Chapters Transcript Use of Cardiovascular Medications During Pregnancy and Lactation Course: Cardio-Obstetrics: A Team-Based Approach to Optimizing Heart Health in Pregnancy and Beyond Now I wanna welcome to the stage my partner in practice, Doctor Halpern. He's an associate professor of medicine here at NYU Grossman School of Medicine and the uh medical director of our adult congenital heart disease program, and today he is gonna talk about the use of cardiovascular uh medications during pregnancy and lactation. So welcome Doctor Halford. So I have no disclosure relevant disclosures for this, um. I think, I think this review that that that uh our team wrote in 2019 uh came to feel a bit of a vacuum that uh I think existed uh in the field. There's a lot of fear about using medications during pregnancy, uh, uh, whether they're gonna cause uh any kind of teratogenicity, are there any implications, how to use them, uh, so. We felt that this, uh, this paper was important to give to give some tools and maybe to, to peel off some concerns and fears. So, um, as you, as you well know by this uh this uh point of the day that cardiovascular disease is the leading cause of non uh non-obstetric mortality, uh, during pregnancy and. It it's it relates to many causes and we spoke about cardiovascular risk factors and pre-existing comorbidities. Uh, I should say that congenital heart disease is what we do here for a living is the most prevalent, uh, is most the most prevalent uh conditions that you will take care of in pregnancy even though the outcome is very good, it, uh. I would say childbearing age, uh, these days when you think about cardiovascular diseases, uh, at least in the developed world, uh, it's congenital heart disease in the developing world, we still have rheumatic heart disease, um, talking about valvular disease related to that. And according toOPAC, 1/3 of women uh with cardiovascular disease will use medications during pregnancy. Um, and as we understand, it does increase the risk and, uh, it doesn't, it could increase the risk of, uh, for example, IUGR and the most common medication that we, that people use in pregnancy are beta blockers, diuretics, and antiplatelets. Uh, adherence and compliance may be in, uh, is reduced, may be an issue, and A lot of the recommendations that you see are based on expert opinion, so there's limited data. There's definitely attempt to try and enlarge, uh, enlarge the, the volume of data in the field and familiarity of hemodynamic changes, pharmackinetics during pregnancy is really key, um, so we always like to show the graph on the right, uh, about, uh, showing the increase in. In plasma volume, the decrease in uh in mean are essentially the SVR and decrease of the PVR and how we use it throughout pregnancy, but on the left here we can see some pharmacokinetics that uh seem to be important like for example, decrease in absorption uh from the GI tract or increase in gastric pH that may change the properties of medications. You have increased clearance in, in the liver, increased clearance in the kidneys. Um, and you have a second, uh, essentially a second human being here, so we're talking about the uteroplantal flow and fetal metabolism that goes into, uh, into play here, the hypercoagulable state of pregnancy and the difference in volume of distributions and, uh, and fat distribution of the body. But I think it's important to say using medications in pregnancy that the net effect is commonly a reduced pharmacological effect of the drug, and that's that's important to, to realize. Interestingly enough, after, after the thalidomide, uh, uh, you know, uh, issues and the teratogenicity, uh, there was uh the FDA created the drug classifications in pregnancy. Interestingly enough, and everybody knows this, uh, classification between A no demonstrated risk to B, C, and D, you can see animal studies have demonstrated some fetal adverse effect. I will make it very simple, uh, especially, uh, according to the ESC guidelines, these recommendations are no longer recommended for decision making, and that's based because C and D, uh, that because of the limit. Data, there's no real difference between necessarily between the medications uh or the description of them, so we, we're at a, we're at a state where the these designations cross over each other and are inaccurate. So Long story short, the FDA classification is no longer recommended for decision making, and still, uh, we see all over the place that people still based on them. So 2015, the FDA, uh, creates the pregnancy and lactation labeling rule. Um, as you can see, interestingly enough, you have female and male of reproductive potential, so that's a new category here. Uh, in terms of the labeling of medications and reproductive slash pregnancy, the interesting, uh, part is that that was 2015 we had 2024, it's slowly phasing in as we don't exactly use it, but at least that's, that's, that's the idea. So that's the PLLR to know about that it's happening. So what are the principles? So the principles are. Pre-pregnancy counseling, if possible, then we can assess necessity, urgency, timing during gestation of using the medications. Uh, we're gonna repeat it multiple times that you should involve the cardio obstetric team, lowest effective dose, uh, to be used, and very important about lactations, about lactations that meds commonly diffuse into the breast milk, so you should consider the effect on the neonate, for example. Uh, alert your alert your pediatrician that you're giving them that you're giving the mother a calcium blocker. Uh, these things are important, but what is regarded as safe is the relative infant dose, less than 10%, and you can, you can find it using databases, manufacturers. This is part of the message here. Go check the updates, see if there's any changes. And during emergency. Cardiopulmonary arrest use standard ACLS protocols and defibrillation. You should use the medication as you have learned to use the medications you, you have to save, you have to save the life now. So going into too many dilemmas now, uh, doesn't work. So these are the recommendations. Uh, so, when, when we, when we summarized, um, the medications, uh, we created, uh, This designation here as you can see in green, considered safe, yellow, uh, in a traffic light designation, limited, contraindicated and conflicting, um. And it has helped us, but again there's, there's a limitation in in data. So I think the first thing to do is is know the medications that are contraindicated in pregnancy before going into the ones that you can use probably very important to know the ones that you cannot use, um, atenolol, atenolol, and this is ESC guidelines, uh, some people argued whether all beta blocker class can have, uh, can have side effects such as IUGR. Um, atenolol seems to be a medication that is worse, and people will argue with me, but, uh, atenolol is in the guidelines as a no. We know the A's and the arbs, uh, are a no. Uh, their side effects are usually in the 2nd and 3rd trimester in pregnancy, so somebody. is on them and you discovered you stopped them immediately, but uh most most concerned about these medications, lung hyperplasia and uh and uh kidney abnormalities are 2nd and 3rd trimester. Uh, aldosterone antagonists are a no, but now we're, we understand that during lactation probably OK, uh, the manufacturer says, uh, not to use, but as part of data shows we can use them, the statin we heard about this, the statin class uh uh contraindicated that now the FDA comes and say, uh, don't use it during pregnancy. Unless discussed unless extreme case, so it's interesting because as shown before Pravastatin was used for the treatment uh of preeclampsia and maybe the study was not as successful for the preeclampsia but uh. I would say the important thing for us is that there were no adverse uh perinatal effect when used later in pregnancy. So again, animal studies showed uh issues with statins. We haven't really seen it in human, but still the FDA would say a no. NoAs and dothyin receptor antagonists Rizo igawatts are in the no category. Interestingly enough, captopril, benazapril, and enalapril may be used during lactation, and that, so somebody with heart failure, the moment that they deliver, you can then if and if they are uh breastfeeding. You can use these medications, and that's, and that's very helpful. Um. Other group of medications, these are more last resort than exactly contraindicators is amodarone, for example, during pregnancy. It's a no. It's a, it's a medication that you should not use during pregnancy. There's fetal carnectus, there's side effects related to it, um. But it's, you can't say it's completely contraindicated uh to save, to save lives. So amiodarone is a last resort. Nitroroide has been associated uh with cyanide toxicity. So again, this, this, it stays on a yellow amiodarone in a red, but they're so they're sort of last resort. My friends here talked about hypertension, so. 140/90, we talked about it a lot. I think, uh, again, the important medications that we use are nifedipine, the labetalol, alphamethyldopa, yes, you're correct, we can't find it in America, um, for the last few years. IV labetalol, hydralazine, nitro uh nitro drip in preeclampsia and now icardipine there's uh data to suggest uh also that it's safe. Hydralazine has, has been pushed down by the ESC guidelines and they don't recommend it necessarily because of uh side effects from, you know, from uh lupus, um. But uh we use it very commonly. The reason I put here the patch, the patch of clonidine is for patients who have, who have nausea and vomiting, a clonidine patch may be helpful. So it's an alpha 2 agonist, um, that you wouldn't use on a daily basis, but for resistant patients, uh, or non-compliant patients, Clonidine may be a solution that is very interesting. Yeah, there are side effects, um, adjustment of dosages, and you can see, you can see here, uh, some of the side effects that we're talking about. Interestingly enough, when we talk about diuretics, usually the, the consensus is if you were on hydrochlorothiazide, it's totally OK to, to continue into the pregnancy with hydrochlorothiazide. You wouldn't necessarily start hydrochlorothiazide as your as your medication during pregnancy. And everybody's talking about the diuretics, furosemide and hydro thiazide and the decreased placenta, placental flow and associated with electrolyte abnormalities, uh, uh, smaller head circumference. The interesting part, um, there, there were recent reviews to suggest that this is not completely an urban legend, but you should not be afraid of diuretics. I think that's that's really the notion that this is the notion now. uh, you should know these side effects do exist, but, uh, I would say, um, we do, we do acknowledge now that it's less than feared when data is actually arising and the other medication contraindicated. Uh, that we talked about heart failure. You can see heart failure, so we do understand you should refer to your heart failure guidelines, the adult, uh, the, the adult heart failure guidelines. The these are medications are contraindicated that we talked about. Diuretics, we said this is the concern, but again if needed, please use. And as you can see here, hydralazine nitrates for after load reduction, um, we're gonna repeat it, but. Heparin and enoxaparin do not cross the placenta, and warfarin does cross the placenta. So it's important to know that when treatment, when treating and metoprolol and carvedilol seem to be safe, uh, bromocriptine, we heard all about this, but this is a consideration according to the ESC guidelines, it's there for the uh for the sick patients. Arrrhythmia, we're going to learn from Doctor Chennitz in a few seconds. Um, probably the question you ask if there is a structured heart disease here and, uh, if it's unstable, please use the cardioversion or defibrillation, and the medications again, adenosine is so uh for SVTs, adenosine is so, uh, the half-life is so short, it's not an issue. We now got used metoprolol, propranolol OK, verapamil. Um, procanamide is used and you can see the other medications here. Interestingly enough, you can give uh digoxin sotalol and fleconide to the mother in order to control fetal arrhythmia. Uh, as, as you expect, medications could have side effects. We're talking about rapidly maternal hypertension and diltiazem fetal abnormalities only in animals, but we do use this. Um, as we say, digoxin levels may be inaccurate. Here's a medication with uh, with reduced effects, um. I'm Yoon, as we said, this is a last resort. When we talked about anticoagulation and antiplatelets, we understand that pregnancy is a hypercoagulable state that that lasts 6 weeks postpartum. Um, aspirin 81 we already discussed for prevention of preeclampsia, and oxaparin and heparin do not cross placenta and warfarin does cross placenta. So when we talked about warfarin, we talk about the famous number of 5 mg. So up to 5 mg could be used in the first trimester for patients on warfarin. Above that, it's a no because it's associated with the malformation. Uh, I always explain to the patient that it's great that we have exactly 5 as a cut off, but you should understand that below 5 you still have risk, but the risk seems to be lower and acceptable. And when we talk about the 2nd and 3rd trimester, yes, you can use, uh, you can use warfarin it. At the regular dosages, uh, with the risk of bleeding and you cannot, uh, according to guidelines, uh, perform labor on warfarin, uh, vaginal delivery on warfarin, so C-section is an indication here. When I, and this we can talk about for hours, but when, when discussing with patients anticoagulation in pregnancy, for example, a mechanical valve, uh, we're talking about risk of thrombosis, we're talking about risks of bleeding, and it really depends on the papers, but, but I would say between 5 to 20% of complications that you already know that could exist. Um, here's the deal. So we know that warfarin does cross placenta, so if it crosses placenta, it could essentially cause bleeding in the babies, including intracranial hemorrhage, um, but you do have less adverse maternal outcomes as opposed to an oxaparin that doesn't cross the placenta, um, so there's less fetal outcome, but we can see maternal outcomes and bleeding and just we discussed yesterday evening subchonic hematoma. That causes placental abruption that That was a maternal complication that that affected the baby because of the bleeding inside the uterus. High dose of aspirin may be associated with ductal closure, so that's a major issue. We are talking about 81 mg or we had some discussion between 81 to 160, but we're not talking about high dose, uh, high dosages of aspirin that can close the doctors and Novax. There's no data and they seem to be contraindicated. Pulmonary hypertension. Pulmonary hypertension is a contraindication for pregnancy, and we had uh uh diff uh Uh, interesting discussions about that. So the endophyin receptor antagonist and Rio cigua's a contraindicated because of teratogenicity. Um, so what can you use if you need? So the sildenafils, the PDA 5 inhibitors, um, could be used as. And as you can see here, also the prostatoids could be used then. Not to teach all not to teach, uh, the whole scope, but uh usually if the right ventricle is functioning well you go more towards the PD 5 inhibitors and if you see the RV is in trouble, um, then we, we speak about protenoids. We heard about hyperlipidemia, I think. I think the message for the general cardiologist and on the lipidologist is you should avoid antilippemic medications during pregnancy. So the statins we understand, uh. The sort of there's emerging data that may make it more acceptable but still I would say contraindicated or use wisely. Uh, b, uh, bile acid sequestrans reduce the soluble, uh, vitamin absorption. So that can hurt the the the forming babies. So you need to think about this. And for hyper triglyceridemia, we talked about omega 3, and again, the other medications that are contraindicated in the first, uh, trimester, like jumfibrozil or phenofibrate. May be allowed in the 2nd and 3rd trimester after you discuss with the mother the risk, the risk and benefit, and what do we do with ouropathies, we consider uh placing them on beta blockers and losartan as part of the Abs is contraindicated. So that was a crash course how to use medications during pregnancy, so. It comes down for you to be familiarized with pharmacokinetics and the hemodynamics of pregnancy and expect when you get the volume overload, when would you need the Lasix? Can I give the medications in the first trimester when organogenesis is happening? Um, pre-gestational counseling is extremely important and constant belligerence and dosing updates. You should definitely I do it all the time. You, you check the medications all the time to see if there's any update, any manufacturer update that is relevant to the use of that medication. So thank you very much. Published March 8, 2024 Created by Related Presenters Dan Halpern, MD View full profile
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