficial. The Number Needed to Treat (NNT) is the number of patients you need to treat to prevent one additional bad outcome (death, stroke, etc.). Reductions in the individual outcomes of nonfatal MI and CV death were not significant. The REWIND Trial The REWIND trial sought to determine if the GLP-1 receptor agonist dulaglutide demonstrated a CV benefit over a longer period of time in a study population that included patients with T2DM and CV risk factors. 2017;10:178-188. 2. This trial also used a run-in period of injecting a placebo to increase compliance, and once this run-in period of 2 weeks was completed, patients were randomly assigned to 1.8 mg liraglutide (or maximum tolerated dose) or volume- matched placebo injection. 2018;doi:10.2337/dci17-0057. Given the lower prevalence of ASCVD in the REWIND trial, it is no surprise that the level of impact in the study was less than other CV outcomes trials (the NNT in EMPA-REG was 63 over 3.1 years,8 53 over 3.8 years in LEADER,3 50 over 1.6 years in Harmony Outcomes,4 and 44 over 2 years in SUSTAIN-62). For those patients on insulin and/or sulfonylurea, it is reasonable to prescribe a GLP-1 receptor agonist either in coordination with the patient’s primary care provider or endocrinologist to help with medication titration to avoid hypoglycemia and/or with close follow-up of the patient’s blood glucose logs. For example, if a drug has an NNT of 5, it means you have to treat 5 people with the drug to prevent one additional bad outcome. Superiority trial. ... NNT 71/5.4 años 00.0% 02.0% 04.0% 06.0% 08.0% 10.0% MACE All analyses were conducted in 2015;doi:10.1177/2042018814559725. No significant adverse side effects were noted with dulaglutide, and the effect size for primary prevention was relatively small. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. But, in the end, data from the Rewind cardiovascular outcomes study of Lilly’s type 2 diabetes drug Trulicity disappointed. The trial showed a significant 12% reduction in major adverse CV events with dulaglutide vs. placebo, a finding driven by a 24% decrease in nonfatal stroke in non-U.S. cohorts. The question remains: Should cardiologists prescribe dulaglutide or other GLP-1 receptor agonists, given that endocrine and diabetes specialists are in very short supply? Worldwide, approximately 50 000-60 000 women die from manifestations of … www.thelancet.com. The aim of the REWIND trial was to assess whether adding dulaglutide to the treatment of patients with type 2 diabetes with either CV risk factors or … Ainsi, il apparaît qu’un traitement par analogue du GLP-1 devient pertinent s’il conduit à un NNT < 40 ou voisin de 40. The NNT for those without established CV disease was 60, whereas the NNT for those with established CV disease was 18. Il reste moyennement pertinent quand le NNT est compris entre 40 et 80 (dulaglutide, NNT = 71). Clearly, further research is needed in this class, as the mechanism for benefit is not clear, although they are excellent weight-reducing agents, and this could be part of their benefit, ie, reducing inflammation. The aim of the REWIND trial was to assess whether adding dulaglutide to the treatment of patients with type 2 diabetes with either CV risk factors or established CVD reduced the occurrence of CV events. Gerstein HC, et al. Trujillo JM, et al. Diabetes Obes Metab. Am Health Drug Benefits. NNT. mum of the largest observed event time in the trial arms) and up to 6 years, which was the highest t* among the included trials (REWIND trial), assuming proportionality of hazards. Discussion The important point of REWIND was the cohort was relatively low with established ASCVD, perhaps closer to the prevalence of ASCVD that might be seen in a typical primary care practice. 2019;doi:10.1016/S0140-6736(19)31149-3. For context, the NNT with a moderate-intensity statin is approximately 40 in a population of patients who have an ASCVD risk of 7.5%. All rights reserved. Primary efficacy outcome: time to first occurrence of vascular death, non-fatal myocardial infarction or non-fatal stroke. 5% or less (with no lower limit) on stable doses of up to two oral glucose-lowering drugs with or without basal insulin therapy were eligible if their body-mass index was at least 23 kg/m 2 . REWIND study description 2,4. Indeed, among patients with a previous cardiovascular event, the NNT was 18 in REWIND. The primary outcome was the first For those with hemoglobin A1c ≥7.2%, the NNT was 59 compared to those with a hemoglobin A1c of <7.2% where the NNT was 91. REWIND trial finds Trulicity reduces risk of heart attack, stroke, and heart-related death: REWIND study results show that Trulicity, a once-weekly injectable GLP-1 agonist therapy for people with type 2 diabetes, reduces heart attacks, strokes, and heart-related death compared to placebo (a “nothing” injection). Diabetes. Number Needed to Treat (NNT) represents the number of patients over a given time period that one would need to treat to achieve one additional study endpoint. Lancet. 111 Views. REWIND Dulaglutide and cardiovascular ... controlled trial. This was not because Rewind was a failure – as previously reported, the trial found a significant reduction in cardiovascular adverse events in patients receiving the drug versus those on placebo. 1. In patients with stable coronary heart disease (CHD), high-dose atorvastatin significantly reduced the risk of major cardiovascular events when compared to low-dose. REWIND 总体人群 ... 1 Gerstein HC, Colhoun HM, Dagenais GR, et al. Disclosures: The authors report no relevant financial disclosures. As an example, in the PROSEVA trial of patients with severe ARDS, prone positioning decreased 28-day all-cause mortality compared to supine positioning (16% vs. 32.8%) with a NNT of 6.