Aspirin resistance: is it real? Is it clinically significant?
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Biomedical subjects
Publications and source records attributed to James E Dalen.
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Despite hundreds of clinical trials, the appropriate dose of aspirin to prevent myocardial infarction (MI) and stroke is uncertain. In the US, the doses most frequently recommended are 80, 160, or 325 mg per day. Because aspirin can cause major bleeding, the appropriate dose is the lowest dose that is effective in preventing both MI and stroke because these two diseases frequently co-exist. Five randomized clinical trials have compared aspirin with placebo or no therapy for the prevention of stroke and MI. These trials varied with regard to the dose of aspirin, the duration of treatment, and, most important, the populations selected for study varied in their baseline risk of stroke and MI. In men, 160 mg/day consistently lowered the risk of MI. In women, doses of 50 mg, 75, and 100 mg/day did not significantly decrease the risk of MI; therefore, the appropriate dose in women must exceed 100 mg/day. The appropriate dose for the primary prevention of stroke in men and women has not been established. Doses of 75 and 100 mg/day have been ineffective in men and women. The appropriate dose must be at least 160 mg/day. The lowest dose to prevent recurrent MI or death in patients with stable coronary artery disease (CAD) is 75 mg/day. In acute MI the lowest dose is 160 mg/day. In patients with a history of stroke or transient ischemic attack (TIA), 50 mg/day has been shown to be effective in men and women. In acute stroke, 160 mg/day is effective in preventing recurrent stroke or death. The risk of major bleeding with 160 mg/day is the same as with 80 mg/day: 1 to 2 cases per 1000 patient years of treatment, and the risk of fatal bleeding is the same with 80 and 160 mg/day. These studies indicate that the most appropriate dose for the primary and secondary prevention of stroke and MI is 160 mg/day.
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Over the past several decades, significant advances have been made in the primary and secondary prevention of coronary artery disease. However, effects of changing lifestyle and treatment practices on demographic and clinical profiles and on hospital outcomes of patients who present with acute myocardial infarction (AMI) have not been well characterized. We carried out a prospective population-based investigation of >25-year trends (1975 to 2001) in demographic and clinical characteristics, treatment practices, and hospital outcomes of patients who had been hospitalized with AMI. Residents of a metropolitan area (Worcester, Massachusetts) who had been hospitalized with validated AMI (n = 10,440) in all greater Worcester hospitals during thirteen 1-year periods between 1975 and 2001 comprised the sample of interest. Patients who had been hospitalized during the most recent study years were significantly older, were more likely to be women, and had a greater prevalence of co-morbidities. Hospitalized patients were increasingly more likely to receive effective cardiac medications and coronary interventions over the period under investigation. Multivariable-adjusted hospital survival rates improved considerably over time, whereas different trends were observed in the occurrence of several important clinical complications. The present results provide insights into the changing characteristics of patients who are hospitalized with AMI, treatment practices, and their short-term outcomes. Given the magnitude of AMI and evolving approaches to manage it, continued monitoring of these trends remains of considerable clinical and public health importance.
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This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range, 2.0 to 3.0): In patients with persistent or paroxysmal AF (PAF) [intermittent AF] at high risk of stroke (ie, having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, age > 75 years, moderately or severely impaired left ventricular systolic function and/or congestive heart failure, history of hypertension, or diabetes mellitus), we recommend anticoagulation with an oral VKA, such as warfarin (Grade 1A). In patients with persistent AF or PAF, age 65 to 75 years, in the absence of other risk factors, we recommend antithrombotic therapy with either an oral VKA or aspirin, 325 mg/d, in this group of patients who are at intermediate risk of stroke (Grade 1A). In patients with persistent AF or PAF < 65 years old and with no other risk factors, we recommend aspirin, 325 mg/d (Grade 1B). For patients with AF and mitral stenosis, we recommend anticoagulation with an oral VKA (Grade 1C+). For patients with AF and prosthetic heart valves, we recommend anticoagulation with an oral VKA (Grade 1C+); the target INR may be increased and aspirin added depending on valve type and position, and on patient factors. For patients with AF of > or = 48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA for 3 weeks before and for at least 4 weeks after successful cardioversion (Grade 1C+). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacologic or electrical cardioversion, an alternative strategy is anticoagulation and screening multiplane transesophageal echocardiography (Grade 1B). If no thrombus is seen and cardioversion is successful, we recommend anticoagulation for at least 4 weeks (Grade 1B). For patients with AF of known duration < 48 h, we suggest cardioversion without anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or low molecular weight heparin at presentation (Grade 2C).
This chapter about prevention of coronary artery bypass occlusion is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: For patients undergoing coronary artery bypass grafting (CABG), we recommend aspirin, 75 to 162 mg/d, starting 6 h after operation over preoperative aspirin (Grade 1A). In patients in whom postoperative bleeding prevents the administration of aspirin at 6 h after CABG, we recommend starting aspirin as soon as possible thereafter (Grade 1C). For patients undergoing CABG, we recommend against addition of dipyridamole to aspirin therapy (Grade 1A). For patients with coronary artery disease undergoing CABG who are allergic to aspirin, we recommend clopidogrel, 300 mg, as a loading dose 6 h after operation followed by 75 mg/d p.o. (Grade 1C+). In patients who undergo CABG for non-ST-segment elevation acute coronary syndrome (ACS), we recommend clopidogrel, 75 mg/d for 9 to 12 months following the procedure in addition to treatment with aspirin (Grade 1A). For patients who have received clopidogrel for ACS and are scheduled for CABG, we recommend discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients undergoing CABG who have no other indication for vitamin K antagonists (VKAs), we suggest clinicians to not administer VKAs (Grade 2B). For patients undergoing CABG in whom oral anticoagulants are indicated, such as those with heart valve replacement, we suggest clinicians administer VKA in addition to aspirin (Grade 2C). For all patients with coronary artery disease who undergo internal mammary artery (IMA) bypass grafting, we recommend aspirin, 75 to 162 mg/d, indefinitely (Grade 1A). For all patients undergoing IMA bypass grafting without other indication for VKA, we suggest clinicians not use VKA (Grade 2C).
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BACKGROUND: The direct-to-consumer advertising (DTCA) of prescription medications is proliferating in the United States. The relationship between patient exposure to DTCA and the response of clinicians is not well understood. METHODS: A randomized postal survey of Arizona primary care provider physicians (n = 1080) and physician assistants (n = 704) was conducted. A questionnaire was created using a hypothetical patient scenario that varied according to the diagnosis of the patient (ie, hypertension, hypercholesterolemia, seasonal allergies, or obesity) and the type of informational exposure generating the patient's questions (ie, DTCA vs drug references such as Physicians' Desk Reference). Clinicians were randomly assigned 1 of 8 forms of the scenario and were asked standardized questions related to their responses when faced with the patient scenario. RESULTS: The response rate was 44% (40.5% of physicians and 49.3% of physician assistants). No statistically significant differences were found between the early and late responders or between responders and nonresponders. Relative to clinicians who received the "drug reference book" patient scenario, clinicians who received the DTCA patient scenario were more likely to become annoyed with a patient for asking for more information about medications (P =.003); less likely to answer the patient's questions (P =.03) or provide additional written information (P =.007); more likely to become frustrated (P =.003) and annoyed (P<.001) with the patient for asking to try a specific medication; and less likely to provide samples (P =.001) or a prescription (P<.001) for a specific medication. CONCLUSION: Clinicians are amenable to patients asking for drug information and medications, but they are less receptive to questions arising from DTCA.