James J. Stevermer, MD, MSPH

Illustrative Case

A 55-year-old man with hypertension and stage 3 chronic kidney disease (CKD) comes in to your office for routine care. His blood pressure is 135/85 mm Hg, and he is presently taking lisinopril 40 mg daily. Should you increase his antihypertensive regimen?

Hypertension is common and leads to significant morbidity and mortality, but pharmacologic treatment reduces incidence of stroke by 35% to 40%, myocardial infarction (MI) by 15% to 25%, and heart failure by up to 64%.^2-4 Specific blood pressure targets for defined populations continue to be studied.

In patients with diabetes, the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial found that more intensive BP targets did not reduce the rate of major CV events, but the study may have been underpowered.⁵ The members of The Eighth Joint National Committee recommended treating patients over age 60 years to BP goals <150/90 mm Hg.⁶ This was based on evidence from 6 randomized controlled trials (RCTs),^7-12 but there remains debate—even among the members of the Committee—as to appropriate BP goals in patients of any age without CV disease who have BP measurements of 140-159/90-99 mm Hg.¹³

Study Summary

Treating to SBP <120 mm Hg lowers mortality

The Systolic Blood Pressure Intervention Trial (SPRINT) was a multicenter RCT designed to determine if treating to lower SBP targets in non-diabetic patients at high risk for CV events improves outcomes as compared to standard care. Patients were at least 50 years of age with SBP of 130 to 180 mm Hg and were at increased CV risk as defined by clinical or subclinical CV disease other than stroke, CKD with glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m², 10-year risk of CV disease >15% on Framingham risk score, or age ≥75 years of age. Patients with diabetes; prior stroke; polycystic kidney disease; significant proteinuria within the past 6 months; symptomatic heart failure within the past 6 months; or left ventricular ejection fraction <35% were excluded.¹

Patients (N=9361) were randomly assigned to an SBP target <120 mm Hg in the intensive group or <140 mm Hg in the standard treatment group, in an open-label design. Allocation was concealed. The study protocol encouraged, but did not require, the use of thiazide-type diuretics, loop diuretics (for those with advanced renal disease), angiotensin-converting enzyme inhibitors or angiotensin receptor blocker agents, calcium channel blockers, and beta-blockers. Clinicians could add other agents as needed. All major classes of antihypertensives were used.

Medication dosing adjustments were based on the average of 3 BP measurements taken with an automated measurement system (Omron Healthcare, Model 907) with the patient seated after 5 minutes of quiet rest. Target SBP in the standard therapy group was 135 to 139 mm Hg. Medication dosages were lowered if SBP was <130 mm Hg at a single visit or <135 mm Hg at 2 consecutive visits.¹

The primary composite outcome included the first occurrence of MI, acute coronary syndrome, stroke, heart failure, or death from CV causes. Secondary outcomes were the individual components of the primary composite outcome, death from any cause, and the composite of the primary outcome or death from any cause.¹

In a group of 1000 patients, an estimated 16 patients will benefit from intensive BP treatment, 22 patients will be seriously harmed, and 962 patients will experience neither benefit nor harm.

Study halted early. The study was stopped early due to significantly lower rates of the primary outcome in the intensive therapy group vs the standard therapy group (1.65% per year vs 2.19% per year, respectively, hazard ratio [HR] with intensive treatment=0.75; 95% confidence interval [CI], 0.64-0.89; P<.001). The resulting median follow-up time was 3.26 years.¹ This corresponds to a 25% lower relative risk of the primary outcome, with a decrease in event rates from 6.8% to 5.2% over the trial period. All-cause mortality was also lower in the intensive therapy group: 3.4% vs 4.5% (HR=0.73; 95% CI, 0.60-0.90; P=.003).

The number needed to treat (NNT) over 3.26 years to prevent a primary outcome event, death from any cause, and death from CV causes was 61, 90, and 172, respectively. Serious adverse events occurred more frequently in the intensive therapy group than in the standard therapy group (38.3% vs 37.1%; HR=1.04; P=.25) with a number needed to harm (NNH) of 46 over the study period.¹ (When looking at serious adverse events identified as likely associated with the intervention, rates were 4.7% vs 2.5%, respectively [P<.001].) Hypotension, syncope, electrolyte abnormalities, and acute kidney injury/acute renal failure reached statistical significance. The incidence of bradycardia and injurious falls was higher in the intensive treatment group, but did not reach statistical significance. In the subgroup of patients ≥75 years of age, 48% in each study group experienced a serious adverse event.¹

Throughout the study, mean SBP was 121.5 mm Hg in the intensive therapy group and 134.6 mm Hg in the standard treatment group. This required an average of one additional BP medication in the intensive therapy group (2.8 vs 1.8, respectively).¹

What’s New

Lower SBP produces mortality benefits in those under, and over, age 75

This trial builds on a body of evidence that shows the advantages of lowering SBP to <150 mm Hg^7,11,12 by demonstrating benefits, including lower all-cause mortality, for lower SBP targets in non-diabetic patients at high risk of CV disease. The SPRINT trial also showed that the benefits of intensive therapy remained true in a subgroup of patients ≥75 years of age.

The incidence of the primary outcome in the cohort ≥75 years of age receiving intensive therapy was 7.7% vs 10.9% for those receiving standard therapy (HR=0.67; 95% CI, 0.51-0.86; NNT=31). All-cause mortality was also lower in the intensive therapy group than in the standard therapy group among patients ≥75 years of age: 5.5% vs 8.04% (HR=0.68; 95% CI, 0.50-0.92; NNT=38).¹

Caveats

Many do not benefit from—or are harmed by—increased medication

Identifying patients most likely to benefit from more intensive blood pressure targets remains challenging.

The absolute risk reduction for the primary outcome is 1.6%, meaning 98.4% of patients receiving more intensive treatment will not benefit. In a group of 1000 patients, an estimated 16 patients will benefit, 22 patients will be seriously harmed, and 962 patients will experience neither benefit nor harm.¹⁴ The difference between how BP was measured in this trial (an average of 3 readings after the patient had rested for 5 minutes) and that which occurs typically in clinical practice could potentially lead to overtreatment in practice.

Also, reducing antihypertensive therapies when the SBP was about 130 to 135 mm Hg in the standard therapy group likely exaggerated the difference in outcomes between the intensive and standard therapy groups, and is neither routine nor recommended in clinical practice.⁶ Finally, the trial specifically studied non-diabetic patients at high risk of CV disease ≥50 years of age, limiting generalizability to other populations.

Challenges to implementation

Who will benefit/who can achieve intensive SBP goals?

Identifying patients most likely to benefit from more intensive BP targets remains challenging. The SPRINT trial showed a mortality benefit, but at a cost of increased morbidity.^1,14 In particular, caution should be exercised in the subgroup of patients ≥75 years. Despite a lower NNT than the rest of the study population, serious adverse events happened more frequently. Also, this particular cohort of volunteers may not be representative of those ≥75 years of age in the general population.

Additionally, achieving intensive SBP goals can be challenging. In the SPRINT trial, only half of the intensive target group achieved an SBP <120 mm Hg.¹ And in a 2011-12 National Health and Nutrition Examination Survey, only 52% of patients in the general population achieved a BP target <140/90 mm Hg.¹⁵ Lower morbidity and mortality should remain the ultimate goals to the management of hypertension, requiring physicians to carefully assess an individual patient’s likelihood of benefit vs harm.

ACKNOWLEDGEMENT 
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Illustrative Case

A 55-year-old man with hypertension and stage 3 chronic kidney disease (CKD) comes in to your office for routine care. His blood pressure is 135/85 mm Hg, and he is presently taking lisinopril 40 mg daily. Should you increase his antihypertensive regimen?

Hypertension is common and leads to significant morbidity and mortality, but pharmacologic treatment reduces incidence of stroke by 35% to 40%, myocardial infarction (MI) by 15% to 25%, and heart failure by up to 64%.^2-4 Specific blood pressure targets for defined populations continue to be studied.

In patients with diabetes, the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial found that more intensive BP targets did not reduce the rate of major CV events, but the study may have been underpowered.⁵ The members of The Eighth Joint National Committee recommended treating patients over age 60 years to BP goals <150/90 mm Hg.⁶ This was based on evidence from 6 randomized controlled trials (RCTs),^7-12 but there remains debate—even among the members of the Committee—as to appropriate BP goals in patients of any age without CV disease who have BP measurements of 140-159/90-99 mm Hg.¹³

Study Summary

Treating to SBP <120 mm Hg lowers mortality

The Systolic Blood Pressure Intervention Trial (SPRINT) was a multicenter RCT designed to determine if treating to lower SBP targets in non-diabetic patients at high risk for CV events improves outcomes as compared to standard care. Patients were at least 50 years of age with SBP of 130 to 180 mm Hg and were at increased CV risk as defined by clinical or subclinical CV disease other than stroke, CKD with glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m², 10-year risk of CV disease >15% on Framingham risk score, or age ≥75 years of age. Patients with diabetes; prior stroke; polycystic kidney disease; significant proteinuria within the past 6 months; symptomatic heart failure within the past 6 months; or left ventricular ejection fraction <35% were excluded.¹

Patients (N=9361) were randomly assigned to an SBP target <120 mm Hg in the intensive group or <140 mm Hg in the standard treatment group, in an open-label design. Allocation was concealed. The study protocol encouraged, but did not require, the use of thiazide-type diuretics, loop diuretics (for those with advanced renal disease), angiotensin-converting enzyme inhibitors or angiotensin receptor blocker agents, calcium channel blockers, and beta-blockers. Clinicians could add other agents as needed. All major classes of antihypertensives were used.

Medication dosing adjustments were based on the average of 3 BP measurements taken with an automated measurement system (Omron Healthcare, Model 907) with the patient seated after 5 minutes of quiet rest. Target SBP in the standard therapy group was 135 to 139 mm Hg. Medication dosages were lowered if SBP was <130 mm Hg at a single visit or <135 mm Hg at 2 consecutive visits.¹

The primary composite outcome included the first occurrence of MI, acute coronary syndrome, stroke, heart failure, or death from CV causes. Secondary outcomes were the individual components of the primary composite outcome, death from any cause, and the composite of the primary outcome or death from any cause.¹

In a group of 1000 patients, an estimated 16 patients will benefit from intensive BP treatment, 22 patients will be seriously harmed, and 962 patients will experience neither benefit nor harm.

Study halted early. The study was stopped early due to significantly lower rates of the primary outcome in the intensive therapy group vs the standard therapy group (1.65% per year vs 2.19% per year, respectively, hazard ratio [HR] with intensive treatment=0.75; 95% confidence interval [CI], 0.64-0.89; P<.001). The resulting median follow-up time was 3.26 years.¹ This corresponds to a 25% lower relative risk of the primary outcome, with a decrease in event rates from 6.8% to 5.2% over the trial period. All-cause mortality was also lower in the intensive therapy group: 3.4% vs 4.5% (HR=0.73; 95% CI, 0.60-0.90; P=.003).

The number needed to treat (NNT) over 3.26 years to prevent a primary outcome event, death from any cause, and death from CV causes was 61, 90, and 172, respectively. Serious adverse events occurred more frequently in the intensive therapy group than in the standard therapy group (38.3% vs 37.1%; HR=1.04; P=.25) with a number needed to harm (NNH) of 46 over the study period.¹ (When looking at serious adverse events identified as likely associated with the intervention, rates were 4.7% vs 2.5%, respectively [P<.001].) Hypotension, syncope, electrolyte abnormalities, and acute kidney injury/acute renal failure reached statistical significance. The incidence of bradycardia and injurious falls was higher in the intensive treatment group, but did not reach statistical significance. In the subgroup of patients ≥75 years of age, 48% in each study group experienced a serious adverse event.¹

Throughout the study, mean SBP was 121.5 mm Hg in the intensive therapy group and 134.6 mm Hg in the standard treatment group. This required an average of one additional BP medication in the intensive therapy group (2.8 vs 1.8, respectively).¹

What’s New

Lower SBP produces mortality benefits in those under, and over, age 75

This trial builds on a body of evidence that shows the advantages of lowering SBP to <150 mm Hg^7,11,12 by demonstrating benefits, including lower all-cause mortality, for lower SBP targets in non-diabetic patients at high risk of CV disease. The SPRINT trial also showed that the benefits of intensive therapy remained true in a subgroup of patients ≥75 years of age.

The incidence of the primary outcome in the cohort ≥75 years of age receiving intensive therapy was 7.7% vs 10.9% for those receiving standard therapy (HR=0.67; 95% CI, 0.51-0.86; NNT=31). All-cause mortality was also lower in the intensive therapy group than in the standard therapy group among patients ≥75 years of age: 5.5% vs 8.04% (HR=0.68; 95% CI, 0.50-0.92; NNT=38).¹

Caveats

Many do not benefit from—or are harmed by—increased medication

Identifying patients most likely to benefit from more intensive blood pressure targets remains challenging.

The absolute risk reduction for the primary outcome is 1.6%, meaning 98.4% of patients receiving more intensive treatment will not benefit. In a group of 1000 patients, an estimated 16 patients will benefit, 22 patients will be seriously harmed, and 962 patients will experience neither benefit nor harm.¹⁴ The difference between how BP was measured in this trial (an average of 3 readings after the patient had rested for 5 minutes) and that which occurs typically in clinical practice could potentially lead to overtreatment in practice.

Also, reducing antihypertensive therapies when the SBP was about 130 to 135 mm Hg in the standard therapy group likely exaggerated the difference in outcomes between the intensive and standard therapy groups, and is neither routine nor recommended in clinical practice.⁶ Finally, the trial specifically studied non-diabetic patients at high risk of CV disease ≥50 years of age, limiting generalizability to other populations.

Challenges to implementation

Who will benefit/who can achieve intensive SBP goals?

Identifying patients most likely to benefit from more intensive BP targets remains challenging. The SPRINT trial showed a mortality benefit, but at a cost of increased morbidity.^1,14 In particular, caution should be exercised in the subgroup of patients ≥75 years. Despite a lower NNT than the rest of the study population, serious adverse events happened more frequently. Also, this particular cohort of volunteers may not be representative of those ≥75 years of age in the general population.

Additionally, achieving intensive SBP goals can be challenging. In the SPRINT trial, only half of the intensive target group achieved an SBP <120 mm Hg.¹ And in a 2011-12 National Health and Nutrition Examination Survey, only 52% of patients in the general population achieved a BP target <140/90 mm Hg.¹⁵ Lower morbidity and mortality should remain the ultimate goals to the management of hypertension, requiring physicians to carefully assess an individual patient’s likelihood of benefit vs harm.

ACKNOWLEDGEMENT 
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Illustrative Case

A 55-year-old man with hypertension and stage 3 chronic kidney disease (CKD) comes in to your office for routine care. His blood pressure is 135/85 mm Hg, and he is presently taking lisinopril 40 mg daily. Should you increase his antihypertensive regimen?

Hypertension is common and leads to significant morbidity and mortality, but pharmacologic treatment reduces incidence of stroke by 35% to 40%, myocardial infarction (MI) by 15% to 25%, and heart failure by up to 64%.^2-4 Specific blood pressure targets for defined populations continue to be studied.

In patients with diabetes, the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial found that more intensive BP targets did not reduce the rate of major CV events, but the study may have been underpowered.⁵ The members of The Eighth Joint National Committee recommended treating patients over age 60 years to BP goals <150/90 mm Hg.⁶ This was based on evidence from 6 randomized controlled trials (RCTs),^7-12 but there remains debate—even among the members of the Committee—as to appropriate BP goals in patients of any age without CV disease who have BP measurements of 140-159/90-99 mm Hg.¹³

Study Summary

Treating to SBP <120 mm Hg lowers mortality

The Systolic Blood Pressure Intervention Trial (SPRINT) was a multicenter RCT designed to determine if treating to lower SBP targets in non-diabetic patients at high risk for CV events improves outcomes as compared to standard care. Patients were at least 50 years of age with SBP of 130 to 180 mm Hg and were at increased CV risk as defined by clinical or subclinical CV disease other than stroke, CKD with glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m², 10-year risk of CV disease >15% on Framingham risk score, or age ≥75 years of age. Patients with diabetes; prior stroke; polycystic kidney disease; significant proteinuria within the past 6 months; symptomatic heart failure within the past 6 months; or left ventricular ejection fraction <35% were excluded.¹

Patients (N=9361) were randomly assigned to an SBP target <120 mm Hg in the intensive group or <140 mm Hg in the standard treatment group, in an open-label design. Allocation was concealed. The study protocol encouraged, but did not require, the use of thiazide-type diuretics, loop diuretics (for those with advanced renal disease), angiotensin-converting enzyme inhibitors or angiotensin receptor blocker agents, calcium channel blockers, and beta-blockers. Clinicians could add other agents as needed. All major classes of antihypertensives were used.

Medication dosing adjustments were based on the average of 3 BP measurements taken with an automated measurement system (Omron Healthcare, Model 907) with the patient seated after 5 minutes of quiet rest. Target SBP in the standard therapy group was 135 to 139 mm Hg. Medication dosages were lowered if SBP was <130 mm Hg at a single visit or <135 mm Hg at 2 consecutive visits.¹

The primary composite outcome included the first occurrence of MI, acute coronary syndrome, stroke, heart failure, or death from CV causes. Secondary outcomes were the individual components of the primary composite outcome, death from any cause, and the composite of the primary outcome or death from any cause.¹

In a group of 1000 patients, an estimated 16 patients will benefit from intensive BP treatment, 22 patients will be seriously harmed, and 962 patients will experience neither benefit nor harm.

Study halted early. The study was stopped early due to significantly lower rates of the primary outcome in the intensive therapy group vs the standard therapy group (1.65% per year vs 2.19% per year, respectively, hazard ratio [HR] with intensive treatment=0.75; 95% confidence interval [CI], 0.64-0.89; P<.001). The resulting median follow-up time was 3.26 years.¹ This corresponds to a 25% lower relative risk of the primary outcome, with a decrease in event rates from 6.8% to 5.2% over the trial period. All-cause mortality was also lower in the intensive therapy group: 3.4% vs 4.5% (HR=0.73; 95% CI, 0.60-0.90; P=.003).

The number needed to treat (NNT) over 3.26 years to prevent a primary outcome event, death from any cause, and death from CV causes was 61, 90, and 172, respectively. Serious adverse events occurred more frequently in the intensive therapy group than in the standard therapy group (38.3% vs 37.1%; HR=1.04; P=.25) with a number needed to harm (NNH) of 46 over the study period.¹ (When looking at serious adverse events identified as likely associated with the intervention, rates were 4.7% vs 2.5%, respectively [P<.001].) Hypotension, syncope, electrolyte abnormalities, and acute kidney injury/acute renal failure reached statistical significance. The incidence of bradycardia and injurious falls was higher in the intensive treatment group, but did not reach statistical significance. In the subgroup of patients ≥75 years of age, 48% in each study group experienced a serious adverse event.¹

Throughout the study, mean SBP was 121.5 mm Hg in the intensive therapy group and 134.6 mm Hg in the standard treatment group. This required an average of one additional BP medication in the intensive therapy group (2.8 vs 1.8, respectively).¹

What’s New

Lower SBP produces mortality benefits in those under, and over, age 75

This trial builds on a body of evidence that shows the advantages of lowering SBP to <150 mm Hg^7,11,12 by demonstrating benefits, including lower all-cause mortality, for lower SBP targets in non-diabetic patients at high risk of CV disease. The SPRINT trial also showed that the benefits of intensive therapy remained true in a subgroup of patients ≥75 years of age.

The incidence of the primary outcome in the cohort ≥75 years of age receiving intensive therapy was 7.7% vs 10.9% for those receiving standard therapy (HR=0.67; 95% CI, 0.51-0.86; NNT=31). All-cause mortality was also lower in the intensive therapy group than in the standard therapy group among patients ≥75 years of age: 5.5% vs 8.04% (HR=0.68; 95% CI, 0.50-0.92; NNT=38).¹

Caveats

Many do not benefit from—or are harmed by—increased medication

Identifying patients most likely to benefit from more intensive blood pressure targets remains challenging.

The absolute risk reduction for the primary outcome is 1.6%, meaning 98.4% of patients receiving more intensive treatment will not benefit. In a group of 1000 patients, an estimated 16 patients will benefit, 22 patients will be seriously harmed, and 962 patients will experience neither benefit nor harm.¹⁴ The difference between how BP was measured in this trial (an average of 3 readings after the patient had rested for 5 minutes) and that which occurs typically in clinical practice could potentially lead to overtreatment in practice.

Also, reducing antihypertensive therapies when the SBP was about 130 to 135 mm Hg in the standard therapy group likely exaggerated the difference in outcomes between the intensive and standard therapy groups, and is neither routine nor recommended in clinical practice.⁶ Finally, the trial specifically studied non-diabetic patients at high risk of CV disease ≥50 years of age, limiting generalizability to other populations.

Challenges to implementation

Who will benefit/who can achieve intensive SBP goals?

Identifying patients most likely to benefit from more intensive BP targets remains challenging. The SPRINT trial showed a mortality benefit, but at a cost of increased morbidity.^1,14 In particular, caution should be exercised in the subgroup of patients ≥75 years. Despite a lower NNT than the rest of the study population, serious adverse events happened more frequently. Also, this particular cohort of volunteers may not be representative of those ≥75 years of age in the general population.

Additionally, achieving intensive SBP goals can be challenging. In the SPRINT trial, only half of the intensive target group achieved an SBP <120 mm Hg.¹ And in a 2011-12 National Health and Nutrition Examination Survey, only 52% of patients in the general population achieved a BP target <140/90 mm Hg.¹⁵ Lower morbidity and mortality should remain the ultimate goals to the management of hypertension, requiring physicians to carefully assess an individual patient’s likelihood of benefit vs harm.

ACKNOWLEDGEMENT 
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

PRACTICE CHANGER
Consider adding simvastatin (40 mg/d) to standard wound care and compression for patients with venous stasis ulcers.¹

STRENGTH OF RECOMMENDATION
B: Based on a high-quality randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE
A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past nine months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrence is common.^2,3

Statins have been found to aid wound healing through their diverse physiologic (pleiotropic) effects. Evidence indicates they can be beneficial in treatment of diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

Continue for study summary >>

STUDY SUMMARY
Ulcers more likely to close when statin added
This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin (40 mg/d) for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Study subjects were 66 patients, ages 41 to 71, who’d had one or more venous ulcers for at least three months. They were randomly assigned to receive either simvastatin (40 mg/d; n = 32) or an identical-appearing placebo (n = 34). Patients were excluded if they were pregnant, had an ulcer that was infected or > 10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤ 5 cm and > 5 cm). There was no statistically significant difference between the two groups in the duration of venous ulceration (3.80 y in the placebo group vs 3.93 y in the simvastatin group) or incidence of diabetes (5% vs 3%, respectively).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed, healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy initiation. The same dermatologist, who was blinded to the patients’ group assignments, evaluated all patients every two weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR], 0.16; number needed to treat [NNT], 2).

Among patients with ulcers ≤ 5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR, 0.10; NNT, 2). Perhaps more importantly, in patients with ulcers > 5 cm, 67% in the simvastatin group had closure with a mean healing time of nine weeks, whereas none of the ulcers of this size closed in the control group (RR, 0.33; NNT, 1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²).

In addition, in the simvastatin group, healing times were significantly reduced (7.53 ± 1.34 wk vs 8.55 ± 1.13 wk) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts were minimal (8%; two in the placebo group and three in the intervention group). Using intention-to-treat analysis and worst-case scenarios for those who dropped out did not affect the primary outcome. There were no withdrawals due to adverse reactions.

WHAT’S NEW
Statins offer significant benefits for treating venous stasis ulcers
This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

Next page: Caveats >>

CAVEATS
Carefully selected patients
Many wounds will heal with compression therapy alone, as occurred in this study, in which 50% of ulcers ≤ 5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when target patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as ACE inhibitors. No data were collected on patient BMI, which is a risk factor for delayed healing.

The prevalence of obesity is lower in the Philippines than in the US. It is uncertain what role this difference would have in the statin’s effectiveness.

Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

Nontheless, we found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies.

This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION
There are no known barriers to implementation of this practice.

REFERENCES
1. Evangelista MT, Casintahan MF, Villafuerte LL. Simvastatin as a novel therapeutic agent for venous ulcers: a randomized, double-blind, placebo-controlled trial. Br J Dermatol. 2014; 170:1151-1157.

2. Collins L, Seraj S. Diagnosis and treatment of venous ulcers. Am Fam Physician. 2010;81: 989-996.

3. The Australian Wound Management Association Inc, New Zealand Wound Care Society Inc. Australian and New Zealand clinical practice guideline for prevention and management of venous leg ulcers (2011). www.nhmrc.gov.au/_files_nhmrc/publications/attachments/ext003_venous_leg_ulcers_aust_nz_0.pdf. Accessed March 21, 2015.

4. Johansen OE, Birkeland KI, Jørgensen AP, et al. Diabetic foot ulcer burden may be modified by high-dose atorvastatin: a 6-month randomized controlled pilot trial. J Diabetes. 2009; 1:182-187.

5. Farsaei S, Khalili H, Farboud ES, et al. Efficacy of topical atorvastatin for the treatment of pressure ulcers: a randomized clinical trial. Pharmacotherapy. 2014;34:19-27.

6. Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol. 2008;35:1801-1808.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(3):182-184.

PRACTICE CHANGER
Consider adding simvastatin (40 mg/d) to standard wound care and compression for patients with venous stasis ulcers.¹

STRENGTH OF RECOMMENDATION
B: Based on a high-quality randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE
A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past nine months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrence is common.^2,3

Statins have been found to aid wound healing through their diverse physiologic (pleiotropic) effects. Evidence indicates they can be beneficial in treatment of diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

Continue for study summary >>

STUDY SUMMARY
Ulcers more likely to close when statin added
This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin (40 mg/d) for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Study subjects were 66 patients, ages 41 to 71, who’d had one or more venous ulcers for at least three months. They were randomly assigned to receive either simvastatin (40 mg/d; n = 32) or an identical-appearing placebo (n = 34). Patients were excluded if they were pregnant, had an ulcer that was infected or > 10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤ 5 cm and > 5 cm). There was no statistically significant difference between the two groups in the duration of venous ulceration (3.80 y in the placebo group vs 3.93 y in the simvastatin group) or incidence of diabetes (5% vs 3%, respectively).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed, healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy initiation. The same dermatologist, who was blinded to the patients’ group assignments, evaluated all patients every two weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR], 0.16; number needed to treat [NNT], 2).

Among patients with ulcers ≤ 5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR, 0.10; NNT, 2). Perhaps more importantly, in patients with ulcers > 5 cm, 67% in the simvastatin group had closure with a mean healing time of nine weeks, whereas none of the ulcers of this size closed in the control group (RR, 0.33; NNT, 1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²).

In addition, in the simvastatin group, healing times were significantly reduced (7.53 ± 1.34 wk vs 8.55 ± 1.13 wk) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts were minimal (8%; two in the placebo group and three in the intervention group). Using intention-to-treat analysis and worst-case scenarios for those who dropped out did not affect the primary outcome. There were no withdrawals due to adverse reactions.

WHAT’S NEW
Statins offer significant benefits for treating venous stasis ulcers
This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

Next page: Caveats >>

CAVEATS
Carefully selected patients
Many wounds will heal with compression therapy alone, as occurred in this study, in which 50% of ulcers ≤ 5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when target patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as ACE inhibitors. No data were collected on patient BMI, which is a risk factor for delayed healing.

The prevalence of obesity is lower in the Philippines than in the US. It is uncertain what role this difference would have in the statin’s effectiveness.

Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

Nontheless, we found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies.

This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION
There are no known barriers to implementation of this practice.

REFERENCES
1. Evangelista MT, Casintahan MF, Villafuerte LL. Simvastatin as a novel therapeutic agent for venous ulcers: a randomized, double-blind, placebo-controlled trial. Br J Dermatol. 2014; 170:1151-1157.

2. Collins L, Seraj S. Diagnosis and treatment of venous ulcers. Am Fam Physician. 2010;81: 989-996.

3. The Australian Wound Management Association Inc, New Zealand Wound Care Society Inc. Australian and New Zealand clinical practice guideline for prevention and management of venous leg ulcers (2011). www.nhmrc.gov.au/_files_nhmrc/publications/attachments/ext003_venous_leg_ulcers_aust_nz_0.pdf. Accessed March 21, 2015.

4. Johansen OE, Birkeland KI, Jørgensen AP, et al. Diabetic foot ulcer burden may be modified by high-dose atorvastatin: a 6-month randomized controlled pilot trial. J Diabetes. 2009; 1:182-187.

5. Farsaei S, Khalili H, Farboud ES, et al. Efficacy of topical atorvastatin for the treatment of pressure ulcers: a randomized clinical trial. Pharmacotherapy. 2014;34:19-27.

6. Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol. 2008;35:1801-1808.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(3):182-184.

PRACTICE CHANGER
Consider adding simvastatin (40 mg/d) to standard wound care and compression for patients with venous stasis ulcers.¹

STRENGTH OF RECOMMENDATION
B: Based on a high-quality randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE
A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past nine months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrence is common.^2,3

Statins have been found to aid wound healing through their diverse physiologic (pleiotropic) effects. Evidence indicates they can be beneficial in treatment of diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

Continue for study summary >>

STUDY SUMMARY
Ulcers more likely to close when statin added
This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin (40 mg/d) for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Study subjects were 66 patients, ages 41 to 71, who’d had one or more venous ulcers for at least three months. They were randomly assigned to receive either simvastatin (40 mg/d; n = 32) or an identical-appearing placebo (n = 34). Patients were excluded if they were pregnant, had an ulcer that was infected or > 10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤ 5 cm and > 5 cm). There was no statistically significant difference between the two groups in the duration of venous ulceration (3.80 y in the placebo group vs 3.93 y in the simvastatin group) or incidence of diabetes (5% vs 3%, respectively).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed, healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy initiation. The same dermatologist, who was blinded to the patients’ group assignments, evaluated all patients every two weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR], 0.16; number needed to treat [NNT], 2).

Among patients with ulcers ≤ 5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR, 0.10; NNT, 2). Perhaps more importantly, in patients with ulcers > 5 cm, 67% in the simvastatin group had closure with a mean healing time of nine weeks, whereas none of the ulcers of this size closed in the control group (RR, 0.33; NNT, 1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²).

In addition, in the simvastatin group, healing times were significantly reduced (7.53 ± 1.34 wk vs 8.55 ± 1.13 wk) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts were minimal (8%; two in the placebo group and three in the intervention group). Using intention-to-treat analysis and worst-case scenarios for those who dropped out did not affect the primary outcome. There were no withdrawals due to adverse reactions.

WHAT’S NEW
Statins offer significant benefits for treating venous stasis ulcers
This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

Next page: Caveats >>

CAVEATS
Carefully selected patients
Many wounds will heal with compression therapy alone, as occurred in this study, in which 50% of ulcers ≤ 5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when target patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as ACE inhibitors. No data were collected on patient BMI, which is a risk factor for delayed healing.

The prevalence of obesity is lower in the Philippines than in the US. It is uncertain what role this difference would have in the statin’s effectiveness.

Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

Nontheless, we found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies.

This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION
There are no known barriers to implementation of this practice.

REFERENCES
1. Evangelista MT, Casintahan MF, Villafuerte LL. Simvastatin as a novel therapeutic agent for venous ulcers: a randomized, double-blind, placebo-controlled trial. Br J Dermatol. 2014; 170:1151-1157.

2. Collins L, Seraj S. Diagnosis and treatment of venous ulcers. Am Fam Physician. 2010;81: 989-996.

3. The Australian Wound Management Association Inc, New Zealand Wound Care Society Inc. Australian and New Zealand clinical practice guideline for prevention and management of venous leg ulcers (2011). www.nhmrc.gov.au/_files_nhmrc/publications/attachments/ext003_venous_leg_ulcers_aust_nz_0.pdf. Accessed March 21, 2015.

4. Johansen OE, Birkeland KI, Jørgensen AP, et al. Diabetic foot ulcer burden may be modified by high-dose atorvastatin: a 6-month randomized controlled pilot trial. J Diabetes. 2009; 1:182-187.

5. Farsaei S, Khalili H, Farboud ES, et al. Efficacy of topical atorvastatin for the treatment of pressure ulcers: a randomized clinical trial. Pharmacotherapy. 2014;34:19-27.

6. Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol. 2008;35:1801-1808.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(3):182-184.

Illustrative case

A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past 9 months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrences are common.^2,3

Statins have been found to help wound healing through their diverse physiologic (pleiotropic) effects. Evidence shows they can be beneficial for treating diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud’s phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

STUDY SUMMARY: Ulcers are more likely to close when a statin is added to standard care

This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin 40 mg/d for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Researchers randomized 66 patients ages 41 to 71 who’d had one or more venous ulcers for at least 3 months to receive either simvastatin 40 mg/d (N=32) or an identical appearing placebo (N=34). Patients were excluded if they were pregnant, had an ulcer that was infected or >10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤5 cm and >5 cm). There was no statistically significant difference between the 2 groups in the duration of venous ulceration (3.80 years in the placebo group vs 3.93 years in the simvastatin group) or incidence of diabetes (5% in the placebo group vs 3% in the simvastatin group).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed and healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy. The same dermatologist, who was blinded to the patients’ assigned group, evaluated all patients every 2 weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR]=0.16; 95% confidence interval [CI], 0.05-0.47; number needed to treat [NNT]=2).

Sixty-seven percent of ulcers >5 cm in the simvastatin group had closure, while none of those in the control group did. Among patients with ulcers ≤5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR=0.10; 95% CI, 0.01-0.71; NNT=2). Perhaps more importantly, in patients with ulcers >5 cm, 67% of the ulcers in the simvastatin group had closure with a mean healing time of 9 weeks, whereas none of the ulcers of this size closed in the control group (RR=0.33; 95% CI, 0.12-0.84; NNT=1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²; P=.03).

In addition, in the simvastatin group, healing times were significantly reduced (7.53±1.34 weeks vs 8.55±1.13 weeks) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts (8%; 2 in the placebo group and 3 in the intervention group) were minimal. Using intention-to-treat analysis and worst-case scenarios for dropouts did not affect the primary outcome. There were no withdrawals for adverse reactions.

WHAT’S NEW: Statins offer significant benefits for treating venous stasis ulcers

This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

CAVEATS: Results were found in a carefully selected group of patients

Many wounds will heal with compression therapy alone, as occurred in this study, where 50% of ulcers ≤5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when these patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as angiotensin-converting enzyme inhibitors. No data were collected on patient body mass index, which is a risk factor for delayed healing. The prevalence of obesity is lower in the Philippines than in the United States, and it is uncertain what role this difference would have in the statin’s effectiveness. Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

We found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies. This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION

There are no known barriers to implementing this practice.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Illustrative case

A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past 9 months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrences are common.^2,3

Statins have been found to help wound healing through their diverse physiologic (pleiotropic) effects. Evidence shows they can be beneficial for treating diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud’s phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

STUDY SUMMARY: Ulcers are more likely to close when a statin is added to standard care

This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin 40 mg/d for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Researchers randomized 66 patients ages 41 to 71 who’d had one or more venous ulcers for at least 3 months to receive either simvastatin 40 mg/d (N=32) or an identical appearing placebo (N=34). Patients were excluded if they were pregnant, had an ulcer that was infected or >10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤5 cm and >5 cm). There was no statistically significant difference between the 2 groups in the duration of venous ulceration (3.80 years in the placebo group vs 3.93 years in the simvastatin group) or incidence of diabetes (5% in the placebo group vs 3% in the simvastatin group).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed and healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy. The same dermatologist, who was blinded to the patients’ assigned group, evaluated all patients every 2 weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR]=0.16; 95% confidence interval [CI], 0.05-0.47; number needed to treat [NNT]=2).

Sixty-seven percent of ulcers >5 cm in the simvastatin group had closure, while none of those in the control group did. Among patients with ulcers ≤5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR=0.10; 95% CI, 0.01-0.71; NNT=2). Perhaps more importantly, in patients with ulcers >5 cm, 67% of the ulcers in the simvastatin group had closure with a mean healing time of 9 weeks, whereas none of the ulcers of this size closed in the control group (RR=0.33; 95% CI, 0.12-0.84; NNT=1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²; P=.03).

In addition, in the simvastatin group, healing times were significantly reduced (7.53±1.34 weeks vs 8.55±1.13 weeks) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts (8%; 2 in the placebo group and 3 in the intervention group) were minimal. Using intention-to-treat analysis and worst-case scenarios for dropouts did not affect the primary outcome. There were no withdrawals for adverse reactions.

WHAT’S NEW: Statins offer significant benefits for treating venous stasis ulcers

This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

CAVEATS: Results were found in a carefully selected group of patients

Many wounds will heal with compression therapy alone, as occurred in this study, where 50% of ulcers ≤5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when these patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as angiotensin-converting enzyme inhibitors. No data were collected on patient body mass index, which is a risk factor for delayed healing. The prevalence of obesity is lower in the Philippines than in the United States, and it is uncertain what role this difference would have in the statin’s effectiveness. Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

We found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies. This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION

There are no known barriers to implementing this practice.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Illustrative case

A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past 9 months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrences are common.^2,3

Statins have been found to help wound healing through their diverse physiologic (pleiotropic) effects. Evidence shows they can be beneficial for treating diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud’s phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

STUDY SUMMARY: Ulcers are more likely to close when a statin is added to standard care

This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin 40 mg/d for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Researchers randomized 66 patients ages 41 to 71 who’d had one or more venous ulcers for at least 3 months to receive either simvastatin 40 mg/d (N=32) or an identical appearing placebo (N=34). Patients were excluded if they were pregnant, had an ulcer that was infected or >10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤5 cm and >5 cm). There was no statistically significant difference between the 2 groups in the duration of venous ulceration (3.80 years in the placebo group vs 3.93 years in the simvastatin group) or incidence of diabetes (5% in the placebo group vs 3% in the simvastatin group).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed and healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy. The same dermatologist, who was blinded to the patients’ assigned group, evaluated all patients every 2 weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR]=0.16; 95% confidence interval [CI], 0.05-0.47; number needed to treat [NNT]=2).

Sixty-seven percent of ulcers >5 cm in the simvastatin group had closure, while none of those in the control group did. Among patients with ulcers ≤5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR=0.10; 95% CI, 0.01-0.71; NNT=2). Perhaps more importantly, in patients with ulcers >5 cm, 67% of the ulcers in the simvastatin group had closure with a mean healing time of 9 weeks, whereas none of the ulcers of this size closed in the control group (RR=0.33; 95% CI, 0.12-0.84; NNT=1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²; P=.03).

In addition, in the simvastatin group, healing times were significantly reduced (7.53±1.34 weeks vs 8.55±1.13 weeks) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts (8%; 2 in the placebo group and 3 in the intervention group) were minimal. Using intention-to-treat analysis and worst-case scenarios for dropouts did not affect the primary outcome. There were no withdrawals for adverse reactions.

WHAT’S NEW: Statins offer significant benefits for treating venous stasis ulcers

This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

CAVEATS: Results were found in a carefully selected group of patients

Many wounds will heal with compression therapy alone, as occurred in this study, where 50% of ulcers ≤5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when these patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as angiotensin-converting enzyme inhibitors. No data were collected on patient body mass index, which is a risk factor for delayed healing. The prevalence of obesity is lower in the Philippines than in the United States, and it is uncertain what role this difference would have in the statin’s effectiveness. Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

We found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies. This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION

There are no known barriers to implementing this practice.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

PRACTICE CHANGER
Prescribe a high-dose statin before any patient with acute coronary syndrome (ACS) undergoes percutaneous coronary intervention (PCI); it may be reasonable to extend this to patients being evaluated for ACS.¹

STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis¹

ILLUSTRATIVE CASE
A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well known for their cholesterol-lowering effect, they also offer benefits independent of lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, those with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk for coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time to start statins in patients with ACS.

Continue for study summary >>

STUDY SUMMARY
Meta-analysis shows statins before PCI cut risk for MI
Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) with those who received low-dose or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and ­CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8,750 patients. Four studies enrolled only patients with ST elevation MI (STEMI), eight were restricted to NSTEMI, and the remaining eight studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 days before. For those started after PCI, the average time to administration was 3.18 days after.

Administering statins before PCI resulted in a greater reduction in the odds of MI than did starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3,621) in the statins group and 5% (179 of 3,577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat = 62.5) and a 33% reduction of the odds of MI (odds ratio [OR] = 0.67). There was also a trend toward reduced mortality in the statin group (OR = 0.66).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR = 0.38) than starting them post-PCI (OR = 0.85) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant; these findings persisted past 30 days.

WHAT’S NEW
Early statin administration is most effective
According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk for subsequent MI.

Next page: Caveats and challenges >>

CAVEATS
Benefits might vary with ­different statins
The studies evaluated in this ­meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION
No barriers to earlier start
Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the associated risks are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

REFERENCES
1. Navarese EP, Kowalewski M, Andreotti F, et al. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2014;113:1753-1764.
2. Pignone M, Phillips C, Mulrow C. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials. BMJ. 2000;321:983-986.
3. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-1357.
4. Liao JK. Beyond lipid lowering: the role of statins in vascular protection. Int J Cardiol. 2002;86:5-18.
5. Li J, Li JJ, He JG, et al. Atorvastatin decreases C-reactive protein-induced inflammatory response in pulmonary artery smooth muscle cells by inhibiting nuclear factor-kappaB pathway. Cardiovasc Ther. 2010;28:8-14.
6. Tandon V, Bano G, Khajuria V, et al. Pleiotropic effects of statins. Indian J Pharmacol. 2005; 37:77-85.
7. Wright RS, Anderson JL, Adams CD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57: e215-e367.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(12):735, 738.

PRACTICE CHANGER
Prescribe a high-dose statin before any patient with acute coronary syndrome (ACS) undergoes percutaneous coronary intervention (PCI); it may be reasonable to extend this to patients being evaluated for ACS.¹

STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis¹

ILLUSTRATIVE CASE
A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well known for their cholesterol-lowering effect, they also offer benefits independent of lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, those with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk for coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time to start statins in patients with ACS.

Continue for study summary >>

STUDY SUMMARY
Meta-analysis shows statins before PCI cut risk for MI
Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) with those who received low-dose or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and ­CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8,750 patients. Four studies enrolled only patients with ST elevation MI (STEMI), eight were restricted to NSTEMI, and the remaining eight studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 days before. For those started after PCI, the average time to administration was 3.18 days after.

Administering statins before PCI resulted in a greater reduction in the odds of MI than did starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3,621) in the statins group and 5% (179 of 3,577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat = 62.5) and a 33% reduction of the odds of MI (odds ratio [OR] = 0.67). There was also a trend toward reduced mortality in the statin group (OR = 0.66).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR = 0.38) than starting them post-PCI (OR = 0.85) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant; these findings persisted past 30 days.

WHAT’S NEW
Early statin administration is most effective
According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk for subsequent MI.

Next page: Caveats and challenges >>

CAVEATS
Benefits might vary with ­different statins
The studies evaluated in this ­meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION
No barriers to earlier start
Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the associated risks are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

REFERENCES
1. Navarese EP, Kowalewski M, Andreotti F, et al. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2014;113:1753-1764.
2. Pignone M, Phillips C, Mulrow C. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials. BMJ. 2000;321:983-986.
3. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-1357.
4. Liao JK. Beyond lipid lowering: the role of statins in vascular protection. Int J Cardiol. 2002;86:5-18.
5. Li J, Li JJ, He JG, et al. Atorvastatin decreases C-reactive protein-induced inflammatory response in pulmonary artery smooth muscle cells by inhibiting nuclear factor-kappaB pathway. Cardiovasc Ther. 2010;28:8-14.
6. Tandon V, Bano G, Khajuria V, et al. Pleiotropic effects of statins. Indian J Pharmacol. 2005; 37:77-85.
7. Wright RS, Anderson JL, Adams CD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57: e215-e367.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(12):735, 738.

PRACTICE CHANGER
Prescribe a high-dose statin before any patient with acute coronary syndrome (ACS) undergoes percutaneous coronary intervention (PCI); it may be reasonable to extend this to patients being evaluated for ACS.¹

STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis¹

ILLUSTRATIVE CASE
A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well known for their cholesterol-lowering effect, they also offer benefits independent of lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, those with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk for coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time to start statins in patients with ACS.

Continue for study summary >>

STUDY SUMMARY
Meta-analysis shows statins before PCI cut risk for MI
Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) with those who received low-dose or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and ­CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8,750 patients. Four studies enrolled only patients with ST elevation MI (STEMI), eight were restricted to NSTEMI, and the remaining eight studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 days before. For those started after PCI, the average time to administration was 3.18 days after.

Administering statins before PCI resulted in a greater reduction in the odds of MI than did starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3,621) in the statins group and 5% (179 of 3,577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat = 62.5) and a 33% reduction of the odds of MI (odds ratio [OR] = 0.67). There was also a trend toward reduced mortality in the statin group (OR = 0.66).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR = 0.38) than starting them post-PCI (OR = 0.85) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant; these findings persisted past 30 days.

WHAT’S NEW
Early statin administration is most effective
According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk for subsequent MI.

Next page: Caveats and challenges >>

CAVEATS
Benefits might vary with ­different statins
The studies evaluated in this ­meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION
No barriers to earlier start
Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the associated risks are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

REFERENCES
1. Navarese EP, Kowalewski M, Andreotti F, et al. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2014;113:1753-1764.
2. Pignone M, Phillips C, Mulrow C. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials. BMJ. 2000;321:983-986.
3. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-1357.
4. Liao JK. Beyond lipid lowering: the role of statins in vascular protection. Int J Cardiol. 2002;86:5-18.
5. Li J, Li JJ, He JG, et al. Atorvastatin decreases C-reactive protein-induced inflammatory response in pulmonary artery smooth muscle cells by inhibiting nuclear factor-kappaB pathway. Cardiovasc Ther. 2010;28:8-14.
6. Tandon V, Bano G, Khajuria V, et al. Pleiotropic effects of statins. Indian J Pharmacol. 2005; 37:77-85.
7. Wright RS, Anderson JL, Adams CD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57: e215-e367.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(12):735, 738.

Illustrative case

A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia, and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well-known for their cholesterol-lowering effect, they also have benefits that are independent of their effects on lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, patients with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk of coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time for starting statins in patients with ACS.

STUDY SUMMARY: Meta-analysis of 20 RCTs shows
 statins before PCI cuts risk of MI

Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) vs those who received low-dose statins or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8750 patients. Four studies enrolled only patients with ST elevation MI, 8 were restricted to NSTEMI, and the remaining 8 studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 ± 0.42 days before. For those started after PCI, the average time to administration was 3.18 ± 3.56 days after.

Administering statins before PCI resulted
 in a greater reduction in the odds of MI than starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3621) in the statins group and 5% (179 of 3577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat=62.5), and a reduction of the odds of MI by 33% (odds ratio [OR]=0.67; 95% confidence interval [CI], 0.53-0.84; P=.0007). There was also a trend toward reduced mortality in the statin group (OR=0.66; 95% CI, 0.43-1.02; P=.06).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR=0.38; 95% CI, 0.24-0.59; P<.0001) than starting them post-PCI (OR=0.85; 95% CI, 0.64-1.13; P=.28) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant (P=.002). These findings persisted past 30 days (P=.06).

WHAT'S NEW: Early statin administration 
is most effective

According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk of subsequent MI.

CAVEATS: Benefits might vary
 with different statins


The studies evaluated in this meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION: No barriers 
to starting statins earlier


Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the risks of taking a statin are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Illustrative case

A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia, and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well-known for their cholesterol-lowering effect, they also have benefits that are independent of their effects on lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, patients with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk of coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time for starting statins in patients with ACS.

STUDY SUMMARY: Meta-analysis of 20 RCTs shows
 statins before PCI cuts risk of MI

Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) vs those who received low-dose statins or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8750 patients. Four studies enrolled only patients with ST elevation MI, 8 were restricted to NSTEMI, and the remaining 8 studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 ± 0.42 days before. For those started after PCI, the average time to administration was 3.18 ± 3.56 days after.

Administering statins before PCI resulted
 in a greater reduction in the odds of MI than starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3621) in the statins group and 5% (179 of 3577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat=62.5), and a reduction of the odds of MI by 33% (odds ratio [OR]=0.67; 95% confidence interval [CI], 0.53-0.84; P=.0007). There was also a trend toward reduced mortality in the statin group (OR=0.66; 95% CI, 0.43-1.02; P=.06).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR=0.38; 95% CI, 0.24-0.59; P<.0001) than starting them post-PCI (OR=0.85; 95% CI, 0.64-1.13; P=.28) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant (P=.002). These findings persisted past 30 days (P=.06).

WHAT'S NEW: Early statin administration 
is most effective

According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk of subsequent MI.

CAVEATS: Benefits might vary
 with different statins


The studies evaluated in this meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION: No barriers 
to starting statins earlier


Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the risks of taking a statin are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Illustrative case

A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia, and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well-known for their cholesterol-lowering effect, they also have benefits that are independent of their effects on lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, patients with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk of coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time for starting statins in patients with ACS.

STUDY SUMMARY: Meta-analysis of 20 RCTs shows
 statins before PCI cuts risk of MI

Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) vs those who received low-dose statins or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8750 patients. Four studies enrolled only patients with ST elevation MI, 8 were restricted to NSTEMI, and the remaining 8 studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 ± 0.42 days before. For those started after PCI, the average time to administration was 3.18 ± 3.56 days after.

Administering statins before PCI resulted
 in a greater reduction in the odds of MI than starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3621) in the statins group and 5% (179 of 3577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat=62.5), and a reduction of the odds of MI by 33% (odds ratio [OR]=0.67; 95% confidence interval [CI], 0.53-0.84; P=.0007). There was also a trend toward reduced mortality in the statin group (OR=0.66; 95% CI, 0.43-1.02; P=.06).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR=0.38; 95% CI, 0.24-0.59; P<.0001) than starting them post-PCI (OR=0.85; 95% CI, 0.64-1.13; P=.28) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant (P=.002). These findings persisted past 30 days (P=.06).

WHAT'S NEW: Early statin administration 
is most effective

According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk of subsequent MI.

CAVEATS: Benefits might vary
 with different statins


The studies evaluated in this meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION: No barriers 
to starting statins earlier


Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the risks of taking a statin are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

PRACTICE CHANGER
Ensure that antibiotics are administered to surgical patients when their urinary catheter is removed to reduce the risk for urinary tract infections (UTIs).¹

STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis.¹

ILLUSTRATIVE CASE
A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and soon his urinary catheter will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.²

Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most ­common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species comprise the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal
Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. CDC guidelines published in 2009 outline which patients are appropriate candidates for catheterization but do not recommend routine use of antibiotics to prevent CAUTIs.² A 2014 Infectious Diseases Society of America practice recommendation, which was published after the study reported on here, states the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY
Analysis shows prophylactic antibiotics reduce UTIs
Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed seven studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of two surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including two that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to three days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of ­CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics and 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17, with a risk ratio (RR) of .45. The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial and remained at .45 when they analyzed only studies of surgical patients.

The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the two studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT’S NEW
We now have an effective way to reduce CAUTIs
Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

Continue for caveats and challenges >>

CAVEATS
Results may not apply to ­nonsurgical patients
This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk for attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION
Which antibiotics to use—and for how long—remains unclear
Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for three days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administration of antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

REFERENCES
1. Marschall J, Carpenter CR, Fowler S, et al; CDC Prevention Epicenters Program. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ. 2013;346:f3147.

2. Gould CV, Umscheid CA, Agarwal RK, et al. Guideline for prevention of catheter-associated urinary tract infections 2009. www.cdc.gov/hicpac/pdf/cauti/cautiguideline2009final.pdf. Accessed November 12, 2014.  

3. Lo E, Nicolle LE, Coffin SE, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:464-479.

4. Pickard R, Lam T, Maclennan G, et al. Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial). Health Technol Assess. 2012;16:1-197.

5. Pickard R, Lam T, MacLennan G, et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. Lancet. 2012;380:1927-1935.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):E10-E12.

PRACTICE CHANGER
Ensure that antibiotics are administered to surgical patients when their urinary catheter is removed to reduce the risk for urinary tract infections (UTIs).¹

STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis.¹

ILLUSTRATIVE CASE
A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and soon his urinary catheter will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.²

Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most ­common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species comprise the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal
Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. CDC guidelines published in 2009 outline which patients are appropriate candidates for catheterization but do not recommend routine use of antibiotics to prevent CAUTIs.² A 2014 Infectious Diseases Society of America practice recommendation, which was published after the study reported on here, states the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY
Analysis shows prophylactic antibiotics reduce UTIs
Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed seven studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of two surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including two that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to three days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of ­CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics and 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17, with a risk ratio (RR) of .45. The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial and remained at .45 when they analyzed only studies of surgical patients.

The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the two studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT’S NEW
We now have an effective way to reduce CAUTIs
Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

Continue for caveats and challenges >>

CAVEATS
Results may not apply to ­nonsurgical patients
This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk for attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION
Which antibiotics to use—and for how long—remains unclear
Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for three days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administration of antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

REFERENCES
1. Marschall J, Carpenter CR, Fowler S, et al; CDC Prevention Epicenters Program. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ. 2013;346:f3147.

2. Gould CV, Umscheid CA, Agarwal RK, et al. Guideline for prevention of catheter-associated urinary tract infections 2009. www.cdc.gov/hicpac/pdf/cauti/cautiguideline2009final.pdf. Accessed November 12, 2014.  

3. Lo E, Nicolle LE, Coffin SE, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:464-479.

4. Pickard R, Lam T, Maclennan G, et al. Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial). Health Technol Assess. 2012;16:1-197.

5. Pickard R, Lam T, MacLennan G, et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. Lancet. 2012;380:1927-1935.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):E10-E12.

PRACTICE CHANGER
Ensure that antibiotics are administered to surgical patients when their urinary catheter is removed to reduce the risk for urinary tract infections (UTIs).¹

STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis.¹

ILLUSTRATIVE CASE
A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and soon his urinary catheter will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.²

Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most ­common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species comprise the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal
Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. CDC guidelines published in 2009 outline which patients are appropriate candidates for catheterization but do not recommend routine use of antibiotics to prevent CAUTIs.² A 2014 Infectious Diseases Society of America practice recommendation, which was published after the study reported on here, states the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY
Analysis shows prophylactic antibiotics reduce UTIs
Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed seven studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of two surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including two that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to three days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of ­CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics and 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17, with a risk ratio (RR) of .45. The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial and remained at .45 when they analyzed only studies of surgical patients.

The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the two studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT’S NEW
We now have an effective way to reduce CAUTIs
Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

Continue for caveats and challenges >>

CAVEATS
Results may not apply to ­nonsurgical patients
This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk for attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION
Which antibiotics to use—and for how long—remains unclear
Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for three days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administration of antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

REFERENCES
1. Marschall J, Carpenter CR, Fowler S, et al; CDC Prevention Epicenters Program. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ. 2013;346:f3147.

2. Gould CV, Umscheid CA, Agarwal RK, et al. Guideline for prevention of catheter-associated urinary tract infections 2009. www.cdc.gov/hicpac/pdf/cauti/cautiguideline2009final.pdf. Accessed November 12, 2014.  

3. Lo E, Nicolle LE, Coffin SE, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:464-479.

4. Pickard R, Lam T, Maclennan G, et al. Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial). Health Technol Assess. 2012;16:1-197.

5. Pickard R, Lam T, MacLennan G, et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. Lancet. 2012;380:1927-1935.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):E10-E12.

Illustrative case

A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and his urinary catheter soon will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.² Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species make up the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal

Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. Centers for Disease Control and Prevention (CDC) guidelines published in 2009 outline which patients are appropriate for catheterization, but do not recommend routine use of antibiotics to prevent CAUTIs.2 The 2014 Infectious Diseases Society of America guidelines, which came out before the study reported on here was published, state the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY: Meta-analysis shows prophylactic antibiotics reduce UTI ris

Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed 7 studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of 2 surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including 2 that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to 3 days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics vs 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17 (95% confidence interval [CI], 12-30), with a risk ratio (RR) of .45 (95% CI, .28-.72). The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial, and remained at .45 when they analyzed only studies of surgical patients.

This meta-analysis suggests that prophylaxis for 3 days or less can reduce the risk of catheter-associated UTIs.The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the 2 studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT'S NEW: We now have an effective way to reduce CAUTIs

Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

CAVEATS: Results may not apply to nonsurgical patients

This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk of attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION: Which antibiotics to use, and for how long, remains unclear

Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for 3 days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administering antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Illustrative case

A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and his urinary catheter soon will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.² Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species make up the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal

Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. Centers for Disease Control and Prevention (CDC) guidelines published in 2009 outline which patients are appropriate for catheterization, but do not recommend routine use of antibiotics to prevent CAUTIs.2 The 2014 Infectious Diseases Society of America guidelines, which came out before the study reported on here was published, state the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY: Meta-analysis shows prophylactic antibiotics reduce UTI ris

Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed 7 studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of 2 surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including 2 that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to 3 days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics vs 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17 (95% confidence interval [CI], 12-30), with a risk ratio (RR) of .45 (95% CI, .28-.72). The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial, and remained at .45 when they analyzed only studies of surgical patients.

This meta-analysis suggests that prophylaxis for 3 days or less can reduce the risk of catheter-associated UTIs.The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the 2 studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT'S NEW: We now have an effective way to reduce CAUTIs

Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

CAVEATS: Results may not apply to nonsurgical patients

This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk of attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION: Which antibiotics to use, and for how long, remains unclear

Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for 3 days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administering antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.

Illustrative case

A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and his urinary catheter soon will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.² Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species make up the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal

Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. Centers for Disease Control and Prevention (CDC) guidelines published in 2009 outline which patients are appropriate for catheterization, but do not recommend routine use of antibiotics to prevent CAUTIs.2 The 2014 Infectious Diseases Society of America guidelines, which came out before the study reported on here was published, state the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY: Meta-analysis shows prophylactic antibiotics reduce UTI ris

Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed 7 studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of 2 surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including 2 that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to 3 days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics vs 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17 (95% confidence interval [CI], 12-30), with a risk ratio (RR) of .45 (95% CI, .28-.72). The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial, and remained at .45 when they analyzed only studies of surgical patients.

This meta-analysis suggests that prophylaxis for 3 days or less can reduce the risk of catheter-associated UTIs.The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the 2 studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT'S NEW: We now have an effective way to reduce CAUTIs

Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

CAVEATS: Results may not apply to nonsurgical patients

This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk of attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION: Which antibiotics to use, and for how long, remains unclear

Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for 3 days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administering antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, 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.