Review of the NICE guidelines for multiple myeloma

In February 2016, the National Institute for Health and Care Excellence (NICE) published guidelines on multiple myeloma. NICE have published numerous guidelines relating to haematology, but this was the first guideline focusing on a single haematological malignancy. The purpose of this review was to highlight the recommendations made in the guideline and the implications for the management of patients in the UK and also internationally. In addition, we review the NICE process and highlight issues around current guideline development.     

Primary care management of chronic stable angina and asymptomatic suspected or known coronary artery disease: a clinical practice guideline from the American College of Physicians

In 1999, the American College of Physicians (ACP), then the American College of Physicians-American Society of Internal Medicine, and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina. The ACC/AHA then published an updated guideline in 2002, which ACP recognized as a scientifically valid review of the evidence and background paper. This ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations most likely to be important to physicians seeing patients in the primary care setting. This guideline is the second of 2 that provide guidance on the management of patients with chronic stable angina. This document covers treatment and follow-up of symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. Sections addressing asymptomatic patients are also included. Asymptomatic refers to patients with known or suspected coronary disease based on a history or electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. A previous guideline covered diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months and asymptomatic patients with known or suspected coronary disease based on a history or electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests.     

NICE to HELP: Operationalizing National Institute for Health and Clinical Excellence Guidelines to Improve Clinical Practice

The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom developed guidelines for the diagnosis, prevention, and management of delirium in July 2010 that included 10 recommendations for delirium prevention. The Hospital Elder Life Program (HELP) is a targeted multicomponent strategy that has proven effective and cost‐effective at preventing functional and cognitive decline in hospitalized older persons. HELP provided much of the basis for seven of the NICE recommendations. Given interest by new HELP sites to meet NICE guidelines, three new protocols addressing hypoxia, infection, and pain that were not previously included in the HELP program were developed. In addition, the NICE dehydration guideline included constipation, which was not specifically addressed in the HELP protocols. This project describes the systematic development of three new protocols (hypoxia, infection, pain) and the expansion of an existing HELP protocol (constipation and dehydration) to achieve alignment between the HELP protocols and NICE guidelines. Following the Institute of Medicine recommendations for developing trustworthy guidelines, an interdisciplinary group of experts conducted a systematic review of current literature, rated the quality of the evidence, developed intervention protocols based on the highest‐quality evidence, and submitted the protocols first to internal review and then to external review by an interdisciplinary panel of experts. The protocols were revised based on the review process and incorporated into the HELP materials. Inclusion of these protocols enhances the scope of the HELP program and allows fulfillment of NICE guideline recommendations for delirium prevention. The rigorous process applied may provide a useful example for updating existing guidelines or protocols that may be applicable to a broad range of clinical applications.     

Management of Stable Angina – Current Guidelines: A Critical Appraisal

Guidelines provide recommendations to improve patient outcomes, but many of the recommendations made for treating patients with stable angina are opinion based rather than evidence based. Risk stratification to predict patients at an increased risk of myocardial infarction (MI) and sudden ischemic death, and selection of patients for possible revascularization, is based on expert opinion. Randomized trials have compared optimal medical therapy to revascularization, after the coronary anatomy was known, and yet routine coronary angiography to exclude left main disease is not recommended. What exactly is optimal antianginal treatment varies considerably from one country’s guideline recommendations to another. None of the antianginal drugs reduce mortality or MI and these drugs are equally effective in treating angina pectoris; and yet beta-blockers and calcium channel blockers are recommended as first line therapy. Double and triple therapy with different classes of antianginal drugs is also expert opinion based rather than evidence based. Recommendations to reduce the incidence of MI and sudden death are appropriate; however the use of a potent, high dose statin, is recommended by AHA/ACC and NICE guidelines for all patients with ischemic heart disease, while the European guidelines recommend a target LDL goal in patients with coronary artery disease (CAD). Management of patients with stable angina pectoris with normal coronary arteries remains ambiguous. This short review critically appraises the recommendations for managing patients with stable angina pectoris.     

Evaluation of primary care patients with chronic stable angina: guidelines from the American College of Physicians

In 1999, the American College of Physicians (ACP), then the American College of Physicians-American Society of Internal Medicine, and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina. The ACC/AHA then published an updated guideline in 2002, which the ACP recognized as a scientifically valid review of the evidence and background paper. This ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations most likely to be important to physicians seeing patients in the primary care setting. This guideline is the first of 2 that will provide guidance on the management of patients with chronic stable angina. This document will cover diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. Sections addressing asymptomatic patients are also included. Asymptomatic refers to patients with known or suspected coronary disease based on history or on electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. A future guideline will cover pharmacologic therapy and follow-up.     

What can we learn from Europe?

The European Society of Cardiology has produced guidelines for the treatment of acute myocardial infarction as well as for chronic heart failure and for the use of beta blockers and angiotensin converting enzyme inhibitors. These documents provide clear evidence and strength of recommendations for the secondary prevention of complications after a myocardial infarction. The identification of heart failure and left ventricular systolic dysfunction are important risk factors in this context. The use of secondary prevention treatments in Europe has been evaluated in several surveys. The use of treatments varies across the participating countries and evidence based therapies in general are under-utilised. Various approaches have been taken to disseminate evidence based secondary prevention. Experience from the Italian BRING-UP collaboration illustrates how the use of beta blockers can be increased. Similarly, the Swedish RIKS-HIA registry of acute myocardial infarction has increased the use of secondary preventive treatments.     

The incidence of implantable cardioverter defibrillator indications in patients admitted to all coronary care units in a single district.

AIMS: Implantable cardioverter defibrillators (ICDs) have been shown to reduce all-cause mortality in groups of patients at high risk of ventricular arrhythmias. The true incidence of ICD indications is unknown but we hypothesize that it far exceeds the number actually implanted. METHODS: In a one month observational audit, we reviewed the clinical records of all 336 patients admitted to coronary care units serving a district with a population of 471,000, to determine the additional screening tests required in myocardial infarction (MI) survivors and the number of additional ICDs which would be implanted for the primary and secondary prevention indications recommended in UK National Institute for Clinical Excellence (NICE) guidance. A further analysis was performed to determine the effect of extending the primary prevention indications to include the selection criteria used in the second multicentre automatic defibrillator trial, MADIT II. RESULTS: Using NICE criteria, we found the incidence of ICD indications to be 98.4/10(6)/year. The addition of patients fulfilling MADIT II selection criteria for primary prevention would have increased this to 453/10(6)/year. CONCLUSION: We conclude that the implementation of national guidance on the use of ICDs for arrhythmias will require the systematic screening of MI survivors, and would identify an incidence of ICD indications at least three times that anticipated by NICE, and eight times as many as were actually implanted in the UK in 2000. If the primary prevention indications were widened to include MADIT II selection criteria, the total would be nearer to 12 times that anticipated, and 47 times the number actually implanted.     

Association of unstable angina guideline care with improved survival

BACKGROUND: An unstable angina guideline was published in 1994 by the Agency for Health Care Policy and Research, Bethesda, Md. However, the relationship between guideline-concordant care and patient outcomes is unknown. OBJECTIVE: To determine whether guideline-concordant care is associated with improved outcomes. METHODS: The study sample consisted of 275 consecutive nonreferral patients hospitalized with primary unstable angina. One-year survival and survival free of myocardial infarction were compared between patients who received care concordant with 8 selected guideline recommendations and patients who received discordant care. RESULTS: Care concordant with the 8 key guideline recommendations was associated with improved 1-year survival (95% vs 81%; log-rank P<.001) and survival free of myocardial infarction (91% vs 74%; P<.001), compared with guideline-discordant care. Patients in high-risk subgroups had the largest survival benefit associated with guideline-concordant care (aged -65 years, 91% vs 74% [P=.005]; heart failure at presentation, 91% vs 68% [P=.10]). Aspirin therapy was the single recommendation most strongly associated with improved 1-year survival (94% vs 78%; P=.002). CONCLUSIONS: Care as outlined in the unstable angina clinical practice guideline is associated with improved 1-year outcomes. Subgroups of patients at highest risk and recommendations firmly based on randomized clinical trial data were most strongly associated with better outcomes. These findings support the use of an evidence-based approach to guideline development and assessment of quality of care in patients with primary unstable angina.     

Secondary prevention after myocardial infarction in the aged (author's transl)

Mortality during the first six to eight months after acute myocardial infarction is primarily due to sudden cardiac death and myocardial reinfarction. Therefore any secondary preventive measures have to be aimed at these complications of coronary heart disease and should be effective during the first six months after myocardial infarction. Results of comprehensive studies permit the following conclusions: application of beta-blocking agents may result in a significant reduction of total mortality, sudden cardiac death and the incidence of reinfarction in the old patient. They should be used as the regimen of first choice in a general routine prevention after myocardial infarction. In special cases coronary artery surgery provides an additional means for effective prevention. Compared to this platelet aggregation inhibitors, modification (resp. treatment) of risk factors and physical methods are of minor importance for secondary prevention after myocardial infarction in old patients.     

Beta Blocker Use After Acute Myocardial Infarction in the Patient with Normal Systolic Function: When is it “Ok” to Discontinue?

Beta-Blockers [BB] have been used extensively in the last 40 years after acute myocardial infarction [AMI] as part of therapy and in secondary prevention. The evidence for "routine" therapy with beta-blocker use post AMI rests largely on results of trials conducted over 25 years ago. However, there remains no clear recommendation regarding the appropriate duration of treatment with BBs in post AMI patients with normal left ventricular ejection fraction [LVEF] who are not experiencing angina, or who require BB for hypertension or dysrhythmia. Based on the latest ACC/AHA guidelines, BBs are recommended for early use in the setting of AMI, except in patients who are at low risk and then indefinitely as secondary prevention after AMI. This recommendation was downgraded to class IIa in low risk patients and the updated 2007 ACC/AHA guidelines suggest that the rationale for BB for secondary prevention is from limited data derived from extrapolations of chronic angina and heart failure trials. In this review, we examine the key trials that have shaped the current guidelines and recommendations. In addition, we attempt to answer the question of the duration of BB use in patients with preserved LVEF after acute MI, as well as which subgroups of patients benefits most from post AMI use of beta blockers.     

National Clinical Guideline Centre cost-effectiveness assessment for the National Institute for Health and Clinical Excellence

The National Clinical Guideline Centre (NCGC) develops evidence-based clinical guidelines on behalf of the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom. The U.K. Department of Health has commissioned NICE to make recommendations on the basis of both clinical effectiveness and cost-effectiveness. This article describes how cost-effectiveness is evaluated and accounted for in NCGC guidelines. Six recent case studies are presented, in which consideration of cost-effectiveness has informed recommendations in various ways for clinical guidelines on alcohol use disorders, chronic obstructive pulmonary disease, glaucoma, lower urinary tract symptoms, non-ST-segment elevation myocardial infarction and unstable angina, and venous thromboembolism prophylaxis. Some of the challenges faced in trying to account for cost-effectiveness in clinical guidelines are outlined, as well as some of the difficulties in adapting cost-effectiveness guidelines for other settings.     

Secondary and primary prevention of coronary heart disease: platelet aggregation inhibitors and anticoagulants

This review presents the results of primary and secondary prevention of coronary heart disease (CHD) with antiplatelet drugs and anticoagulants; therapeutic recommendations are derived. According to the results of the trials and due to its low price aspirin (ASS) can be still considered as the drug of choice. Its protective action has been documented for secondary prevention in patients with previous myocardial infarction, coronary angioplasty (PCI), unstable and stable angina, but not in patients with coronary artery bypass surgery, heart failure as well as in primary prevention. The doses recommended are 75-325 mg/d. If ASS is not tolerated clopidogrel is an alternative, but an expensive one. Anticoagulation for primary prevention of CHD may be considered in high risk patients, who do not tolerate ASS (alternative: clopidogrel). In secondary prevention anticoagulation is only recommended for special conditions, such as ASS intolerance (alternative: clopidogrel), ventricular aneurysm, ventricular thrombus, severe heart failure and/or atrial fibrillation.     

Anti-aggregants in 1990

Antiplatelet drugs are increasingly used in the prevention of arterial thrombosis. Aspirin in doses of circa 300 mg day may be recommended for the primary prevention of myocardial infarction, but only in subjects at moderate to high risk of cardiovascular disease. Antiplatelet agents are useless in stable angina, but aspirin reduced by about 50% the risk of myocardial infarction and the overall mortality rate among patients with unstable angina. A lower dose of aspirin (150 mg/day) also reduces mortality by 23% in the acute phase of myocardial infarction. In doses of 300 mg/day, aspirin is useful in the secondary prevention of myocardial infarction and reduces the overall mortality rate by 15%. Various antiplatelet agents, including aspirin (alone or combined with dipyridamole) and ticlopidine, have proved useful to avoid thrombosis in aorto-coronary grafts, provided treatment begins at the latest 6 hours after surgery. The usefulness of antiplatelets has been well established in the prevention of immediate reocclusion following coronary angioplasty, but not in the prevention of late reocclusion. Aspirin and ticlopidine are useful in the extracorporeal circulation techniques. In patients with cardiac valve prosthesis, antivitamin K anticoagulants are still indispensable, but their antithrombotic effect can be reinforced by dipyridamole or aspirin. Diuretics probably provide the best primary protection against cerebrovascular accidents, although medium doses of aspirin may be considered in elderly people at high risk of such accidents. Aspirin (alone or combined with dipyridamole) and ticlopidine may be recommended for the secondary prevention of cerebral ischaemic accidents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aspirin in the prophylaxis of coronary artery disease

Aspirin has been used for more than 100 years, but its mechanisms of action have only been understood in the past 20 years. Aspirin interferes with arachidonic acid metabolism in platelets and endothelial cells and thereby reduces thromboxane A2 and prostacyclin. It also has other mechanisms of action, including anti-inflammatory roles, protection from oxidative stress, enhancement of fibrinolysis, and suppression of plasma coagulation and platelet-dependent inhibition of thrombin generation. It has been used for primary and secondary prevention of myocardial ischemia, and for primary and secondary prevention of cerebrovascular ischemia. We review the 5 pivotal studies relating to primary prevention for cardiovascular risk and the many studies relating to secondary prevention of myocardial ischemia. We also review the utility of aspirin in primary prevention of myocardial infarction and stroke. We conclude that aspirin is one of the most potent drugs ever discovered and that its effects extend well beyond those of cycloxoxygenase enzyme inhibition. Aspirin treatment does not preclude control of underlying and comorbid conditions such as diabetes mellitus, hypertension, and dyslipidemia. For most patients, a daily dose of 325 mg is optimal. Patients must understand the potential for gastrointestinal upset and hemorrhagic complications. The utility of aspirin is greater in coronary artery disease prevention than in cerebrovascular prevention.     

Thrombusaspiration bei Patienten mit akutem Myokardinfarkt

Recent advances in percutaneous coronary intervention and antiplatelet therapy as well as faster door-to-balloon times have markedly improved the therapy of patients with acute myocardial infarction. However, impaired myocardial perfusion despite revascularization of the infarcted vessel remains an ongoing problem with high prognostic relevance. In initial clinical trials thrombus aspiration in addition to conventional percutaneous coronary intervention demonstrated benefits regarding coronary flow and myocardial perfusion and was therefore recommended in practice guidelines. These improvements in surrogate endpoints did not translate into a favorable clinical outcome in recent large-scale multicenter randomized trials investigating the routine use of thrombus aspiration in patients with acute myocardial infarction. Furthermore, an increased risk of stroke after thrombus aspiration raises safety concerns. Therefore, thrombus aspiration has been downgraded in the recent guideline updates. The current article reviews the evidence from clinical trials and the recommendations in practice guidelines regarding thrombus aspiration in acute myocardial infarction.     

Which drugs benefit diabetic patients for secondary prevention of myocardial infarction?

Diabetic patients have increased mortality following myocardial infarction. We review the evidence for benefit in diabetic patients, of the major drug groups used as secondary prevention. Beta blockers: meta-analyses suggest a reduction in mortality of 35 % with beta blockers. Diabetic patients should receive beta blockers post myocardial infarction. In many patients, the benefits of beta blockers will outweigh relative contraindications. Aspirin: meta-analyses of antiplatelet therapy in high-risk subjects have shown substantial benefits. Aspirin should be prescribed for secondary prevention. Lipid lowering with statins: subgroup analyses of the major secondary prevention trials show substantial benefits across a wide range of baseline cholesterol and LDL levels. These drugs should be prescribed as secondary prevention to patients with diabetes whose total cholesterol is > 4.0 mmol⁻¹. Angiotensin converting enzyme inhibitors (ACEIs): the few subgroup analyses that exist from ACEI trials suggest that diabetic and non-diabetic patients derive similar benefits. Diabetic subjects who have systolic dysfunction after myocardial infarction should receive ACEIs. Treatment combination: data exist to suggest that most of these drugs produce benefit independently. Conclusion: diabetic patients benefit from secondary prevention with drug treatment as much as, or more than, non-diabetic patients. © 1998 John Wiley & Sons, Ltd.     

Secondary prevention after myocardial infarction: Subgroup analysis of patients at risk in the norwegian timolol multicenter study

Timolol treatment after myocardial infarction is generally related to a significant reduction in both morality and reinfarction compared with placebo. Retrospective analyses of the timolol study are performed on subgroups of patients with a high placebo mortality. The present study shows that these patients are target groups for secondary prevention, as they benefit most from timolol treatment after myocardial infarction. In patients 65-75 years of age, the number of cardiac deaths and reinfarctions prevented by timolol treatment is twice as high as that of patients below 65 years of age. Timolol treatment is well tolerated in the older age group and the contraindications for timolol treatment are independent of age up to 75 years. The reduction in mortality and reinfarction is independent of heart size at baseline. However, in patients with cardiomegaly and compensated heart failure on treatment with digitalis and diuretics, timolol treatment may be of special importance because of the very high incidence of cardiac death in this group of patients. In patients with compensated heart failure on treatment with digitalis and diuretics, timolol treatment does not precipitate heart failure. Patients with stable diabetes mellitus basically behave like nondiabetic patients regarding inclusion rate, side effects, and timolol-related reduction in mortality and reinfarction. Decisions concerning secondary prevention with timolol should be independent of preinfarction and postinfarction angina. In conclusion, 70-80% of all the patients below 75 years of age surviving myocardial infarction, without contraindication to betablocker treatment, can be treated with timolol 10 mg twice daily to reduce mortality and reinfarction. In contrast to previous routines, secondary prevention with beta blockers should be especially directed to high-risk patients.     

Herzinfarktregister in Deutschland

Current national and international guidelines for patients with ST elevation myocardial infarction (STEMI) are mainly based on the results of randomised clinical trials. However, it is well perceived that patients in such trials often represent a low risk population. Therefore the results of randomised clinical trials are not necessarily applicable to patients in clinical practice. This gap can be filled by prospective registries. Since the early nineties a number of prospective large registries in patients with STEMI have been performed in Germany. It could be shown that guideline adherent acute therapies and secondary prevention therapies were associated with an improvement in inhospital and mid-term outcomes. The benefit of guideline adherent therapy observed was especially high in patients with higher baseline risk. Registries are not able to replace randomised clinical trials, but can help to test if the results of these trials are comprehensible in clinical practice. Therefore prospective STEMI registries are an important part of clinical research to optimize therapies and improve outcome in patients with STEMI.     

Heparin in the treatment and secondary prevention of myocardial infarction. A critical review of the main trials]

The aim of this article is to assess the therapeutic value of standard heparin in the acute phase and secondary prevention of myocardial infarction. Only clinical trials with an adequate methodology have been analysed. In patients having undergone thrombolytic therapy associated with aspirin, heparin slightly reduces the mortality but only during the period of its administration. In a metaanalysis of approximately twenty clinical trials of patients not receiving thrombolytic or aspirin therapy, heparin was associated with a significant reduction of deep vein thrombosis, pulmonary embolism, recurrent myocardial infarction and cerebrovascular accidents. In the context of secondary prevention of myocardial infarction, the administration of a moderate dose of subcutaneous heparin resulted in a beneficial effect on morbidity and mortality in one published trial. The use of low molecular weight heparins for the prevention of coronary thrombosis merits attention because of the pharmacological and pharmacokinetic properties of these products.     

Reperfusion syndrome after direct myocardial revascularization on beating heart in patients with ischemic heart disease. Possibilities of prevention with amlodipine

Possibilities of secondary prevention of reperfusion syndrome with amlodipine was assessed in 46 patients (39 with class III-IV angina after myocardial infarction and 7 with non ST elevation acute coronary syndrome). Twenty six patients received basic therapy, in 20 patients this therapy was supplemented with amlodipine (5-10 mg/day). In all patients complete direct arterial myocardial revascularization on beating heart was carried out. Methods of dynamic control included echocardiography, paired bicycle exercise tests, 6 minute walk test, myocardial scintigraphy with thallium-199. The results evidence for efficacy and feasibility of secondary prevention of reversible myocardial dysfunction with amlodipine.