Conservative strategy for treatment of stable coronary artery disease

Patients with coronary artery disease vary widely in terms of prognosis, which is mainly dependent on ventricular function. In relation to the major outcomes of death and myocardial infarction, it is not clear in the literature if an invasive strategy of myocardial revascularization is superior to a conservative strategy of optimized medical therapy. Moreover, with the exception of patients with left main coronary disease, this similarity in prognosis also occurs in different subgroups of patients.     

Ranolazine for the management of coronary artery disease

BACKGROUND: Despite coronary revascularization and standard antianginal therapy, many patients continue to experience symptoms of stable angina and progression of their disease. Ranolazine is a new class of antianginal agent. Unlike standard antianginal agents, it alters glucose and fatty acid metabolism for a different approach to the management of coronary artery disease. OBJECTIVE: This article discusses the clinical pharmacology of ranolazine and its use in the management of chronic stable angina. METHODS: Peer-reviewed articles and abstracts were identified from MEDLINE and the Current Contents database (both from 1966 to September 20, 2006) using the search terms ranolazine, angina, pharmacokinetics, and pharmacology. Citations from available articles were reviewed for additional references. Abstracts presented at recent professional meetings were also reviewed. RESULTS: Ranolazine is a cell membrane inhibitor of the late sodium current. Extended-release ranolazine was recently approved in the United States for the treatment of chronic angina. Ranolazine is metabolized in the liver by the cytochrome P-450 (CYP) 3A4 system. Because of its potential to prolong corrected QT (QTc) intervals, ranolazine should not be used in patients with hepatic impairment, those with QTc prolongation, or those taking drugs known to prolong QTc intervals or drugs that are potent CYP 3A4 inhibitors. Other adverse effects of ranolazine include dizziness, headache, constipation, and nausea. Placebo-controlled clinical studies performed to date have found that sustained-release ranolazine 500 to 1500 mg PO BID was associated with significantly increased time to onset of angina (range of increase, 27.0-144.0 s; P < 0.05 [varied among studies]), exercise duration (range of increase, 23.8-99.0 s; P < 0.05 [varied among studies] ), and time to 1-mm ST depression (range of increase, 27.6-146.2 s; P < 0.05 [varied among studies]). In addition, exercise duration was found to be significantly longer with ranolazine compared with atenolol (453 vs 430 s; P = 0.006). CONCLUSIONS: Ranolazine is a new antianginal agent that is effective in the management of chronic angina. Its unique mechanism of action warrants further study in other cardiovascular conditions such as heart failure and arrhythmias. Ongoing studies will address whether ranolazine can reduce clinical end points such as cardiovascular death and myocardial infarction.     

Myeloperoxidase level in patients with stable coronary artery disease and acute coronary syndromes

Background No studies have measured plasma myeloperoxidase (MPO) across the entire spectrum of patients with coronary artery disease (CAD). The aim of the study was to compare MPO level across the entire spectrum of CAD, to assess the accuracy of MPO in predicting acute coronary syndromes and to define independent correlates of MPO level. Design This case–control study included 874 patients with angiographically proven CAD. Cases included 680 patients with CAD (382 patients with stable CAD, 107 patients with non-ST-segment elevation acute coronary syndromes and 191 patients with ST-segment elevation acute myocardial infarction). Controls included 194 subjects with normal coronary angiograms. MPO was measured using an enzyme immunoassay before angiography and heparin administration. Results MPO level [median (25th–75th percentiles)] was 74·5 (52·5–135·3) µg L⁻¹ in cases vs. 61·2 (44·6–80·9), µg L⁻¹ in controls (P < 0·001). MPO level was 61·2 (47·5–85·8), µg L⁻¹ in patients with stable CAD, 99·2 (62·2–154·9), µg L⁻¹ in patients with non-ST-segment elevation acute coronary syndromes and 129·5 (72·2–216·0) µg L⁻¹ in patients with acute myocardial infarction (P < 0·001). Elevated MPO level was associated with acute coronary syndromes with an area under receiver operating characteristic (ROC) curve of 0·731 (95% confidence interval 0·692–0·770; P < 0·001). Independent correlates of MPO level were acute coronary syndrome (P < 0·001), high-sensitivity C-reactive protein (P = 0·007), creatinine (P = 0·026), left ventricular ejection fraction (P = 0·027, negative association) and smoking (P = 0·028). Conclusions MPO level is elevated in patients with CAD and higher levels of MPO were found with progression of CAD from stable CAD to non-ST-segment elevation acute coronary syndromes and to acute myocardial infarction.     

Current percutaneous coronary intervention technology for management of coronary artery disease

Enormous advance was obtained in the field of percutaneous coronary intervention, treatment for coronary artery disease. Drug eluting stent (DES) offers advantages over bare metal stent (BMS) such as reduction in restenosis rates. However, several concerns were proposed when compared with BMS. Currently, numerous technologies are under development to avert the complications of DES, such as stent thrombosis, or to challenge complex lesion, such as left main trunk/bifurcation. We summarized some of the development that is emerging on current management of coronary intervention.     

B-type natriuretic peptides: prognostic markers in stable coronary artery disease

Circulating concentrations of B-type natriuretic peptide (BNP) and the N-terminal fragment (NT) of its prohormone (proBNP) are related to cardiac function and have emerged as clinically useful tools for the diagnosis of heart failure and for the estimation of prognosis in patients with heart failure and acute coronary syndromes. Recent studies have also convincingly documented that both BNP and NT-proBNP are powerful, independent prognostic indicators in patients with stable coronary artery disease. The associations are strongest for the end-points of death and heart failure, whereas the association with cardiac ischemic events is weaker or nonexistent, after adjustment for confounding factors. Importantly, BNP and NT-proBNP appear to provide incremental prognostic information to conventional risk factors, including markers of ventricular function and ischemia. Data documenting that BNP or NT-proBNP measurements can be used to guide treatment decisions in patients with stable coronary artery disease are still lacking.     

ADAMTS4 level in patients with stable coronary artery disease and acute coronary syndromes

Objective

A recent study indicates that ADAMTS4 (a disintegrin and metalloprotease with thrombospondin motifs 4) was expressed in macrophage rich areas of human atherosclerotic carotid plaques and coronary unstable plaques suggesting a pathogenic role in the development of acute coronary syndromes (ACS). The aim of the study was to compare ADAMTS4 across the entire spectrum of coronary artery disease (CAD) and to investigate the temporal profiles of ADAMTS4.

Methods

Plasma levels of ADAMTS4 were measured in patients with stable effort angina pectoris (SAP), ACS and in controls. Venous blood was sampled upon admission before angiography and drug administration. In patients with ACS who underwent medical treatment, serial blood samples were also collected on days 1, 2, 3, 5 and 7 after admission. ADAMTS4 was measured using an enzyme immunoassay.

Results

Plasma ADAMTS4 level in cases was significantly greater than in controls (P < 0.001). Higher levels of ADAMTS4 were found with progression of CAD from SAP to unstable angina pectoris (UAP) to non-ST-segment elevation acute myocardial infarction (NSTEMI) and to ST-segment elevation acute myocardial infarction (STEMI) (P < 0.001). Elevated ADAMTS4 level was associated with ACS with an area under receiver operating characteristic (ROC) curve of 0.753 (95% CI 0.654–0.851; P < 0.001). The pattern of ADAMTS4 release observed was clearly different in various forms of ACS. ADAMTS4 showed a weak correlation with high-sensitivity C-reactive protein (hs-CRP); however, no significant correlation was found between ADAMTS4 and troponin T (TnT) in ACS patients.

Conclusions

Serial changes in plasma ADAMTS4 were documented in patients with ACS and may serve as a marker of plaque destabilization.     

New directions in nonoperative management of coronary artery disease

This review has discussed several nonoperative approaches designed to restore or maintain coronary artery patency in patients with coronary artery disease. Information obtained during the last decade concerning the use of thrombolytic, anticoagulant, and antiplatelet drugs and the development of the technique of PTCA have dramatically changed the clinical management of patients with coronary artery disease. It is likely that the application of these therapies will continue to evolve during the next several years as new pathophysiological insights are obtained and large ongoing or planned clinical trials testing current hypotheses are completed.     

Role of coronary physiology in the contemporary management of coronary artery disease

Coronary artery disease (CAD) remains the leading cause of death worldwide with approximately 1 in 30 patients with stable CAD experiencing death or acute myocardial infarction each year. The presence and extent of resultant myocardial ischaemia has been shown to confer an increased risk of adverse outcomes. Whilst, optimal medical therapy (OMT) forms the cornerstone of the management of patients with stable CAD, a significant number of patients present with ischaemia refractory to OMT. Historically coronary angiography alone has been used to determine coronary lesion severity in both stable and acute settings. It is increasingly clear that this approach fails to accurately identify the haemodynamic significance of lesions; especially those that are visually “intermediate” in severity. Revascularisation based upon angiographic appearances alone may not reduce coronary events above OMT. Technological advances have enabled the measurement of physiological indices including the fractional flow reserve, the index of microcirculatory resistance and the coronary flow reserve. The integration of these parameters into the routine management of patients presenting to the cardiac catheterization laboratory with CAD represents a critical adjunctive tool in the optimal management of these patients by identifying patients that would most benefit from revascularisation and importantly also highlighting patients that would not gain benefit and therefore reducing the likelihood of adverse outcomes associated with coronary revascularisation. Furthermore, these techniques are applicable to a broad range of patients including those with left main stem disease, proximal coronary disease, diabetes mellitus, previous percutaneous coronary intervention and with previous coronary artery bypass grafting. This review will discuss current concepts relevant to coronary physiology assessment, its role in the management of both stable and acute patients and future applications.     

Surgical management of unstable angina and symptomatic coronary artery disease

The treatment of coronary artery disease and, in particular, acute coronary syndromes has evolved from watchful waiting to an early aggressive intervention strategy. Patients are currently receiving either percutaneous or surgical revascularization. Several major clinical trials have identified those patients mostly likely to benefit from surgical intervention. These patients typically include those with left-main coronary artery disease, triple vessel disease with decreased left ventricular function, and other clinical risk factors. As a result of these studies, unique needs and outcomes of special populations have been identified. This article will present an overview of surgical treatment of coronary artery disease with emphasis on patient selection with particular attention to women, older persons, diabetic patients, and innovations in surgical techniques that may improve patient outcomes.     

Use of stress testing prior to percutaneous coronary intervention in patients with stable coronary artery disease

The majority of percutaneous coronary interventions (PCIs) are carried out in nonurgent situations, primarily in patients with stable coronary artery disease. Recent trials have concluded that for patients with stable coronary artery disease, treatment with optimal medical therapy versus optimal medical therapy plus PCI yields equivalent outcomes in terms of morbidity and future risk of myocardial infarction. Since PCI is a procedure with risk, it is important to identify patients for whom the benefit of the procedure outweighs the harms. PCI may be beneficial in certain subgroups, such as patients with moderate-to-severe ischemia on noninvasive testing. Although current guidelines require documentation of ischemia prior to elective PCI and this strategy is cost effective, pre-PCI stress testing appears to be underutilized, potentially leading to PCI being performed in patients who may not derive benefit from the procedure.     

Sirolimus-eluting coronary stents: novel devices for the management of coronary artery disease

Despite major technological advances in the practice of percutaneous coronary intervention, restenosis of the treated arteries remains a challenge for many interventional cardiologists. Sirolimus is a macrolide antibiotic with potent antifungal, immunosuppressive, and antimitotic activities. Sirolimus inhibits in-stent restenosis via 2 major mechanisms of action: by blocking the process of neointimal hyperplasia by inhibiting smooth muscle cell proliferation and by inhibiting inflammatory cell activity. In pivotal clinical trials, the sirolimus-eluting stent has demonstrated significant improvements in angiographic and clinical outcomes compared with bare metal stents in patients with de novo lesions in native coronary arteries. Since the systemic exposure of sirolimus in patients who received the drug-eluting stent is minimal, adverse effects resulting from systemic exposure of sirolimus are unlikely to occur. Further studies are needed to determine the safety and effectiveness of sirolimus-eluting stents in patients with more complex coronary artery lesions. In addition, the long-term safety, efficacy, and cost-effectiveness of this novel drug-eluting device will need to be established in ongoing clinical trials. This review article focuses on the pharmacology as well as clinical studies of the sirolimus-eluting stent.     

Long-term effects of cardiac rehabilitation in elderly individuals with stable coronary artery disease

Purpose: To compare exercise capacity and cardiovascular response to exercise in elderly individuals with coronary artery disease (CAD) who attend ongoing community-based maintenance cardiac rehabilitation (CR) versus age- and gender-matched healthy “very active” (HVA;?≥?2000?kcal/week) and healthy “less active” (HLA; <2000?kcal/week) individuals. Method: Sixty-three participants (age: 72.3?±?5.1 years; 62% men; n?=?21 per group) completed the following assessments: (1) symptom-limited graded exercise test with expired gas analysis and bioimpedance assessment of cardiovascular function during exercise; (2) walking tests; (3) physical function; (4) anthropometry and (5) 12-month physical activity recall. Results: The CR group achieved 98% (range: 73–154%) of age- and gender-predicted peak oxygen consumption for healthy individuals. Peak oxygen consumption was lower in CR compared to HVA but not HLA group (VO_2peak: CR: 19.0?±?4.5, HVA: 23.7?±?2.9, HLA: 20.7?±?4.7?ml ·kg^?1?min^?1, p?=?0.001 versus HVA; p?=?0.390 versus HLA). Peak heart rate was lower in CR compared to both HVA and HLA. Walking test results and cardiovascular and physical function were not different between the groups. Conclusions: Elderly individuals with CAD participating in maintenance CR have similar exercise capacity and cardiorespiratory response to exercise compared to their age- and gender-matched less active healthy peers. The findings support referral of elderly patients to community-based CR.

• Implications for Rehabilitation

• Fitness benefits of long-term maintenance cardiac rehabilitation (CR) programs remain unknown.

• Elderly individuals with coronary artery disease participating in maintenance CR have exercise capacity and cardiorespiratory response to exercise similar to their less active healthy peers.

• Maintenance CR may play an important role prolonging independent living in elderly individuals.