Clinical Reminders Attached to Echocardiography Reports of Patients With Reduced Left Ventricular Ejection Fraction Increase Use of β-Blockers
A Randomized Trial
Background— Although β-blockers are known to prolong survival for patients with reduced left ventricular ejection fraction, they are often underused. We hypothesized that a reminder attached to the echocardiography report would increase the use of β-blockers for patients with reduced left ventricular ejection fraction.
Methods and Results— We randomized 1546 consecutive patients with a left ventricular ejection fraction <45% found on echocardiography at 1 of 3 laboratories to a reminder for use of β-blockers or no reminder. Patients were excluded from analysis if they died within 30 days of randomization (n=89), did not receive medications through the Veterans Affairs system after 30 days (n=180), or underwent echocardiography at >1 laboratory (n=6). The primary outcome was a prescription for an oral β-blocker between 1 and 9 months after randomization. The mean age of the 1271 included patients was 69 years; 60% had a history of heart failure, and 51% were receiving treatment with β-blockers at the time of echocardiography. More patients randomized to the reminder had a subsequent β-blocker prescription (74%, 458 of 621) compared with those randomized to no reminder (66%, 428 of 650; P=0.002). The effect of the reminder was not significantly different for subgroups based on patient location (inpatient versus outpatient) or prior use of β-blockers.
Conclusions— A reminder attached to the echocardiography report increased the use of β-blockers in patients with depressed left ventricular systolic function.
Received December 15, 2006; accepted April 3, 2007.
Treatment with β-blockers is known to improve outcome for patients with left ventricular dysfunction,1–3 and their use is now a performance measure of the American College of Cardiology and the American Heart Association.4 However, recent studies have found the use of β-blockers to be only 30% to 60% among ideal candidates.5–7
One method of improving compliance with treatment guidelines is a clinical reminder.8,9 Reminders are low-cost interventions that have been shown to be most effective when delivered at the time of the patient encounter.10,11 We previously demonstrated in a randomized trial that adding a clinical reminder to the echocardiography report was successful in increasing the prescribed dosage of angiotensin-converting enzyme (ACE) inhibitors in patients with reduced left ventricular ejection fraction (LVEF).12 We hypothesized that a similar reminder would be effective in increasing the use of β-blockers for patients with reduced LVEF.
Patients undergoing echocardiography between May 2001 and November 2005 at 1 of 3 echocardiography laboratories in the Veterans Affairs (VA) Palo Alto Health Care System were eligible if they had an LVEF <45% as determined by the attending echocardiographer. Patients were excluded if they had aortic stenosis with a mean aortic valve gradient of ≥20 mm Hg or mitral stenosis with a mean gradient of ≥5 mm Hg.
Randomization was carried out in conjunction with the formation of the echocardiography report with an electronic database (Microsoft Access, Microsoft Corp, Redmond, Wash). In the process of printing the completed report, the computer algorithm checked the electronic report for eligibility and exclusion criteria. Patients meeting study criteria were randomized with a computerized random-number generator either to have a reminder attached to their report or to have no reminder. Randomization was performed separately at each site. Allocation was concealed from all echocardiographers until the reminder appeared in the report. The implementation process (identification of patients, determination of eligibility, randomization, and addition of reminder) was entirely computerized, occurring within 3 seconds of report approval and invisible to the attending echocardiographer. The final report was approved and signed by the attending echocardiographer.
Patients undergoing >1 echocardiogram at each site either received a reminder for all studies or did not receive a reminder for any study based on the initial randomization. The study was approved (including waiver of consent) by the Administrative Panel on Human Subjects at Stanford University.
Echocardiography reports randomized to the reminder included the following statement: “Note: Patients with reduced left ventricular ejection fraction have a survival benefit with beta-blockers (initial dose: carvedilol 3.125 mg BID or metoprolol succinate 12.5 mg BID).” The drug examples were chosen because they are the β-blockers known to improve survival and are available on the VA Palo Alto Health Care System formulary. The reminder also recommended cardiology follow-up if the patient had New York Heart Association class III or IV symptoms.
Outcome and Baseline Data
The primary outcome was a prescription for any β-blocker during the 9 months after echocardiography determined with the VA pharmacy database. A secondary outcome was a prescription for the β-blockers shown to prolong survival in randomized trials of patients with systolic heart failure and available on the formulary (carvedilol and metoprolol succinate).
Prior diagnoses were defined as any encounter with the diagnosis in any of the previous 5 years using International Classification of Diseases, 9th revision, clinical modification, diagnostic codes as follows: ischemic heart disease (410 to 414), heart failure (CM 428), diabetes mellitus (250), hypertension (401 to 405), malignancy (140 to 208), and chronic obstructive pulmonary disease (490 to 496). Previous work has demonstrated reasonable accuracy of International Classification of Diseases, 9th revision, codes within this healthcare system.13 The following laboratory abnormalities were defined as present at baseline if recorded within 12 months before randomization: troponin I >0.1 ng/mL, creatinine >2 mg/dL, and hemoglobin A1c >7%. A baseline medication was defined as a prescription in the 12 months before randomization.
After the study, all 50 primary care providers at the 3 sites were surveyed by e-mail (with 1 additional e-mail if no initial response) to determine their awareness (aware/not aware) of the β-blocker reminder and their interest in having the reminders continue (continue/do not continue/no opinion).
Patients were excluded from analysis (Figure 1) if they died within 1 month of the echocardiogram (n=89), left the healthcare system (n=180; defined as no prescriptions after the echocardiogram), or had echocardiography at >1 site and were randomized to different groups (n=6).
All patients randomized to the intervention received the reminder. We used t tests to compare 2 continuous variables and χ2 tests for multiple categorical variables. Fisher exact test was used for categorical variables for cells with <10 observations. We used logistic regression models to determine the association of β-blocker use with patient and provider characteristics. We also used logistic regression to examine interactions between selected variables and the reminder effect on β-blocker use. A proportional hazards model was used to determine the hazard ratio for survival free of heart failure hospitalization for those randomized to a reminder compared with no reminder. Subgroups for analysis were defined by patient location (inpatients or outpatient clinic type), history of heart failure, LVEF (above and below the median), history of chronic obstructive pulmonary disease, prior use of β-blockers, and time period of the study. The study was designed to have at least 90% power (α error=0.05) to detect a 10% absolute increase in β-blocker use, assuming a control group β-blocker use rate of 50% (combined sample size, 1076). We planned to randomize at least 1500 patients, assuming that 400 patients would leave the healthcare system before the follow-up time. All analyses were performed with STATA 9.0 (STATA Corp, College Station, Tex). The sample size calculation for a 2-sample test of equality of proportions uses a normal approximation with continuity correction (STATA command sampsi). All significance tests were 2 sided.
The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
We identified 1546 consecutive eligible patients during the 4.5-year study period. All were randomized (allocation concealed) to have either a clinical reminder attached to their echocardiography report (n=755) or no reminder (n=791). We excluded 275 patients as shown in Figure 1.
The mean age of the 1271 included patients used in the analyses was 69±7 years; 98% were male; 77% were white; 60% had a prior diagnosis of heart failure; and 51% had an active prescription for a β-blocker at the time of randomization (the Table).
Primary Outcome: β-Blocker Use During Follow-Up
Of those randomized to the reminder, 74% (458 of 621) were prescribed a β-blocker by 9 months compared with 66% (428 of 650; P=0.002) for those randomized to no reminder. When those already on a β-blockers were excluded, reminders remained associated with β-blocker use (56%, 163 of 292) compared with the no-reminder group (44%, 144 of 327; P=0.003). Use of one of the guideline-recommended β-blockers mentioned in the reminder (carvedilol and metoprolol succinate) also was greater for those who received the reminder (42%, 261 of 621) compared with those who did not receive a reminder in their echocardiography report (37%, 238 of 650; P=0.048).
Reminders had a similar effect on the use of β-blockers for both inpatients and outpatients (Figure 2). Inpatients randomized to the reminder received a prescription in 75% (190 of 254) compared with 64% (171 of 266) for those not receiving a reminder. Outpatients randomized to the reminder received a prescription in 73% (268 of 367) compared with 67% (257 of 284) for those not receiving a reminder. Although no positive reminder effect on β-blocker use was observed for patients referred from cardiology clinics (74%, 108 of 145 reminder, versus 77%, 86 of 111 no reminder), there was no significant interaction between clinic source and the reminder impact on β-blocker use (P=0.55).
A borderline-significant interaction with the reminder effect on β-blocker use was present for prior heart failure (P=0.07) and chronic obstructive pulmonary disease (P=0.09; Figure 3). In both cases, the reminder was more effective in those without a prior history of disease. There was no clear impact of prior β-blocker use (P=0.32 for interaction) or LVEF (P=0.81 for interaction) on the effect of the reminder.
Survival Free of Hospitalization
One-year survival free of heart failure hospitalization was 77%. Reminders had no measurable effect on survival free of hospitalization for heart failure (hazard ratio, 0.99; 95% CI, 0.83 to 1.18).
Effect of Reminders Over Time
There was no clear relationship between reminder effect and time period of the study (Figure 4). However, a clear temporal trend was present of increasing β-blocker use in the control group. β-Blocker use in the control group was 55% in 2001 compared with 68% by 2004.
Predictors of β-Blocker Use
We used a logistic model of β-blocker use after randomization that examined the association with patient demographic (age, gender, race) and clinical variables (medical history, LVEF, medication, and clinical laboratory findings). We found that randomization to a reminder (odds ratio [OR], 1.30; 95% CI, 1.04 to 1.63), a history of ischemic heart disease (OR, 1.35; 95% CI, 1.04 to 1.75), prior statin use (OR, 1.57; 95% CI, 1.22 to 2.03), and prior ACE inhibitor or angiotensin receptor blocker use (OR, 1.53; 95% CI, 1.19 to 1.97) were significantly associated with increased use, whereas older age (OR, 0.79 per 10-year increase; 95% CI, 0.72 to 0.88) and a history of chronic obstructive pulmonary disease were associated with decreased use (OR, 0.74; 95% CI, 0.59 to 0.94). However, these factors explained only 5% (adjusted R2) of the variation in β-blocker use.
Of the 50 primary care providers (45 physicians, 5 nurse practitioners), 41 (82%) returned a poststudy survey that did not include the trial results. Thirty-one providers (76%) recalled seeing the β-blocker reminders. A majority (35 of 41, 85%) thought they should continue to be placed in the echocardiography reports, 2 (5%) thought they should be discontinued, and 4 (10%) had no opinion.
This randomized trial demonstrated that a reminder added to the echocardiography report for patients with depressed LVEF can increase prescriptions for β-blockers. The effect of the reminder was noted for multiple subgroups and persisted throughout the 4-year study period.
We examined the effect of reminders in different patient care settings using the location at the time of referral for echocardiography. Reminders appeared to be effective in both inpatient and outpatient settings with the possible exception of those referred from cardiology clinic. These patients had the highest use of β-blockers, and a ceiling effect may have contributed. Cardiologists caring for patients with reduced LVEF may be less likely to benefit from a reminder for β-blocker use given that the focus of their clinic visit is likely to be the treatment or prevention of heart failure.
Our findings demonstrating the effectiveness of a reminder attached to echocardiography reports are consistent with 2 recent studies.12,14 In a nonrandomized study, Sanders et al14 examined the impact of an endocarditis prophylaxis reminder on compliance with AHA recommendations. The present study found that AHA guideline compliance for endocarditis prophylaxis15 was greater among those with a reminder (73%) than in a control group without a reminder (65%; P=0.01). In a randomized trial with a design similar to that of Sanders et al study, we evaluated the impact of a reminder attached to the echocardiography that recommended at least moderate doses of ACE inhibitors for 277 patients with reduced LVEF.12 Those randomized to the reminder received moderate or greater ACE inhibitor doses in 38% compared with 26% (P=0.04) for those not receiving the reminder.
Other studies have not shown a clear effect of a β-blocker reminder. In 1 investigation, Demakis et al10 evaluated computer-generated reminders that appeared with printed material for patients attending general medical clinics at 12 VA medical centers. Physicians randomized to reminders had significantly greater improvement in compliance with 5 prevention standards (eg, pneumococcal vaccination), but for patients with a recent myocardial infarction, β-blocker use was 45% in the reminder group and 41% in the control group (P=0.42). Possible explanations for the larger effect size observed in the present study include the different patient groups (heart failure versus post–myocardial infarction) and the fact that our reminders were included in a report signed by a staff cardiologist, who may be viewed as a local expert and opinion leader.16
We observed an increase in β-blocker use over time in both the control and reminder groups. We cannot exclude the possibility of a learning effect of the reminder in which clinicians increased the use of β-blockers for other patients after seeing a reminder. Although the reminder may have contributed to provider education, we feel it is more likely that clinicians became increasingly comfortable with prescribing β-blockers for multiple reasons, including colleague recommendations and guideline publication. If the latter is correct, reminders will be most beneficial early in the dissemination of a new guideline and may not be effective indefinitely.
Although we did not perform a formal economic analysis, the cost-effectiveness of reminders for β-blockers can be estimated through the use of prior cost-effectiveness studies of β-blocker use in heart failure patients. Economic analyses of randomized trials have found that β-blocker use in patients with heart failure is either cost-saving or highly cost-effective (<$20 000 per quality-adjusted life-year gained).17–20 We found that the number needed to remind for every additional treated patient was 12.5. If reminders cost $2.50 each (≈1 minute of physician time), then it would cost $23 for every additional person treated with β-blockers. Given that treatment with β-blockers is economically attractive and that the use of a reminder adds only minimal cost, the incremental cost-effectiveness of reminders appears highly favorable.
The strengths of the study include the randomized design and the “real-world” enrollment and intervention. Nonrandomized (eg, before and after) designs are subject to bias from temporal trends. We found a large increase in β-blocker use over time in the control group during the study period. Only through the use of a randomized trial could we have demonstrated that the reminder had an independent benefit. Because of waiver of informed consent, we were able to include every candidate for β-blocker therapy. Furthermore, our inclusion and exclusion criteria (eg, aortic or mitral stenosis) were based on characteristics available to the attending echocardiographer at the time he or she completed the report. Thus, the applicability of our findings is not limited by a highly selected population seen in most randomized trials.
An additional strength is the ease with which the intervention can be implemented. The reminder can be entered using the same process of report generation (dictation, computer generated) currently used by each echocardiography laboratory. The extra time required is minimal, and no additional infrastructure is needed. Finally, we showed evidence that reminders were well received by the providers, who encouraged continued use.
The results of the present study suggest that reminders for β-blockers will increase use in 8 patients for every 100 receiving a reminder in their echocardiography reports. Given the similar results seen with ACE inhibitor reminders, it appears that the echocardiography report is an effective vehicle for reminding providers regarding heart failure–related care. The implications extend beyond echocardiography to other cardiovascular and noncardiovascular reports. Electrocardiography reports may be used to distribute reminders for acute or post–myocardial infarction care, and clinical laboratory test results may include suggestions for treatment. Although reminders are a simple method of improving care, additional interventions are needed to maximize recommended treatments given the modest effect of reminders.
The present study has several potential limitations. We tested our reminder in the system in which providers frequently encounter reminders (VA Health Care System).8 In a healthcare system in which reminders are used infrequently, the impact of the echocardiography report based reminder may be greater (no competing reminders) or smaller (providers less comfortable with reminders). Another potential limitation is that the patient population was predominantly male. If physicians respond to reminders differently on the basis of the gender of the patient, then our results can be applied only to men. Our exclusions were limited to those relative contraindications that would be available to the echocardiographer at the time of report generation (eg, aortic stenosis). Thus, it is possible that the reminder caused providers to prescribe β-blockers in patients with other important contraindications (eg, allergy). We believe that it is unlikely that the reminder led to inappropriate treatment given that it was not patient specific but instead noted that in general patients with depressed LVEF benefit from β-blockers. Finally, the present study was not powered to detect differences in survival or hospitalization for heart failure.
In summary, our randomized trial found that a clinical reminder attached to the echocardiography report was effective in increasing the use of β-blockers in patients with reduced LVEF. This quality improvement intervention is attractive given its low cost, wide acceptance by clinicians, and ease of implantation.
Sources of Funding
The present study was supported by grants from the VA Health Services Research Development Office Investigator Initiated Research (IIR-01–108) and the American Society of Echocardiography.
The views expressed are those of the authors and not necessarily those of the Department of Veterans Affairs or other affiliated organizations.
Clinical trial registration information—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414401.
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