Risk Of Subsequent Ischemic Events Research Articles

Subsequent ischemic events associated with lower extremity amputations in patients with type 2 diabetes: A population-based cohort study

AimsTo explore the risk of subsequent ischemic events in type 2 diabetes mellitus (DM) patients who had lower extremity amputations (LEAs) were compared with DM patients without LEAs. MethodsA population-based cohort study was conducted utilizing the data of 2011 patients with newly diagnosed DM with and without LEAs sourced from the Longitudinal Health Insurance Database 2000 (LHID 2000) of the Taiwan National Health Insurance (NHI) program between 1996 and 2008. Main outcome measuresRelative risks (RRs), hazard ratios (HRs), and disease-free rates for various ischemic events. ResultsIn contrast with the comparison group, subjects with LEAs were more likely to reside in less urbanized areas, be white collar workers, and have higher DM-related costs (p<0.05). Subjects with LEAs also had significantly higher risks of developing ischemic diseases, except intestinal ischemia. In the multivariate Cox proportional hazards regression model analysis, the HR of end-stage renal disease (ESRD) was highest (HR=3.91, 95% CI=2.38–6.42), followed by embolism and thrombosis (HR=3.47, 95% CI=2.12–5.67), other peripheral vascular diseases (HR=3.11, 95% CI=2.11–4.57), atherosclerosis (HR=2.64, 95% CI=1.60–4.35), retinopathy (HR=2.24, 95% CI=1.79–2.80), cerebral ischemia (HR=1.61, 95% CI=1.25–2.06), and coronary artery disease (HR=1.44, 95% CI=1.18–1.74). ConclusionsDM patients with LEAs had significantly higher risks for subsequent ischemic events, particularly among men. The greatest risk detected among DM patients with LEA's was for end-stage renal disease. Disease free survival rates also indicated that the course of generalized DM ischemia proceeded despite treatment.

SECONDARY PREVENTION AFTER CORONARY ARTERY BYPASS GRAFT SURGERY: PRESENTATION OF A SCIENTIFIC STATEMENT

BackgroundA proven therapy for nearly 50 years, CABG is the most durable and complete treatment of ischemic heart disease. However, in the months and years that follow surgery, patients who have undergone CABG remain at risk for subsequent ischemic events as a result of native coronary artery disease progression and the development of graft atherosclerosis. Secondary therapies therefore play a key role in the maintenance of native and graft vessel patency and for the prevention of adverse cardiovascular outcomes.Methods and ResultsWe present a Scientific Statement prepared for the American Heart Association (AHA) to expand on two 2011 AHA and American College of Cardiology documents that provided a general overview of secondary prevention and briefly summarized the use of medical therapy after surgical coronary revascularization. Since the writing of those two statements, important evidence from clinical and observational trials has emerged that further supports and broadens the merits of intensive risk-reduction therapies for CABG patients. The present statement, specifically focused on the CABG population, thoroughly evaluates the current state of evidence regarding preventative therapies after surgery. Postoperative antiplatelet agents and lipid-lowering therapy continue to be the mainstay of secondary prevention following coronary surgical revascularization. Other opportunities for improving long-term clinical outcomes after CABG include the aggressive management of hypertension and diabetes mellitus, smoking cessation, weight loss, and cardiac rehabilitation. Select Class I and IIa recommendations are summarized in the Table below.Conclusion BackgroundA proven therapy for nearly 50 years, CABG is the most durable and complete treatment of ischemic heart disease. However, in the months and years that follow surgery, patients who have undergone CABG remain at risk for subsequent ischemic events as a result of native coronary artery disease progression and the development of graft atherosclerosis. Secondary therapies therefore play a key role in the maintenance of native and graft vessel patency and for the prevention of adverse cardiovascular outcomes. A proven therapy for nearly 50 years, CABG is the most durable and complete treatment of ischemic heart disease. However, in the months and years that follow surgery, patients who have undergone CABG remain at risk for subsequent ischemic events as a result of native coronary artery disease progression and the development of graft atherosclerosis. Secondary therapies therefore play a key role in the maintenance of native and graft vessel patency and for the prevention of adverse cardiovascular outcomes. Methods and ResultsWe present a Scientific Statement prepared for the American Heart Association (AHA) to expand on two 2011 AHA and American College of Cardiology documents that provided a general overview of secondary prevention and briefly summarized the use of medical therapy after surgical coronary revascularization. Since the writing of those two statements, important evidence from clinical and observational trials has emerged that further supports and broadens the merits of intensive risk-reduction therapies for CABG patients. The present statement, specifically focused on the CABG population, thoroughly evaluates the current state of evidence regarding preventative therapies after surgery. Postoperative antiplatelet agents and lipid-lowering therapy continue to be the mainstay of secondary prevention following coronary surgical revascularization. Other opportunities for improving long-term clinical outcomes after CABG include the aggressive management of hypertension and diabetes mellitus, smoking cessation, weight loss, and cardiac rehabilitation. Select Class I and IIa recommendations are summarized in the Table below. We present a Scientific Statement prepared for the American Heart Association (AHA) to expand on two 2011 AHA and American College of Cardiology documents that provided a general overview of secondary prevention and briefly summarized the use of medical therapy after surgical coronary revascularization. Since the writing of those two statements, important evidence from clinical and observational trials has emerged that further supports and broadens the merits of intensive risk-reduction therapies for CABG patients. The present statement, specifically focused on the CABG population, thoroughly evaluates the current state of evidence regarding preventative therapies after surgery. Postoperative antiplatelet agents and lipid-lowering therapy continue to be the mainstay of secondary prevention following coronary surgical revascularization. Other opportunities for improving long-term clinical outcomes after CABG include the aggressive management of hypertension and diabetes mellitus, smoking cessation, weight loss, and cardiac rehabilitation. Select Class I and IIa recommendations are summarized in the Table below. Conclusion

Cilostazol and outcome in outpatients with peripheral artery disease

BackgroundCilostazol increases the walking distance in patients with intermittent claudication, but there is scarce evidence of any effect on the risk for subsequent ischemic events, bleeding or death. Patients and MethodsWe used data from the FRENA Registry to compare the clinical outcome in stable outpatients with intermittent claudication, according to the use of cilostazol. ResultsAs of January 2013, 1,317 patients with intermittent claudication were recruited in FRENA, of whom 191 (14.5%) received cilostazol. Over a mean follow-up of 18months, 39 patients developed myocardial infarction, 23 ischemic stroke, 20 underwent limb amputation, 15 had major bleeding and 70 died. There were no significant differences in the rate of subsequent ischemic events, major bleeding or death between patients receiving or not receiving cilostazol. On multivariate analysis, the use of cilostazol had no influence on the risk for subsequent myocardial infarction (hazard ratio [HR]: 0.97; 95% CI: 0.33-20.8), ischemic stroke (HR: 1.46; 95% CI: 0.48-4.43), limb amputation (HR: 0.34; 95% CI: 0.04-20.6), major bleeding (HR: 1.52; 95% CI: 0.33-7.09) or death (HR: 0.90; 95% CI: 0.40-20.0). ConclusionsIn stable outpatients with intermittent claudication, the use of cilostazol was not associated with increased rates of subsequent ischemic events, major bleeding or death.

Cardiac Rehabilitation and Outcome in Stable Outpatients With Recent Myocardial Infarction

ObjectiveTo compare the mortality rate and the rate of subsequent ischemic events (myocardial infarction [MI], ischemic stroke, or limb amputation) in patients with recent MI according to the use of cardiac rehabilitation or no rehabilitation. DesignLongitudinal observational study. SettingOngoing registry of outpatients. ParticipantsPatients (N=1043) with recent acute MI were recruited; of these, 521 (50%) participated in cardiac rehabilitation. InterventionsNot applicable. Main Outcome MeasuresSubsequent ischemic events and mortality rates were registered. ResultsOver a mean follow-up of 18 months, 50 patients (4.8%) died and 49 (4.7%) developed 52 subsequent ischemic events (MI: n=43, ischemic stroke: n=6, limb amputation: n=3). Both the mortality rate (.16 vs 5.57 deaths per 100 patient-years; rate ratio=.03; 95% confidence interval [CI], 0.0–0.1]) and the rate of subsequent ischemic events (1.65 vs 4.54 events per 100 patient-years; rate ratio=0.4; 95% CI, 0.2–0.7) were significantly lower in cardiac rehabilitation participants than in nonparticipants. Multivariate analysis confirmed that patients in cardiac rehabilitation had a significantly lower risk of death (hazard ratio=.08; 95% CI, .01–.63; P=.016) and a nonsignificant lower risk of subsequent ischemic events (hazard ratio=.65; 95% CI, .30–1.42). ConclusionsThe use of cardiac rehabilitation in patients with recent MI was independently associated with a significant decrease in the mortality rate and a nonsignificant decrease in the rate of subsequent ischemic events.

Predictors of outcome in stable outpatients with peripheral artery disease

Patients with peripheral artery disease (PAD) are at increased risk for subsequent ischemic events. We used data from the FRENA Registry to find predictors of subsequent myocardial infarction (MI), ischemic stroke, and limb amputation in stable outpatients with PAD. As of January 2012, 1,270 patients with PAD were recruited, of whom 1,042 (82%) had Fontaine stage II; 113 (8.9%) stage III; and 115 (9.1%) stage IV. Over a mean follow-up of 14months, 35 patients developed MI, 25 had stroke, 39 underwent limb amputation, and 91 died. Among patients with Fontaine stage II, the incidence of MI (2.09 events per 100 patient-years; 95% CI 1.43-2.97) or stroke (0.93; 95% CI 0.52-1.56) was similar to that of limb amputation (3.22; 95% CI 2.37-4.29). On multivariate analysis, patients with diabetes [hazard ratio (HR) 2.09; 95% CI 1.05-4.18], prior coronary disease (HR 5.35; 95% CI 2.24-12.8), or atrial fibrillation (HR 3.11; 95% CI 1.52-6.37) were at increased risk for MI; female (HR 2.94; 95% CI 1.32-6.67), those with prior stroke (HR 5.21; 95% CI 1.22-22.2) or atrial fibrillation (HR 3.37; 95% CI 1.45-7.85) at increased risk for stroke; and female (HR 2.38; 95% CI 1.23-4.55), those with diabetes (HR 3.50; 95% CI 1.58-7.73) or advanced stages of PAD were at increased risk for limb amputation. Prior coronary artery disease, diabetes and atrial fibrillation predicted subsequent MI; female gender, prior stroke and atrial fibrillation predicted stroke; and female gender, diabetes, and advanced stages of PAD predicted limb amputation.

Bupropion for Smoking Cessation in Patients With Acute Coronary Syndrome

Smokers hospitalized with acute coronary syndrome (ACS) are at high risk for subsequent ischemic events. Nevertheless, over two-thirds of patients continue to smoke after an acute myocardial infarction. Bupropion hydrochloride has proven efficacy as a smoking cessation aid, but data regarding its safety and efficacy in ACS patients are limited. In a double-blind, randomized controlled trial, we compared the safety and efficacy of 8 weeks of treatment with bupropion slow-release (SR) or placebo for smokers hospitalized with ACS as an adjunct to nurse-led hospital- and telephone-based support. Primary efficacy outcome was smoking abstinence at 1 year. Primary safety outcome was clinical events at 1 year. A total of 151 patients were enrolled; all but 2 completed follow-up. Abstinence rates at 3 months were 45% and 44% in the bupropion SR and placebo groups, respectively (P=.99); 37% vs 42% (P=.61) at 6 months; and 31% vs 33% (P=.86) at 1 year. On multivariate analysis, an invasive procedure performed during index hospitalization was an independent predictor for smoking abstinence at 1 year (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.22-14.19). Presence of adverse effects attributed to treatment was a negative predictor for smoking cessation (OR, 0.23; 95% CI, 0.07-0.78). Treatment with bupropion SR was not associated with an increase in clinical events or change in blood pressure or body mass index, but dizziness was more common compared with placebo (14% vs 1.4%; P=.005). In hospitalized patients with ACS who received continuous, intensive nurse counseling about smoking cessation, bupropion did not increase the rates of smoking abstinence.

Concomitant Use of Proton Pump Inhibitors and Clopidogrel in Patients With Coronary, Cerebrovascular, or Peripheral Artery Disease in the Factores de Riesgo y ENfermedad Arterial (FRENA) Registry

Among patients receiving clopidogrel for coronary artery disease, concomitant therapy with proton pump inhibitors (PPIs) has been associated with an increased risk for recurrent coronary events. Factores de Riesgo y ENfermedad Arterial (FRENA) is an ongoing, multicenter, observational registry of consecutive outpatients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. We retrospectively examined the influence of concomitant use of PPIs on outcome in patients receiving clopidogrel. As of March 2009, 1222 patients were using clopidogrel: 595 had coronary artery disease, 329 cerebrovascular disease, and 298 had peripheral artery disease. Of these, 519 (42%) were concomitantly using PPIs. Over a mean follow-up of 15 months, 131 patients (11%) had 139 subsequent ischemic events: myocardial infarction 44, ischemic stroke 40, and critical limb ischemia 55. Seventeen of them (13%) died within 15 days of the subsequent event. PPI users had a higher incidence of myocardial infarction (rate ratio, 2.5; 95% confidence interval [CI], 1.3-4.8), ischemic stroke (rate ratio, 1.9; 95% CI, 1.03-3.7), and a nonsignificantly higher rate of critical limb ischemia (rate ratio, 1.6; 95% CI, 0.95-2.8) than nonusers. On multivariate analysis, concomitant use of clopidogrel and PPIs was independently associated with an increased risk for subsequent ischemic events both in the whole series of patients (hazard ratio, 1.8; 95% CI, 1.1-2.7) and in those with cerebrovascular disease or peripheral artery disease (hazard ratio, 1.5; 95% CI, 1.01-2.4). In patients with established arterial disease, concomitant use of PPIs and clopidogrel was associated with a nearly doubling of the incidence of subsequent myocardial infarction or ischemic stroke. This higher incidence persisted after multivariate adjustment.

Acute coronary syndrome update for hospitalists

Acute coronary syndromes (ACSs)--unstable angina, non-ST-segment (ST, part of an electrocardiogram between the QRS complex and the T wave) or ST-segment elevation myocardial infarction (MI)--remain extremely common and clinically challenging. In addition to electrocardiography and biomarkers, formal risk stratification using risk scores has become an important part of the initial evaluation of patients with ACS. On the basis of the estimated risk of subsequent ischemic events, the optimal use and timing of cardiac catheterization and revascularization procedures can be determined. Additionally, antiplatelet and anticoagulant therapy can be instituted, with consideration given to both the ischemic and bleeding risks in an individual patient. A particular challenge in ACS management has been the rapid evolution of guidelines in response to new randomized clinical trial and registry data. Understanding and implementing the recommendations in these evidence-based guidelines are important parts of hospitalists' practice.

Preventing Serious Sequelae After an Acute Coronary Syndrome: The Consequences of Thrombosis Versus Bleeding With Antiplatelet Therapy

Acute coronary syndrome (ACS) is associated with a persistent prothrombotic state, placing patients at high risk of subsequent ischemic events. Guidelines recommend the use of dual antiplatelet therapy with aspirin + a thienopyridine (clopidogrel) for at least a year after ACS in most patients, except those who undergo coronary artery bypass grafting. Clinical studies demonstrate that this strategy significantly reduces the risk of ischemic events at the expense of a small increase in the risk of bleeding. Physicians must balance the risk of bleeding against the benefit of ischemia prevention, bearing in mind that ischemic events are generally more common than major bleeding and often associated with more catastrophic consequences or ongoing morbidity. The relationship between bleeding and mortality is complicated by the fact that many risk factors for bleeding are also those for mortality and that bleeding may lead to discontinuation of antiplatelet therapy, thereby increasing the risk for an ischemic event. Data suggest that physicians tend to overestimate the risk of bleeding and underestimate the risk of ischemia. Careful patient selection and thorough patient education are the keys to managing antiplatelet therapy after ACS, especially as newer more potent antiplatelet agents, such as prasugrel, become available.

Bleeding Increases the Risk of Ischemic Events in Patients With Peripheral Arterial Disease

Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease. All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7). In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.

Antiplatelet Polypharmacy in Primary Percutaneous Coronary Intervention

Timely and sustained reperfusion in the ST-elevation myocardial infarction setting improves mortality, and primary percutaneous coronary intervention (PCI) is the guideline-favored revascularization strategy.1 Primary PCI requires pharmacological support with antiplatelet and antithrombin therapy, and many drugs and combinations are established for this purpose. Likewise, patients with ST-elevation myocardial infarction are at risk for subsequent ischemic events in the weeks to months after their index event, and long-term antiplatelet therapy is needed. Aspirin alone provides an inadequate effect on a substantial number of patients with atherosclerotic plaque rupture, whether the vascular disruption occurs as part of an acute coronary syndrome (ACS) or a PCI procedure. Indeed, patients with concomitant spontaneous plaque rupture (ie, troponin-positive ACS) and subsequent disruption from PCI have a particularly high rate of ischemic events with aspirin therapy alone and a notably large risk reduction with antiplatelet adjuncts, such as thienopyridines and glycoprotein IIb/IIIa inhibitors. Article see p 3207 Platelet glycoprotein IIb/IIIa inhibitors have been studied in many placebo-controlled primary PCI trials. De Luca and colleagues performed a meta-analysis of such trials testing abciximab on 3949 patients. They reported an ≈30% reduction in mortality at 6 to 12 months.2 When these studies were performed, procedural thienopyridine use was infrequent, and appropriate loading doses had not been established. Of the 8 primary PCI trials in the meta-analysis, only 2 described administration of a thienopyridine loading dose, and maintenance therapy was continued for only several weeks. Since then, clopidogrel use has become commonplace, yet for a variety of reasons a placebo-controlled trial testing procedural clopidogrel in primary PCI was never performed. In the most recent scientific society guidelines, clopidogrel was given a class I recommendation for use in ST-elevation myocardial infarction1 and …

Cerebral dysautoregulation and the risk of ischemic events in occlusive carotid artery disease

Dynamic cerebral autoregulation assessed from blood pressure transients can be considerably impaired in severe internal carotid artery (ICA) obstruction. It is unknown whether impaired autoregulation indicates an increased risk of subsequent ischemic events in this situation. 165 patients with ICA stenosis (> 70 %) or occlusion were prospectively followed until anterior circulation stroke, transient ischemic attack, carotid recanalization without prior event, death or study end. Transcranial Doppler sonography was used to determine autoregulation in both middle cerebral arteries from spontaneous blood pressure fluctuations (correlation coefficient indices Dx and Mx) and respiratory- induced 0.1 Hz oscillations (phase). Standard CO(2) reactivity (CO(2)R) was additionally assessed. All indices were classified as impaired vs. preserved according to reference values from 79 agematched controls. During median follow-up of 24.5 months, there were 16 ischemic events over ipsilateral sides. Competing risk analysis revealed a significant predictive effect on ipsilateral ischemic events for impaired Dx (rate ratio 8.2 [95 % confidence interval 1.7-39], p = 0.0079), phase (5.0 [2-13], p = 0.0007) and CO(2)R (9.4 [2.2-40], p = 0.0025). Restricting analysis to severe stenosis alone (n = 103), only impaired phase (rate ratio 8.6 [1.6-45], p = 0.01) remained as a significant predictor. In a continuous statistical model, only Dx and Mx were significant predictors of ischemic events (p = 0.012 and p = 0.016). In conclusion, impaired dynamic cerebral autoregulation indicates an increased risk of subsequent ischemic events in severe obstructive ICA disease. Its clinical application might thus be of help in identifying higher risk patients.

Prevalence of American Heart Association Type VI Carotid Atherosclerotic Lesions Identified by Magnetic Resonance Imaging for Different Levels of Stenosis as Measured by Duplex Ultrasound

Via magnetic resonance imaging (MRI), we sought to determine the prevalence of atherosclerotic American Heart Association type VI lesions (AHA-LT6) (lesions with luminal surface defect, hemorrhage/thrombus, or calcified nodule) in carotid arteries that represented all categories of stenosis as measured by duplex ultrasound. Arterial stenosis alone has been shown to be a poor predictor of cardiovascular events. Autopsy studies suggest that features associated with AHA-LT6 lesions, rather than the degree of luminal narrowing, characterize the high-risk plaque. A total of 192 subjects underwent bilateral carotid artery magnetic resonance imaging (MRI) scans at 1.5T after evaluation with ultrasound to determine stenosis. After excluding arteries with a previous endarterectomy, poor image quality, or missing ultrasound data, there were 175 patients with 260 arteries available for analysis. The AHA lesion type was determined by the consensus opinion of 2 experienced carotid MRI reviewers. In total, 96 of 260 (37.0%) arteries had >or=1 location with AHA-LT6. Of the arteries with AHA-LT6, 84.4% had hemorrhage, 45.8% had a ruptured fibrous cap, and 14.6% showed other type of complications. Prevalence of AHA-LT6 was an increasing sequence of 8.1% in the 37 arteries with 1% to 15% stenosis, 21.7% in the 60 arteries with 16% to 49% stenosis, 36.8% in the 114 arteries with 50% to 79% stenosis, and 77.6% in the 49 arteries with 80% to 99% stenosis. Complicated AHA-LT6 are frequently found in arteries with <or=50% stenosis. These findings indicate that complex lesions develop in a substantial number of arteries in the absence of high-grade stenosis. Ongoing prospective studies will determine the predictive value of vulnerable plaque features, as visualized by MRI, for risk of subsequent ischemic events.

Characterization of Ischemic Events and Use of Prescription Antiplatelet and Anticoagulant Agents After Stroke or Transient Ischemic Attack

Stroke patients are at risk for subsequent ischemic events; yet preventive therapy is often underused. An analysis was performed to determine the rate of secondary ischemic events and use of prescription antiplatelets or anticoagulants after ischemic stroke or transient ischemic attack (TIA). Patients age 25 years or older with a medical claim for stroke or TIA between July 1, 1998 and September 30, 1999 were identified from a managed care database. Patients sustaining a stroke or TIA within 6 months before the index event were excluded. Patients were categorized as hospitalized stroke, nonhospitalized stroke, or TIA and were followed for 24 months for a secondary stroke, TIA, or acute myocardial infarction (AMI). Use of prescription antiplatelet or anticoagulant agents was determined for each subgroup. Over 2 years, subsequent stroke occurred in 5.8% of patients, TIA occurred in 3.8%, and AMI occurred in 4.9%. Death occurred in 32.3% during follow-up. Hospitalized stroke patients were the subgroup at highest risk, with a 7.6% stroke rate and a 45.4% death rate within 2 years. Prescription antiplatelet or warfarin therapy was given in 45.7% of hospitalized stroke cases, 29.5% of nonhospitalized stroke cases, and 39.2% of TIA cases. Against the background of current treatment, patients who suffer a stroke or TIA are at high risk of death and a subsequent stroke within 2 years. These outcomes highlight the importance of effective secondary stroke prevention efforts for those suffering acute stroke, whether or not they are hospitalized.

Vascular viewpoint

Question: Is a history of pre-existing atherothrombotic disease associated with an increased risk of subsequent ischemic events, and is it associated with a reduction in efficacy of clopidogrel? Population: Patients with recent ischemic stroke (IS), myocardial infarction (MI), or established peripheral arterial disease, and a history of pre-existing symptomatic atherothrombotic disease (IS and=or MI) were enrolled in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial. CAPRIE was a randomized, blinded, clinical trial comparing the efficacy of clopidogrel with aspirin in patients at risk of ischemic events. Design and methods: Retrospective, subgroup analysis of 4496 patients with a prior history of symptomatic atherothrombotic disease from the CAPRIE study. Results: Compared with the overall population of CAPRIE, patients with pre-existing symptomatic atherothrombotic disease have elevated rates of IS, MI, or vascular death. The 3-year rates of IS, MI, or vascular death were 20.4% with clopidogrel and 23.8% with aspirin (absolute risk reduction: 3.4%; 95% CI: -0.2 to 7.0; number needed to treat: 29; relative risk reduction: 14.9% (95% CI: 0.3 to 27.3; p = 0.045)). Conclusion: Patients with a history of previous symptomatic atherothrombotic disease suffer a high rate of subsequent ischemic events. Among these patients, the absolute risk reduction of clopidogrel over aspirin is greater compared with patients without pre-existing atherothrombotic disease.

Risk Stratification in Patients With Unstable Angina

Considerable progress has occurred in our understanding of the pathophysiology and therapy of unstable angina pectoris.1 2 3 Knowledge concerning the importance of plaque rupture and thrombosis formation has led to the use of intravenous heparin, aspirin, and exploration of new antiplatelet strategies in conjunction with antianginal therapy. Despite this increased understanding in the use of antithrombotic and antianginal therapy, the fear of subsequent infarction and death remains great. These fears have led to a strategy in clinically determined high-risk and many intermediate-risk patients of coronary angiography and revascularization after stabilization before or soon after hospital discharge.1 Delay in performing coronary angiography for several weeks to months because of inadequate resources has been associated with a relatively high risk of ischemic events and death.4 While a strategy of coronary angiography and revascularization (often without prior stress testing) may reduce the risk of ischemic events and death, it is nevertheless associated with an increased risk of acute complications and restenosis as well as increased cost. New strategies such as the use of stents and/or the platelet 7E3 glycoprotein 2B3A antibody hold great promise for further benefit, with a reduction in ischemic events and restenosis, but may add to cost. While the strategy of coronary angiography, revascularization, and exploration of new but expensive antithrombotic strategies is in my opinion appropriate in patients at high or intermediate risk of recurrent ischemic events, it may not be necessary in all. One of the most important challenges in the management of patients with unstable angina is risk stratification, most importantly to identify patients at low risk of subsequent ischemic events who could be treated by conventional medical therapy without the need for new and expensive antiplatelet agents and/or revascularization. Several studies have suggested that determination of biochemical markers such as myoglobin, CK-MB …