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CLINICAL STATEMENTS AND GUIDELINES Circulation. 2023;148:e9–e119. DOI: 10.1161/CIR.0000000000001168 August 29, 2023 Virani et al 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline 6.5 Women, Including Pregnancy and Postmenopausal Hormone Therapy Recommendations for Women, Including Pregnancy and Postmenopausal Hormone Therapy Referenced studies that support the recommendations are summarized in the Online Data Supplement. COR LOE Recommendations Pregnancy 1 C-LD 1 Women with CCD who are contemplating preg- nancy or who are pregnant should be risk-stratified and counseled regarding risks of adverse maternal, obstetric, and fetal outcomes.1–4 1 C-LD 2 Women with CCD who are contemplating preg- nancy or who are pregnant should receive care from a multidisciplinary cardio-obstetric care team beginning before conception and continuing throughout pregnancy, delivery, and postpartum to improve maternal and fetal outcomes.1,2,5 2b C-LD 3. In women with CCD, continuation of statin use dur- ing pregnancy may be considered.6 3: Harm C-LD 4 Women with CCD who are contemplating pregnancy or who are pregnant should not use ACE inhibitors, ARBs, direct renin inhibitors, angiotensin receptorneprilysin inhibitors, or aldosterone antagonists during pregnancy to prevent harm to the fetus.2,7,8 Postmenopausal Hormone Therapy 3: Harm A 5 Women with CCD should not receive systemic postmenopausal hormone therapy because of a lack of benefit on MACE and mortality, and an increased risk of venous thromboembolism.9–11 Synopsis CCD remains uncommon among pregnant women ranging from <2% to 3.6% in published registries.12–14 Physiologic changes in pregnancy that could influence myocardial workload and myocardial perfusion and thus precipitate acute cardiovascular events that include increases in circulating blood volume, stroke volume, heart rate, and cardiac output, decreases in systemic vascular resistance, diastolic BP and LV end-diastolic pressure, physiologic anemia, and a hypercoagulable state.2,15 Women with CCD who become pregnant are at high risk of adverse maternal and fetal outcomes1,3 and are best managed by a multidisciplinary cardioobstetrics team.16 Pharmacologic therapy should balance maternal benefit and fetal risk.7 Postmenopausal hormone therapy has been assessed among women with CCD in trials with angiographic endpoints17–20 and in trials designed to evaluate angina or morbidity and mortality rates.9,10,21–23 Trials tested either estrogen-only regimens (in women without a uterus) or combined estrogen and progestin regimens (in women with a uterus). None of these trials showed benefits on recurrent cardiovascular events. Venous thromboembolism was significantly increased in these trials. No RCTs exist that have tested transdermal hormone regimens to assess their effect on MACE and mortality. Recommendation-Specific Supportive Text 1. A systematic review of 37 studies including 124 pregnancies in 116 women with CCD1 reported cardiovascular complications in 32% of pregnancies, including ischemic cardiovascular events in 9%, and obstetric and fetal/neonatal complications in 58% and 42%, respectively. Only 21% of pregnancies were uncomplicated. In a study of 79 women with CCD (92 pregnancies of at least 24 weeks’ gestation), 66% had adverse cardiac events and 14% developed preeclampsia; 25% of infants were delivered preterm, and 25% were born small for gestational age.13 In the CARPREG II (Pregnancy Outcomes in Women with Heart Disease) prospective registry, a history of CCD was independently associated with adverse cardiac events (odds ratio, 3.0 [95% CI, 1.1-7.6]).3 Women with CCD, including women with previous SCAD (Section 6.1.1), who are contemplating pregnancy should undergo thorough evaluation and risk stratification using a validated instrument such as the CARPREG Table 20. CARPREG II Risk Prediction Model CARPREG II Predictors Points Previous cardiac event or arrhythmia 3 Baseline NYHA functional class III to IV or cyanosis 3 Mechanical valve 3 Ventricular dysfunction 2 High-risk left-sided valve disease and LVOT obstruction 2 Pulmonary hypertension 2 CAD 2 High-risk aortopathy 2 No previous cardiac intervention 1 Late pregnancy assessment 1 CARPREG II Score Predicted Risk, % 0 to 1 5 2 10 3 15 4 22 >4 41 The CARPREG (Cardiac Disease in Pregnancy Study) II risk score is based on 10 predictors, shown in the table. Each predictor is assigned a weighted point score. The sum of points represents the risk score. Risk scores are categorized into 5 groups. The predicted and observed frequency of primary cardiac events* in the derivation and validation groups is available at the CARPREG II Study https://doi.org/10.1016/j.jacc.2018.02.076. *Primary cardiac events were defined as any of these: maternal cardiac death; cardiac arrest; sustained arrhythmia requiring treatment; left-sided HF defined as pulmonary edema; right-sided HF; stroke or TIA; cardiac thromboembolism; MI; and vascular dissection. CAD indicates coronary artery disease; HF, heart failure; LVOT, left ventricular outflow tract; MI, myocardial infarction; NYHA, New York Heart Association; and TIA, transient ischemic attack. Modified with permission from Silversides CK, et al.3 Copyright 2018 American College of Cardiology Foundation. Downloaded from http://ahajournals.org by on October 7, 2026