Diabetes clinical trials: helped or hindered by the current shift in regulatory requirements?

Abstract:

:Glycaemic control is an inadequate surrogate marker of cardiovascular event reduction in patients with type 2 diabetes. Clinical trials to date have been unsuccessful in identifying a therapeutic approach that addresses the underlying problem in diabetes (glycaemic control) and reduces cardiovascular risk. The potential for some agents to increase the risk of cardiovascular events has led to substantial changes in regulatory requirements for new anti-diabetic therapies. These requirements, while key to ensuring the cardiovascular safety of new agents, fail to emphasize the need to show clinical benefits, such as less visual impairment, less need for dialysis, or fewer cardiovascular events and deaths. Changes in test results such as glycaemic control, serum creatinine, micro-albuminuria, or retinopathy are inadequate surrogates. Regulators should consider the potential advantages of offering extended patent protection in order to encourage companies to conduct long-term trials in diabetes and many other chronic medical conditions. Cooperative efforts among physicians, clinical trialists, regulators, and sponsors are needed to address unresolved issues including re-defining therapeutic targets that are meaningful to patients with diabetes, determining the appropriate length of follow-up for future trials, and considering the ethical and operational challenges of non-inferiority designs.

journal_name

Eur Heart J

journal_title

European heart journal

authors

Zannad F,Stough WG,Pocock SJ,Sleight P,Cushman WC,Cleland JG,McMurray JJ,Lonn E,Geller NL,Wedel H,Abadie E,Alonso-Garcia A,Pitt B

doi

10.1093/eurheartj/ehr437

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

1049-57

issue

9

eissn

0195-668X

issn

1522-9645

pii

ehr437

journal_volume

33

pub_type

杂志文章,评审
  • Coronary microembolization during early reperfusion: infarct extension, but protection by ischaemic postconditioning.

    abstract:AIMS:Reperfusion injury following acute myocardial infarction impacts not only on the myocardium but also on the coronary microcirculation, and microembolization from the culprit lesion contributes to microvascular obstruction. Prior experimental studies have not accounted for microembolization in ischaemia/reperfusion...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehs434

    authors: Skyschally A,Walter B,Heusch G

    更新日期:2013-11-01 00:00:00

  • The impact of 'Shahal' (a new cardiac emergency service) on subscribers' requests for medical assistance: characteristics and distribution of calls.

    abstract::The objectives of this study were to assess the impact of the new 'Shahal' (pre-hospital cardiac service) on subscribers' 'decision time'. A professional 24-h mobile emergency cardiac service has been set up, monitored by intensive care nurses via a central computerized operation unit. All subscribers carry a cardiobe...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/16.1.129

    authors: Roth A,Herling M,Vishlitzki V

    更新日期:1995-01-01 00:00:00

  • Triglycerides, a major coronary risk factor in elderly men. A study of men born in 1913.

    abstract::We examined two 'cohorts' of elderly men, 60 and 67 years old. The two 'cohorts' overlapped to a large extent in terms of numbers but not in the follow-up periods. The mean have been followed-up for 7 and 8 years respectively. Among the 748 60-year-old men without prior myocardial infarction the 7-year incidence of co...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:

    authors: Welin L,Eriksson H,Larsson B,Ohlson LO,Svärdsudd K,Tibblin G,Wilhelmsen L

    更新日期:1991-06-01 00:00:00

  • Running: the risk of coronary events : Prevalence and prognostic relevance of coronary atherosclerosis in marathon runners.

    abstract:AIMS:To quantify the prevalence of coronary artery calcification (CAC) in relation to cardiovascular risk factors in marathon runners, and to study its role for myocardial damage and coronary events. METHODS AND RESULTS:In 108 apparently healthy male marathon runners aged >or=50 years, with >or=5 marathon competitions...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehn163

    authors: Möhlenkamp S,Lehmann N,Breuckmann F,Bröcker-Preuss M,Nassenstein K,Halle M,Budde T,Mann K,Barkhausen J,Heusch G,Jöckel KH,Erbel R,Marathon Study Investigators.,Heinz Nixdorf Recall Study Investigators.

    更新日期:2008-08-01 00:00:00

  • The Belgian Heart Disease Prevention Project: 10-year mortality follow-up.

    abstract::The Belgian Heart Disease Prevention Project was a controlled, randomized multifactorial intervention trial in middle-aged men which lasted 6 years. Significant net differences between intervention and control groups were observed in change in risk profile, in total mortality and in CHD incidence. The net difference i...

    journal_title:European heart journal

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/oxfordjournals.eurheartj.a062491

    authors: De Backer G,Kornitzer M,Dramaix M,Kittel F,Thilly C,Graffar M,Vuylsteek K

    更新日期:1988-03-01 00:00:00

  • Characterization of endothelin synthetic pathways and receptor subtypes: physiological and pathophysiological implications.

    abstract::The endothelins are a family of three widely expressed 21 amino acid peptides. Apart from the ability to constrict vascular smooth muscle, they have numerous other potent effects, from enhancing mitogenesis to influencing nervous function. The pathway of their production involves the initial synthesis of a predominant...

    journal_title:European heart journal

    pub_type: 杂志文章,评审

    doi:

    authors: Warner TD

    更新日期:1993-11-01 00:00:00

  • Safety and effectiveness of bivalirudin in routine care of patients undergoing percutaneous coronary intervention.

    abstract:AIMS:To evaluate the effectiveness and safety of bivalirudin as used in routine care. Bivalirudin has been studied as an alternative to heparin plus glycoprotein IIb/IIIa inhibitor (GPI) during percutaneous coronary intervention (PCI). Trials have indicated that bivalirudin is non-inferior to heparin with respect to de...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehp437

    authors: Rassen JA,Mittleman MA,Glynn RJ,Alan Brookhart M,Schneeweiss S

    更新日期:2010-03-01 00:00:00

  • Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind echo-Doppler study.

    abstract::The haemodynamic effects on the peripheral vascular bed of L-acetylcarnitine, L-propionylcarnitine, and nitroglycerin were tested by echo-Doppler in a double blind cross-over study. Eleven male patients suffering from peripheral arterial obliterative disease (PAOD) in the second stage of Fontaine's classification, and...

    journal_title:European heart journal

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/oxfordjournals.eurheartj.a060392

    authors: Sabbá C,Berardi E,Antonica G,Ferraioli G,Buonamico P,Godi L,Brevetti G,Albano O

    更新日期:1994-10-01 00:00:00

  • Intrapericardial treatment of autoreactive pericardial effusion with triamcinolone; the way to avoid side effects of systemic corticosteroid therapy.

    abstract:AIMS:To evaluate efficacy and safety of intrapericardial treatment with the crystalloid corticosteroid triamcinolone in autoreactive pericardial effusion. METHODS AND RESULTS:Two hundred and sixty consecutive patients with pericarditis/myopericarditis underwent pericardiocentesis, pericardioscopy (Storz-AF1101B1), and...

    journal_title:European heart journal

    pub_type: 临床试验,杂志文章

    doi:10.1053/euhj.2002.3152

    authors: Maisch B,Ristić AD,Pankuweit S

    更新日期:2002-10-01 00:00:00

  • Failure of provision of antibiotic prophylaxis for 'at risk' cardiac patients: impetus for improvement required from cardiologists.

    abstract::We conducted a survey by questionnaire to assess whether patients 'at risk' from infective endocarditis are aware of the need for good dental hygiene and antibiotic prophylaxis, and receive appropriate advice or treatment. Of 189 patients surveyed, half had told a dentist about their heart, 8% were aware of a dental p...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/14.6.812

    authors: Forbat LN,Skehan JD

    更新日期:1993-06-01 00:00:00

  • Impact of diabetes mellitus on long-term survival in patients with congestive heart failure.

    abstract:AIMS:To test the hypothesis that diabetic status may be used as a prognostic indicator in heart failure (HF) patients. METHODS AND RESULTS:We studied 1246 consecutive patients with left ventricular dysfunction. All patients had a cardiopulmonary exercise test and an echocardiogram. Cardiac catheterisation was systemat...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1016/j.ehj.2004.01.010

    authors: De Groote P,Lamblin N,Mouquet F,Plichon D,McFadden E,Van Belle E,Bauters C

    更新日期:2004-04-01 00:00:00

  • Regional myocardial deformation in children with hypertrophic cardiomyopathy: morphological and clinical correlations.

    abstract:AIMS:Hypertrophic cardiomyopathy (HCM) is a disease with marked regional differences in wall thickness. However, the relation between myocardial function and wall thickness has not been well studied. Ultrasonic strain rate (SR) imaging makes it possible to study the regional myocardial deformation. We investigated whet...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehm444

    authors: Ganame J,Mertens L,Eidem BW,Claus P,D'hooge J,Havemann LM,McMahon CJ,Elayda MA,Vaughn WK,Towbin JA,Ayres NA,Pignatelli RH

    更新日期:2007-12-01 00:00:00

  • Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease.

    abstract:AIM:Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD. METH...

    journal_title:European heart journal

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1016/s0195-668x(02)00312-3

    authors: Oldgren J,Wallentin L,Grip L,Linder R,Nørgaard BL,Siegbahn A

    更新日期:2003-01-01 00:00:00

  • Effect of irbesartan and enalapril in non-ST elevation acute coronary syndrome: results of the randomized, double-blind ARCHIPELAGO study.

    abstract:AIMS:This study investigated the effects of irbesartan vs. enalapril, with early vs. late treatment, on markers of inflammation and ischaemic heart disease in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS AND RESULTS:Patients hospitalized with ischaemic symptoms and evidence of NSTE...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1093/eurheartj/ehp301

    authors: Montalescot G,Drexler H,Gallo R,Pearson T,Thoenes M,Bhatt DL

    更新日期:2009-11-01 00:00:00

  • Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir.

    abstract:AIMS:Monocytes are critical mediators of healing following acute myocardial infarction (AMI), making them an interesting target to improve myocardial repair. The purpose of this study was a gain of insight into the source and recruitment of monocytes following AMI in humans. METHODS AND RESULTS:Post-mortem tissue spec...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/eht331

    authors: van der Laan AM,Ter Horst EN,Delewi R,Begieneman MP,Krijnen PA,Hirsch A,Lavaei M,Nahrendorf M,Horrevoets AJ,Niessen HW,Piek JJ

    更新日期:2014-02-01 00:00:00

  • Head to head comparison of dobutamine-transoesophageal echocardiography and dobutamine-magnetic resonance imaging for the prediction of left ventricular functional recovery in patients with chronic coronary artery disease.

    abstract:AIMS:A substantial number of patients with dysfunctional but potentially viable myocardium cannot be accurately evaluated by transthoracic echocardiography due to a poor acoustic window. This study compares the diagnostic value of alternative functional imaging techniques, such as dobutamine-transoesophageal echocardio...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1053/euhj.2000.1946

    authors: Baer FM,Theissen P,Crnac J,Schmidt M,Deutsch HJ,Sechtem U,Schicha H,Erdmann E

    更新日期:2000-06-01 00:00:00

  • High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study.

    abstract:AIMS:The aim of this study was to compare on-thienopyridine platelet reactivity of elderly patients (≥75 years) vs. younger patients (<75 years). Elderly patients represent a growing and challenging segment of the coronary population for whom the effect of dual antiplatelet therapy on platelet inhibition has not been s...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehr407

    authors: Silvain J,Cayla G,Hulot JS,Finzi J,Kerneis M,O'Connor SA,Bellemain-Appaix A,Barthélémy O,Beygui F,Collet JP,Montalescot G

    更新日期:2012-05-01 00:00:00

  • May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension.

    abstract:AIMS:Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening wo...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehz300

    authors: Beaney T,Burrell LM,Castillo RR,Charchar FJ,Cro S,Damasceno A,Kruger R,Nilsson PM,Prabhakaran D,Ramirez AJ,Schlaich MP,Schutte AE,Tomaszewski M,Touyz R,Wang JG,Weber MA,Poulter NR,MMM Investigators.

    更新日期:2019-07-01 00:00:00

  • In-hospital mortality of habitual cigarette smokers after acute myocardial infarction; the "smoker's paradox" in a countrywide study.

    abstract:AIMS:Habitual cigarette smokers, paradoxically, present improved short-term prognosis after acute myocardial infarction, a phenomenon often termed "smoker's paradox". We sought to examine cigarette smokers' post-infarction survival advantage in a countrywide survey of unselected, consecutive patients presenting with ac...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1053/euhj.2000.2315

    authors: Andrikopoulos GK,Richter DJ,Dilaveris PE,Pipilis A,Zaharoulis A,Gialafos JE,Toutouzas PK,Chimonas ET

    更新日期:2001-05-01 00:00:00

  • Tropheryma whippelii endocarditis confirmed by polymerase chain reaction.

    abstract::This report concerns a patient with cardiac manifestation of Whipple's disease. For the first time, the gene that encodes the 16s rRNA of Tropheryma whippelii was identified in a native aortic valve by means of a polymerase chain reaction technique. DNA amplification gives evidence of Tropheryma whippelii as a causati...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/oxfordjournals.eurheartj.a060928

    authors: Wendler D,Mendoza E,Schleiffer T,Zander M,Maier M

    更新日期:1995-03-01 00:00:00

  • Effect of uniformly prolonged, and increased basic dispersion of repolarization on premature dispersion on ventricular surface in dogs: role of action potential duration and activation time differences.

    abstract::Strong experimental evidence links ventricular fibrillation to an increased temporal dispersion of the recovery of excitability. The effect of an overall prolongation of repolarization and an increased basic dispersion of repolarization on premature dispersion was studied on ventricular surface in 10 dogs. Our observa...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/6.suppl_d.15

    authors: Amlie JP,Kuo CS,Munakata K,Reddy PS,Surawicz B

    更新日期:1985-11-01 00:00:00

  • Risk stratification by pharmacological stress echocardiography in a primary care cardiology centre. Experience in 1082 patients.

    abstract:AIM:In this study we sought to determine the safety, feasibility and prognostic value of pharmacological stress echocardiography performed in a primary care cardiology centre, populated by unselected patients evaluated with the aid of limited financial and technological resources. METHODS AND RESULTS:The study populat...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1053/euhj.1998.1096

    authors: Cortigiani L,Lombardi M,Landi P,Paolini EA,Nannini E

    更新日期:1998-11-01 00:00:00

  • High-sensitivity C-reactive protein, statin therapy, and risks of atrial fibrillation: an exploratory analysis of the JUPITER trial.

    abstract:AIMS:Increasing evidence supports a role for inflammation in promoting atrial fibrillation (AF) and statins have anti-inflammatory effects that may be relevant for the prevention of AF. However, studies of statin therapy and incident AF have yielded mixed results and not focused on individuals with an underlying pro-in...

    journal_title:European heart journal

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/eurheartj/ehr460

    authors: Peña JM,MacFadyen J,Glynn RJ,Ridker PM

    更新日期:2012-02-01 00:00:00

  • Predictive value of ventricular premature beats for subsequent ischaemic heart disease in apparently healthy subjects.

    abstract::From 1978 to 1980, 260 healthy subjects, 40-79 years of age, underwent 24 h ambulatory electrocardiography in order to determine the prevalence and complexity of ventricular premature beats (VPBs) in adults without apparent heart disease. The number of types of VPBs seem in 5% or less were considered 'abnormal' and th...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/oxfordjournals.eurheartj.a059946

    authors: Bjerregaard P,Sorensen KE,Molgaard H

    更新日期:1991-05-01 00:00:00

  • Fascicular tachycardia sensitive to calcium antagonists.

    abstract::Five patients with recurrent tachycardias exhibiting right bundle branch block with left axis deviation were referred for investigation. In each case, a supraventricular mechanism was suspected. During sinus rhythm the QRS morphology and axis (-10 to +60 degrees) and HV intervals were normal. Tachycardia was initiated...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/oxfordjournals.eurheartj.a061589

    authors: Ward DE,Nathan AW,Camm AJ

    更新日期:1984-11-01 00:00:00

  • Cardiac anatomy, function and metabolism in elite cyclists assessed by magnetic resonance imaging and spectroscopy.

    abstract::We investigated whether left ventricular hypertrophy in elite cyclists is associated with functional changes or abnormal energy metabolism. Left ventricular hypertrophy is a powerful risk factor for sudden cardiac death with different prognostic significance among the various geometric forms. Cyclists may have a combi...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/oxfordjournals.eurheartj.a015046

    authors: Pluim BM,Chin JC,De Roos A,Doornbos J,Siebelink HM,Van der Laarse A,Vliegen HW,Lamerichs RM,Bruschke AV,Van der Wall EE

    更新日期:1996-08-01 00:00:00

  • Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease.

    abstract:AIMS:To investigate the effects of secretory phospholipase A2 (sPLA(2)) inhibition on plasma lipoproteins. Secretory phospholipase A2 isoenzymes promote atherosclerosis by mechanisms that include lipoprotein modification, retention, and oxidation. METHODS AND RESULTS:Phospholipase Levels And Serological Markers of Ath...

    journal_title:European heart journal

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/eurheartj/ehq374

    authors: Rosenson RS,Elliott M,Stasiv Y,Hislop C,PLASMA II Investigators.

    更新日期:2011-04-01 00:00:00

  • Angiographic assessment of human coronary artery endothelial function by measurement of endothelium-dependent vasodilation.

    abstract::In isolated atherosclerotic human coronary arteries endothelium-dependent vascular relaxation is abolished with acetylcholine whereas another EDRF-dependent vasodilator, substance P, still produces significant relaxation. To study further these in vitro findings, graded doses of acetylcholine and substance P, which pr...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/10.suppl_f.44

    authors: Bossaller C,Hehlert-Friedrich C,Jost S,Rafflenbeul W,Lichtlen P

    更新日期:1989-11-01 00:00:00

  • Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial.

    abstract:AIMS:Long-term randomized comparisons of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in left main coronary (LM) disease and/or three-vessel disease (3VD) patients have been limited. This analysis compares 3-year outcomes in LM and/or 3VD patients treated with CABG or PCI with TAXU...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1093/eurheartj/ehr213

    authors: Kappetein AP,Feldman TE,Mack MJ,Morice MC,Holmes DR,Ståhle E,Dawkins KD,Mohr FW,Serruys PW,Colombo A

    更新日期:2011-09-01 00:00:00

  • Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial.

    abstract:Aims:To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mm...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1093/eurheartj/ehx162

    authors: Hagiwara N,Kawada-Watanabe E,Koyanagi R,Arashi H,Yamaguchi J,Nakao K,Tobaru T,Tanaka H,Oka T,Endoh Y,Saito K,Uchida T,Matsui K,Ogawa H

    更新日期:2017-08-01 00:00:00