Acute coronary syndromes in women: Is treatment different? should it be?

The vast majority of acute coronary syndrome (ACS) trials conducted over the past two decades support the view that women have persistently higher mortality and morbidity despite the introduction of new medical therapies and devices. Even after adjustment for older age, higher prevalence of diabetes, hypertension, heart failure, smaller vessel size, and late presentation, some studies still point to a persistent sex disadvantage. Even in contemporary practice, women continue to have longer delays in presentation and treatment. Selection bias in unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) trials allows inclusion of large numbers of women with clinically insignificant coronary disease and may mistakenly shift results toward apparent benefit of a less aggressive approach. This bias causes further difficulty in determining efficacy and safety of new antithrombotic agents such as direct thrombin inhibitors and glycoprotein IIb/IIa inhibitors across the spectrum of ACS. In trials of UA/NSTEMI, use of objective evidence of ischemia such as elevated troponin levels, would greatly assist the determination of efficacy and benefit in women. Enrollment of more women in clinical trials and timely sex-specific analysis would promote a better understanding of the role of female gender in ACS and would facilitate better care of all patients.     

Acute coronary syndromes: should women receive less antithrombotic medication than men?

A recent meta-analysis of all randomised trials assessing the efficacy and safety of glycoprotein IIb/IIIa agents with acute coronary syndromes showed that there was a significant interaction with sex. Explaining this difference requires an analysis of whether it has any pathophysiological basis, whether antithrombotic medications are indeed less efficacious in women in different clinical situations, and whether there are any specific reasons that may have led to the provocative results of the meta-analysis.     

Clopidogrel treatment surrounding percutaneous coronary intervention: When should it be started and stopped?

Clopidogrel pretreatment before percutaneous coronary intervention (PCI) has been shown to decrease major adverse cardiovascular events (MACE) at 1 month. This benefit has been demonstrated in patients spanning the entire spectrum of coronary artery disease. Subsequent dual antiplatelet therapy with aspirin and clopidogrel after stent placement is necessary for the prevention of stent thrombosis. The duration of clopidogrel therapy after stent placement is dependent upon the type of stent placed, and is recommended for a minimum of 4 weeks after bare-metal stent placement, 3 months after sirolimus-eluting stent placement, and 6 months after paclitaxel-eluting stent placement. A longer course of therapy with clopidogrel (12 months) has been recommended by the most recent American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for PCI based upon incremental reduction in cardiovascular complications (primarily myocardial infarction). This article reviews the data presently available regarding pretreatment with clopidogrel before PCI, and the strength of evidence supporting long-term dual antiplatelet therapy.     

Eplerenone: Will it have a role in the treatment of acute coronary syndromes?

Aldosterone is known to have multiple adverse cardiovascular effects that are reminiscent of but independent from angiotensin II. These effects include endothelial dysfunction, heightened thrombogenicity, inflammation, and reparative fibrosis, and have been described in experimental and human models of aldosterone excess. Recently a number of clinical investigations have demonstrated that mineralocorticoid receptor (MR) antagonism, even in conditions not traditionally associated with systemic activation of the renin-angiotensin II-aldosterone pathway, may provide additional benefits above and beyond angiotensin-converting enzyme (ACE) inhibition and angiotensin receptor blockade. The Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS) with eplerenone in patients who were post-myocardial infarction underscores the additive benefit of such a strategy in postinfarction patients that typify an at-risk population for recurrent cardiovascular events. The mechanisms operative in acute coronary syndromes (ACS), including inflammation, altered hemostasis, and endothelial dysfunction, overlap significantly with those seen in the EPHESUS patient population. One may therefore hypothesize that MR antagonism with eplerenone may be beneficial in patients with ACS. Another advantage of using eplerenone is that it offers the advantages of MR antagonism without the side effects due to blockade of other nuclear receptors such as the androgen and progesterone receptors. If MR blockade is found to be beneficial in patients with ACS, the potential reduction in morbidity, mortality, and health care costs are profound.     

How aggressive should lipid lowering be among patients with acute coronary syndromes?

Results from recent clinical trials have advanced our understanding of the role of HMG-CoA reductase inhibitors (statins) in the management of patients following acute coronary syndrome (ACS) episodes. In aggregate, these trials have demonstrated the safety and efficacy associated with initiation of intensive statin therapy prior to hospital discharge following an ACS episode, independent of baseline low-density lipoprotein (LDL) cholesterol concentrations. Based on the results of these trials, there is now compelling evidence to support intensive lipid lowering with high-dose statins initiated prior to hospital discharge for all patients suffering ACS episodes with a target for LDL cholesterol of 70 mg/dL or lower, recommendations that have been incorporated into clinical practice guideline recommendations in the most recent position statement from the National Cholesterol Education Panel.     

Acute coronary syndromes in patients with renal disease: What are the issues?

Patients with chronic kidney disease and acute coronary syndromes are at high risk for both bleeding and ischemic events. This risk increases with the severity of renal insufficiency. Management for acute coronary syndromes in the setting of kidney disease is a paradox; as the benefit of current treatment is high, so is the risk for complications. Patients with chronic renal disease are frequently excluded from randomized clinical trials, and therefore, the optimal treatment strategies are often speculative in this high-risk patient population. Additional research is needed to further refine the optimal management of patients with chronic kidney disease in the setting of acute coronary syndromes.     

Systolic hypertension in older persons: how aggressive should treatment be?

Systolic hypertension (SH) is a major public health concern predominantly affecting older persons. A key message of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is that SH is a much more important cardiovascular disease risk factor than diastolic hypertension, particularly in older persons. Consequently, aggressive control of elevations of systolic blood pressure (SBP) is recommended. Despite increasing attention, SH is on the rise: isolated elevations of SBP in a national sampling of Veteran's Administration patients have increased from 57% in 1990 to 1995 to 76% of patients in 1999. This article considers several clinically pertinent issues, including the evidence for treating older patients with elevations in SBP, treating SH in the "oldest old" (those aged >85 years), and how aggressively these patients should be treated. In addition, issues regarding clinical decision making in older patients with SH are discussed.     

Is pediatric IBD treatment different than in adults?

The incidence of pediatric inflammatory bowel disease (IBD) continues to rise in most countries. Approximately 20-25% of IBD patients present before the age of 20, and their management is associated with many unique challenges. These challenges stem both from the inherent differences between children and adults, and from the differences in the nature and course of the disease. Children with IBD are more likely than adults to present with extensive disease ? both in Crohn's disease (CD) and ulcerative colitis (UC). Diagnosis requires a high index of suspicion, as children may present with less typical signs such as poor growth and delayed puberty. In the very young patients with inflammatory bowel disease, the pediatric clinician must consider a broader range of immunological and allergic disorders. Optimal management requires recognition of pediatric patterns of presentation, efficacy and adverse-effect profiles, and understanding monitoring aspects unique to pediatrics. These aspects include pediatric disease-related psychological issues, adherence to therapy and transition to adult care. Inadequate attention to growth, puberty or bone health in childhood can result in long-term consequences, such as impaired adult height and increased risk of fractures. Management of pediatric IBD and prevention of adverse long-term consequences relies on a variety of therapies well-known to the adult practitioner, along with therapies that are not widespread in adults, most notably exclusive enteral nutrition (EEN). The latter is as effective as corticosteroids in achieving clinical remission in children, while achieving better results than corticosteroids with regard to mucosal healing and growth. This review discusses the broad variety of issues that form the basis for management of pediatric IBD.     

Radionuclide viability testing: should it affect treatment strategy in patients with cardiomyopathy and significant coronary artery disease?

Background

Ischemic heart failure is a significant source of morbidity and mortality, yet it has an unclear treatment strategy. The assessment of viable myocardium by nuclear imaging studies has shown promise in predicting improvements in ejection fraction and symptoms. However, the relationship of viability to long-term mortality has not been fully established.

Methods

A number of studies have addressed long-term mortality with nuclear viability imaging in patients with impaired left ventricular function and significant coronary artery disease. These studies were analyzed to determine differences in design, results, trends, and limitations. They were then evaluated by use of qualitative criteria established for prognostic studies.

Results

Fourteen studies met our criteria. Although the conclusions differed, it appears that patients with viability who undergo revascularization have the highest survival rate, whereas patients with viability who are treated medically have a much lower survival rate. Patients without viability have an intermediate survival rate, regardless of treatment. Several limitations were identified, including a lack of randomization, small sample size, inadequate follow-up, and extensive study protocol and design differences.

Conclusions

The use of viability testing in patients with heart failure and significant coronary artery disease has shown promise in predicting the long-term mortality rate with treatment allocation. However, there is a need for further study involving larger cohorts with a randomized design, longer periods of follow-up, improved study designs, and identification of referral bias and viability prevalence.     

Acute coronary syndromes: more or less antithrombotic medication for the elderly?

The treatment of elderly patients with acute coronary syndromes (ACS) remains challenging. About two thirds of patients with ACS and four fifth of patients who died from ACS are older than 65 years. In spite of the tremendous advances in our understanding of its pathophysiolgy during the past decades and multiple treatment options we now have, ACS is still a leading cause of death., both in developed countries and in many developing countries, including China. ACS result from the disruption of the atherosclerotic plaque, leading to intracoronary thrombus formation with aggregated platelets within a fibrin mesh. In light of this, fibrinolitics, antiplatelet and anticoagulant agents, together with revascularizations and beta blockers, are currently major components of therapy for ACS .Because of the shift of risk benefit ratio among different age groups, it is extremely complex to evaluate the potential risk and benefit for each of these intervention. For example, there has been considerable controversy around whether the results of thrombolysis trials, conducted mainly in younger patients, can be applied to elderly patients. Frequently the evaluation should be performed on an individualized basis at the treating physician's discretion.