Claim: Timely use of Novartis' Entresto could prevent or postpone over 28,000 US deaths per year among HFrEF patients, according to an expert analysis in JAMA Cardiology
Verdict: SUPPORTS

Retrieved passages:
title: Tegaserod
text: compared with 1 of 7,031 patients treated with placebo (a rate of 0.01%). Novartis alleges all of the affected patients had preexisting cardiovascular disease or risk factors for such, and further alleges that no causal relationship between tegaserod use and cardiovascular events has been demonstrated. On the same day as the FDA announcement, Novartis Pharmaceuticals Canada announced that it was suspending marketing and sales of the drug in Canada in response to a request from Health Canada. In a large cohort study based on a US health insurance database, no increase in the risk of cardiovascular events were found under

title: Rosiglitazone
text: stroke, heart failure, or all-cause mortality in patients 65 years or older". The number needed to harm with roziglitazone was sixty. Graham argued rosiglitazone caused 500 more heart attacks and 300 more heart failures than its main competitor. Two meta analyses released in 2010, one incorporating 56 trials and a second incorporating 164 trials reached conflicting conclusions. Nissen et al. found again an increased risk for heart infarction against control, but no increased risk for cardiovascular death. Mannucci et al. found no statistically significant increase in cardiac events but a significant increase in heart failure. A 2011 drug class review

title: Levosimendan
text: and III double-blind randomized studies. In the SURVIVE study, despite a reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group, levosimendan did not significantly reduce all-cause mortality at 180 days. However, the drug was proven to be superior to dobutamine for treating patients with a history of CHF or those on beta-blocker therapy when they are hospitalized with acute decompensations. The Orion Corporation originally developed levosimendan and applied for a new drug application in 1998 in the U.S. However the Food and Drug Administration (FDA) requested further trials be

title: Myocardial infarction
text: Beta blocker therapy such as metoprolol or carvedilol is recommended to be started within 24 hours, provided there is no acute heart failure or heart block. The dose should be increased to the highest tolerated. Contrary to what was long believed, the use of beta blockers does not appear to affect the risk of death, possibly because other treatments for MI have improved. When beta blocker medication is given within the first 24–72 hours of a STEMI no lives are saved. However, 1 in 200 people were prevented from a repeat heart attack, and another 1 in 200 from having

title: Systolic Blood Pressure Intervention Trial
text: outcome in the intensive treatment group (1.65% per year) compared to the standard treatment group (2.19% per year). The risk of experiencing a primary outcome (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes) was 25% lower than in the standard treatment group, and the risk of death from any cause was 27% lower. The number needed to treat with intensive therapy instead of standard therapy to prevent one death was 90. The results were so much more superior for the intensive treatment group that the trial was stopped early. Although the trial showed that

title: Aspirin
text: heart disease, aspirin has been thought to decrease the risk of a non-fatal myocardial infarction but not to change the overall risk of death. One study found that among those who have never had a heart attack or stroke, taking aspirin daily for 1 year prevents 1 in 1,667 from having a non-fatal heart attack or stroke, but caused 1 in 3,333 to have a non-fatal bleeding event. However, the study population were at relatively higher risk than those who had never had a heart attack or stroke. A large trial from 2018 in healthy people who were at least

title: Raymond L. Woosley
text: co-director of the landmark NIH-sponsored Cardiac Arrhythmia Suppression Trial (CAST) that found arrhythmia suppression by drugs to be an invalid biomarker for the prediction of drug therapy that prevents sudden death. Dr. Woosley's research at Georgetown contributed substantially to the recognition that non-cardiovascular drugs, such as antihistamines (e.g., terfenadine (Seldane)), may have arrhythmogenic effects. Dr. Woosley's invention, fexofenadine (Allegra), resulted from this research and is today marketed as a safer non-sedating antihistamine replacing Seldane. His research on drug safety led Dr. Woosley to champion the development of the Centers for Education and Research on Therapeutics (CERTs), until 2016, a network

title: Ivabradine
text: with coronary artery disease and a heart rate greater than 70, but without clinical heart failure to ivabradine or placebo in addition to standard therapy. Ivabradine did not improve outcomes in this patient group. In the SHIFT study, ivabradine significantly reduced the risk of the primary composite endpoint of hospitalization for worsening heart failure or cardiovascular death by 18% (P<0.0001) compared with placebo on top of optimal therapy. These benefits were observed after 3 months of treatment. SHIFT also showed that administration of ivabradine to heart failure patients significantly reduced the risk of death from heart failure by 26% (P=0.014)

title: Adverse event
text: most recent available official study (1995) indicated 18,000 deaths per year are a result of hospital care. The Medical Error Action Group is lobbying for legislation to improve the reporting of AEs and through quality control, minimize the needless deaths. Researchers participating in a clinical trial must report all adverse events to the drug regulatory authority of the respective country where the drug or device is to be registered [e.g. Food and Drug Administration (FDA) if it is US]. Serious AEs must be reported immediately; minor AEs are 'bundled' by the sponsor and submitted later. Clinical trial results often report

title: Artemether/lumefantrine
text: the U.S. Food and Drug Administration (FDA). Coartem is provided without profit to developing countries using grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria, US President's Malaria Initiative along with other donors. Novartis has lowered the price of Coartem by 50% since 2001, increasing access to patients around the world. The first significant price reduction occurred in 2006, when the price of Coartem decreased from an average of US $1.57 to US $1.00. In 2006, due to an improved supply situation for the natural ingredient artemisinin, Novartis was able to undertake the pharmaceutical industry’s most aggressive manufacturing

title: Scandinavian Simvastatin Survival Study
text: patients were assigned placebo and 2221 were assigned simvastatin treatment for a median period of 5.4 years. There was a 30% relative reduction in the risk of death with simvastatin treatment. The absolute coronary-heart-disease mortality was reduced from 8.5% to 5.0%, making the number needed to treat around 30 (30 patients would need to be treated to prevent one death). Additionally there was no excess morbidity of non-cardiac deaths from causes like cancer or suicide, a concern that has occasionally arisen in respect to statins. The treatment of 100 patients for six years would prevent four deaths of the disease

title: Evacetrapib
text: the American College of Cardiology cardiologists first saw the data for Eli Lilly's ACCELERATE trial of Evacetrapib involving 12,000 patients. They were "stunned" by the result which showed there was no benefit from taking evacetrapib—434 participants who took Evacetrapib died from "cardiovascular disease, such as a heart attack or a stroke" and 444 participants who took a placebo died. The ACCELERATE trial led by Dr. Stephen J. Nicholls who observed, Evacetrapib Evacetrapib was a drug under development by Eli Lilly & Company (investigational name LY2484595) that inhibits cholesterylester transfer protein (CETP inhibitor). CETP collects triglycerides from very low-density lipoproteins (VLDL)

title: Imatinib
text: portopulmonary hypertension. However, a long-term trial of Imatinib in people with pulmonary arterial hypertension was unsuccessful, and serious and unexpected adverse events were frequent. These included 6 subdural hematomas and 17 deaths during or within 30 days of study end. In systemic sclerosis, the drug has been tested for potential use in slowing down pulmonary fibrosis. In laboratory settings, imatinib is being used as an experimental agent to suppress platelet-derived growth factor (PDGF) by inhibiting its receptor (PDGF-Rβ). One of its effects is delaying atherosclerosis in mice without or with diabetes. Mouse animal studies have suggested that imatinib and related

title: Paul Ridker
text: from the National Heart Lung and Blood Institute and from the pharmaceutical industry to design and conduct two multi-national cardiovascular inflammation reduction trials known as CANTOS and CIRT. The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) reported in late 2017 that inflammation inhibition with Canakinumab, a monoclonal antibody targeting interleukin-1-beta, can significantly reduce future risks of heart attack, need for expensive coronary revascularization procedures, and cardiovascular deaths among high-risk heart disease patients with residual inflammatory risk. Canakinumab had no effects on either cholesterol or blood pressure, and thus these data provided the fundamental first proof-of-concept for the inflammation hypothesis of Atherosclerosis.

title: Pharmaceutical industry
text: Novello of Merck and Co. discovered and developed chlorothiazide, which remains the most widely used antihypertensive drug today. This development was associated with a substantial decline in the mortality rate among people with hypertension. The inventors were recognized by a Public Health Lasker Award in 1975 for "the saving of untold thousands of lives and the alleviation of the suffering of millions of victims of hypertension". A 2009 Cochrane review concluded that thiazide antihypertensive drugs reduce the risk of death (RR 0.89), stroke (RR 0.63), coronary heart disease (RR 0.84), and cardiovascular events (RR 0.70) in people with high blood

title: Epoetin alfa
text: a randomized controlled trial, erythropoietin was shown to not change the number of blood transfusions required by critically ill patients. A surprising finding in this study was a small mortality reduction in patients receiving erythropoietin. This result was statistically significant after 29 days but not at 140 days. The mortality difference was most marked in patients admitted to the ICU for trauma. The authors provide several hypotheses for potential etiologies of this reduced mortality, but, given the known increase in thrombosis and increased benefit in trauma patients as well as marginal nonsignificant benefit (adjusted hazard ratio of 0.9) in surgery

title: Désiré Collen
text: head-to-head comparison between rt-PA and streptokinase. In the GUSTO-trial 41,021 heart attack patients were treated in 1,081 hospitals in 15 countries. Cardiologist Eric Topol of the Cleveland Clinic (USA), cardiologist/statistician Robert Califf of Duke University Medical Center (USA) and David Stump of Genentech coordinated the trial. In absolute figures the 30-day mortality rate in the rt-PA group was 1% lower (or in relative figures 14%) compared to the mortality in the streptokinase group. After the GUSTO studies, rt-PA became the thrombolytic drug of choice for most of the cardiologists in the Western world and would save the lives of many

title: Myocardial infarction
text: not been confirmed. Following a heart attack, nitrates, when taken for two days, and ACE-inhibitors decrease the risk of death. Other medications include: Aspirin is continued indefinitely, as well as another antiplatelet agent such as clopidogrel or ticagrelor ("dual antiplatelet therapy" or DAPT) for up to twelve months. If someone has another medical condition that requires anticoagulation (e.g. with warfarin) this may need to be adjusted based on risk of further cardiac events as well as bleeding risk. In those who have had a stent, more than 12 months of clopidogrel plus aspirin does not affect the risk of death.

title: Antibiotic misuse
text: resistance, from 2014 - 2050 it is estimated that 300 million people could die prematurely due to drug resistance and $60 – 100 trillion of economic output would be lost. If the current worldwide development of antimicrobial resistance is delayed by just 10 years, $65 trillion of the world’s GDP output can be saved from 2014-2050. Prescribing by an infectious disease specialist compared with prescribing by a non-infectious disease specialist decreases antibiotic consumption and reduces costs. Though antibiotics are required to treat severe bacterial infections, misuse has contributed to a rise in bacterial resistance. The overuse of fluoroquinolone and other

title: Women's Health Initiative
text: years. However, interim monitoring of the combined estrogen/progestin treatment group indicated an increased risk of breast cancer, coronary heart disease, stroke, and pulmonary embolism, which outweighed the evidence indicating a benefit in preventing colorectal cancer and fractures. As a consequence, the HT study pills were stopped in July 2002, with an average follow-up period of 5.2 years. The unopposed estrogen trial was halted in February 2004, after an average follow-up period of 6.8 years, on the basis that unopposed estrogen did not appear to affect the risk of heart disease, the primary outcome, which was in contrast to the findings