Background: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. Methods: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel 8300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were echeduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an ocluded infarct-related artery (defined by a Thrombolysus in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. Results: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds ol the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. Conclusions: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

Context Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear. Objective To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors. Design, Setting, and Patients Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009. Main Outcome Measures Rates of cardiovascular death, myocardial infarction, and stroke. Results A total of 45 227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21 890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15 264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P  Conclusion Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.

https://jamanetwork.com/journals/jama/articlepdf/186626/joc05122_1350_1357.pdf

Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis

Lower extremity atherosclerotic peripheral artery disease (PAD) has a very high prevalence in most nations and in the United States.1–8 Lower extremity PAD is now known to be associated with equal morbidity and mortality and comparable (or higher) health economic costs as coronary heart disease (CHD) and ischemic stroke.9,10 Yet where surveyed, the public and clinicians (as well as health payers and government agencies) do not yet fully recognize the risks associated with PAD.11

For decades, clinicians did not recognize the impact of coronary disease in women.12 As such, women were not informed of their CHD risk. For any common disease, whether infectious, oncological, or traumatic, when more than half of the population at risk is not aware of this risk, and when this risk is not managed, preventable morbid and mortal events are inevitable.

Certain health facts are now evident: Women suffer the consequences of PAD at rates at least as high as those observed in men. But major knowledge gaps exist. Clinical research to evaluate gender-based differences that might underlie the delayed, postmenopausal presentation of PAD in women has not been conducted. Whether subtle but important gender-based distinctions in clinical presentations exist is unknown. The relative sensitivity and specificity of PAD diagnostic tests and pathways by gender are unclear. Although there is suggestive evidence that treatment benefits and harms are different in women and men, this cannot yet be confirmed from current clinical trial data because of the limited inclusion of women in past investigations.

Other facts provide encouragement. Women with or at risk for CHD now better understand this risk. Thus, collation of accurate PAD-specific health information for women is likely to improve their own health and that of society at large.

The American Heart Association, in collaboration with …

A Call to Action: Women and Peripheral Artery Disease A Scientific Statement From the American Heart Association

Key Clinical PointsPeripheral Artery Disease Atherosclerotic peripheral artery disease affects more than 200 million persons worldwide, including at least 8.5 million persons in the United States, and is associated with high rates of cardiovascular events and death. Smoking and diabetes are the strongest risk factors. Noninvasive vascular testing provides information on the presence, severity, and location of peripheral artery disease. Exercise testing can uncover mild disease and quantify functional capacity. In the treatment of peripheral artery disease, the main goals are to reduce cardiovascular risk and improve functional capacity. Supervised exercise increases walking distance. Cilostazol can be used as an adjunct to an exercise program. Conventional angiography is typically performed when revascularization is being considered. Computed tomography or magnetic resonance angiography can also be useful in planning for revascularization. Revascularization, endovascular or surgical, is indicated for symp...

https://www.nejm.org/doi/suppl/10.1056/NEJMcp1507631/suppl_file/nejmcp1507631_appendix.pdf

CLINICAL PRACTICE. Peripheral Artery Disease.

Background—Peripheral artery disease (PAD) is common and imposes a high risk of major systemic and limb ischemic events. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international prospective registry of patients at risk of atherothrombosis caused by established arterial disease or the presence of ≥3 atherothrombotic risk factors. Methods and Results—We compared the 2-year rates of vascular-related hospitalizations and associated costs in US patients with established PAD across patient subgroups. Symptomatic PAD at enrollment was identified on the basis of current intermittent claudication with an ankle-brachial index (ABI) <0.90 or a history of lower-limb revascularization or amputation. Asymptomatic PAD was diagnosed on the basis of an enrollment ABI <0.90 in the absence of symptoms. Overall, 25 763 of the total 68 236–patient REACH cohort were enrolled from US sites; 2396 (9.3%) had symptomatic and 213 (0.8%) had asymptomatic PAD at baseline. One- and cumulative 2-year ...

Vascular Hospitalization Rates and Costs in Patients With Peripheral Artery Disease in the United States

Background— Atherothrombosis is the underlying cause of cardiovascular, cerebrovascular, and peripheral arterial disease and is the leading cause of death in the industrialized world. The objectives of the present study are (1) to examine the annual costs associated with vascular events and interventions that require hospitalization, as well as long-term medication use for the management of associated risk factors, in a US population of outpatients with multiple atherothrombotic risk factors or a history of symptomatic disease and (2) to compare costs across patient subgroups defined according to specific arterial bed(s) affected and the number of affected arterial beds. Methods and Results— The international REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled outpatients ≥45 years of age who had established coronary artery, cerebrovascular, or peripheral artery disease or ≥3 atherothrombotic risk factors. Data on risk factors, associated medications, and vascular hospitalizations...

Frederique Mosse

Papers

One-Year Costs in Patients With a History of or at Risk for Atherothrombosis in the United States

Long-term cost-effectiveness of clopidogrel in STEMI patients.