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The objective is to conduct a double-blinded randomized controlled trial of atorvastatin vs. placebo among postpartum individuals with hypertensive disorders of pregnancy, to improve cardiovascular risk score postpartum. For this, 76 individuals with hypertensive disorders of pregnancy (HDP) will be randomized to atorvastatin 10mg or placebo, which will be started in the postpartum period after cessation of breast feeding and continued for 3 months.
Individuals will be followed for up to 1 year to address the following specific aims:
Specific Aim 1: To determine if among individuals diagnosed with hypertensive disorders of pregnancy (HDP), the use of atorvastatin 10 mg daily initiated in the postpartum period following cessation of breastfeeding and continued for 3 months, lowers cardiovascular risk, as measured by the Framingham Risk Score for Cardiovascular Disease (30 year risk, primary outcome) and cardiovascular risk prediction model (PREVENT, secondary outcome) compared with placebo; and if the benefit will persist for at least 3-6 months following discontinuation of atorvastatin treatment.
Specific Aim 2: To determine if among individuals diagnosed with HDP the use of atorvastatin 10 mg daily initiated in the postpartum period following cessation of breastfeeding and continued for 3 months lowers the frequency of metabolic syndrome, improves lipid levels, and reduces inflammatory markers compared with placebo; and if this benefit will persist for at least 3-6 months following discontinuation of atorvastatin treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10 mg Atorvastatin | Active Comparator | Atorvastatin 10 mg daily for 3 months |
|
| Placebo | Placebo Comparator | Identical appearing placebo for 3 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin 10 mg | Drug | Participants will be assigned to 10 mg Atorvastatin |
| |
| Measure | Description | Time Frame |
|---|---|---|
| The 30-year Framingham Risk Score for Cardiovascular Disease | Predicts 0-100% risk of "hard" CVD events (coronary death, myocardial infarction, stroke) based on sex, systolic blood pressure, antihypertensive treatment, total and high-density lipoprotein cholesterol, smoking, and diabetes mellitus. A higher number reflects a greater risk of adverse CVD events, whereas a lower number reflects lower risk. | After 3 months of study treatment, up to 9 months after enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| Drug Use and Side Effects | Individuals will be contacted monthly via phone call to assess drug tolerability and use using a survey, which reviews any adverse events or concerns related to use of the study drug. | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Framingham Risk Score for Cardiovascular Disease 3-6 months following medication cessation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tracy C Bank, MD | Contact | 614-293-2222 | Tracy.Bank@osumc.edu | |
| Maged Costantine, MD, MBA | Contact | 614-293-2222 | Maged.Costantine@osumc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Tracy C Bank, MD | Ohio State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine | Recruiting | Columbus | Ohio | 43210 | United States |
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| ID | Term |
|---|---|
| D011225 | Pre-Eclampsia |
| D046110 | Hypertension, Pregnancy-Induced |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D006973 | Hypertension |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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a double-blinded randomized controlled trial
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Neither participants, providers, investigators or outcome assessors will know to which of these groups participants are assigned. In case of an emergency, however, the study doctor can get this information.
| Placebo |
| Drug |
Participants will be assigned to identical appearing placebo |
|
Enrolled individuals will be contacted via telephone at 3-6 months after they complete medication use and will be invited to a visit for a Framingham Risk Score calculation. The Framingham Risk Score predicts 0-100% risk of CVD events, with a higher number reflecting a greater risk of adverse CVD events, whereas a lower number reflects lower risk. |
| Anytime after 3-6 months of stopping to use the study drug, up to 9 months from randomization |
| PREVENT (AHA Predicting Risk of CVD Events) score | A glomerular filtration rate will be calculated for each enrolled individual upon enrollment and at the additional biospecimen visits in order to enable calculation of the PREVENT score. | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Rates of primary care provider (PCP) visits within 9-12 months of delivery | Enrolled individuals will undergo a telephone survey at 9-12 months postpartum, assessing whether they have attended a visit with a primary care provider (internal medicine, family medicine or primary care nurse practitioner), and for what reason, since the time of their delivery | From randomization until 6 months after stopping to use the study drug, up to 12 months from delivery |
| Waist circumference | Waist circumference in centimeters will be measured at the study visits to help identify those with metabolic syndrome (circumference of 88 cm or more). | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Fasting glucose | Fasting glucose levels will be measured at the study visits to help identify those with metabolic syndrome (fasting glucose above or equal to 100 mg/dL). | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Number of individuals diagnosed with metabolic syndrome | The presence of metabolic syndrome will be defined as 3 or more of the following, which are also listed as individual outcomes: waist circumference greater or equal to 88 cm, triglycerides greater or equal to 150 mg/dL, HDL cholesterol <50 mg/dL, blood pressure greater or equal to 130/85, and fasting glucose greater or equal to 100 mg/dL. | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Lipid levels | Serum testing for total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Hypertension diagnosis & need for antihypertensive therapy | Blood pressure will be measured at the study visits to identify new development of hypertension; enrolled individuals will be asked if they have started medication for hypertension | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Diabetes diagnosis & need for anti-glycemic therapy | Hemoglobin A1C will be measured at the study visits to identify new development of diabetes mellitus (HbA1C > 6.5%) and individuals will be asked if they have started anti-glycemic medication | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Systolic blood pressure | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Estimated glomerular filtration rate | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| High-sensitivity C-reactive protein (Hs-CRP) level | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Lipoprotein (a) level | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| Apolipoprotein (b) level | From randomization until 6 months after stopping to use the study drug, up to 9 months |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |