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PSA testing: When it’s useful, when it’s not
Do not routinely screen all men over the age of 50 for prostate cancer with the prostate-specific antigen (PSA) test. Consider screening men younger than 75 with no cardiovascular or cancer risk factors—the only patient population for whom PSA testing appears to provide even a small benefit.1,2
STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis of 6 randomized controlled trials (RCTs) with methodological limitations, and a post hoc analysis of a large RCT.
Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomized controlled trials. BMJ. 2010;341:c4543.
Crawford ED, Grubb R 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-361.
ILLUSTRATIVE CASES
A 65-year-old obese man with high blood pressure comes in for a complete physical and asks if he should have the “blood test for cancer.” He had a normal prostate specific antigen (PSA) the last time he was tested, but that was 10 years ago. What should you tell him?
A 55-year-old man schedules a routine check-up and requests a PSA test. His last test, at age 50, was normal. The patient has no known medical problems and no family history of prostate cancer, and he exercises regularly and doesn’t smoke. How should you respond to his request for a PSA test?
Prostate cancer is the second leading cause of cancer deaths among men in the United States, after lung cancer. One in 6 American men will be diagnosed with prostate cancer; for about 3% of them, the cancer will be fatal.3,4
Widespread testing without evidence of efficacy
The PSA test was approved by the US Food and Drug Administration (FDA) in 1986.5 Its potential to detect early prostate cancer in the hope of decreasing morbidity and mortality led to widespread PSA screening in the 1990s, before data on the efficacy of routine screening existed.
By 2002, only one low-quality RCT that compared screening with no screening had been published. The investigators concluded that screening resulted in lower mortality rates, but a subsequent (and superior) intention-to-treat analysis showed no mortality benefit.6 Two large RCTs, both published in 2009, reported conflicting results.7,8
The European Randomized Study of Screening for Prostate Cancer (ERSPC) enrolled 182,000 men ages 50 to 74 years and randomized them to either PSA screening every 4 years or no screening. Prostate cancer-specific mortality was 20% lower for those in the screening group compared with the no-screening group; however, the absolute risk reduction was only 0.71 deaths per 1000 men.7
The US Prostate, Lung, Colorectal, Ovarian Cancer (PLCO) Screening Trial randomized 77,000 men ages 55 to 74 years to either annual PSA and digital rectal examination (DRE) screening or usual care. After 7 years of follow-up, no significant difference was found in prostate cancer deaths or all-cause mortality in the screening group vs the control group. It is important to note, however, that 52% of the men in the control group had ≥1 PSA screening during the study period, which decreased the researchers’ ability to fully assess the benefits of screening.8
PSA’s limitations and potential harmful effects
The PSA test’s significant limitations and potentially harmful effects counter the potential benefits of screening. About 75% of positive tests are false positives, which are associated with psychological harm in some men for up to a year after the test.6 In addition, diagnostic testing and treatment for what may be nonlife-threatening prostate cancer can cause harm, including erectile dysfunction (ED), urinary incontinence, bowel dysfunction, and death. Rates of ED and incontinence 18 months after radical prostatectomy are an estimated 59.9% and 8.4%, respectively.9
Do the benefits of PSA testing outweigh the harms—and for which men? The meta-analysis and post hoc analysis detailed in this PURL help clear up the controversy.
STUDY SUMMARY: Widespread screening doesn’t save lives
Djulbegovic et al examined 6 RCTs, including the ERSPC and PLCO studies described earlier, that compared screening for prostate cancer (PSA with or without DRE) with no screening or usual care.1 Together, the studies included nearly 390,000 men ages 45 to 80 years, and had 4 to 15 years of follow-up. The results showed that routine screening for prostate cancer had no statistically significant effect on all-cause mortality (relative risk [RR]=0.99; 95% confidence interval [CI], 0.97-1.01), death from prostate cancer (RR=0.88; 95% CI, 0.71-1.09), or diagnosis of stage III or IV prostate cancer (RR=0.94; 95% CI, 0.85-1.04). Routine screening did, however, increase the probability of being diagnosed with prostate cancer at any stage, especially at stage I. For every 1000 men screened, on average, 20 more cases of prostate cancer were diagnosed.
Healthy men may benefit from screening
Crawford et al conducted a post hoc analysis of the PLCO trial, which had found no benefit to annual PSA testing and serial DRE compared with usual care for the general population.2 Their analysis compared the mortality benefits (both prostate cancer–specific and overall) of annual PSA screening for healthy men with no or minimal comorbidities vs the mortality benefits for men with any risk factor for the 2 leading causes of death: cancer and cardiovascular disease.
Annual PSA testing yielded more diagnoses of prostate cancer in both healthy and at-risk men. Deaths from prostate cancer were infrequent in both groups, occurring in 0.22% (164/73,378) of all participants.
Men with ≥1 risk factor had similar prostate cancer–specific deaths with both yearly screening and usual care (62 vs 42 deaths, adjusted hazard ratio [AHR]=1.43; 95% CI, 0.96-2.11); their prostate cancer–specific mortality rate was 0.27% (95% CI, 0.21-0.34) and 0.19% (95% CI, 0.14-0.25), respectively.
However, healthy men younger than 75 years had fewer prostate cancer–specific deaths with annual PSA screenings (22 vs 38; AHR=0.56; 95% CI, 0.33-0.95; P=.03). Specifically, the prostate cancer mortality rate was 0.17% (95% CI, 0.11-0.25) in the group that received screening vs 0.31% (95% CI, 0.22-0.42) in the usual care group. Thus, the absolute risk reduction for prostate cancer-specific mortality in men without comorbidities who received yearly screening instead of usual care was 0.14% (0.31% vs 0.17%, P=.03), with a number needed to screen of 723 to prevent one death from prostate cancer. There was a non-significant reduction in all-cause mortality in the intervention group vs the control group (AHR=0.93; 95% CI, 0.86-1.02; P=.11).
WHAT’S NEW: At best, screening has a small benefit
These trials indicate that only a small group of men will potentially benefit from PSA screening. Prior to this meta-analysis, a Cochrane review published in 2006 had concluded that there was insufficient evidence to support or refute the routine use of mass screening for prostate can-cer.10 The meta-analysis by Djulbegovic et al, which included 4 additional trials, 2 of them large, found no benefit of PSA screening in reducing mortality from prostate cancer for the general population.1
Annual screening does appear to provide a small reduction in prostate cancer deaths but no significant reduction in all-cause mortality in men younger than age 75 who have no risk factors for cancer or cardiovascular disease.
CAVEATS: Study limitations, some unknowns
These studies did not address whether certain groups at higher risk of developing prostate cancer, such as African American men and those with a family history of prostate cancer, would benefit from PSA screening. In addition, both of the studies detailed in this PURL had substantive weaknesses.
Methodological limitations of the studies in the meta-analysis included the lack of intention-to-treat analysis and allocation concealment, which favors finding a benefit for the screening arm, and PSA screening in the nonscreening arm, which biases the results toward not finding a screening benefit that might exist. Despite these weaknesses, this meta-analysis brings together the best available evidence of the value of screening for prostate cancer.
In addition, there was no quantitative assessment of complication rates included in the meta-analysis. None of the 6 trials collected data on the effect of screening or treatment on participants’ quality of life.
In the post hoc study showing a benefit for screening healthy men, the decrease in prostate cancer deaths was small in magnitude, did not have an impact on all-cause mortality, and was of marginal statistical significance. Although the data came from the largest multicenter study to date of prostate cancer screening, the results of a post hoc analysis of a single trial should be interpreted with caution. The study was initially designed to test the effect of screening on a general population. Whenever a study deviates from the original hypothesis to evaluate a subset of the study population, the investigators increase the risk of finding a difference where none exists. Thus, it is possible that the findings of benefit for healthy men may not truly be present.
What’s more, the risk factors identified by the authors could be interpreted as arbitrary. They included diverticulosis, which is not known to increase the likelihood of cancer or heart disease, as a risk factor. By the same token, smoking—a known risk factor for both cancer and cardiovascular disease—was not addressed. Finally, potential harms associated with false-positive tests and prostate cancer treatment were not addressed in these studies.
CHALLENGES TO IMPLEMENTATION: Old habits die hard
Clinicians have recommended PSA screening for men >50 years, and men have requested such screening, for more than 2 decades. Physicians often opt to order a PSA test rather than to take the time to explain potential harms and benefits and listen to the patient’s thoughts and feelings about the value of screening. In addition, physicians who believe the lack of benefit from screening does not apply to their patients will continue to order the PSA test. (See “The perils of PSA screening”.)
Patients may opt to continue to be screened although they have developed a risk factor for cardiovascular disease. Also, a decision not to screen directly contradicts the recommendation of the American Urological Association, which calls for annual PSA testing for asymptomatic men with a life expectancy >10 years starting at 40 years of age.11
Shared decision-making
The US Preventive Services Task Force (USPSTF) provides a basis for shared decision-making between physicians and patients concerning prostate cancer screening. The USPSTF states that there is insufficient evidence to recommend for or against prostate cancer screening for the general male population younger than age 75 and recommends against screening men age 75 and older or those with a life expectancy of less than 10 years.12
Decisions regarding PSA screening should be shared and documented for all men between the ages of 50 and 75 years. Advise patients with risk factors that the evidence shows little value and possible harm from screening. Tell healthier men that PSA testing appears to offer a small benefit, at best.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources; the grant is a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
1. Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomized controlled trials. BMJ. 2010;341:c4543.-
2. Crawford ED, Grubb R, 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-361.
3. American Cancer Society. Cancer facts & figures 2010. Atlanta, Ga: American Cancer Society; 2010. Available at: http://www.cancer.org/acs/groups/content/@nho/documents/document/acspc-024113.pdf. Accessed April 13, 2011.
4. American Cancer Society. Prostate cancer. Last medical review November 22, 2010. Available at: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics. Accessed April 13, 2011.
5. National Institutes of Health. Prostate cancer. Last updated February 14, 2011. Available at: http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=60. Accessed May 9, 2011.
6. Lin K, Lipsitz R, Miller T, et al. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149:192-199.
7. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328.
8. Andriole GL, Crawford ED, Grubb RL, 3rd, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319.
9. Stanford JL, Feng Z, Hamilton AS, et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA. 2000;283:354-360.
10. Ilic D, O’Connor D, Greens, Wilt T. Screening for prostate cancer. Cochrane Database Syst Rev. 2006;(3):CD004720.-
11. American Urological Association. Prostate-specific antigen best practice statement: 2009 update. Available at: http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/psa09.pdf. Accessed March 16, 2011.
12. US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:185-191.
Do not routinely screen all men over the age of 50 for prostate cancer with the prostate-specific antigen (PSA) test. Consider screening men younger than 75 with no cardiovascular or cancer risk factors—the only patient population for whom PSA testing appears to provide even a small benefit.1,2
STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis of 6 randomized controlled trials (RCTs) with methodological limitations, and a post hoc analysis of a large RCT.
Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomized controlled trials. BMJ. 2010;341:c4543.
Crawford ED, Grubb R 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-361.
ILLUSTRATIVE CASES
A 65-year-old obese man with high blood pressure comes in for a complete physical and asks if he should have the “blood test for cancer.” He had a normal prostate specific antigen (PSA) the last time he was tested, but that was 10 years ago. What should you tell him?
A 55-year-old man schedules a routine check-up and requests a PSA test. His last test, at age 50, was normal. The patient has no known medical problems and no family history of prostate cancer, and he exercises regularly and doesn’t smoke. How should you respond to his request for a PSA test?
Prostate cancer is the second leading cause of cancer deaths among men in the United States, after lung cancer. One in 6 American men will be diagnosed with prostate cancer; for about 3% of them, the cancer will be fatal.3,4
Widespread testing without evidence of efficacy
The PSA test was approved by the US Food and Drug Administration (FDA) in 1986.5 Its potential to detect early prostate cancer in the hope of decreasing morbidity and mortality led to widespread PSA screening in the 1990s, before data on the efficacy of routine screening existed.
By 2002, only one low-quality RCT that compared screening with no screening had been published. The investigators concluded that screening resulted in lower mortality rates, but a subsequent (and superior) intention-to-treat analysis showed no mortality benefit.6 Two large RCTs, both published in 2009, reported conflicting results.7,8
The European Randomized Study of Screening for Prostate Cancer (ERSPC) enrolled 182,000 men ages 50 to 74 years and randomized them to either PSA screening every 4 years or no screening. Prostate cancer-specific mortality was 20% lower for those in the screening group compared with the no-screening group; however, the absolute risk reduction was only 0.71 deaths per 1000 men.7
The US Prostate, Lung, Colorectal, Ovarian Cancer (PLCO) Screening Trial randomized 77,000 men ages 55 to 74 years to either annual PSA and digital rectal examination (DRE) screening or usual care. After 7 years of follow-up, no significant difference was found in prostate cancer deaths or all-cause mortality in the screening group vs the control group. It is important to note, however, that 52% of the men in the control group had ≥1 PSA screening during the study period, which decreased the researchers’ ability to fully assess the benefits of screening.8
PSA’s limitations and potential harmful effects
The PSA test’s significant limitations and potentially harmful effects counter the potential benefits of screening. About 75% of positive tests are false positives, which are associated with psychological harm in some men for up to a year after the test.6 In addition, diagnostic testing and treatment for what may be nonlife-threatening prostate cancer can cause harm, including erectile dysfunction (ED), urinary incontinence, bowel dysfunction, and death. Rates of ED and incontinence 18 months after radical prostatectomy are an estimated 59.9% and 8.4%, respectively.9
Do the benefits of PSA testing outweigh the harms—and for which men? The meta-analysis and post hoc analysis detailed in this PURL help clear up the controversy.
STUDY SUMMARY: Widespread screening doesn’t save lives
Djulbegovic et al examined 6 RCTs, including the ERSPC and PLCO studies described earlier, that compared screening for prostate cancer (PSA with or without DRE) with no screening or usual care.1 Together, the studies included nearly 390,000 men ages 45 to 80 years, and had 4 to 15 years of follow-up. The results showed that routine screening for prostate cancer had no statistically significant effect on all-cause mortality (relative risk [RR]=0.99; 95% confidence interval [CI], 0.97-1.01), death from prostate cancer (RR=0.88; 95% CI, 0.71-1.09), or diagnosis of stage III or IV prostate cancer (RR=0.94; 95% CI, 0.85-1.04). Routine screening did, however, increase the probability of being diagnosed with prostate cancer at any stage, especially at stage I. For every 1000 men screened, on average, 20 more cases of prostate cancer were diagnosed.
Healthy men may benefit from screening
Crawford et al conducted a post hoc analysis of the PLCO trial, which had found no benefit to annual PSA testing and serial DRE compared with usual care for the general population.2 Their analysis compared the mortality benefits (both prostate cancer–specific and overall) of annual PSA screening for healthy men with no or minimal comorbidities vs the mortality benefits for men with any risk factor for the 2 leading causes of death: cancer and cardiovascular disease.
Annual PSA testing yielded more diagnoses of prostate cancer in both healthy and at-risk men. Deaths from prostate cancer were infrequent in both groups, occurring in 0.22% (164/73,378) of all participants.
Men with ≥1 risk factor had similar prostate cancer–specific deaths with both yearly screening and usual care (62 vs 42 deaths, adjusted hazard ratio [AHR]=1.43; 95% CI, 0.96-2.11); their prostate cancer–specific mortality rate was 0.27% (95% CI, 0.21-0.34) and 0.19% (95% CI, 0.14-0.25), respectively.
However, healthy men younger than 75 years had fewer prostate cancer–specific deaths with annual PSA screenings (22 vs 38; AHR=0.56; 95% CI, 0.33-0.95; P=.03). Specifically, the prostate cancer mortality rate was 0.17% (95% CI, 0.11-0.25) in the group that received screening vs 0.31% (95% CI, 0.22-0.42) in the usual care group. Thus, the absolute risk reduction for prostate cancer-specific mortality in men without comorbidities who received yearly screening instead of usual care was 0.14% (0.31% vs 0.17%, P=.03), with a number needed to screen of 723 to prevent one death from prostate cancer. There was a non-significant reduction in all-cause mortality in the intervention group vs the control group (AHR=0.93; 95% CI, 0.86-1.02; P=.11).
WHAT’S NEW: At best, screening has a small benefit
These trials indicate that only a small group of men will potentially benefit from PSA screening. Prior to this meta-analysis, a Cochrane review published in 2006 had concluded that there was insufficient evidence to support or refute the routine use of mass screening for prostate can-cer.10 The meta-analysis by Djulbegovic et al, which included 4 additional trials, 2 of them large, found no benefit of PSA screening in reducing mortality from prostate cancer for the general population.1
Annual screening does appear to provide a small reduction in prostate cancer deaths but no significant reduction in all-cause mortality in men younger than age 75 who have no risk factors for cancer or cardiovascular disease.
CAVEATS: Study limitations, some unknowns
These studies did not address whether certain groups at higher risk of developing prostate cancer, such as African American men and those with a family history of prostate cancer, would benefit from PSA screening. In addition, both of the studies detailed in this PURL had substantive weaknesses.
Methodological limitations of the studies in the meta-analysis included the lack of intention-to-treat analysis and allocation concealment, which favors finding a benefit for the screening arm, and PSA screening in the nonscreening arm, which biases the results toward not finding a screening benefit that might exist. Despite these weaknesses, this meta-analysis brings together the best available evidence of the value of screening for prostate cancer.
In addition, there was no quantitative assessment of complication rates included in the meta-analysis. None of the 6 trials collected data on the effect of screening or treatment on participants’ quality of life.
In the post hoc study showing a benefit for screening healthy men, the decrease in prostate cancer deaths was small in magnitude, did not have an impact on all-cause mortality, and was of marginal statistical significance. Although the data came from the largest multicenter study to date of prostate cancer screening, the results of a post hoc analysis of a single trial should be interpreted with caution. The study was initially designed to test the effect of screening on a general population. Whenever a study deviates from the original hypothesis to evaluate a subset of the study population, the investigators increase the risk of finding a difference where none exists. Thus, it is possible that the findings of benefit for healthy men may not truly be present.
What’s more, the risk factors identified by the authors could be interpreted as arbitrary. They included diverticulosis, which is not known to increase the likelihood of cancer or heart disease, as a risk factor. By the same token, smoking—a known risk factor for both cancer and cardiovascular disease—was not addressed. Finally, potential harms associated with false-positive tests and prostate cancer treatment were not addressed in these studies.
CHALLENGES TO IMPLEMENTATION: Old habits die hard
Clinicians have recommended PSA screening for men >50 years, and men have requested such screening, for more than 2 decades. Physicians often opt to order a PSA test rather than to take the time to explain potential harms and benefits and listen to the patient’s thoughts and feelings about the value of screening. In addition, physicians who believe the lack of benefit from screening does not apply to their patients will continue to order the PSA test. (See “The perils of PSA screening”.)
Patients may opt to continue to be screened although they have developed a risk factor for cardiovascular disease. Also, a decision not to screen directly contradicts the recommendation of the American Urological Association, which calls for annual PSA testing for asymptomatic men with a life expectancy >10 years starting at 40 years of age.11
Shared decision-making
The US Preventive Services Task Force (USPSTF) provides a basis for shared decision-making between physicians and patients concerning prostate cancer screening. The USPSTF states that there is insufficient evidence to recommend for or against prostate cancer screening for the general male population younger than age 75 and recommends against screening men age 75 and older or those with a life expectancy of less than 10 years.12
Decisions regarding PSA screening should be shared and documented for all men between the ages of 50 and 75 years. Advise patients with risk factors that the evidence shows little value and possible harm from screening. Tell healthier men that PSA testing appears to offer a small benefit, at best.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources; the grant is a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
Do not routinely screen all men over the age of 50 for prostate cancer with the prostate-specific antigen (PSA) test. Consider screening men younger than 75 with no cardiovascular or cancer risk factors—the only patient population for whom PSA testing appears to provide even a small benefit.1,2
STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis of 6 randomized controlled trials (RCTs) with methodological limitations, and a post hoc analysis of a large RCT.
Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomized controlled trials. BMJ. 2010;341:c4543.
Crawford ED, Grubb R 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-361.
ILLUSTRATIVE CASES
A 65-year-old obese man with high blood pressure comes in for a complete physical and asks if he should have the “blood test for cancer.” He had a normal prostate specific antigen (PSA) the last time he was tested, but that was 10 years ago. What should you tell him?
A 55-year-old man schedules a routine check-up and requests a PSA test. His last test, at age 50, was normal. The patient has no known medical problems and no family history of prostate cancer, and he exercises regularly and doesn’t smoke. How should you respond to his request for a PSA test?
Prostate cancer is the second leading cause of cancer deaths among men in the United States, after lung cancer. One in 6 American men will be diagnosed with prostate cancer; for about 3% of them, the cancer will be fatal.3,4
Widespread testing without evidence of efficacy
The PSA test was approved by the US Food and Drug Administration (FDA) in 1986.5 Its potential to detect early prostate cancer in the hope of decreasing morbidity and mortality led to widespread PSA screening in the 1990s, before data on the efficacy of routine screening existed.
By 2002, only one low-quality RCT that compared screening with no screening had been published. The investigators concluded that screening resulted in lower mortality rates, but a subsequent (and superior) intention-to-treat analysis showed no mortality benefit.6 Two large RCTs, both published in 2009, reported conflicting results.7,8
The European Randomized Study of Screening for Prostate Cancer (ERSPC) enrolled 182,000 men ages 50 to 74 years and randomized them to either PSA screening every 4 years or no screening. Prostate cancer-specific mortality was 20% lower for those in the screening group compared with the no-screening group; however, the absolute risk reduction was only 0.71 deaths per 1000 men.7
The US Prostate, Lung, Colorectal, Ovarian Cancer (PLCO) Screening Trial randomized 77,000 men ages 55 to 74 years to either annual PSA and digital rectal examination (DRE) screening or usual care. After 7 years of follow-up, no significant difference was found in prostate cancer deaths or all-cause mortality in the screening group vs the control group. It is important to note, however, that 52% of the men in the control group had ≥1 PSA screening during the study period, which decreased the researchers’ ability to fully assess the benefits of screening.8
PSA’s limitations and potential harmful effects
The PSA test’s significant limitations and potentially harmful effects counter the potential benefits of screening. About 75% of positive tests are false positives, which are associated with psychological harm in some men for up to a year after the test.6 In addition, diagnostic testing and treatment for what may be nonlife-threatening prostate cancer can cause harm, including erectile dysfunction (ED), urinary incontinence, bowel dysfunction, and death. Rates of ED and incontinence 18 months after radical prostatectomy are an estimated 59.9% and 8.4%, respectively.9
Do the benefits of PSA testing outweigh the harms—and for which men? The meta-analysis and post hoc analysis detailed in this PURL help clear up the controversy.
STUDY SUMMARY: Widespread screening doesn’t save lives
Djulbegovic et al examined 6 RCTs, including the ERSPC and PLCO studies described earlier, that compared screening for prostate cancer (PSA with or without DRE) with no screening or usual care.1 Together, the studies included nearly 390,000 men ages 45 to 80 years, and had 4 to 15 years of follow-up. The results showed that routine screening for prostate cancer had no statistically significant effect on all-cause mortality (relative risk [RR]=0.99; 95% confidence interval [CI], 0.97-1.01), death from prostate cancer (RR=0.88; 95% CI, 0.71-1.09), or diagnosis of stage III or IV prostate cancer (RR=0.94; 95% CI, 0.85-1.04). Routine screening did, however, increase the probability of being diagnosed with prostate cancer at any stage, especially at stage I. For every 1000 men screened, on average, 20 more cases of prostate cancer were diagnosed.
Healthy men may benefit from screening
Crawford et al conducted a post hoc analysis of the PLCO trial, which had found no benefit to annual PSA testing and serial DRE compared with usual care for the general population.2 Their analysis compared the mortality benefits (both prostate cancer–specific and overall) of annual PSA screening for healthy men with no or minimal comorbidities vs the mortality benefits for men with any risk factor for the 2 leading causes of death: cancer and cardiovascular disease.
Annual PSA testing yielded more diagnoses of prostate cancer in both healthy and at-risk men. Deaths from prostate cancer were infrequent in both groups, occurring in 0.22% (164/73,378) of all participants.
Men with ≥1 risk factor had similar prostate cancer–specific deaths with both yearly screening and usual care (62 vs 42 deaths, adjusted hazard ratio [AHR]=1.43; 95% CI, 0.96-2.11); their prostate cancer–specific mortality rate was 0.27% (95% CI, 0.21-0.34) and 0.19% (95% CI, 0.14-0.25), respectively.
However, healthy men younger than 75 years had fewer prostate cancer–specific deaths with annual PSA screenings (22 vs 38; AHR=0.56; 95% CI, 0.33-0.95; P=.03). Specifically, the prostate cancer mortality rate was 0.17% (95% CI, 0.11-0.25) in the group that received screening vs 0.31% (95% CI, 0.22-0.42) in the usual care group. Thus, the absolute risk reduction for prostate cancer-specific mortality in men without comorbidities who received yearly screening instead of usual care was 0.14% (0.31% vs 0.17%, P=.03), with a number needed to screen of 723 to prevent one death from prostate cancer. There was a non-significant reduction in all-cause mortality in the intervention group vs the control group (AHR=0.93; 95% CI, 0.86-1.02; P=.11).
WHAT’S NEW: At best, screening has a small benefit
These trials indicate that only a small group of men will potentially benefit from PSA screening. Prior to this meta-analysis, a Cochrane review published in 2006 had concluded that there was insufficient evidence to support or refute the routine use of mass screening for prostate can-cer.10 The meta-analysis by Djulbegovic et al, which included 4 additional trials, 2 of them large, found no benefit of PSA screening in reducing mortality from prostate cancer for the general population.1
Annual screening does appear to provide a small reduction in prostate cancer deaths but no significant reduction in all-cause mortality in men younger than age 75 who have no risk factors for cancer or cardiovascular disease.
CAVEATS: Study limitations, some unknowns
These studies did not address whether certain groups at higher risk of developing prostate cancer, such as African American men and those with a family history of prostate cancer, would benefit from PSA screening. In addition, both of the studies detailed in this PURL had substantive weaknesses.
Methodological limitations of the studies in the meta-analysis included the lack of intention-to-treat analysis and allocation concealment, which favors finding a benefit for the screening arm, and PSA screening in the nonscreening arm, which biases the results toward not finding a screening benefit that might exist. Despite these weaknesses, this meta-analysis brings together the best available evidence of the value of screening for prostate cancer.
In addition, there was no quantitative assessment of complication rates included in the meta-analysis. None of the 6 trials collected data on the effect of screening or treatment on participants’ quality of life.
In the post hoc study showing a benefit for screening healthy men, the decrease in prostate cancer deaths was small in magnitude, did not have an impact on all-cause mortality, and was of marginal statistical significance. Although the data came from the largest multicenter study to date of prostate cancer screening, the results of a post hoc analysis of a single trial should be interpreted with caution. The study was initially designed to test the effect of screening on a general population. Whenever a study deviates from the original hypothesis to evaluate a subset of the study population, the investigators increase the risk of finding a difference where none exists. Thus, it is possible that the findings of benefit for healthy men may not truly be present.
What’s more, the risk factors identified by the authors could be interpreted as arbitrary. They included diverticulosis, which is not known to increase the likelihood of cancer or heart disease, as a risk factor. By the same token, smoking—a known risk factor for both cancer and cardiovascular disease—was not addressed. Finally, potential harms associated with false-positive tests and prostate cancer treatment were not addressed in these studies.
CHALLENGES TO IMPLEMENTATION: Old habits die hard
Clinicians have recommended PSA screening for men >50 years, and men have requested such screening, for more than 2 decades. Physicians often opt to order a PSA test rather than to take the time to explain potential harms and benefits and listen to the patient’s thoughts and feelings about the value of screening. In addition, physicians who believe the lack of benefit from screening does not apply to their patients will continue to order the PSA test. (See “The perils of PSA screening”.)
Patients may opt to continue to be screened although they have developed a risk factor for cardiovascular disease. Also, a decision not to screen directly contradicts the recommendation of the American Urological Association, which calls for annual PSA testing for asymptomatic men with a life expectancy >10 years starting at 40 years of age.11
Shared decision-making
The US Preventive Services Task Force (USPSTF) provides a basis for shared decision-making between physicians and patients concerning prostate cancer screening. The USPSTF states that there is insufficient evidence to recommend for or against prostate cancer screening for the general male population younger than age 75 and recommends against screening men age 75 and older or those with a life expectancy of less than 10 years.12
Decisions regarding PSA screening should be shared and documented for all men between the ages of 50 and 75 years. Advise patients with risk factors that the evidence shows little value and possible harm from screening. Tell healthier men that PSA testing appears to offer a small benefit, at best.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources; the grant is a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
1. Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomized controlled trials. BMJ. 2010;341:c4543.-
2. Crawford ED, Grubb R, 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-361.
3. American Cancer Society. Cancer facts & figures 2010. Atlanta, Ga: American Cancer Society; 2010. Available at: http://www.cancer.org/acs/groups/content/@nho/documents/document/acspc-024113.pdf. Accessed April 13, 2011.
4. American Cancer Society. Prostate cancer. Last medical review November 22, 2010. Available at: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics. Accessed April 13, 2011.
5. National Institutes of Health. Prostate cancer. Last updated February 14, 2011. Available at: http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=60. Accessed May 9, 2011.
6. Lin K, Lipsitz R, Miller T, et al. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149:192-199.
7. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328.
8. Andriole GL, Crawford ED, Grubb RL, 3rd, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319.
9. Stanford JL, Feng Z, Hamilton AS, et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA. 2000;283:354-360.
10. Ilic D, O’Connor D, Greens, Wilt T. Screening for prostate cancer. Cochrane Database Syst Rev. 2006;(3):CD004720.-
11. American Urological Association. Prostate-specific antigen best practice statement: 2009 update. Available at: http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/psa09.pdf. Accessed March 16, 2011.
12. US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:185-191.
1. Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomized controlled trials. BMJ. 2010;341:c4543.-
2. Crawford ED, Grubb R, 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-361.
3. American Cancer Society. Cancer facts & figures 2010. Atlanta, Ga: American Cancer Society; 2010. Available at: http://www.cancer.org/acs/groups/content/@nho/documents/document/acspc-024113.pdf. Accessed April 13, 2011.
4. American Cancer Society. Prostate cancer. Last medical review November 22, 2010. Available at: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics. Accessed April 13, 2011.
5. National Institutes of Health. Prostate cancer. Last updated February 14, 2011. Available at: http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=60. Accessed May 9, 2011.
6. Lin K, Lipsitz R, Miller T, et al. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149:192-199.
7. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328.
8. Andriole GL, Crawford ED, Grubb RL, 3rd, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319.
9. Stanford JL, Feng Z, Hamilton AS, et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA. 2000;283:354-360.
10. Ilic D, O’Connor D, Greens, Wilt T. Screening for prostate cancer. Cochrane Database Syst Rev. 2006;(3):CD004720.-
11. American Urological Association. Prostate-specific antigen best practice statement: 2009 update. Available at: http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/psa09.pdf. Accessed March 16, 2011.
12. US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:185-191.
Copyright © 2011 The Family Physicians Inquiries Network.
All rights reserved.
How should we use the coronary artery calcium score to predict cardiovascular risk?
THE CORONARY ARTERY CALCIUM (CAC) SCORE—an independent predictor of cardiovascular events (strength of recommendation [SOR]: C, systematic review of disease-oriented outcomes)—can be used, in addition to traditional risk factor assessment, to further stratify the risk of coronary heart disease (CHD) in asymptomatic patients (SOR: C, multiple large observational studies with disease-oriented outcomes).
Although a high CAC score is associated with a greater risk of cardiovascular disease, no studies have evaluated cardiovascular outcomes of CAC-guided treatment, so its value remains theoretical.
Evidence summary
Most atherosclerotic lesions are calcified. The degree of calcification is proportional to the severity of atherosclerosis and can be quantified by the CAC score as measured by electron beam computed tomography (EBCT).1
As the CAC score rises, so does risk
A systematic review of 9 studies evaluated the relationship between CAC scores and coronary artery disease (CAD) in asymptomatic patients (TABLE). CAD was measured by such clinical outcomes as unstable angina, myocardial infarction, stroke, coronary death, all-cause mortality, or need for revascularization. The relative risk of CAD for a moderate CAC score compared with a low score was 3.5 (95% confidence interval [CI], 2.4-5.1) and for a high score compared with a low score was 9.9 (95% CI, 5.3-17.6). Some of the studies were of poor quality, including self-referred patients, for example.2
A subsequent study found similar associations. The observational study of 25,253 asymptomatic individuals referred for CAC testing to assess cardiovascular risk demonstrated that CAC was an independent predictor of all-cause mortality. After a mean of 6.8 years, the adjusted relative risk increased incrementally from 1.48 (95% CI, 0.71-3.07) for a CAC score of 1 to 10, to 9.36 (95% CI, 5.36-16.33) for a score ≥1,000, compared with a score of 0.3
Table
What does that CAC score mean?1
| Score | Severity of disease |
|---|---|
| <1 | No identifiable disease |
| 1-10 | Mild |
| 11-100 | Moderate |
| 101-400 | Moderate to high |
| >400 | Severe |
| CAC, coronary artery calcium. | |
CAC predicts risk, but does it improve treatment or outcomes?
Analysis of 3201 women followed for an average of 3.75 years in the Multi-Ethnic Study of Atherosclerosis cohort revealed that women at low Framingham risk, but with detectable CAC, had an increased risk of CHD (hazard ratio [HR]=6.5; 95% CI, 2.6-16.4) and cardiovascular disease events (HR=5.2; 95% CI, 2.5-10.8).4
The St. Francis Heart Study prospectively compared CAC with standard CHD risk factors for predicting atherosclerotic cardiovascular disease (ASCVD) events in 4903 asymptomatic people between 50 and 70 years of age. For CAC scores ≥100 compared with scores <100, relative risk was 9.6 (95% CI, 6.7-13.9) for all ASCVD events, 11.1 (95% CI, 7.3-16.7) for all CHD events, and 9.2 (95% CI, 4.9-17.3) for nonfatal myocardial infarction and death. The CAC score predicted CHD events more accurately than standard risk factors and reclassified 24% of intermediate-risk women and 17% of intermediate-risk men into a higher-risk group.5
Despite studies that correlate higher CAC score with increased cardiovascular risk, we found no evidence that testing leads to improved treatment for preventing CHD or better cardiovascular outcomes.
Recommendations
The American College of Cardiology suggests that measuring CAC may be reasonable for asymptomatic patients with intermediate CHD risk (10%-20% 10-year risk of CHD events), for whom elevated CAC scores could lead to a higher-risk classification and subsequent modification of management.6 The College doesn’t recommend evaluating CAC in patients with low CHD risk, because it would constitute screening the general population, or asymptomatic patients with high CHD risk, who are already candidates for intensive risk modification.
The US Preventive Services Task Force conducted its own review and concluded that although the CAC score is an independent predictor of major CHD events, insufficient evidence exists to support its use to further stratify risk in intermediate-risk patients.7
1. Rumberger JA, Brundage BH, Rader DJ, et al. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc. 1999;74:243-252.
2. Dendukuri N, Chiu K, Brophy JM. Validity of electron beam computed tomography for coronary artery disease: a systematic review and meta-analysis. BMC Med. 2007;5:35.-
3. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49:1860-1870.
4. Lakoski SG, Greenland P, Wong N, et al. Coronary artery calcium scores and risk for cardiovascular events in women classified as “low risk” based on Framingham risk score: the multi-ethnic study of atherosclerosis (MESA). Arch Intern Med. 2007;167:2437-2442.
5. Arad Y, Goodman KJ, Roth M, et al. Coronary calcification, coronary disease risk factors, creactive protein, and atherosclerotic cardiovascular disease events. J Am Coll Cardiol. 2005;46:158-165.
6. Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document of Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol. 2007;49:378-402.
7. US Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:474-482.
THE CORONARY ARTERY CALCIUM (CAC) SCORE—an independent predictor of cardiovascular events (strength of recommendation [SOR]: C, systematic review of disease-oriented outcomes)—can be used, in addition to traditional risk factor assessment, to further stratify the risk of coronary heart disease (CHD) in asymptomatic patients (SOR: C, multiple large observational studies with disease-oriented outcomes).
Although a high CAC score is associated with a greater risk of cardiovascular disease, no studies have evaluated cardiovascular outcomes of CAC-guided treatment, so its value remains theoretical.
Evidence summary
Most atherosclerotic lesions are calcified. The degree of calcification is proportional to the severity of atherosclerosis and can be quantified by the CAC score as measured by electron beam computed tomography (EBCT).1
As the CAC score rises, so does risk
A systematic review of 9 studies evaluated the relationship between CAC scores and coronary artery disease (CAD) in asymptomatic patients (TABLE). CAD was measured by such clinical outcomes as unstable angina, myocardial infarction, stroke, coronary death, all-cause mortality, or need for revascularization. The relative risk of CAD for a moderate CAC score compared with a low score was 3.5 (95% confidence interval [CI], 2.4-5.1) and for a high score compared with a low score was 9.9 (95% CI, 5.3-17.6). Some of the studies were of poor quality, including self-referred patients, for example.2
A subsequent study found similar associations. The observational study of 25,253 asymptomatic individuals referred for CAC testing to assess cardiovascular risk demonstrated that CAC was an independent predictor of all-cause mortality. After a mean of 6.8 years, the adjusted relative risk increased incrementally from 1.48 (95% CI, 0.71-3.07) for a CAC score of 1 to 10, to 9.36 (95% CI, 5.36-16.33) for a score ≥1,000, compared with a score of 0.3
Table
What does that CAC score mean?1
| Score | Severity of disease |
|---|---|
| <1 | No identifiable disease |
| 1-10 | Mild |
| 11-100 | Moderate |
| 101-400 | Moderate to high |
| >400 | Severe |
| CAC, coronary artery calcium. | |
CAC predicts risk, but does it improve treatment or outcomes?
Analysis of 3201 women followed for an average of 3.75 years in the Multi-Ethnic Study of Atherosclerosis cohort revealed that women at low Framingham risk, but with detectable CAC, had an increased risk of CHD (hazard ratio [HR]=6.5; 95% CI, 2.6-16.4) and cardiovascular disease events (HR=5.2; 95% CI, 2.5-10.8).4
The St. Francis Heart Study prospectively compared CAC with standard CHD risk factors for predicting atherosclerotic cardiovascular disease (ASCVD) events in 4903 asymptomatic people between 50 and 70 years of age. For CAC scores ≥100 compared with scores <100, relative risk was 9.6 (95% CI, 6.7-13.9) for all ASCVD events, 11.1 (95% CI, 7.3-16.7) for all CHD events, and 9.2 (95% CI, 4.9-17.3) for nonfatal myocardial infarction and death. The CAC score predicted CHD events more accurately than standard risk factors and reclassified 24% of intermediate-risk women and 17% of intermediate-risk men into a higher-risk group.5
Despite studies that correlate higher CAC score with increased cardiovascular risk, we found no evidence that testing leads to improved treatment for preventing CHD or better cardiovascular outcomes.
Recommendations
The American College of Cardiology suggests that measuring CAC may be reasonable for asymptomatic patients with intermediate CHD risk (10%-20% 10-year risk of CHD events), for whom elevated CAC scores could lead to a higher-risk classification and subsequent modification of management.6 The College doesn’t recommend evaluating CAC in patients with low CHD risk, because it would constitute screening the general population, or asymptomatic patients with high CHD risk, who are already candidates for intensive risk modification.
The US Preventive Services Task Force conducted its own review and concluded that although the CAC score is an independent predictor of major CHD events, insufficient evidence exists to support its use to further stratify risk in intermediate-risk patients.7
THE CORONARY ARTERY CALCIUM (CAC) SCORE—an independent predictor of cardiovascular events (strength of recommendation [SOR]: C, systematic review of disease-oriented outcomes)—can be used, in addition to traditional risk factor assessment, to further stratify the risk of coronary heart disease (CHD) in asymptomatic patients (SOR: C, multiple large observational studies with disease-oriented outcomes).
Although a high CAC score is associated with a greater risk of cardiovascular disease, no studies have evaluated cardiovascular outcomes of CAC-guided treatment, so its value remains theoretical.
Evidence summary
Most atherosclerotic lesions are calcified. The degree of calcification is proportional to the severity of atherosclerosis and can be quantified by the CAC score as measured by electron beam computed tomography (EBCT).1
As the CAC score rises, so does risk
A systematic review of 9 studies evaluated the relationship between CAC scores and coronary artery disease (CAD) in asymptomatic patients (TABLE). CAD was measured by such clinical outcomes as unstable angina, myocardial infarction, stroke, coronary death, all-cause mortality, or need for revascularization. The relative risk of CAD for a moderate CAC score compared with a low score was 3.5 (95% confidence interval [CI], 2.4-5.1) and for a high score compared with a low score was 9.9 (95% CI, 5.3-17.6). Some of the studies were of poor quality, including self-referred patients, for example.2
A subsequent study found similar associations. The observational study of 25,253 asymptomatic individuals referred for CAC testing to assess cardiovascular risk demonstrated that CAC was an independent predictor of all-cause mortality. After a mean of 6.8 years, the adjusted relative risk increased incrementally from 1.48 (95% CI, 0.71-3.07) for a CAC score of 1 to 10, to 9.36 (95% CI, 5.36-16.33) for a score ≥1,000, compared with a score of 0.3
Table
What does that CAC score mean?1
| Score | Severity of disease |
|---|---|
| <1 | No identifiable disease |
| 1-10 | Mild |
| 11-100 | Moderate |
| 101-400 | Moderate to high |
| >400 | Severe |
| CAC, coronary artery calcium. | |
CAC predicts risk, but does it improve treatment or outcomes?
Analysis of 3201 women followed for an average of 3.75 years in the Multi-Ethnic Study of Atherosclerosis cohort revealed that women at low Framingham risk, but with detectable CAC, had an increased risk of CHD (hazard ratio [HR]=6.5; 95% CI, 2.6-16.4) and cardiovascular disease events (HR=5.2; 95% CI, 2.5-10.8).4
The St. Francis Heart Study prospectively compared CAC with standard CHD risk factors for predicting atherosclerotic cardiovascular disease (ASCVD) events in 4903 asymptomatic people between 50 and 70 years of age. For CAC scores ≥100 compared with scores <100, relative risk was 9.6 (95% CI, 6.7-13.9) for all ASCVD events, 11.1 (95% CI, 7.3-16.7) for all CHD events, and 9.2 (95% CI, 4.9-17.3) for nonfatal myocardial infarction and death. The CAC score predicted CHD events more accurately than standard risk factors and reclassified 24% of intermediate-risk women and 17% of intermediate-risk men into a higher-risk group.5
Despite studies that correlate higher CAC score with increased cardiovascular risk, we found no evidence that testing leads to improved treatment for preventing CHD or better cardiovascular outcomes.
Recommendations
The American College of Cardiology suggests that measuring CAC may be reasonable for asymptomatic patients with intermediate CHD risk (10%-20% 10-year risk of CHD events), for whom elevated CAC scores could lead to a higher-risk classification and subsequent modification of management.6 The College doesn’t recommend evaluating CAC in patients with low CHD risk, because it would constitute screening the general population, or asymptomatic patients with high CHD risk, who are already candidates for intensive risk modification.
The US Preventive Services Task Force conducted its own review and concluded that although the CAC score is an independent predictor of major CHD events, insufficient evidence exists to support its use to further stratify risk in intermediate-risk patients.7
1. Rumberger JA, Brundage BH, Rader DJ, et al. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc. 1999;74:243-252.
2. Dendukuri N, Chiu K, Brophy JM. Validity of electron beam computed tomography for coronary artery disease: a systematic review and meta-analysis. BMC Med. 2007;5:35.-
3. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49:1860-1870.
4. Lakoski SG, Greenland P, Wong N, et al. Coronary artery calcium scores and risk for cardiovascular events in women classified as “low risk” based on Framingham risk score: the multi-ethnic study of atherosclerosis (MESA). Arch Intern Med. 2007;167:2437-2442.
5. Arad Y, Goodman KJ, Roth M, et al. Coronary calcification, coronary disease risk factors, creactive protein, and atherosclerotic cardiovascular disease events. J Am Coll Cardiol. 2005;46:158-165.
6. Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document of Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol. 2007;49:378-402.
7. US Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:474-482.
1. Rumberger JA, Brundage BH, Rader DJ, et al. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc. 1999;74:243-252.
2. Dendukuri N, Chiu K, Brophy JM. Validity of electron beam computed tomography for coronary artery disease: a systematic review and meta-analysis. BMC Med. 2007;5:35.-
3. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49:1860-1870.
4. Lakoski SG, Greenland P, Wong N, et al. Coronary artery calcium scores and risk for cardiovascular events in women classified as “low risk” based on Framingham risk score: the multi-ethnic study of atherosclerosis (MESA). Arch Intern Med. 2007;167:2437-2442.
5. Arad Y, Goodman KJ, Roth M, et al. Coronary calcification, coronary disease risk factors, creactive protein, and atherosclerotic cardiovascular disease events. J Am Coll Cardiol. 2005;46:158-165.
6. Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document of Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol. 2007;49:378-402.
7. US Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:474-482.
Evidence-based answers from the Family Physicians Inquiries Network
Which treatments work best for hemorrhoids?
Excision is the most effective treatment for thrombosed external hemorrhoids (strength of recommendation [SOR]: B, retrospective studies). For prolapsed internal hemorrhoids, the best definitive treatment is traditional hemorrhoidectomy (SOR: A, systematic reviews). Of nonoperative techniques, rubber band ligation produces the lowest rate of recurrence (SOR: A, systematic reviews).
Evidence summary
External hemorrhoids originate below the dentate line and become acutely painful with thrombosis. They can cause perianal pruritus and excoriation because of interference with perianal hygiene. Internal hemorrhoids become symptomatic when they bleed or prolapse (TABLE).
TABLE
Classification of symptomatic internal hemorrhoids
| GRADE | DESCRIPTION |
|---|---|
| I | Hemorrhoids do not protrude, but may bleed |
| II | Hemorrhoids protrude with defecation, but reduce spontaneously |
| III | Hemorrhoids protrude and must be reduced by hand |
| IV | Hemorrhoids are permanently prolapsed |
| Source: Madoff RD, et al. Gastroenterology. 2004.10 | |
For thrombosed external hemorrhoids, surgery works best
Few studies have evaluated the best treatment for thrombosed external hemorrhoids. A retrospective study of 231 patients treated conservatively or surgically found that the 48.5% of patients treated surgically had a lower recurrence rate than the conservative group (number needed to treat [NNT]=2 for recurrence at mean follow-up of 7.6 months) and earlier resolution of symptoms (average 3.9 days compared with 24 days for conservative treatment).1
Another retrospective analysis of 340 patients who underwent outpatient excision of thrombosed external hemorrhoids under local anesthesia reported a low recurrence rate of 6.5% at a mean follow-up of 17.3 months.2
A prospective, randomized controlled trial (RCT) of 98 patients treated nonsurgically found improved pain relief with a combination of topical nifedipine 0.3% and lidocaine 1.5% compared with lidocaine alone. The NNT for complete pain relief at 7 days was 3.3
Conventional hemorrhoidectomy beats stapling
Many studies have evaluated the best treatment for prolapsed hemorrhoids. A Cochrane systematic review of 12 RCTs that compared conventional hemorrhoidectomy with stapled hemorrhoidectomy in patients with grades I to III hemorrhoids found a lower rate of recurrence (follow-up ranged from 6 to 39 months) in patients who had conventional hemorrhoidectomy (NNT=14).4 Conventional hemorrhoidectomy showed a nonsignificant trend in decreased bleeding and decreased incontinence.
A second systematic review of 25 studies, including some that were of lower quality, showed a higher recurrence rate at 1 year with stapled hemorrhoidectomy than with conventional surgery.5
Nonoperative techniques? Consider rubber band ligation
A systematic review of 3 poor-quality trials comparing rubber band ligation with excisional hemorrhoidectomy in patients with grade III hemorrhoids found that excisional hemorrhoidectomy produced better long-term symptom control but more immediate postoperative complications of anal stenosis and hemorrhage.6 Rubber band ligation had the lowest recurrence rate at 12 months compared with the other nonoperative techniques of sclerotherapy and infrared coagulation.7
Fiber supplements help relieve symptoms
A Cochrane systematic review of 7 RCTs enrolling a total of 378 patients with grade I to III hemorrhoids evaluated the effect of fiber supplements on pain, itching, and bleeding. Persistent hemorrhoid symptoms decreased by 53% in the group receiving fiber.8
When surgical hemorrhoidectomy is recommended
The American Society of Colon and Rectal Surgeons recommends adequate fluid and fiber intake for all patients with symptomatic hemorrhoids. For grade I to III hemorrhoids, the society states that banding is usually most effective. When office treatments fail, the society recommends surgical hemorrhoidectomy (SOR: B).
The society recommends excision of thrombosed hemorrhoids less than 72 hours old and expectant treatment with analgesia and sitz baths for thrombosed hemorrhoids present for longer than 72 hours (SOR: B).9
The American Gastroenterological Association recommends excision of symptomatic thrombosed external hemorrhoids that present early. Surgical hemorrhoidectomy should be reserved for when conservative treatment fails and for patients with symptomatic grade III and IV hemorrhoids.10
1. Greenspon J, Williams SB, Young HA, et al. Thrombosed external hemorrhoids: outcome after conservative or surgical management. Dis Colon Rectum. 2004;47:1493-1498.
2. Jongen J, Bach S, Stubinger SH, et al. Excision of thrombosed external hemorrhoids under local anesthesia: a retrospective evaluation of 340 patients. Dis Colon Rectum. 2003;46:1226-1231.
3. Perrotti P, Antropoli C, Molino D, et al. Conservative treatment of acute thrombosed external hemorrhoids with topical nifedipine. Dis Colon Rectum. 2001;44:405-409.
4. Jayaraman S, Colquhoun PH, Malthaner RA. Stapled versus conventional surgery for hemorrhoids. Cochrane Database Syst Rev. 2006;(4):CD005393.-
5. Tjandra JJ, Chan MK. Systematic review on the procedure for prolapse and hemorrhoids (stapled hemorrhoidopexy). Dis Colon Rectum. 2007;50:878-892.
6. Shanmugam V, Thaha MA, Rabindranath KS, et al. Systematic review of randomized trials comparing rubber band ligation with excisional haemorrhoidectomy. Br J Surg. 2005;92:1481-1487.
7. Johanson JF, Rimm A. Optimal nonsurgical treatment of hemorrhoids: a comparative analysis of infrared coagulation, rubber band ligation, and injection sclerotherapy. Am J Gastroenterol. 1992;87:1600-1606.
8. Alonso-Coello P, Guyatt G, Heels-Ansdell D, et al. Laxatives for the treatment of hemorrhoids. Cochrane Database Syst Rev. 2005(4):CD004649.-
9. Cataldo P, Ellis CN, Gregorcyk S, et al. Practice parameters for the management of hemorrhoids (revised). Dis Colon Rectum. 2005;48:189-194.
10. Madoff RD, Fleshman JW. American Gastroenterological Association Clinical Practice Committee. American Gastroenterological Association technical review on the diagnosis and treatment of hemorrhoids. Gastroenterology. 2004;126:1463-1473.
Excision is the most effective treatment for thrombosed external hemorrhoids (strength of recommendation [SOR]: B, retrospective studies). For prolapsed internal hemorrhoids, the best definitive treatment is traditional hemorrhoidectomy (SOR: A, systematic reviews). Of nonoperative techniques, rubber band ligation produces the lowest rate of recurrence (SOR: A, systematic reviews).
Evidence summary
External hemorrhoids originate below the dentate line and become acutely painful with thrombosis. They can cause perianal pruritus and excoriation because of interference with perianal hygiene. Internal hemorrhoids become symptomatic when they bleed or prolapse (TABLE).
TABLE
Classification of symptomatic internal hemorrhoids
| GRADE | DESCRIPTION |
|---|---|
| I | Hemorrhoids do not protrude, but may bleed |
| II | Hemorrhoids protrude with defecation, but reduce spontaneously |
| III | Hemorrhoids protrude and must be reduced by hand |
| IV | Hemorrhoids are permanently prolapsed |
| Source: Madoff RD, et al. Gastroenterology. 2004.10 | |
For thrombosed external hemorrhoids, surgery works best
Few studies have evaluated the best treatment for thrombosed external hemorrhoids. A retrospective study of 231 patients treated conservatively or surgically found that the 48.5% of patients treated surgically had a lower recurrence rate than the conservative group (number needed to treat [NNT]=2 for recurrence at mean follow-up of 7.6 months) and earlier resolution of symptoms (average 3.9 days compared with 24 days for conservative treatment).1
Another retrospective analysis of 340 patients who underwent outpatient excision of thrombosed external hemorrhoids under local anesthesia reported a low recurrence rate of 6.5% at a mean follow-up of 17.3 months.2
A prospective, randomized controlled trial (RCT) of 98 patients treated nonsurgically found improved pain relief with a combination of topical nifedipine 0.3% and lidocaine 1.5% compared with lidocaine alone. The NNT for complete pain relief at 7 days was 3.3
Conventional hemorrhoidectomy beats stapling
Many studies have evaluated the best treatment for prolapsed hemorrhoids. A Cochrane systematic review of 12 RCTs that compared conventional hemorrhoidectomy with stapled hemorrhoidectomy in patients with grades I to III hemorrhoids found a lower rate of recurrence (follow-up ranged from 6 to 39 months) in patients who had conventional hemorrhoidectomy (NNT=14).4 Conventional hemorrhoidectomy showed a nonsignificant trend in decreased bleeding and decreased incontinence.
A second systematic review of 25 studies, including some that were of lower quality, showed a higher recurrence rate at 1 year with stapled hemorrhoidectomy than with conventional surgery.5
Nonoperative techniques? Consider rubber band ligation
A systematic review of 3 poor-quality trials comparing rubber band ligation with excisional hemorrhoidectomy in patients with grade III hemorrhoids found that excisional hemorrhoidectomy produced better long-term symptom control but more immediate postoperative complications of anal stenosis and hemorrhage.6 Rubber band ligation had the lowest recurrence rate at 12 months compared with the other nonoperative techniques of sclerotherapy and infrared coagulation.7
Fiber supplements help relieve symptoms
A Cochrane systematic review of 7 RCTs enrolling a total of 378 patients with grade I to III hemorrhoids evaluated the effect of fiber supplements on pain, itching, and bleeding. Persistent hemorrhoid symptoms decreased by 53% in the group receiving fiber.8
When surgical hemorrhoidectomy is recommended
The American Society of Colon and Rectal Surgeons recommends adequate fluid and fiber intake for all patients with symptomatic hemorrhoids. For grade I to III hemorrhoids, the society states that banding is usually most effective. When office treatments fail, the society recommends surgical hemorrhoidectomy (SOR: B).
The society recommends excision of thrombosed hemorrhoids less than 72 hours old and expectant treatment with analgesia and sitz baths for thrombosed hemorrhoids present for longer than 72 hours (SOR: B).9
The American Gastroenterological Association recommends excision of symptomatic thrombosed external hemorrhoids that present early. Surgical hemorrhoidectomy should be reserved for when conservative treatment fails and for patients with symptomatic grade III and IV hemorrhoids.10
Excision is the most effective treatment for thrombosed external hemorrhoids (strength of recommendation [SOR]: B, retrospective studies). For prolapsed internal hemorrhoids, the best definitive treatment is traditional hemorrhoidectomy (SOR: A, systematic reviews). Of nonoperative techniques, rubber band ligation produces the lowest rate of recurrence (SOR: A, systematic reviews).
Evidence summary
External hemorrhoids originate below the dentate line and become acutely painful with thrombosis. They can cause perianal pruritus and excoriation because of interference with perianal hygiene. Internal hemorrhoids become symptomatic when they bleed or prolapse (TABLE).
TABLE
Classification of symptomatic internal hemorrhoids
| GRADE | DESCRIPTION |
|---|---|
| I | Hemorrhoids do not protrude, but may bleed |
| II | Hemorrhoids protrude with defecation, but reduce spontaneously |
| III | Hemorrhoids protrude and must be reduced by hand |
| IV | Hemorrhoids are permanently prolapsed |
| Source: Madoff RD, et al. Gastroenterology. 2004.10 | |
For thrombosed external hemorrhoids, surgery works best
Few studies have evaluated the best treatment for thrombosed external hemorrhoids. A retrospective study of 231 patients treated conservatively or surgically found that the 48.5% of patients treated surgically had a lower recurrence rate than the conservative group (number needed to treat [NNT]=2 for recurrence at mean follow-up of 7.6 months) and earlier resolution of symptoms (average 3.9 days compared with 24 days for conservative treatment).1
Another retrospective analysis of 340 patients who underwent outpatient excision of thrombosed external hemorrhoids under local anesthesia reported a low recurrence rate of 6.5% at a mean follow-up of 17.3 months.2
A prospective, randomized controlled trial (RCT) of 98 patients treated nonsurgically found improved pain relief with a combination of topical nifedipine 0.3% and lidocaine 1.5% compared with lidocaine alone. The NNT for complete pain relief at 7 days was 3.3
Conventional hemorrhoidectomy beats stapling
Many studies have evaluated the best treatment for prolapsed hemorrhoids. A Cochrane systematic review of 12 RCTs that compared conventional hemorrhoidectomy with stapled hemorrhoidectomy in patients with grades I to III hemorrhoids found a lower rate of recurrence (follow-up ranged from 6 to 39 months) in patients who had conventional hemorrhoidectomy (NNT=14).4 Conventional hemorrhoidectomy showed a nonsignificant trend in decreased bleeding and decreased incontinence.
A second systematic review of 25 studies, including some that were of lower quality, showed a higher recurrence rate at 1 year with stapled hemorrhoidectomy than with conventional surgery.5
Nonoperative techniques? Consider rubber band ligation
A systematic review of 3 poor-quality trials comparing rubber band ligation with excisional hemorrhoidectomy in patients with grade III hemorrhoids found that excisional hemorrhoidectomy produced better long-term symptom control but more immediate postoperative complications of anal stenosis and hemorrhage.6 Rubber band ligation had the lowest recurrence rate at 12 months compared with the other nonoperative techniques of sclerotherapy and infrared coagulation.7
Fiber supplements help relieve symptoms
A Cochrane systematic review of 7 RCTs enrolling a total of 378 patients with grade I to III hemorrhoids evaluated the effect of fiber supplements on pain, itching, and bleeding. Persistent hemorrhoid symptoms decreased by 53% in the group receiving fiber.8
When surgical hemorrhoidectomy is recommended
The American Society of Colon and Rectal Surgeons recommends adequate fluid and fiber intake for all patients with symptomatic hemorrhoids. For grade I to III hemorrhoids, the society states that banding is usually most effective. When office treatments fail, the society recommends surgical hemorrhoidectomy (SOR: B).
The society recommends excision of thrombosed hemorrhoids less than 72 hours old and expectant treatment with analgesia and sitz baths for thrombosed hemorrhoids present for longer than 72 hours (SOR: B).9
The American Gastroenterological Association recommends excision of symptomatic thrombosed external hemorrhoids that present early. Surgical hemorrhoidectomy should be reserved for when conservative treatment fails and for patients with symptomatic grade III and IV hemorrhoids.10
1. Greenspon J, Williams SB, Young HA, et al. Thrombosed external hemorrhoids: outcome after conservative or surgical management. Dis Colon Rectum. 2004;47:1493-1498.
2. Jongen J, Bach S, Stubinger SH, et al. Excision of thrombosed external hemorrhoids under local anesthesia: a retrospective evaluation of 340 patients. Dis Colon Rectum. 2003;46:1226-1231.
3. Perrotti P, Antropoli C, Molino D, et al. Conservative treatment of acute thrombosed external hemorrhoids with topical nifedipine. Dis Colon Rectum. 2001;44:405-409.
4. Jayaraman S, Colquhoun PH, Malthaner RA. Stapled versus conventional surgery for hemorrhoids. Cochrane Database Syst Rev. 2006;(4):CD005393.-
5. Tjandra JJ, Chan MK. Systematic review on the procedure for prolapse and hemorrhoids (stapled hemorrhoidopexy). Dis Colon Rectum. 2007;50:878-892.
6. Shanmugam V, Thaha MA, Rabindranath KS, et al. Systematic review of randomized trials comparing rubber band ligation with excisional haemorrhoidectomy. Br J Surg. 2005;92:1481-1487.
7. Johanson JF, Rimm A. Optimal nonsurgical treatment of hemorrhoids: a comparative analysis of infrared coagulation, rubber band ligation, and injection sclerotherapy. Am J Gastroenterol. 1992;87:1600-1606.
8. Alonso-Coello P, Guyatt G, Heels-Ansdell D, et al. Laxatives for the treatment of hemorrhoids. Cochrane Database Syst Rev. 2005(4):CD004649.-
9. Cataldo P, Ellis CN, Gregorcyk S, et al. Practice parameters for the management of hemorrhoids (revised). Dis Colon Rectum. 2005;48:189-194.
10. Madoff RD, Fleshman JW. American Gastroenterological Association Clinical Practice Committee. American Gastroenterological Association technical review on the diagnosis and treatment of hemorrhoids. Gastroenterology. 2004;126:1463-1473.
1. Greenspon J, Williams SB, Young HA, et al. Thrombosed external hemorrhoids: outcome after conservative or surgical management. Dis Colon Rectum. 2004;47:1493-1498.
2. Jongen J, Bach S, Stubinger SH, et al. Excision of thrombosed external hemorrhoids under local anesthesia: a retrospective evaluation of 340 patients. Dis Colon Rectum. 2003;46:1226-1231.
3. Perrotti P, Antropoli C, Molino D, et al. Conservative treatment of acute thrombosed external hemorrhoids with topical nifedipine. Dis Colon Rectum. 2001;44:405-409.
4. Jayaraman S, Colquhoun PH, Malthaner RA. Stapled versus conventional surgery for hemorrhoids. Cochrane Database Syst Rev. 2006;(4):CD005393.-
5. Tjandra JJ, Chan MK. Systematic review on the procedure for prolapse and hemorrhoids (stapled hemorrhoidopexy). Dis Colon Rectum. 2007;50:878-892.
6. Shanmugam V, Thaha MA, Rabindranath KS, et al. Systematic review of randomized trials comparing rubber band ligation with excisional haemorrhoidectomy. Br J Surg. 2005;92:1481-1487.
7. Johanson JF, Rimm A. Optimal nonsurgical treatment of hemorrhoids: a comparative analysis of infrared coagulation, rubber band ligation, and injection sclerotherapy. Am J Gastroenterol. 1992;87:1600-1606.
8. Alonso-Coello P, Guyatt G, Heels-Ansdell D, et al. Laxatives for the treatment of hemorrhoids. Cochrane Database Syst Rev. 2005(4):CD004649.-
9. Cataldo P, Ellis CN, Gregorcyk S, et al. Practice parameters for the management of hemorrhoids (revised). Dis Colon Rectum. 2005;48:189-194.
10. Madoff RD, Fleshman JW. American Gastroenterological Association Clinical Practice Committee. American Gastroenterological Association technical review on the diagnosis and treatment of hemorrhoids. Gastroenterology. 2004;126:1463-1473.
Evidence-based answers from the Family Physicians Inquiries Network
Lansoprazole ineffective for functional dyspepsia
ABSTRACT
BACKGROUND: Acid suppressants such as H2 blockers and proton pump inhibitors are often used for the treatment of non-ulcer dyspepsia, also known as functional dyspepsia. This study evaluated the efficacy of different doses of lansoprazole for the treatment of non-ulcer dyspepsia.
POPULATION STUDIED: The patients in this study (335 women and 118 men) were all Chinese, aged 18 to 80 years, and had been referred to an endoscopy unit. All patients had a normal upper gastrointestinal endoscopy and had had functional dyspepsia for at least 12 weeks during the previous 12 months. Functional dyspepsia was defined as persistent pain or discomfort in the upper abdomen with no evidence of organic disease, irritable bowel syndrome, or chronic severe constipation. Patients were excluded if they had classical acid regurgitation as their only symptom, or had used any acid suppressants, nonsteroidal anti-inflammatory drugs, or antibiotics in the previous 4 weeks. To be eligible for the study they had to have moderate symptoms defined by a dyspepsia score in the preceding 2 weeks.
STUDY DESIGN AND VALIDITY: This randomized controlled trial was triple blinded (the managing physicians, patients, and investigators were all blinded). The 453 patients were randomized to receive placebo or lansoprazole 15 or 30 mg daily for 4 weeks. Patient compliance was satisfactory and checked by pill counting.
OUTCOMES MEASURED: The outcomes assessed were dyspepsia and quality-of-life scores, and complete relief of symptoms. The dyspepsia score was calculated from a questionnaire that comprised 12 questions relating to dyspepsia, each of which was graded on a 5-point Likert scale. The quality-of-life score was assessed from the Short Form (SF-36) Health Survey, which contains 11 items related to general well-being.
RESULTS: Significant improvement in the dyspepsia scores at 4 weeks was noted in each of the 3 groups. The changes in dyspepsia score from baseline to the 4-week visit were similar between lansoprazole 30 mg and placebo, and lansoprazole 15 mg and placebo (approximate change from 22 at baseline to 18.7 out of a possible 60 points at 4 weeks). The changes in mean quality-of-life score from baseline to the score at 4 weeks were also similar for both doses of lansoprazole and placebo (approximate change from 60 to 64.8 out of a possible score of 100 at 4 weeks). No difference was noted in the proportion of patients with complete symptom relief between the lansoprazole groups (23%) and the placebo group (30%). Even when the results were analyzed in groups according to the severity of the dyspepsia, there was still no difference in complete relief of symptoms between the 3 groups.
Patients with functional dyspepsia, which involves no organic disease and no reflux, do not benefit from lansoprazole, a proton pump inhibitor. Any improvement seen is probably related to a placebo effect. Prescribing proton pump inhibitors for these patients just for their placebo effect is going to further raise health care costs. Antacids and H2 blockers are less expensive alternatives.
ABSTRACT
BACKGROUND: Acid suppressants such as H2 blockers and proton pump inhibitors are often used for the treatment of non-ulcer dyspepsia, also known as functional dyspepsia. This study evaluated the efficacy of different doses of lansoprazole for the treatment of non-ulcer dyspepsia.
POPULATION STUDIED: The patients in this study (335 women and 118 men) were all Chinese, aged 18 to 80 years, and had been referred to an endoscopy unit. All patients had a normal upper gastrointestinal endoscopy and had had functional dyspepsia for at least 12 weeks during the previous 12 months. Functional dyspepsia was defined as persistent pain or discomfort in the upper abdomen with no evidence of organic disease, irritable bowel syndrome, or chronic severe constipation. Patients were excluded if they had classical acid regurgitation as their only symptom, or had used any acid suppressants, nonsteroidal anti-inflammatory drugs, or antibiotics in the previous 4 weeks. To be eligible for the study they had to have moderate symptoms defined by a dyspepsia score in the preceding 2 weeks.
STUDY DESIGN AND VALIDITY: This randomized controlled trial was triple blinded (the managing physicians, patients, and investigators were all blinded). The 453 patients were randomized to receive placebo or lansoprazole 15 or 30 mg daily for 4 weeks. Patient compliance was satisfactory and checked by pill counting.
OUTCOMES MEASURED: The outcomes assessed were dyspepsia and quality-of-life scores, and complete relief of symptoms. The dyspepsia score was calculated from a questionnaire that comprised 12 questions relating to dyspepsia, each of which was graded on a 5-point Likert scale. The quality-of-life score was assessed from the Short Form (SF-36) Health Survey, which contains 11 items related to general well-being.
RESULTS: Significant improvement in the dyspepsia scores at 4 weeks was noted in each of the 3 groups. The changes in dyspepsia score from baseline to the 4-week visit were similar between lansoprazole 30 mg and placebo, and lansoprazole 15 mg and placebo (approximate change from 22 at baseline to 18.7 out of a possible 60 points at 4 weeks). The changes in mean quality-of-life score from baseline to the score at 4 weeks were also similar for both doses of lansoprazole and placebo (approximate change from 60 to 64.8 out of a possible score of 100 at 4 weeks). No difference was noted in the proportion of patients with complete symptom relief between the lansoprazole groups (23%) and the placebo group (30%). Even when the results were analyzed in groups according to the severity of the dyspepsia, there was still no difference in complete relief of symptoms between the 3 groups.
Patients with functional dyspepsia, which involves no organic disease and no reflux, do not benefit from lansoprazole, a proton pump inhibitor. Any improvement seen is probably related to a placebo effect. Prescribing proton pump inhibitors for these patients just for their placebo effect is going to further raise health care costs. Antacids and H2 blockers are less expensive alternatives.
ABSTRACT
BACKGROUND: Acid suppressants such as H2 blockers and proton pump inhibitors are often used for the treatment of non-ulcer dyspepsia, also known as functional dyspepsia. This study evaluated the efficacy of different doses of lansoprazole for the treatment of non-ulcer dyspepsia.
POPULATION STUDIED: The patients in this study (335 women and 118 men) were all Chinese, aged 18 to 80 years, and had been referred to an endoscopy unit. All patients had a normal upper gastrointestinal endoscopy and had had functional dyspepsia for at least 12 weeks during the previous 12 months. Functional dyspepsia was defined as persistent pain or discomfort in the upper abdomen with no evidence of organic disease, irritable bowel syndrome, or chronic severe constipation. Patients were excluded if they had classical acid regurgitation as their only symptom, or had used any acid suppressants, nonsteroidal anti-inflammatory drugs, or antibiotics in the previous 4 weeks. To be eligible for the study they had to have moderate symptoms defined by a dyspepsia score in the preceding 2 weeks.
STUDY DESIGN AND VALIDITY: This randomized controlled trial was triple blinded (the managing physicians, patients, and investigators were all blinded). The 453 patients were randomized to receive placebo or lansoprazole 15 or 30 mg daily for 4 weeks. Patient compliance was satisfactory and checked by pill counting.
OUTCOMES MEASURED: The outcomes assessed were dyspepsia and quality-of-life scores, and complete relief of symptoms. The dyspepsia score was calculated from a questionnaire that comprised 12 questions relating to dyspepsia, each of which was graded on a 5-point Likert scale. The quality-of-life score was assessed from the Short Form (SF-36) Health Survey, which contains 11 items related to general well-being.
RESULTS: Significant improvement in the dyspepsia scores at 4 weeks was noted in each of the 3 groups. The changes in dyspepsia score from baseline to the 4-week visit were similar between lansoprazole 30 mg and placebo, and lansoprazole 15 mg and placebo (approximate change from 22 at baseline to 18.7 out of a possible 60 points at 4 weeks). The changes in mean quality-of-life score from baseline to the score at 4 weeks were also similar for both doses of lansoprazole and placebo (approximate change from 60 to 64.8 out of a possible score of 100 at 4 weeks). No difference was noted in the proportion of patients with complete symptom relief between the lansoprazole groups (23%) and the placebo group (30%). Even when the results were analyzed in groups according to the severity of the dyspepsia, there was still no difference in complete relief of symptoms between the 3 groups.
Patients with functional dyspepsia, which involves no organic disease and no reflux, do not benefit from lansoprazole, a proton pump inhibitor. Any improvement seen is probably related to a placebo effect. Prescribing proton pump inhibitors for these patients just for their placebo effect is going to further raise health care costs. Antacids and H2 blockers are less expensive alternatives.
How common is peripheral arterial disease, and should primary care physicians be screening for it?
Patients at risk for atherosclerotic disease frequently have undiagnosed and asymptomatic PAD. Also, patients with unknown PAD are less intensively treated for hyperlipidemia and hypertension and less likely to be taking antiplatelet therapy than patients already diagnosed with PAD or CVD. This study does not provide evidence, however, that early detection of PAD will lead to behavioral changes on the part of either patients or physicians resulting in improved patient-oriented outcomes. Until further studies have been done that demonstrate improved outcomes as a result of early detection of PAD with the Doppler ABI, screening should not be routine.
Patients at risk for atherosclerotic disease frequently have undiagnosed and asymptomatic PAD. Also, patients with unknown PAD are less intensively treated for hyperlipidemia and hypertension and less likely to be taking antiplatelet therapy than patients already diagnosed with PAD or CVD. This study does not provide evidence, however, that early detection of PAD will lead to behavioral changes on the part of either patients or physicians resulting in improved patient-oriented outcomes. Until further studies have been done that demonstrate improved outcomes as a result of early detection of PAD with the Doppler ABI, screening should not be routine.
Patients at risk for atherosclerotic disease frequently have undiagnosed and asymptomatic PAD. Also, patients with unknown PAD are less intensively treated for hyperlipidemia and hypertension and less likely to be taking antiplatelet therapy than patients already diagnosed with PAD or CVD. This study does not provide evidence, however, that early detection of PAD will lead to behavioral changes on the part of either patients or physicians resulting in improved patient-oriented outcomes. Until further studies have been done that demonstrate improved outcomes as a result of early detection of PAD with the Doppler ABI, screening should not be routine.