Evidence-based management of coronary artery disease in the elderly--current perspectives

Cardiovascular disease accounts for significant morbidity and mortality in the elderly. The clinical trial data available to guide therapy in this growing population subset are relatively limited. This review will focus on treatment approaches and recommendations obtained from subgroup analyses of elderly patients from major clinical trials for the management of chronic stable angina, acute coronary syndromes (unstable angina and non-ST-segment elevation myocardial infarction), and coronary revascularization. Recent advances in the treatment of stable angina have shown that use of angiotensin-converting enzyme inhibitors and lipid-lowering therapy as adjunctive measures show benefit in the elderly by reducing the occurrence of death, nonfatal myocardial infarction, and unstable angina. However, if patients experience disabling or unstable anginal symptoms despite effective medical therapy, coronary revascularization must be considered. Several clinical trials have shown a significant reduction in major adverse cardiac events when using intravenous glycoprotein receptor antagonists periprocedurally during percutaneous revascularization approaches in elderly patients with unstable angina or non-ST-segment elevation myocardial infarction, especially when these measures are performed as soon as possible. However, the success of myocardial revascularization by a percutaneous or surgical approach is highly dependent on the patient's associated comorbidities, especially in patients over age 80 years.     

Debate: Should the elderly receive thrombolytic therapy, or primary angioplasty, for acute myocardial infarction? The case for primary angioplasty

As the population ages the number of elderly patients presenting with acute myocardial infarction (AMI) will continue to increase. There has been no head-to-head trial of thrombolytic therapy versus primary percutaneous coronary intervention (PCI) in this patient cohort, but there is evidence that favors primary PCI. Most elderly patients are candidates for primary PCI, but many have contraindications to thrombolytic therapy. Hemorrhagic complications are more common in the elderly, and many of these patients present with conditions in which thrombolytic agents have decreased efficacy, such as heart failure or prior bypass surgery. PCI can also obviate the need for further risk stratification in most patients.     

Debate: Should the elderly receive thrombolytic therapy or primary angioplasty?

Thrombolysis and primary angioplasty are both recommended reperfusion strategies for elderly patients presenting with myocardial infarction (MI). Primary angioplasty is most beneficial in high-risk patients. While the elderly have a high absolute risk of dying or developing complications after MI, they also have an increased risk of intracranial haemorrhage if they are given thrombolytic therapy. It could therefore be reasonably argued that primary angioplasty is the reperfusion strategy of choice in the elderly. However, primary angioplasty has not been shown to have a greater relative benefit than thrombolytic therapy in the elderly. Recent data from the Fibrinolytic Therapy Trialists' (FTT) Collaborative Group show that thrombolytic therapy significantly reduces mortality compared with control treatment in patients over 75 years of age presenting within 12 h of symptom onset, with ST-segment elevation or bundle branch block. Future advances in adjunctive therapies may improve myocyte perfusion and hence the outcomes achieved by both invasive and noninvasive reperfusion strategies. Better thrombolytic regimens incorporating adjunctive agents such as bivalirudin may reduce the risk of intracranial haemorrhage. Few hospitals can provide a 24-h primary angioplasty service with door-to-balloon times consistently less than 90 min, and thrombolytic therapy is therefore a far more practical option in most instances.     

Coronary revascularization after thrombolytic therapy for myocardial infarction: what caseloads could Canadian centres face?

A simple model was developed to project the potential effect of intravenous thrombolytic therapy on the caseloads of revascularization early after acute myocardial infarction. Published data were used to estimate the proportion of infarct patients eligible for thrombolytic treatment and their subsequent rates of percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery (CABS) within 2 weeks and up to 6 to 12 weeks after treatment. Toronto regional caseload data were obtained from registries and hospital discharge records. Our primary projections, based only on coronary angiography for evidence of spontaneous or exercise-induced ischemia, suggest a 165% increase in the post-thrombolysis use of PTCA within 2 weeks of infarction and even greater increases 6 to 12 weeks after infarction. Adding in selective use of salvage PTCA for some patients with persisting pain despite thrombolysis increases the overall PTCA caseload within 2 weeks by 242%. Data on the current caseload of post-thrombolysis CABS are unavailable. However, our projected caseload for the 30% of infarct patients treated with thrombolytic drugs equals or exceeds the current number of CABS procedures performed on all infarct patients within a month of the event. All these projections are conservative, in that they consider neither procedures 3 to 12 months after infarction nor restenosis after PTCA. This analysis illustrates that current approaches to revascularization after thrombolytic therapy could have a substantial effect on PTCA and CABS caseloads. Further studies with improved caseload data are needed to validate these preliminary projections.     

Platelet glycoprotein IIb/IIIa receptor inhibition in primary angioplasty for acute myocardial infarction: The new paradigm of direct revascularization

Acute myocardial infarction results from thrombotic occlusion superimposed on a ruptured athersoclerotic plaque. Immediate restoration of normal flow in the infarct-related artery can be achieved either with fibrinolytic or with direct mechanical revascularization. Primary PTCA has been shown to be superior to fibrinolytic therapy with respect to mortality, reinfarction, non-fatal stroke and length of hospitalization. Its results can be further improved by the addition of potent platelet inhibitors directed against the final common component of all stimuli for platelet aggregation, the glycoprotein (GP) IIb/IIIa receptor. In randomized clinical trials, primary angioplasty with adjunctive abciximab - a monoclonal antibody against the GP IIb/IIIa - was better than conventional primary angioplasty with heparin only. Abciximab use was associated with a significant reduction in reinfarction, need for urgent target vessel revascularization, microcirculatory dysfunction and regional left ventricular dysfunction as well as with a strong trend towards a reduction in mortality, even in patients receiving coronary stents.     

Multivessel coronary thrombosis secondary to cocaine use successfully treated with multivessel primary angioplasty

Cocaine use has been associated with a significant risk of myocardial ischemia and myocardial infarction (MI). The previous approach to the treatment of cocaine-induced MI focused on medical treatment with verapamil, nitroglycerine and thrombolytics. Percutaneous revascularization for the cocaine-associated MI has been reported and is the preferred treatment modality. Identification of culprit vessel in the patients presenting with acute myocardial infarction associated with cocaine use is problematic owing to the frequent presence of baseline electrocardiogram (ECG) changes. Chronic cocaine use predisposes to diffuse coronary vasculopathy and may cause systemic alteration of coagulation parameters. Multivessel coronary thrombosis presenting as myocardial infarction associated with cocaine use has not been previously reported. This study describes a case of multivessel coronary thrombosis caused by cocaine ingestion successfully treated with multivessel primary angioplasty.     

The impact of adjunctive eptifibatide therapy with percutaneous coronary intervention for acute myocardial infarction

The role of small molecules anti-glycoprotein (GP) IIb/IIIa pharmacotherapy during acute myocardial infarction (AMI) has not been established. The purpose of our study was to evaluate the clinical outcomes of patients sustaining AMI who underwent emergent percutaneous coronary intervention (PCI) and who were distinguished by the use of the anti-GP IIb/IIIa agent eptifibatide. We studied a consecutive group of 216 patients who underwent PCI for acute ST-elevation myocardial infarction and compared the outcomes of patients who received eptifibatide just prior and following the procedure (n=167) to those who were not on anti GP IIb/IIIa inhibitors (n=49). On average, patients treated using eptifibatide were younger and were more likely to be men, hypertensive, and smokers. The eptifibatide treated patients were less likely to have diabetes and renal failure and had worse angiographic characteristics. There were no significant differences between the groups in any of the clinical outcomes, including the composite endpoint (e.g. death, MI, repeat revascularization) and the rate of sub-acute stent thrombosis. Nonetheless, there was a non-significant trend towards lower 30 day mortality in the eptifibatide group (4.8% versus 12%, P=0.09). We concluded that in our comparative study of periprocedural administration of eptifibatide during emergent AMI angioplasty, there was a non-significant trend towards better short-term survival among eptifibatide treated patients although the composite endpoint did not differ between patients distinguished by the use of anti GP IIb/IIIa small molecule pharmacotherapy.     

Early and long-term outcome of elective stenting of the infarct-related artery in patients with viability in the infarct-area: Rationale and design of the Viability-guided Angioplasty after acute Myocardial Infarction-trial (The VIAMI-trial)

BACKGROUND: Although percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery.Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction. METHODS: The VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care).The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years. CONCLUSION: The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction.     

Multivessel versus Single Vessel Angioplasty in Non-ST Elevation Acute Coronary Syndromes: A Systematic Review and Metaanalysis

Background

Multivessel disease is common in acute coronary syndrome patients. However, if multivessel percutaneous coronary intervention is superior to culprit-vessel angioplasty has not been systematically addressed.

Methods

A metaanalysis was conducted including studies that compared multivessel angioplasty with culprit-vessel angioplasty among non-ST elevation ACS patients. Since all studies were observational adjusted estimates of effects were used. Pooled estimates of effects were computed using the generic inverse of variance with a random effects model.

Results

Twelve studies were included (n = 117,685). Median age was 64.1 years, most patients were male, 29.3% were diabetic and 36,9% had previous myocardial infarction. Median follow-up was 12 months. There were no significant differences in mortality risk (HR 0.79; 95% CI 0.58 to 1.09; I² 67.9%), with moderate inconsistency. Also, there were no significant differences in the risk of death or MI (HR 0.90; 95% CI 0.69 to 1.17; I² 62.3%), revascularization (HR 0.76; 95% CI 0.55 to 1.05; I² 49.9%) or in the combined incidence of death, myocardial infarction or revascularization (HR 0.83; 95% CI 0.66 to 1.03; I² 70.8%). All analyses exhibited a moderate degree of inconsistency. Subgroup analyses by design reduced the inconsistency of the analyses on death or myocardial infarction, revascularization and death, myocardial infarction or revascularization. There was evidence of publication bias (Egger’s test p = 0.097).

Conclusion

Routine multivessel angioplasty in non-ST elevation acute coronary syndrome patients with multivessel disease was not superior to culprit-vessel angioplasty. Randomized controlled trials comparing safety and effectiveness of both strategies in this setting are needed.     

Oxidative stress in myocardial ischaemia reperfusion injury: a renewed focus on a long-standing area of heart research

Advances in the treatment of coronary artery disease have seen a significant drop in mortality and morbidity particularly amongst patients with acute myocardial infarction (MI). In particular, percutaneous trans-luminal balloon angioplasty (PTCA) with stenting to re-open atherosclerotic coronary arteries has yielded marked improvement in clinical outcome for patients with acute MI. Furthermore, with the advent of drug-eluting stents occurrence rates for coronary artery restenosis, one common clinical problem associated with angioplasty and stent deployment, have declined markedly. However, coronary restenosis in diabetic patients remains an on-going problem. The success of drug-eluting stents has seen a renewed focus on myocardial ischaemia reperfusion (IR) injury as this represents one area of research where many questions remain unanswered. In particular, the relationship between myocardial IR injury and decreased myocardial micro-vasculature re-flow post PTCA (that ultimately leads to poor clinical outcome and myocardial damage/dysfunction) is one area of research with the potential to decrease current complication rates further in patients suffering myocardial IR injury sustained during MI. This review discusses the role for oxidative stress, oxidant source(s) and both gene regulation and stem-cell therapy as potential strategic targets in the ischaemic myocardium, with the ultimate aim of providing significant cardioprotection in the setting of acute MI.     

Platelet aggregation and antiplatelet agents in acute coronary syndromes

Antiplatelet agents are the cornerstone therapy of acute coronary syndromes. In the setting of ST elevation myocardial infarction, antiplatelet therapy prevent the prothrombotic effect of reperfusion therapy including thrombolysis and primary percutaneous coronary intervention. In non ST-elevation acute coronary syndromes, antiplatelet therapy prevent s complete coronary thrombotic occlusion and therefore the occurrence of ST elevation myocardial infarction. Antiplatelet agent benefit is related to the patient's risk profile. It is well established that combined antiplatelet therapy is the most effective in high risk patients. Several important issues have to be faced including the identification of non responders, dose adjustment and the management of temporary interruption of antiplatelet agents in stable coronary artery disease patients.     

Primary PCI: false positives versus false negatives

Primary percutaneous coronary intervention (PCI) performed within 12 hours after onset of symptoms in acute ST-elevation myocardial infarction (STEMI) is the currently recommended therapy in the guidelines of the European Society of Cardiology.1 The basis of these recommendations is an array of clinical trials comparing PCI with thrombolysis on short-term as well as long-term follow-up.2 Initially and intuitively larger STEMIs in younger patients were eligible for this therapy, but increasingly also smaller infarcts and older patients have proven to benefit from primary PCI.3 Typically, in centres providing the service of primary PCI in the Netherlands, about a third of the total number of PCIs is now for STEMI.     

Final benefit of primary percutaneous coronary intervention for ST-elevation myocardial infarction in older patients: long-term results of a randomised trial

Netherlands Heart Journal - Although the short-term benefit of primary percutaneous coronary intervention (PCI) in elderly patients with ST-elevation myocardial infarction (STEMI) has been...     

Provisional stenting in the real world: results in 1058 consecutive patients undergoing percutaneous coronary angioplasty

OBJECTIVE: To study a strategy of aggressive coronary balloon angioplasty with provisional stenting in allcomers. In randomized trials, stenting has improved the outcome of patients undergoing coronary intervention. However, whether these results hold up in clinical practice is largely unknown. Furthermore, the results of balloon angioplasty have also improved dramatically. It is therefore essential to evaluate the current results of balloon angioplasty and to assess whether stents are required in all patients. METHODS: The authors prospectively studied the occurrence of death, myocardial infarction (MI) and target lesion revascularization (TLR) of a large consecutive group of patients undergoing aggressive balloon angioplasty with provisional stenting. None of the patients received a platelet glycoprotein IIb/IIIa receptor blocker. The results were compared with the outcome of routine stenting in recent randomized trials. RESULTS: Angioplasty was performed in 1058 patients of whom 369 (34.9%) received a stent. The angiographic success rate was 98.9%. During hospital stay, 4.8% of the patients suffered any cardiac event. At one-year follow-up, death occurred in 1.1%, MI in 3.3%, TLR in 12.4% and any event in 16.7% of the patients. Event-free survival at one-year was 82.3%. These results compare favorably with routine stenting in recent trials. CONCLUSIONS: Aggressive balloon angioplasty with provisional stenting yields excellent results in a general patient population.     

Recommendations from the Consensus Conference on Hypertension in the Elderly.

Since 1978 there have been dramatic advances in the understanding of the pathophysiologic features of unstable angina pectoris and in the availability of new therapies of proven efficacy. Coronary artery spasm has been shown to be an important mechanism of acute myocardial ischemia in patients with unstable angina, and coronary thrombosis has been established as an early event in the development of acute myocardial infarction and, possibly, sudden death. Intravenous nitrates and oral calcium antagonists have been made available and are now widely used. Acetylsalicylic acid has been shown to be of benefit. Improved techniques of myocardial preservation and the introduction of percutaneous transluminal coronary angioplasty have modified the surgical management of coronary artery disease.     

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

Background

Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).

Methods

Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.

Results

The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).

Conclusion

We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.

Trial registration

ClinicalTrials.gov: NCT00149591.     

Primary angioplasty: preprocedural pharmacological therapy

Primary coronary angioplasty has been shown to be an effective reperfusion therapy for patients with acute myocardial infarction, not only for those who present to PTCA centres but also for patients who present to hospitals without angioplasty facilities. With the increasing use of primary angioplasty more patients will be transferred to a (tertiary) PTCA centre. An increase in treatment delay is associated with a worse clinical outcome. The importance of an open infarct-related vessel at acute angiography is becoming clear. Pharmacological pretreatment of patients during transportation to a PTCA centre with the aim to open the infarct-related vessel in advance might be beneficial. Glycoprotein IIb/IIIa receptor blockers seem to be the agents of choice for facilitated PTCA. The safety and (cost) effectiveness of this pretreatment of patients transported to undergo primary angioplasty remain to be evaluated.     

Efficacy of Coronary Angioplasty on Long-Term Outcome in Elderly Chinese Patients with ST Elevated Myocardial Infarction

The benefit and efficacy of interventional coronary therapies in elderly patients is still a controversial subject, especially in parts of the world where traditional and conservative medicine is still mainstream. In China, the benefit of intervention is still questionable, hence, this study investigated the prognostic significance of coronary angioplasty on outcomes of elderly patients presenting with ST-segment elevated myocardial infarction (STEMI). The study cohort comprised of 270 elderly (age ≥ 75 years) patients who had confirmed STEMI. Some 116 patients underwent coronary angioplasty (called CA group) and their prognoses and survival over the short- and long-term periods (up to 80 months) were compared to 154 comparable patients who received a noninvasive, more conservative medical therapy (non-CA group). The subsequent Kaplan–Meier survival curves and statistical analyses were used to ascertain any difference between the groups. There was no significant differences between the two groups in terms of their clinical presentation, clinical risk, cardiac features, medications and medical procedures, except that the peak creatine kinase was significantly higher in the CA group. The success rate of interventional percutaneous coronary intervention observed in the CA group was 92.4% and during the hospitalization period, there were fewer deaths in the CA group (11 vs. 61 in the non-CA group). Furthermore, after 1-year and up to 7 years postsurgery, the CA group had a significant survival when compared to the non-CA cohort. Analysis of the longer-term data, using multivariate Cox regression analysis after 80 months indicated a hazard ratio of mortality for patients in CA group to be 0.283 (95% CI: 0.140–0.534, P < 0.001). Also, multivariate logistic regression analysis identified conservative treatment, chronic renal failure, cardiac arrhythmia, chronic lung disease and left ventricular ejection fraction, as predictors of higher long-term mortality in elderly patients with STEMI. In conclusion, this study clearly indicates that elderly Chinese patients with STEMI who undergo coronary angioplasty benefit and have a better survival rates in both the short- and long-term.     

The Effects of Intra-Aortic Balloon Pumps on Mortality in Patients Undergoing High-Risk Coronary Revascularization: A Meta-Analysis of Randomized Controlled Trials of Coronary Artery Bypass Grafting and Stenting Era

Background

Intra-aortic balloon pumps (IABP) have generally been used for patients undergoing high-risk mechanical coronary revascularization. However, there is still insufficient evidence to determine whether they can improve outcomes in reperfusion therapy patients, mainly by percutaneous coronary intervention (PCI) with stenting or coronary artery bypass graft (CABG). This study was designed to determine the difference between high-risk mechanical coronary revascularization with and without IABPs on mortality, by performing a meta-analysis on randomized controlled trials of the current era.

Methods

Pubmed and Embase databases were searched from inception to May 2015. Unpublished data were obtained from the investigators. Randomized clinical trials of IABP and non-IABP in high-risk coronary revascularization procedures (PCI or CABG) were included. In the case of PCI procedures, stents should be used in more than 80% of patients. Numbers of events at the short-term and long-term follow-up were extracted.

Results

A total of 12 randomized trials enrolling 2155 patients were included. IABPs did not significantly decrease short-term mortality (relative risk (RR) 0.66; 95% CI, 0.42–1.01), or long-term mortality (RR 0.79; 95% CI, 0.47–1.35), with low heterogeneity across the studies. The findings remained stable in patients with acute myocardial infarction with or without cardiogenic shock. But in high-risk CABG patients, IABP was associated with reduced mortality (71 events in 846 patients; RR 0.40; 95%CI 0.25–0.67).

Conclusion

In patients undergoing high-risk coronary revascularization, IABP did not significantly decrease mortality. But high-risk CABG patients may be benefit from IABP. Rigorous criteria should be applied to the use of IABPs.     

Acute coronary syndrome during pregnancy

Two cases of myocardial infarction during the second trimester of pregnancy are presented. Both patients were treated with thrombolytic therapy. In the first case the treatment was successful, in the other patient thrombolysis only temporarily relieved the symptoms. Therefore, angiography was performed and a significant stenosis in the left anterior descending coronary artery was successfully treated with balloon angioplasty. Both women delivered a healthy child, the first child was born at term, the second at a gestational age of 33 weeks. Percutaneous intervention versus thrombolytic therapy in pregnancy is discussed.