Eric Henley, MD, MPH

Eighty percent of the people in the United States report low back pain at some point in their lives. It is one of the top 10 reasons for visits to family physicians and is responsible for one third of all US disability costs. Direct costs of diagnosis and treatment were $25 billion in 1991, in addition to the cost of lost earnings.^1-3 The natural history of acute low back pain in those presenting for care is for half to recover in 1 to 2 weeks and 90% in 1 month.⁴ In a cohort of 1246 patients presenting for treatment of acute low back pain, approximately 100 patients (8%) went on to have chronic continuous symptoms for 3 months, and two thirds of these patients had disabling symptoms at 22 months (almost 5% of the original cohort), although many were employed.⁵

Therapy

What is known about therapy for low back pain? The author of an evidence-based systematic review of randomized control (RCTs) trials⁷ reported that nonsteroidal anti-inflammatory drugs (NSAIDs) and staying active are beneficial for acute low back pain; analgesics and spinal manipulation are likely to be beneficial; muscle relaxants are likely to have benefits and harms; and bed rest and traction are likely to be ineffective. The following were of unknown effectiveness: antidepressants, epidural steroids, trigger point injections, back schools, behavioral therapy, back exercises, multidisciplinary treatment programs, lumbar supports, and acupuncture. For chronic low back pain, back exercises and multidisciplinary programs are beneficial; analgesics, NSAIDs, back schools, trigger point injections, behavioral therapy, and spinal manipulation are likely to be beneficial; bed rest, biofeedback, and traction are unlikely to be beneficial; and other treatments are of unknown effectiveness.

Given the nature of the pain and the lack of curative medical therapies, it is not surprising that low back pain is one of the most common reasons people give for using alternative therapies. In a 1997 national telephone survey, 24% of the respondents reported a history of back pain in the preceeding 12 months. Of these, 48% used an alternative therapy in the previous 12 months; 30% saw an alternative practitioner; and 39% saw a physician and an alternative practitioner. Chiropractic and massage were the most common alternative therapies.⁸

Several well-done investigations of manipulative therapy have been reported. These include an observational study of chiropractors and physicians, a randomized trial of osteopathic manual therapy versus standard medical therapy, and a randomized trial comparing chiropractic, physical therapy, and an education booklet.^9-11 These studies generally show that manual therapy (including physical therapy) is associated with greater patient satisfaction, higher health care costs, and at best marginally improved functional outcomes compared with traditional medical therapy. This should not be surprising since the natural history of back pain is for it to resolve relatively quickly.

To further investigate the potential benefits of manual therapy, Curtis and colleagues recently conducted an RCT of low back pain management in which family physicians and internists received special training in the care of low back pain (enhanced care) and simple manual therapy techniques (enhanced care plus). After the training, the physicians reported increased confidence in managing low back pain, and all subsequently used manual therapy in their practices. These same physicians were then involved in a trial in which they randomly assigned their acute back pain patients to receive enhanced care or enhanced care plus. The complete results of that study will be reported elsewhere.¹²

Patient Satisfaction

In this issue of the Journal Curtis and colleagues¹³ compare the outcomes of those patients treated in their manual therapy RCT to the outcomes of patients treated by primary care clinicians in their previously reported observational study comparing chiropractic, orthopedic, and primary care. To do this, the authors focused on the 13 generalists (presumably family physicians and internists) who participated in both studies. They hoped to determine if training in enhanced care and manual therapy skills would improve patient outcomes and satisfaction.

For this study, the authors used the patients of the 13 physicians in the original observation study as the control group and the patients treated in the RCT as the intervention group. Their results showed that patients treated in the RCT assessed physicians’ skills in history taking, examination skills, patient education, overall treatment, provision of pain relief, and success in getting patients to engage in social activities more highly. The differences in outcomes between the 2 treatment methods in the RCT (enhanced care and enhanced care plus) were relatively small. Functional outcomes as measured by scores on the Roland-Morris questionnaire (a standardized tool used in back pain research) showed a significant difference in favor of the intervention patients over the control patients at 2, 4, and 8 weeks. Time to functional recovery also showed that both groups in the RCT improved more quickly, although the confidence intervals around the hazard ratios included 1, and therefore were not significantly different.

Validity

The results suggest a positive effect of the intervention, but the complex nature of the study design raises some concerns. To conclude that the educational program in the RCT led to improved patient outcomes, one has to assume that patients (1) treated in both the RCT and observational studies were similar in terms of the risk factors affecting back pain duration and recovery, and (2) and that nothing besides the educational intervention changed the way the physicians treated back pain patients in the 2 different studies. In fact, there were some significant differences between the patients in the 2 studies, such as income, workers’ compensation and employment status, and baseline functioning. The authors controlled for these factors in determining functional outcomes; however, the extent of the differences between the 2 patient groups casts some doubt as to whether they were similar enough to be compared. I would conclude that there is a positive benefit of the education program on patient satisfaction with physician performance and a smaller benefit on patient outcomes. Given the number of studies showing low patient satisfaction with physician care, this result is encouraging and should be explored in other settings.

Population-Based Care

As an alternative to focusing on the treatment end of back pain, it might be useful for primary care physicians to step back from the patient (the numerator) and consider the larger population with back pain (the denominator). For instance, the Agency for Health Care Policy and Research clinical guideline indicates the yearly prevalence of back pain as 50% in working-age adults of whom only approximately one sixth seek care.¹ Are there some specific characteristics of these people that lead them to our offices?

Efforts to identify the risk factors of those who seek medical care for acute back pain and who develop chronic back pain have not produced clear results. The strongest predictor is a history of back pain. Effects of psychosocial factors, the work environment, and workers’ compensation may have a role. Hadler^14-16 has written extensively on the lack of research to support the role of physical stress, particularly that which is work related, as an explanation. He argues persuasively that the workers’ compensation system has changed the concept of back pain from that of an illness or predicament into an injury. This transformation has often been aided by the efforts of physicians, pharmaceutical companies, and alternative medicine providers, who proffer ways to fix the pain. Hadler proposes that we identify the different ways people have for coping with this common ailment while it takes its natural course.

The argument about the role of the workers’ compensation system in the care of back pain suggests that a public health approach—one that takes into account policy development, as well as treatment—may be a useful strategy. Recent research on whiplash injuries that demonstrates a decrease in insurance claims for pain and suffering after changes in the tort system may offer different strategies to better support recovery from back pain.¹⁷ This is not to suggest that patient malingering is the problem; it is not. It does suggest that some back pain may result from a complex interaction of biologic, psychosocial, and economic factors and incentives, and that addressing these issues in both the policy and medical arenas may be of more help to patients.¹⁸

Hadler¹⁴ offers some simple advice for caring for patients with back pain who lack significant neurologic findings; his suggestions are echoed and elaborated on by Gillette.¹⁹ His approach emphasizes identifying the array of factors that may impede recovery (various forms of stress, depression or somatization, and counterproductive beliefs about back disorders), developing a constructive physician-patient relationship, addressing stresses, keeping patients active, and prescribing medication when appropriate. This is good advice for physicians dealing with this common and sometimes frustrating problem.

Eighty percent of the people in the United States report low back pain at some point in their lives. It is one of the top 10 reasons for visits to family physicians and is responsible for one third of all US disability costs. Direct costs of diagnosis and treatment were $25 billion in 1991, in addition to the cost of lost earnings.^1-3 The natural history of acute low back pain in those presenting for care is for half to recover in 1 to 2 weeks and 90% in 1 month.⁴ In a cohort of 1246 patients presenting for treatment of acute low back pain, approximately 100 patients (8%) went on to have chronic continuous symptoms for 3 months, and two thirds of these patients had disabling symptoms at 22 months (almost 5% of the original cohort), although many were employed.⁵

Therapy

What is known about therapy for low back pain? The author of an evidence-based systematic review of randomized control (RCTs) trials⁷ reported that nonsteroidal anti-inflammatory drugs (NSAIDs) and staying active are beneficial for acute low back pain; analgesics and spinal manipulation are likely to be beneficial; muscle relaxants are likely to have benefits and harms; and bed rest and traction are likely to be ineffective. The following were of unknown effectiveness: antidepressants, epidural steroids, trigger point injections, back schools, behavioral therapy, back exercises, multidisciplinary treatment programs, lumbar supports, and acupuncture. For chronic low back pain, back exercises and multidisciplinary programs are beneficial; analgesics, NSAIDs, back schools, trigger point injections, behavioral therapy, and spinal manipulation are likely to be beneficial; bed rest, biofeedback, and traction are unlikely to be beneficial; and other treatments are of unknown effectiveness.

Given the nature of the pain and the lack of curative medical therapies, it is not surprising that low back pain is one of the most common reasons people give for using alternative therapies. In a 1997 national telephone survey, 24% of the respondents reported a history of back pain in the preceeding 12 months. Of these, 48% used an alternative therapy in the previous 12 months; 30% saw an alternative practitioner; and 39% saw a physician and an alternative practitioner. Chiropractic and massage were the most common alternative therapies.⁸

Several well-done investigations of manipulative therapy have been reported. These include an observational study of chiropractors and physicians, a randomized trial of osteopathic manual therapy versus standard medical therapy, and a randomized trial comparing chiropractic, physical therapy, and an education booklet.^9-11 These studies generally show that manual therapy (including physical therapy) is associated with greater patient satisfaction, higher health care costs, and at best marginally improved functional outcomes compared with traditional medical therapy. This should not be surprising since the natural history of back pain is for it to resolve relatively quickly.

To further investigate the potential benefits of manual therapy, Curtis and colleagues recently conducted an RCT of low back pain management in which family physicians and internists received special training in the care of low back pain (enhanced care) and simple manual therapy techniques (enhanced care plus). After the training, the physicians reported increased confidence in managing low back pain, and all subsequently used manual therapy in their practices. These same physicians were then involved in a trial in which they randomly assigned their acute back pain patients to receive enhanced care or enhanced care plus. The complete results of that study will be reported elsewhere.¹²

Patient Satisfaction

In this issue of the Journal Curtis and colleagues¹³ compare the outcomes of those patients treated in their manual therapy RCT to the outcomes of patients treated by primary care clinicians in their previously reported observational study comparing chiropractic, orthopedic, and primary care. To do this, the authors focused on the 13 generalists (presumably family physicians and internists) who participated in both studies. They hoped to determine if training in enhanced care and manual therapy skills would improve patient outcomes and satisfaction.

For this study, the authors used the patients of the 13 physicians in the original observation study as the control group and the patients treated in the RCT as the intervention group. Their results showed that patients treated in the RCT assessed physicians’ skills in history taking, examination skills, patient education, overall treatment, provision of pain relief, and success in getting patients to engage in social activities more highly. The differences in outcomes between the 2 treatment methods in the RCT (enhanced care and enhanced care plus) were relatively small. Functional outcomes as measured by scores on the Roland-Morris questionnaire (a standardized tool used in back pain research) showed a significant difference in favor of the intervention patients over the control patients at 2, 4, and 8 weeks. Time to functional recovery also showed that both groups in the RCT improved more quickly, although the confidence intervals around the hazard ratios included 1, and therefore were not significantly different.

Validity

The results suggest a positive effect of the intervention, but the complex nature of the study design raises some concerns. To conclude that the educational program in the RCT led to improved patient outcomes, one has to assume that patients (1) treated in both the RCT and observational studies were similar in terms of the risk factors affecting back pain duration and recovery, and (2) and that nothing besides the educational intervention changed the way the physicians treated back pain patients in the 2 different studies. In fact, there were some significant differences between the patients in the 2 studies, such as income, workers’ compensation and employment status, and baseline functioning. The authors controlled for these factors in determining functional outcomes; however, the extent of the differences between the 2 patient groups casts some doubt as to whether they were similar enough to be compared. I would conclude that there is a positive benefit of the education program on patient satisfaction with physician performance and a smaller benefit on patient outcomes. Given the number of studies showing low patient satisfaction with physician care, this result is encouraging and should be explored in other settings.

Population-Based Care

As an alternative to focusing on the treatment end of back pain, it might be useful for primary care physicians to step back from the patient (the numerator) and consider the larger population with back pain (the denominator). For instance, the Agency for Health Care Policy and Research clinical guideline indicates the yearly prevalence of back pain as 50% in working-age adults of whom only approximately one sixth seek care.¹ Are there some specific characteristics of these people that lead them to our offices?

Efforts to identify the risk factors of those who seek medical care for acute back pain and who develop chronic back pain have not produced clear results. The strongest predictor is a history of back pain. Effects of psychosocial factors, the work environment, and workers’ compensation may have a role. Hadler^14-16 has written extensively on the lack of research to support the role of physical stress, particularly that which is work related, as an explanation. He argues persuasively that the workers’ compensation system has changed the concept of back pain from that of an illness or predicament into an injury. This transformation has often been aided by the efforts of physicians, pharmaceutical companies, and alternative medicine providers, who proffer ways to fix the pain. Hadler proposes that we identify the different ways people have for coping with this common ailment while it takes its natural course.

The argument about the role of the workers’ compensation system in the care of back pain suggests that a public health approach—one that takes into account policy development, as well as treatment—may be a useful strategy. Recent research on whiplash injuries that demonstrates a decrease in insurance claims for pain and suffering after changes in the tort system may offer different strategies to better support recovery from back pain.¹⁷ This is not to suggest that patient malingering is the problem; it is not. It does suggest that some back pain may result from a complex interaction of biologic, psychosocial, and economic factors and incentives, and that addressing these issues in both the policy and medical arenas may be of more help to patients.¹⁸

Hadler¹⁴ offers some simple advice for caring for patients with back pain who lack significant neurologic findings; his suggestions are echoed and elaborated on by Gillette.¹⁹ His approach emphasizes identifying the array of factors that may impede recovery (various forms of stress, depression or somatization, and counterproductive beliefs about back disorders), developing a constructive physician-patient relationship, addressing stresses, keeping patients active, and prescribing medication when appropriate. This is good advice for physicians dealing with this common and sometimes frustrating problem.

Eighty percent of the people in the United States report low back pain at some point in their lives. It is one of the top 10 reasons for visits to family physicians and is responsible for one third of all US disability costs. Direct costs of diagnosis and treatment were $25 billion in 1991, in addition to the cost of lost earnings.^1-3 The natural history of acute low back pain in those presenting for care is for half to recover in 1 to 2 weeks and 90% in 1 month.⁴ In a cohort of 1246 patients presenting for treatment of acute low back pain, approximately 100 patients (8%) went on to have chronic continuous symptoms for 3 months, and two thirds of these patients had disabling symptoms at 22 months (almost 5% of the original cohort), although many were employed.⁵

Therapy

What is known about therapy for low back pain? The author of an evidence-based systematic review of randomized control (RCTs) trials⁷ reported that nonsteroidal anti-inflammatory drugs (NSAIDs) and staying active are beneficial for acute low back pain; analgesics and spinal manipulation are likely to be beneficial; muscle relaxants are likely to have benefits and harms; and bed rest and traction are likely to be ineffective. The following were of unknown effectiveness: antidepressants, epidural steroids, trigger point injections, back schools, behavioral therapy, back exercises, multidisciplinary treatment programs, lumbar supports, and acupuncture. For chronic low back pain, back exercises and multidisciplinary programs are beneficial; analgesics, NSAIDs, back schools, trigger point injections, behavioral therapy, and spinal manipulation are likely to be beneficial; bed rest, biofeedback, and traction are unlikely to be beneficial; and other treatments are of unknown effectiveness.

Given the nature of the pain and the lack of curative medical therapies, it is not surprising that low back pain is one of the most common reasons people give for using alternative therapies. In a 1997 national telephone survey, 24% of the respondents reported a history of back pain in the preceeding 12 months. Of these, 48% used an alternative therapy in the previous 12 months; 30% saw an alternative practitioner; and 39% saw a physician and an alternative practitioner. Chiropractic and massage were the most common alternative therapies.⁸

Several well-done investigations of manipulative therapy have been reported. These include an observational study of chiropractors and physicians, a randomized trial of osteopathic manual therapy versus standard medical therapy, and a randomized trial comparing chiropractic, physical therapy, and an education booklet.^9-11 These studies generally show that manual therapy (including physical therapy) is associated with greater patient satisfaction, higher health care costs, and at best marginally improved functional outcomes compared with traditional medical therapy. This should not be surprising since the natural history of back pain is for it to resolve relatively quickly.

To further investigate the potential benefits of manual therapy, Curtis and colleagues recently conducted an RCT of low back pain management in which family physicians and internists received special training in the care of low back pain (enhanced care) and simple manual therapy techniques (enhanced care plus). After the training, the physicians reported increased confidence in managing low back pain, and all subsequently used manual therapy in their practices. These same physicians were then involved in a trial in which they randomly assigned their acute back pain patients to receive enhanced care or enhanced care plus. The complete results of that study will be reported elsewhere.¹²

Patient Satisfaction

In this issue of the Journal Curtis and colleagues¹³ compare the outcomes of those patients treated in their manual therapy RCT to the outcomes of patients treated by primary care clinicians in their previously reported observational study comparing chiropractic, orthopedic, and primary care. To do this, the authors focused on the 13 generalists (presumably family physicians and internists) who participated in both studies. They hoped to determine if training in enhanced care and manual therapy skills would improve patient outcomes and satisfaction.

For this study, the authors used the patients of the 13 physicians in the original observation study as the control group and the patients treated in the RCT as the intervention group. Their results showed that patients treated in the RCT assessed physicians’ skills in history taking, examination skills, patient education, overall treatment, provision of pain relief, and success in getting patients to engage in social activities more highly. The differences in outcomes between the 2 treatment methods in the RCT (enhanced care and enhanced care plus) were relatively small. Functional outcomes as measured by scores on the Roland-Morris questionnaire (a standardized tool used in back pain research) showed a significant difference in favor of the intervention patients over the control patients at 2, 4, and 8 weeks. Time to functional recovery also showed that both groups in the RCT improved more quickly, although the confidence intervals around the hazard ratios included 1, and therefore were not significantly different.

Validity

The results suggest a positive effect of the intervention, but the complex nature of the study design raises some concerns. To conclude that the educational program in the RCT led to improved patient outcomes, one has to assume that patients (1) treated in both the RCT and observational studies were similar in terms of the risk factors affecting back pain duration and recovery, and (2) and that nothing besides the educational intervention changed the way the physicians treated back pain patients in the 2 different studies. In fact, there were some significant differences between the patients in the 2 studies, such as income, workers’ compensation and employment status, and baseline functioning. The authors controlled for these factors in determining functional outcomes; however, the extent of the differences between the 2 patient groups casts some doubt as to whether they were similar enough to be compared. I would conclude that there is a positive benefit of the education program on patient satisfaction with physician performance and a smaller benefit on patient outcomes. Given the number of studies showing low patient satisfaction with physician care, this result is encouraging and should be explored in other settings.

Population-Based Care

As an alternative to focusing on the treatment end of back pain, it might be useful for primary care physicians to step back from the patient (the numerator) and consider the larger population with back pain (the denominator). For instance, the Agency for Health Care Policy and Research clinical guideline indicates the yearly prevalence of back pain as 50% in working-age adults of whom only approximately one sixth seek care.¹ Are there some specific characteristics of these people that lead them to our offices?

Efforts to identify the risk factors of those who seek medical care for acute back pain and who develop chronic back pain have not produced clear results. The strongest predictor is a history of back pain. Effects of psychosocial factors, the work environment, and workers’ compensation may have a role. Hadler^14-16 has written extensively on the lack of research to support the role of physical stress, particularly that which is work related, as an explanation. He argues persuasively that the workers’ compensation system has changed the concept of back pain from that of an illness or predicament into an injury. This transformation has often been aided by the efforts of physicians, pharmaceutical companies, and alternative medicine providers, who proffer ways to fix the pain. Hadler proposes that we identify the different ways people have for coping with this common ailment while it takes its natural course.

The argument about the role of the workers’ compensation system in the care of back pain suggests that a public health approach—one that takes into account policy development, as well as treatment—may be a useful strategy. Recent research on whiplash injuries that demonstrates a decrease in insurance claims for pain and suffering after changes in the tort system may offer different strategies to better support recovery from back pain.¹⁷ This is not to suggest that patient malingering is the problem; it is not. It does suggest that some back pain may result from a complex interaction of biologic, psychosocial, and economic factors and incentives, and that addressing these issues in both the policy and medical arenas may be of more help to patients.¹⁸

Hadler¹⁴ offers some simple advice for caring for patients with back pain who lack significant neurologic findings; his suggestions are echoed and elaborated on by Gillette.¹⁹ His approach emphasizes identifying the array of factors that may impede recovery (various forms of stress, depression or somatization, and counterproductive beliefs about back disorders), developing a constructive physician-patient relationship, addressing stresses, keeping patients active, and prescribing medication when appropriate. This is good advice for physicians dealing with this common and sometimes frustrating problem.

BACKGROUND: Unfractionated and low-molecular-weight (LMW) heparins are popular and successful agents for preventing pulmonary embolism (PE) and deep vein thrombosis (DVT) after major surgery, but they are usually stopped at hospital discharge. The use of an antiplatelet agent such as low-dose aspirin might provide additional benefits. A meta-analysis of data from 8000 patients indicated several weeks of such therapy reduced the frequency of PE and DVT by 40% to 60%. The Pulmonary Embolism Prevention (PEP) trial of low-dose aspirin was a large randomized control trial (RCT) designed to confirm or refute these findings.

POPULATION STUDIED: This was a multicountry trial (Australia, New Zealand, South Africa, Sweden, and the United Kingdom) of patients with proximal femur fractures or undergoing hip or knee arthroplasty. Patients with a clear indication for aspirin (such as a recent myocardial infarction) or clear contraindication (such as an active peptic ulcer) were not eligible. Concurrent use of other thromboprophylactic agents and previous use of nonsteroidal anti-inflammatory drugs (NSAIDs) were allowed.

STUDY DESIGN AND VALIDITY: The PEP study was a double-blind placebo-controlled trial in which eligible patients who gave consent were randomly assigned to receive either 160 mg enteric-coated aspirin or placebo daily for 5 weeks, starting before surgery. The authors described the methods used to prevent researchers from knowing to which group the patient would be assigned (ie, concealed allocation). Patients were advised to avoid other NSAIDs during this time. A diagnosis of DVT required confirmation by venography or ultrasound; PEs were classified as definite or probable by an independent committee on the basis of a combination of clinical findings, angiogram, ventilation-perfusion scan, or venographic evidence of DVT. Follow-up assessed in-hospital morbidity and mortality and out-of-hospital mortality for the month following surgery. Analysis was by intention to treat. This was a large well-conducted trial involving at least 150 hospitals, with complete follow-up of 99.4% of enrollees. Randomization resulted in equal distribution on the basis of age and sex; no data on race or ethnicity were presented. The concurrent use of heparin agents was equally distributed between the intervention and control groups. Diagnosis of DVT, PE, MI, and cerebrovascular accident was made by a committee unaware of the subjects' group assignment.

OUTCOMES MEASURED: Follow-up was for cause of death through day 35 and for nonfatal events during the hospitalization (mean duration=16 days).

RESULTS: Approximately 13,000 patients with hip fracture were randomized, with 92% initiating treatment preoperatively or immediately postoperatively and 80% taking the assigned medication for the entire 35-day follow-up. Approximately 45% of the participants were receiving a form of heparin (similar numbers in both groups). Symptomatic DVT was confirmed in 1.03% of those assigned aspirin and 1.45% of those assigned placebo (P=.03; number needed to treat [NNT]=238). Definite or probable PE was confirmed in 0.69% of patients taking aspirin and 1.21% of those taking placebo (P=.002; NNT=192). For fatal PE, the NNT was 270 (P=.002). The overall mortality was identical in both groups. Aspirin had statistically significant benefits on total thromboembolic events in those patients taking unfractionated heparin or no heparin but not in those who received LMW heparin. Nonfatal and fatal cardiac ischemic events occurred more frequently in the aspirin group (1.57% vs 1.18%, P=.05). A total of 256 patients would need to receive aspirin for one additional event to occur (number needed to harm [NNH]=256). Fatal bleeding episodes were approximately equal in both groups; however, 2.95% of the patients assigned to aspirin required transfusion versus 2.35% of patients assigned to placebo (P=.04; NNH=167). The number of patients in the arthroplasty section of the trial was smaller (n=4000), and none of the comparisons between the intervention and placebo groups showed statistically significant results.

BACKGROUND: Unfractionated and low-molecular-weight (LMW) heparins are popular and successful agents for preventing pulmonary embolism (PE) and deep vein thrombosis (DVT) after major surgery, but they are usually stopped at hospital discharge. The use of an antiplatelet agent such as low-dose aspirin might provide additional benefits. A meta-analysis of data from 8000 patients indicated several weeks of such therapy reduced the frequency of PE and DVT by 40% to 60%. The Pulmonary Embolism Prevention (PEP) trial of low-dose aspirin was a large randomized control trial (RCT) designed to confirm or refute these findings.

POPULATION STUDIED: This was a multicountry trial (Australia, New Zealand, South Africa, Sweden, and the United Kingdom) of patients with proximal femur fractures or undergoing hip or knee arthroplasty. Patients with a clear indication for aspirin (such as a recent myocardial infarction) or clear contraindication (such as an active peptic ulcer) were not eligible. Concurrent use of other thromboprophylactic agents and previous use of nonsteroidal anti-inflammatory drugs (NSAIDs) were allowed.

STUDY DESIGN AND VALIDITY: The PEP study was a double-blind placebo-controlled trial in which eligible patients who gave consent were randomly assigned to receive either 160 mg enteric-coated aspirin or placebo daily for 5 weeks, starting before surgery. The authors described the methods used to prevent researchers from knowing to which group the patient would be assigned (ie, concealed allocation). Patients were advised to avoid other NSAIDs during this time. A diagnosis of DVT required confirmation by venography or ultrasound; PEs were classified as definite or probable by an independent committee on the basis of a combination of clinical findings, angiogram, ventilation-perfusion scan, or venographic evidence of DVT. Follow-up assessed in-hospital morbidity and mortality and out-of-hospital mortality for the month following surgery. Analysis was by intention to treat. This was a large well-conducted trial involving at least 150 hospitals, with complete follow-up of 99.4% of enrollees. Randomization resulted in equal distribution on the basis of age and sex; no data on race or ethnicity were presented. The concurrent use of heparin agents was equally distributed between the intervention and control groups. Diagnosis of DVT, PE, MI, and cerebrovascular accident was made by a committee unaware of the subjects' group assignment.

OUTCOMES MEASURED: Follow-up was for cause of death through day 35 and for nonfatal events during the hospitalization (mean duration=16 days).

RESULTS: Approximately 13,000 patients with hip fracture were randomized, with 92% initiating treatment preoperatively or immediately postoperatively and 80% taking the assigned medication for the entire 35-day follow-up. Approximately 45% of the participants were receiving a form of heparin (similar numbers in both groups). Symptomatic DVT was confirmed in 1.03% of those assigned aspirin and 1.45% of those assigned placebo (P=.03; number needed to treat [NNT]=238). Definite or probable PE was confirmed in 0.69% of patients taking aspirin and 1.21% of those taking placebo (P=.002; NNT=192). For fatal PE, the NNT was 270 (P=.002). The overall mortality was identical in both groups. Aspirin had statistically significant benefits on total thromboembolic events in those patients taking unfractionated heparin or no heparin but not in those who received LMW heparin. Nonfatal and fatal cardiac ischemic events occurred more frequently in the aspirin group (1.57% vs 1.18%, P=.05). A total of 256 patients would need to receive aspirin for one additional event to occur (number needed to harm [NNH]=256). Fatal bleeding episodes were approximately equal in both groups; however, 2.95% of the patients assigned to aspirin required transfusion versus 2.35% of patients assigned to placebo (P=.04; NNH=167). The number of patients in the arthroplasty section of the trial was smaller (n=4000), and none of the comparisons between the intervention and placebo groups showed statistically significant results.

BACKGROUND: Unfractionated and low-molecular-weight (LMW) heparins are popular and successful agents for preventing pulmonary embolism (PE) and deep vein thrombosis (DVT) after major surgery, but they are usually stopped at hospital discharge. The use of an antiplatelet agent such as low-dose aspirin might provide additional benefits. A meta-analysis of data from 8000 patients indicated several weeks of such therapy reduced the frequency of PE and DVT by 40% to 60%. The Pulmonary Embolism Prevention (PEP) trial of low-dose aspirin was a large randomized control trial (RCT) designed to confirm or refute these findings.

POPULATION STUDIED: This was a multicountry trial (Australia, New Zealand, South Africa, Sweden, and the United Kingdom) of patients with proximal femur fractures or undergoing hip or knee arthroplasty. Patients with a clear indication for aspirin (such as a recent myocardial infarction) or clear contraindication (such as an active peptic ulcer) were not eligible. Concurrent use of other thromboprophylactic agents and previous use of nonsteroidal anti-inflammatory drugs (NSAIDs) were allowed.

STUDY DESIGN AND VALIDITY: The PEP study was a double-blind placebo-controlled trial in which eligible patients who gave consent were randomly assigned to receive either 160 mg enteric-coated aspirin or placebo daily for 5 weeks, starting before surgery. The authors described the methods used to prevent researchers from knowing to which group the patient would be assigned (ie, concealed allocation). Patients were advised to avoid other NSAIDs during this time. A diagnosis of DVT required confirmation by venography or ultrasound; PEs were classified as definite or probable by an independent committee on the basis of a combination of clinical findings, angiogram, ventilation-perfusion scan, or venographic evidence of DVT. Follow-up assessed in-hospital morbidity and mortality and out-of-hospital mortality for the month following surgery. Analysis was by intention to treat. This was a large well-conducted trial involving at least 150 hospitals, with complete follow-up of 99.4% of enrollees. Randomization resulted in equal distribution on the basis of age and sex; no data on race or ethnicity were presented. The concurrent use of heparin agents was equally distributed between the intervention and control groups. Diagnosis of DVT, PE, MI, and cerebrovascular accident was made by a committee unaware of the subjects' group assignment.

OUTCOMES MEASURED: Follow-up was for cause of death through day 35 and for nonfatal events during the hospitalization (mean duration=16 days).

RESULTS: Approximately 13,000 patients with hip fracture were randomized, with 92% initiating treatment preoperatively or immediately postoperatively and 80% taking the assigned medication for the entire 35-day follow-up. Approximately 45% of the participants were receiving a form of heparin (similar numbers in both groups). Symptomatic DVT was confirmed in 1.03% of those assigned aspirin and 1.45% of those assigned placebo (P=.03; number needed to treat [NNT]=238). Definite or probable PE was confirmed in 0.69% of patients taking aspirin and 1.21% of those taking placebo (P=.002; NNT=192). For fatal PE, the NNT was 270 (P=.002). The overall mortality was identical in both groups. Aspirin had statistically significant benefits on total thromboembolic events in those patients taking unfractionated heparin or no heparin but not in those who received LMW heparin. Nonfatal and fatal cardiac ischemic events occurred more frequently in the aspirin group (1.57% vs 1.18%, P=.05). A total of 256 patients would need to receive aspirin for one additional event to occur (number needed to harm [NNH]=256). Fatal bleeding episodes were approximately equal in both groups; however, 2.95% of the patients assigned to aspirin required transfusion versus 2.35% of patients assigned to placebo (P=.04; NNH=167). The number of patients in the arthroplasty section of the trial was smaller (n=4000), and none of the comparisons between the intervention and placebo groups showed statistically significant results.

CLINICAL QUESTION: What is the best treatment for left anterior descending artery stenosis in patients with stable angina?

BACKGROUND: Long-term studies comparing surgical bypass, angioplasty (PTCA), and medical therapy in the treatment of patients with stable angina and left anterior descending (LAD) artery stenosis are not available. LAD lesions are thought to have a worse prognosis than other singe-vessel lesions; therefore, more aggressive strategies have been promoted.

POPULATION STUDIED: Consecutive patients at a single institution in Brazil were selected from 1988 to 1991. Patients had stable angina, a proximal LAD stenosis, no previous myocardial infarction, and normal left ventricular function. Of 313 patients, approximately 15% did not meet the medical or angiographic criteria, and 15% refused to participate. Baseline characteristics were similar in the 3 groups, except mean total cholesterol levels, which were 240 in the medical group, 213 in the PTCA group, and 230 in the bypass group (no test of significance was performed).

STUDY DESIGN AND VALIDITY: This was a randomized control trial in which participants were randomly assigned to one of the 3 treatment groups (with approximately 70 patients in each group). Crossover from one group to another, according to symptoms, was allowed at any time. Medical therapy could include b-blockers, nitrates, calcium antagonists, and antiplatelet agents. Angiograms were repeated with the occurrence of a new ischemic event and after 5 years of follow-up. Analysis was by intention to treat. Advantages of the study design include careful clinical and angiographic case definitions, care at a single institution, and long-term and complete follow-up. Limitations included generalizability of the study (as most of the patients were Brazilian men) and lack of blinding of the physicians caring for the patients. Researchers may not have been prevented from knowing to which group the patient would be assigned before entering him in the trial (concealed allocation), which could introduce selective randomization of patients.

OUTCOMES MEASURED: The primary end point was the occurrence of cardiac-related death, acute myocardial infarction, or refractory angina requiring revascularization.

RESULTS: Patients treated either with bypass or medical therapy were significantly more likely than patients treated with PTCA to be event-free at the end of 5 years: 91% in the bypass group, 76% in the medical group, and 60% in the PTCA group (P = .001 for PTCA vs the other 2 treatments). Cardiac-related deaths were similar in the 3 groups. Of 72 medically treated patients, 8 required surgery, and 4 were treated with PTCA. Of 72 PTCA patients, 30% received repeat PTCA, and 8 underwent surgery. After 5 years, significantly fewer patients treated medically were free of angina: 26% of the medical group compared with 65% of the PTCA group and 73% of the surgery group (P <.001). No study patients had refractory angina. During follow-up, 50% of all patients developed new stenoses >50%) with no differences among groups. Rates of return to regular employment were similar among the groups.

CLINICAL QUESTION: What is the best treatment for left anterior descending artery stenosis in patients with stable angina?

BACKGROUND: Long-term studies comparing surgical bypass, angioplasty (PTCA), and medical therapy in the treatment of patients with stable angina and left anterior descending (LAD) artery stenosis are not available. LAD lesions are thought to have a worse prognosis than other singe-vessel lesions; therefore, more aggressive strategies have been promoted.

POPULATION STUDIED: Consecutive patients at a single institution in Brazil were selected from 1988 to 1991. Patients had stable angina, a proximal LAD stenosis, no previous myocardial infarction, and normal left ventricular function. Of 313 patients, approximately 15% did not meet the medical or angiographic criteria, and 15% refused to participate. Baseline characteristics were similar in the 3 groups, except mean total cholesterol levels, which were 240 in the medical group, 213 in the PTCA group, and 230 in the bypass group (no test of significance was performed).

STUDY DESIGN AND VALIDITY: This was a randomized control trial in which participants were randomly assigned to one of the 3 treatment groups (with approximately 70 patients in each group). Crossover from one group to another, according to symptoms, was allowed at any time. Medical therapy could include b-blockers, nitrates, calcium antagonists, and antiplatelet agents. Angiograms were repeated with the occurrence of a new ischemic event and after 5 years of follow-up. Analysis was by intention to treat. Advantages of the study design include careful clinical and angiographic case definitions, care at a single institution, and long-term and complete follow-up. Limitations included generalizability of the study (as most of the patients were Brazilian men) and lack of blinding of the physicians caring for the patients. Researchers may not have been prevented from knowing to which group the patient would be assigned before entering him in the trial (concealed allocation), which could introduce selective randomization of patients.

OUTCOMES MEASURED: The primary end point was the occurrence of cardiac-related death, acute myocardial infarction, or refractory angina requiring revascularization.

RESULTS: Patients treated either with bypass or medical therapy were significantly more likely than patients treated with PTCA to be event-free at the end of 5 years: 91% in the bypass group, 76% in the medical group, and 60% in the PTCA group (P = .001 for PTCA vs the other 2 treatments). Cardiac-related deaths were similar in the 3 groups. Of 72 medically treated patients, 8 required surgery, and 4 were treated with PTCA. Of 72 PTCA patients, 30% received repeat PTCA, and 8 underwent surgery. After 5 years, significantly fewer patients treated medically were free of angina: 26% of the medical group compared with 65% of the PTCA group and 73% of the surgery group (P <.001). No study patients had refractory angina. During follow-up, 50% of all patients developed new stenoses >50%) with no differences among groups. Rates of return to regular employment were similar among the groups.

CLINICAL QUESTION: What is the best treatment for left anterior descending artery stenosis in patients with stable angina?

BACKGROUND: Long-term studies comparing surgical bypass, angioplasty (PTCA), and medical therapy in the treatment of patients with stable angina and left anterior descending (LAD) artery stenosis are not available. LAD lesions are thought to have a worse prognosis than other singe-vessel lesions; therefore, more aggressive strategies have been promoted.

POPULATION STUDIED: Consecutive patients at a single institution in Brazil were selected from 1988 to 1991. Patients had stable angina, a proximal LAD stenosis, no previous myocardial infarction, and normal left ventricular function. Of 313 patients, approximately 15% did not meet the medical or angiographic criteria, and 15% refused to participate. Baseline characteristics were similar in the 3 groups, except mean total cholesterol levels, which were 240 in the medical group, 213 in the PTCA group, and 230 in the bypass group (no test of significance was performed).

STUDY DESIGN AND VALIDITY: This was a randomized control trial in which participants were randomly assigned to one of the 3 treatment groups (with approximately 70 patients in each group). Crossover from one group to another, according to symptoms, was allowed at any time. Medical therapy could include b-blockers, nitrates, calcium antagonists, and antiplatelet agents. Angiograms were repeated with the occurrence of a new ischemic event and after 5 years of follow-up. Analysis was by intention to treat. Advantages of the study design include careful clinical and angiographic case definitions, care at a single institution, and long-term and complete follow-up. Limitations included generalizability of the study (as most of the patients were Brazilian men) and lack of blinding of the physicians caring for the patients. Researchers may not have been prevented from knowing to which group the patient would be assigned before entering him in the trial (concealed allocation), which could introduce selective randomization of patients.

OUTCOMES MEASURED: The primary end point was the occurrence of cardiac-related death, acute myocardial infarction, or refractory angina requiring revascularization.

RESULTS: Patients treated either with bypass or medical therapy were significantly more likely than patients treated with PTCA to be event-free at the end of 5 years: 91% in the bypass group, 76% in the medical group, and 60% in the PTCA group (P = .001 for PTCA vs the other 2 treatments). Cardiac-related deaths were similar in the 3 groups. Of 72 medically treated patients, 8 required surgery, and 4 were treated with PTCA. Of 72 PTCA patients, 30% received repeat PTCA, and 8 underwent surgery. After 5 years, significantly fewer patients treated medically were free of angina: 26% of the medical group compared with 65% of the PTCA group and 73% of the surgery group (P <.001). No study patients had refractory angina. During follow-up, 50% of all patients developed new stenoses >50%) with no differences among groups. Rates of return to regular employment were similar among the groups.