High Risk Atherosclerotic Cardiovascular Disease
Conditions
Keywords
electronic alerts, hyperlipidemia
Brief summary
This study is designed to evaluate the efficacy of automated electronic alerts in the electronic health record to improve rates of best practices in the treatment of patients with hyperlipidemia who present in the setting of outpatient primary care and family medicine practices within the Yale New Haven Health System.
Detailed description
Cardiovascular disease (CVD) remains the leading cause of death in most developed countries, including the United States. A key risk factor for CVD is an elevation in low-density lipoprotein cholesterol, or LDL-C. Based on favorable results from large clinical trials, guidelines support the use of high intensity statin therapy for the reduction of LDL-C in very high risk patients and addition of non-statin therapies including ezetimibe and PCSK9 inhibitors if the LDL-C remains above 70 mg/dL. However, implementation of these guidelines is poor and there remains substantial underuse of evidence-based lipid lowering therapies across healthcare systems. Real-time alerting to important clinical conditions, when fired in an appropriate and timely manner, can have positive impacts on patient outcomes through increased physician awareness and adherence to best practices. To this end, this study has been designed to evaluate whether automated electronic alerts built into the Epic electronic health record can improve the management of hyperlipidemia among patients of outpatient internal medicine and cardiology practices within the Yale New Haven Health System who are at very high risk for future atherosclerotic CVD (ASCVD) events. One hundred physicians will undergo cluster randomization to either the alert group or the control (usual care) group. Upon opening the order entry screen of an eligible patient with hyperlipidemia, the alert group will receive an informational alert that informs the provider that the patient has hyperlipidemia and is at very high risk for future ASCVD events and provides ACC/AHA-guideline-directed actionable items, including a link to a hyperlipidemia order set to include both diagnostic and therapeutic options. The primary outcome will be the proportion of patients who have intensification of their lipid lowering therapy (increase in statin dose or addition of ezetimibe or addition of a PCSK9 inhibitor) at 90-days. The secondary outcomes will be achieved LDL-C at 6-months and proportion of patients with LDL-C levels less than 70 mg/dL and less than 55 mg/dL. In an optional extension phase, long-term exploratory outcomes looking at the rate of major cardiovascular cardiac events (MACE), defined as hospitalization for myocardial infarction, stroke, unstable angina, or coronary or peripheral artery revascularization will be evaluated at 2 years.
Interventions
OTHERElectronic Alert
Providers will see an automated electronic alert for each eligible hyperlipidemia patient at high risk for future atherosclerotic CVD events. This alert will appear when the provider enters the order entry screen in the patient's medical record during the patient's first eligible outpatient visit. The alert consists of a pop up that notifies the physician that the patient is at very high risk for ASCVD events, displays the most recent cholesterol values and the patient's current lipid lowering therapy. It also includes a link to full treatment guidelines for hyperlipidemia, which includes a continuing medical education (CME) option to obtain CME credits.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Patient Subjects: * Adults 18 years of age or greater * Currently being seen as an outpatient of Internal Medicine or Cardiology within the Yale New Haven Health System * At very high risk for ASCVD, defined by a history of a major ASCVD event, and most recent lipid profile with LDL-C greater than 70 mg/dL, with or without other high-risk features (diabetes, CKD, age \>65 years)
Exclusion criteria
for Patient Subjects: * Heart transplant recipient * Left ventricular assist device recipient * Hospital inpatient status * Pregnancy * Have opted out of clinical research in MyChart Inclusion Criteria for Provider Subjects: * Practicing at an outpatient cardiology or internal medicine practice with the Yale New Haven Health System * High frequency of eligible patients seen, based on retrospective review of outpatient records
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Intensification of Lipid Lowering Therapy | 90 days from first alert for any given patient | Intensification of lipid lowering therapy is defined as an increase in statin dose, an addition of ezetimibe, or addition of PCSK9. Any one of the three will be sufficient to meet this endpoint. Proportion of patients who meet this endpoint will be compared between study arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achieved LDL-C at 6 Months | 6 months from first alert for any given patient | LDL-C at 6 months as measured by medical record review |
| Proportion of Patients With an LDL-C of Less Than 70 mg/dL | 6 months from first alert for any given patient | Number of patients with LDL-C levels less than 70 mg/dL based on medical record review. Number of patients who meet this endpoint will be compared between study arms. |
| Proportion of Patients With an LDL-C of Less Than 55 mg/dL | 6 months from first alert for any given patient | Number of patients with LDL-C levels less than 55 mg/dL based on medical record review. Number of patients who meet this endpoint will be compared between study arms. |
Countries
United States
Participant flow
Recruitment details
One hundred providers who prescribed the highest volume of PCSK9i in 2020 were retrospectively identified and then consented into the study, followed by randomization into alert group versus usual care group. Patients were automatically enrolled as trial participants if they were seen by a consented provider and met the inclusion criteria as determined by the best practice alert algorithm.
Pre-assignment details
Four of the 100 providers were excluded from the study before randomization, as recruitment finished before these four providers saw an eligible patient. All 2500 patient subjects were randomized, with zero loss to follow up.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Providers will see an electronic alert for eligible patients who are at very high risk for future ASCVD events upon opening of the patient's order entry screen in the medical record.
Electronic Alert: Providers will see an automated electronic alert for each eligible hyperlipidemia patient at high risk for future atherosclerotic CVD events. This alert will appear when the provider enters the order entry screen in the patient's medical record during the patient's first eligible outpatient visit. The alert consists of a pop up that notifies the physician that the patient is at very high risk for ASCVD events, displays the most recent cholesterol values and the patient's current lipid lowering therapy. It also includes a link to full treatment guidelines for hyperlipidemia, which includes a continuing medical education (CME) option to obtain CME credits. | 1,130 |
| Control Providers will not see an electronic alert for any patients and will provide usual care. Silent alerts will be generated that will be sent to study team members. | 1,370 |
| Total | 2,500 |
Baseline characteristics
| Characteristic | Total | Control | Intervention |
|---|---|---|---|
| Age, Continuous | 72 years | 71 years | 72 years |
| ALT | 21 U/L | 21 U/L | 20 U/L |
| AST | 21 U/L | 21 U/L | 21 U/L |
| Baseline Blood Pressure Diastolic BP | 74 mmHg | 74 mmHg | 74 mmHg |
| Baseline Blood Pressure Systolic BP | 129 mmHg | 129 mmHg | 130 mmHg |
| Baseline Elixhauser Score | 5 units on a scale | 5 units on a scale | 5 units on a scale |
| Baseline Heart Rate | 72 beats/minute | 72 beats/minute | 72 beats/minute |
| Baseline Number of Lipid Lowering Therapy (LLT) Medications | 1 Number of medications | 1 Number of medications | 1 Number of medications |
| Cholesterol | 170 mg/dL | 172 mg/dL | 169 mg/dL |
| Creatinine | 1 mg/dL | .96 mg/dL | 1 mg/dL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 241 Participants | 132 Participants | 109 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2207 Participants | 1212 Participants | 995 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 52 Participants | 26 Participants | 26 Participants |
| HDL | 50 mg/dL | 50 mg/dL | 50 mg/dL |
| Insurance Type Commercial | 1087 Participants | 582 Participants | 505 Participants |
| Insurance Type Medicaid | 692 Participants | 398 Participants | 294 Participants |
| Insurance Type Medicare | 1788 Participants | 974 Participants | 814 Participants |
| Insurance Type Other | 569 Participants | 315 Participants | 254 Participants |
| LDL | 92 mg/dL | 93 mg/dL | 91 mg/dL |
| Medical History Atrial Arrythmias | 1259 Participants | 711 Participants | 548 Participants |
| Medical History Cerebrovascular Disease | 1729 Participants | 1002 Participants | 727 Participants |
| Medical History Chronic Pulmonary Disorder | 768 Participants | 423 Participants | 345 Participants |
| Medical History Depression | 566 Participants | 320 Participants | 246 Participants |
| Medical History Diabetes | 819 Participants | 466 Participants | 353 Participants |
| Medical History Hypertension | 2193 Participants | 1205 Participants | 988 Participants |
| Medical History Myocardial Infarction | 1876 Participants | 1008 Participants | 868 Participants |
| Medical History Obesity | 573 Participants | 329 Participants | 244 Participants |
| Medical History Peripheral Artery Disease | 975 Participants | 562 Participants | 413 Participants |
| Medical History Renal Failure | 529 Participants | 299 Participants | 230 Participants |
| Medical History Stroke | 1321 Participants | 766 Participants | 555 Participants |
| Number of subjects on Lipid Lowering Therapy Medications Any statin | 1785 Participants | 982 Participants | 803 Participants |
| Number of subjects on Lipid Lowering Therapy Medications Ezetimibe | 219 Participants | 134 Participants | 85 Participants |
| Number of subjects on Lipid Lowering Therapy Medications High intensity statin | 1088 Participants | 600 Participants | 488 Participants |
| Number of subjects on Lipid Lowering Therapy Medications Low intensity statin | 89 Participants | 52 Participants | 37 Participants |
| Number of subjects on Lipid Lowering Therapy Medications Moderate intensity statin | 608 Participants | 330 Participants | 278 Participants |
| Number of subjects on Lipid Lowering Therapy Medications PCSK9i | 66 Participants | 38 Participants | 28 Participants |
| Patients per Provider Type Cardiology Advanced Practice Provider | 186 Participants | 118 Participants | 68 Participants |
| Patients per Provider Type Cardiology Physician | 1515 Participants | 785 Participants | 730 Participants |
| Patients per Provider Type Internal Medicine Advanced Practice Provider | 239 Participants | 187 Participants | 52 Participants |
| Patients per Provider Type Internal Medicine Physician | 560 Participants | 280 Participants | 280 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 15 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 326 Participants | 212 Participants | 114 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 190 Participants | 86 Participants | 104 Participants |
| Race (NIH/OMB) White | 1944 Participants | 1054 Participants | 890 Participants |
| Sex: Female, Male Female | 1218 Participants | 687 Participants | 531 Participants |
| Sex: Female, Male Male | 1282 Participants | 683 Participants | 599 Participants |
| Triglycerides | 112 mg/dL | 112 mg/dL | 112 mg/dL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 18 / 1,130 | 29 / 1,370 |
| other Total, other adverse events | 0 / 1,130 | 0 / 1,370 |
| serious Total, serious adverse events | 0 / 1,130 | 0 / 1,370 |
Outcome results
Primary
Proportion of Patients With Intensification of Lipid Lowering Therapy
Intensification of lipid lowering therapy is defined as an increase in statin dose, an addition of ezetimibe, or addition of PCSK9. Any one of the three will be sufficient to meet this endpoint. Proportion of patients who meet this endpoint will be compared between study arms.
Time frame: 90 days from first alert for any given patient
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Proportion of Patients With Intensification of Lipid Lowering Therapy | 159 Participants |
| Control | Proportion of Patients With Intensification of Lipid Lowering Therapy | 142 Participants |
Secondary
Achieved LDL-C at 6 Months
LDL-C at 6 months as measured by medical record review
Time frame: 6 months from first alert for any given patient
Population: This outcome was only observed in 824 patient subjects in which data for LDL-C at 6 months was available. 368 patient subjects in the intervention arm and 456 patient subjects in the control arm received 6 month LDL-C measurements that were placed in the medical record, thus this is the population analyzed for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention | Achieved LDL-C at 6 Months | 83 mg/dL |
| Control | Achieved LDL-C at 6 Months | 83 mg/dL |
Secondary
Proportion of Patients With an LDL-C of Less Than 55 mg/dL
Number of patients with LDL-C levels less than 55 mg/dL based on medical record review. Number of patients who meet this endpoint will be compared between study arms.
Time frame: 6 months from first alert for any given patient
Population: This outcome was only observed in 824 patient subjects in which data for LDL-C at 6 months was available. 368 patient subjects in the intervention arm and 456 patient subjects in the control arm received 6 month LDL-C measurements that were placed in the medical record, thus this is the population analyzed for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Proportion of Patients With an LDL-C of Less Than 55 mg/dL | 45 Participants |
| Control | Proportion of Patients With an LDL-C of Less Than 55 mg/dL | 53 Participants |
Secondary
Proportion of Patients With an LDL-C of Less Than 70 mg/dL
Number of patients with LDL-C levels less than 70 mg/dL based on medical record review. Number of patients who meet this endpoint will be compared between study arms.
Time frame: 6 months from first alert for any given patient
Population: This outcome was only observed in 824 patient subjects in which data for LDL-C at 6 months was available. 368 patient subjects in the intervention arm and 456 patient subjects in the control arm received 6 month LDL-C measurements that were placed in the medical record, thus this is the population analyzed for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Proportion of Patients With an LDL-C of Less Than 70 mg/dL | 115 Participants |
| Control | Proportion of Patients With an LDL-C of Less Than 70 mg/dL | 133 Participants |