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jasbg, dementia in patients with AD may have some component of vascular issue which could be prevented by V. Risk of V use is low and it may be worth trying, but it is very difficult to know if V is working or not. If I were you, I would try it.
https://academic.oup.com/ajcn/article/114/3/914/6296119
https://pubmed.ncbi.nlm.nih.gov/33573174/
Hola. No no. No habrá datos previos.
— Pablo Corral MD (@drpablocorral) September 1, 2021
What I know is it has not been listed in clinicaltrial.gov yet.
No I don’t
PD, no late breaker trials have been announced on AHA website yet, but probably will be announced within a month. Prepare-it part 2 has been most likely accepted based on its trial design, but not its results. If the results were strongly positive, presentation at AHA with simultaneous peer-reviewed journal publication is most likely.
If it's a home run, it will be simultaneous peer-reviewed journal publication and we will see it on Nov 13-15.
Statin use is not the part of criteria.
Inclusion criteria
• Men and women age ≥50 years
• Able to provide informed consent
• No prior history of confirmed COVID-19 (ie, based on a positive PCR or other FDA-approved assay for SARS-CoV-2 and no documented serological (FDA-approved) test results for SARS-CoV-2 antibodies
• Established ASCVD (ie, defined as prior MI, PCI, CABG, ischemic stroke, and/or PAD)
• At least 12 months of continuous KPNC membership and prescription drug benefit prior to enrollment
• A registered e-mail address at kp.org in order to obtain eConsent for study participation
Exclusion criteria
• Receipt of IPE on or within 12 months before the day of enrollment
• Known hypersensitivity to IPE, fish and/or shellfish
• Ongoing use of any omega-3 fatty acid medications or dietary supplements containing omega-3 fatty acids
• Women who are pregnant or planning to become pregnant
• Hospitalization for MI and/or elective PCI within the past 1 month.
• Currently receiving triple therapy (ie, defined as aspirin + a second antiplatelet agent + warfarin or a direct acting oral anticoagulant)
• Stage D HF (ie, defined as inotrope-dependent, prior/planned left ventricular assist device, and/or prior/current listing for cardiac transplant) • Severe liver disease (ie, defined as documented compensated and/or decompensated cirrhosis)
• ESRD requiring chronic dialysis or eGFR <15 mL/min/1.73 m2
• Metastatic cancer and/or receiving active systemic chemotherapy
• Institutionalized and/or receiving palliative care
They may wait subgroup analysis of PI2. V may only work for people with high cardiac risk.
Interesting article re: statin and COVID
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254635
Ishouldknowbetter,
Rob, I think the article written by Pale Horse Trading is relatively fair. I feel that many traders/investors have too high expectation regarding Vascepa's short-term sale growth. Unless PREPARE-IT part 2 and/or MITIGATE trial are successful, Vascepa's sales growth will be likely slow. It is common and normal for medications in patients with chronic conditions. We need significant patience which I don't mind.
Has pfizer ever mentioned Cologuard in their PR? (following site is not PR)
https://www.pfizer.com/sites/default/files/investors/financial_reports/annual_reports/2018/our-innovation/partnering-in-innovation/colorectal-cancer-screening/index.html
Capt, looks great! I think it may be better not to have a shadow in "Now Available in". It's slightly difficult to see.
P-IT 2 is investigator- initiated trials (IITs), sponsored by Estudios Clínicos Latino América.
In the US, we don't need IRB approval or patients' consent for quality improvement despite HIPPA. I don't know in Canada.
Just my thoughts/questions re: PREPARE-IT part 2
1) If it is positive, does it need an Emergency Use Authorization from FDA to be used for COVID-19?
From my understanding, the investigators of PREPARE-IT want the data to be peer-reviewed before going public to maintain its integrity, which is why the topline data won't be announced before AHA. However, because the data will be evaluated by FDA in order to get EUA if needed, which definitely maintain the integrity, there is no reason to wait EUA application until AHA from Amarin's standpoint.
So next question is,
2)Should/will Amarin/research sponsor/collaborator know the result before AHA?
If they will know the data before AHA, they should submit application of EUA ASAP.
Skip,
Rose, I don’t really care whether generics infringe or not if COVID study is positive, but supply.
Kiwi,
Kiwi, it depends how big you think TAM and penetration can be.
Canadian Cardiovascular Society Guideline 2021
PD, I haven't finished watching the video, but I learned that American Heart Association/American Stroke Association recommend IPE in patients with stroke in their new guidelines. That is huge.
Kiwi, maximally tolerated statin or LDL under 100 on statins?
EU label
Almost all prevention is cost-effective, but NOT cost-saving.
It was totally allowed before reduce-it. After reduce-it, removal of Limitation of Use for CVD in generics label may induce physicians’ infringement.
Rob, thank you for posting it. I saw the article this morning for the first time.
duke, Amarin might have already used my idea for Delaware case.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=159353689
NS, my point is there HAS BEEN a physicians' intention to use Vascepa (icosapent ethyl) in order to prevent CVD and pancreatitis since MARINE label, which is why there were 2 Limitation of Use. The purpose of those Limitation of Use was for physicians to consider different medications for prevention of CVD and pancreatitis.
And now, Hikma and Dr.Reddy's have removed CVD limitation of use although there HAS BEEN a physicians' intention to use Vascepa (icosapent ethyl) in order to prevent CVD and pancreatitis. What would physicians think when they see Hikma and Dr.Reddy's labels which do not include CVD limitation of use? They would think icosapent ethyl is beneficial for CVD prevention.
ralphey,
NS,
NS, You are correct that physicians would treat VHTG to prevent CVD and/or pancreatitis (no other intention). That is why Vascepa original label included 2 limitation of use (for CVD and pancreatitis)
NS, nobody will do it.
NS,
Triglyceride levels above 885 mg/dL
In patients with TG levels persistently above 885 mg/dL who have been treated with lifestyle interventions and optimal statin therapy (if indicated to reduce ASCVD risk), we start drug therapy to lower the risk of a first episode of pancreatitis after discussing with the patient the benefits and risks. It is reasonable to consider drug therapy at a lower level of 500 mg/dL (5.6 mmol/L) in patients with a prior episode of pancreatitis. Patients with values above 1000 mg/dL may need extreme dietary restriction. (See 'Management' above.)
We start treatment with a fibrate, which may lower TGs by up to 70 percent [55]. We choose fenofibrate rather than gemfibrozil due to the likelihood of either concurrent or later use of a statin. Gemfibrozil has a higher risk of muscle toxicity, especially when administered with many statins [121] (see 'Fibrates' below). We aim for a TG level <500 mg/dL (5.6 mmol/L) to minimize the large (two- to threefold) postprandial elevations in TG concentrations that may occur after a meal where fat, carbohydrate, or alcohol intake is excessive, which may lead to the development of pancreatitis.
For patients with recurrent pancreatitis treated with fibrate and persistent hypertriglyceridemia, we advocate a strict reduction in refined carbohydrates, complete avoidance of alcohol, and caloric restriction to obtain an ideal body weight. In addition, we add high-dose omega-3 fatty acids (see 'Marine omega-3 fatty acids' below). For patients taking a fibrate and an omega-3 fatty acid who have recurrent pancreatitis, we evaluate the patient for other causes of pancreatitis, particularly if TG level is <500 mg/dL.
Pharmacologic therapies vary in how quickly they reduce triglyceride levels. A response to fibrates is seen as early as two weeks into therapy, with a maximal effect in six to eight weeks [122-124]. We typically check TG levels six to eight weeks after starting or altering therapy. The majority of the response with nicotinic acid is seen in six weeks and with fish oil in two weeks.
Triglyceride levels between 150 and 885 mg/dL
Our approach — The following outlines our approach to deciding when to consider TG-lowering drugs for the purpose of attempting to prevent ASCVD events in patients with TG levels between 150 and 885 mg/dL. These patients generally do not need treatment to reduce the risk of pancreatitis. (See 'Triglyceride levels above 885 mg/dL' above.)
The following is our initial approach to patients with TG levels between 150 and 885 mg/dL (algorithm 1):
?All patients should adopt lifestyle modifications similar to those recommended for individuals at high risk of ASCVD [55]. (See 'General measures' above.)
All patients not at their LDL-C goal should be treated with a statin.
Statins typically lower TG levels by 5 to 15 percent; however, high-intensity statin therapy can lower TGs by 25 to 30 percent in patients with fasting TGs <400 mg/dL. Larger reductions in TGs of 40 percent have been reported in patients with fasting TGs as high as 800 mg/dL with treatment with a moderate- to high-dose high-intensity statin (atorvastatin 80 mg daily, rosuvastatin 20 or 40 mg daily) [125,126]. Goals for the treatment of LDL-C are presented elsewhere. (See "Management of elevated low density lipoprotein-cholesterol (LDL-C) in primary prevention of cardiovascular disease", section on 'Summary and recommendations' and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease", section on 'Our approach'.)
?For patients who are not at LDL-C goal with maximally tolerated statin dose, we add ezetimibe.
?For patients with a TG level >150 mg/dL who have been managed with the above approach and who are at high risk of cardiovascular disease, we consider adding a drug that lowers non-HDL-C through effects of VLDL (eg, fenofibrate, icosapent ethyl, or rarely niacin) to further lower TG. High cardiovascular risk includes patients with known ASCVD or diabetes and those with a 10-year risk of a cardiovascular disease event >10 percent. (See "Cardiovascular disease risk assessment for primary prevention in adults: Our approach", section on 'Summary and recommendations'.)
For these high-risk patients we usually start with icosapent ethyl. However, if the patient has a history of pancreatitis, we might start with fenofibrate. If after adding either icosapent ethyl or fenofibrate the TG level remains >150 mg/dL, we consider adding the other drug based on clinical circumstances. For example, if the cardiovascular risk is high and we had started with fenofibrate, we consider adding icosapent ethyl.
Evidence — In patients with moderate hypertriglyceridemia receiving statins, a randomized trial found that icosapent ethyl reduced risk of ASCVD compared to mineral oil, but studies of other omega-3 fatty acids have failed to show a benefit [127-130] (see 'Association with ASCVD' above). This class of drugs typically lower triglycerides by 20 to 35 percent. (See "Fish oil: Physiologic effects and administration", section on 'Potential effects on cardiovascular and metabolic systems' and "Lipid management with diet or dietary supplements", section on 'Our approach' and "Overview of primary prevention of cardiovascular disease", section on 'Fish oil'.)
REDUCE-IT and STRENGTH, published in 2019 and 2020, respectively, are two randomized trials that attempted to evaluate the effect of icosapent ethyl on cardiovascular disease outcomes:
?The REDUCE-IT trial used a highly purified fish oil (icosapent ethyl) and found benefit. In this trial, over 8000 patients with elevated TG levels (fasting levels 135 to 499 mg/dL [1.52 to 5.63 mmol/L]), on statin, and with either established cardiovascular disease or diabetes plus other cardiovascular risk factors were randomly assigned to supplementation with icosapent ethyl 4 g daily or mineral oil. Icosapent ethyl reduced the risk of the primary combined cardiovascular disease endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina (17.2 versus 22.0 percent; hazard ratio 0.75, 95% CI 0.68-0.83) after median follow-up of 4.9 years [131]. From baseline to one year, the median TG level decreased 18 percent in the treatment group, increased 2.2 percent in the control group, and LDL-C levels increased in both groups (treatment group 3.1 percent, control group 10.2 percent). At two years, C-reactive protein levels decreased by 13.9 percent in the treatment group and increased by 32.2 percent in the control group. Two prespecified analyses showed reductions in the rates of both first and subsequent (ie, total) ischemic events [132] as well as the need for subsequent first and second revascularizations [133].
Limitations of the REDUCE-IT trial include concerns that mineral oil may have caused the increases in atherogenic lipoproteins and C-reactive proteins in the control group and thus did not function as a true placebo. These adverse effects of mineral oil may have raised the risk of cardiovascular events in the control group and may partially account for the favorable risk reduction observed in the treatment group. However, examining data from two different randomized controlled trials wherein mineral oil was used as the placebo, a 2020 report found no differences in the progression of coronary plaque volume by coronary computed tomographic angiography in mineral oil placebo compared with nonmineral oil placebo participants [134]. In addition, hospitalization for atrial fibrillation or flutter was more common in the icosapent ethyl group, as was serious bleeding; however, no significant differences in the rates of hemorrhagic stroke, serious central nervous system, or gastrointestinal bleeding were seen between groups. In December 2019, the U S Food and Drug Administration approved icosapent ethyl "as an adjunctive (secondary) therapy to reduce the risk of cardiovascular events among adults with elevated triglyceride levels of 150 milligrams per deciliter or higher. Patients must also have either established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease. Patients are advised to continue physical activity and maintain a healthy diet." Further investigations to explain the mechanisms for the reduction in cardiovascular events with icosapent ethyl are warranted, considering that the modest reductions in fasting TG are unlikely to account for the magnitude of benefit. Pleiotropic effects include favorable effects on platelet aggregation, endothelial function, and inflammation [135]. It is also unknown whether other omega-3 preparations or doses would be similarly effective.
?The 2020 STRENGTH trial randomly assigned 13,078 statin-treated patients at high cardiovascular risk to a carboxylic acid formulation of omega-3 fatty acids (eg, eicosapentaenoic acid [EPA] and docosahexanoic acid [DHA]; omega-3 CA) or corn oil [136]. All patients had TG baseline levels between 180 and 500 mg/dL (median level of 240 mg/dL), as well as HDL-C <42 mg/dL for men and <47 mg/dL for women. After a median treatment of 38.2 months, the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization was similar in both groups (12.0 versus 12.2 percent, respectively; hazard ratio 0.99, 95% CI 0.90-1.09). There were no significant differences in the individual components of the composite. The trial was stopped early for futility.
Of note, both REDUCE-IT and STRENGTH found a significantly higher rate of atrial fibrillation in the omega-3 CA-treated group.
Fibrates are more potent (25 to 35 percent TG lowering) and have a better side-effect profile than nicotinic acid (niacin). In the prestatin era, the use of gemfibrozil monotherapy reduced the risk of cardiovascular events in a primary [137] and secondary prevention population [138]. Patients in these trials had moderate hypertriglyceridemia. (See "Low density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors", section on 'Fibrates' and "HDL cholesterol: Clinical aspects of abnormal values", section on 'Effect of increasing HDL cholesterol on clinical outcome'.)
In the absence of a history of pancreatitis, we rarely use nicotinic acid to reduce TG levels, as no study has shown an improvement in cardiovascular outcomes. We acknowledge that at doses of 1500 to 2000 mg daily, nicotinic acid can reduce TG levels by 15 to 25 percent [39]. In addition, niacin has a number of adverse side effects, including a worsening of insulin resistance that may result in new onset type 2 diabetes or worsening of diabetes control in patients with type 2 diabetes [139]. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease" and "Low density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors", section on 'Nicotinic acid (niacin)'.)
NS,
NS,
Rob,
That's why we need an indication for "EPA deficiency", not for hypertriglyceridemia. But I don't expect that will happen for the next 10 years.