By K. Dolok. Sarah Lawrence College.

How I treat women with aspirin or LMWH to prevent pregnancy complications My approach in most patients My alternatives (not exhaustive) Recurrent pregnancy loss (2 or more) discount 150mg bupron sr mastercard, No LMWH order 150mg bupron sr overnight delivery, no aspirin unexplained Recurrent pregnancy loss (3 or more) and Aspirin 80 mg preconceptionally Start aspirin as soon as a pregnancy test is APS positive (Low-dose) LMWH as soon as a pregnancy In case of a history of venous or arterial test is positive thromboembolism and long term use of anticoagulant therapy; therapeutic dose LMWH and no aspirin In case of a history of a single episode of venous thromboembolism generic bupron sr 150mg with visa, antepartum and postpartum LMWH according to current guidelines and no aspirin24 Recurrent pregnancy loss (2 or more) and Enroll in ALIFE2 trial after informed In case of a history of venous or arterial inherited thrombophilia consent, and randomize to either LMWH thromboembolism and long term use of or no LMWH anticoagulant therapy; therapeutic dose LMWH and no aspirin If no informed consent for trial participation, In case of a history of a single episode of venous no LMWH thromboembolism, antepartum and No aspirin postpartum LMWH according to current guidelines24 History of severe preeclampsia, unexplained Counsel about the modest risk reduction of aspirin and prescribe on an individual basis No LMWH History of severe preeclampsia, a single late Aspirin 80 mg as soon as a pregnancy test Start aspirin in the second trimester pregnancy loss, placental abruption, or is positive severe intra-uterine growth restriction and (Low dose) LMWH as soon as a pregnancy In case of a history of venous or arterial APS test is positive thromboembolism and long term use of anticoagulant therapy; therapeutic dose LMWH added to aspirin In case of a history of a single episode of venous thromboembolism, antepartum and postpartum LMWH according to current guidelines added to aspirin24 History of severe preeclampsia and Counsel about the modest risk reduction of In case of a history of venous or arterial inherited thrombophilia aspirin and prescribe on an individual thromboembolism and long term use of basis anticoagulant therapy; therapeutic dose LMWH and no aspirin No LMWH In case of a history of a single episode of venous thromboembolism, antepartum and postpartum LMWH according to current guidelines24 History of a single late pregnancy loss, No LMWH In case of a history of venous or arterial placental abruption or severe intra-uterine thromboembolism and long term use of growth restriction and inherited anticoagulant therapy; therapeutic dose thrombophilia LMWH and no aspirin In case of a history of a single episode of venous thromboembolism, antepartum and postpartum LMWH according to current guidelines24 Forjustification,pleaseseefulltext. In a few small studies, the use of LMWH and with aspirin only (n 109; RR 0. Comparing any heparin (unfractionated observed a profound effect of unfractionated heparin added to heparin or LMWH) combined with aspirin (n 199) with aspirin aspirin; this is markedly lower than in the comparator arms of only (n 199), the beneficial effect of heparin of reducing the risk studies comparing LMWH and aspirin with aspirin only or aspirin 396 American Society of Hematology with placebo, in which the chances of a live birth varied between study, a nonsignificant increase in live birth was observed in the 2 68% and 80%. This indicates clinical heterogeneity between the active treatment arms for women with inherited thrombophilia (RR trials. We are currently performing the observed (RR for live birth for women treated with bemiparin ALIFE2 study (NTR 3361; www. The ACCP guidelines recommend unfractionated hepa- pregnancy surveillance only. The Royal College of without aspirin compared with no treatment in women with a history Obstetricians and Gynaecologists guidelines state that pregnant of various pregnancy complications, including preeclampsia, small- women with APS should be considered for treatment with aspirin for-gestational age babies, and placental abruption, to reduce the combined with heparin to prevent further miscarriage, without 29 risk of recurrence in subsequent pregnancies. These 6 studies were specifying clinical criteria of APS in the recommendation. The primary outcome was a composite of preeclampsia, birth of a small-for-gestational- Therefore, although evidence for a beneficial effect of heparin th age newborn ( 10 percentile), placental abruption, or pregnancy combined with aspirin in women with APS and 3 or more loss later than 20 weeks. The effect of antithrombotic agents in mediated pregnancy complications, compared with 127 of 296 different subgroups of women with APS based on laboratory or (42. Nevertheless, based on the currently available evidence thrombophilia. Although the pooled risk reduction is statistically of studies with small numbers of participants, clinicians worldwide significant, the results are strikingly positive in some studies, with have adopted the practice of prescribing aspirin with or without 36-39 relative risk reductions up to 85%, whereas in the 2 most heparin to all women with APS. This is reflected by the statistical heterogeneity that no sufficiently sized trials have been performed that show an effect 2 17 was also observed in the meta-analysis (I 69%). In all studies of heparin on the prognosis of a subsequent pregnancy. The combined, 25% of women had thrombophilia and only the FRUIT Habenox trial randomized women with at least 3 consecutive first 40 study was dedicated to thrombophilic women only. In this trial, trimester miscarriages to enoxaparin 40 mg and placebo once daily women with inherited thrombophilia and a history of preeclampsia (n 68), enoxaparin 40 mg and aspirin 100 mg (n 63), or aspirin th 33 or intrauterine growth restriction, 10 percentile requiring deliv- 100 mg (n 76); there was no control group without intervention. The primary outcomes were recurrence of a hyperten- 0. Almost a quarter of the included women gestation or recurrence at any gestational age. The overall primary had either hereditary thrombophilia or anticardiolipin antibodies outcome did not differ between the 2 groups; hypertensive disorders 40 GPL or beta 2 glycoprotein I antibodies, and no differential occurred in 18. None of the women in after 10 weeks gestation and heterozygous factor V Leiden muta- the LMWH aspirin group developed recurrent hypertensive disor- tion, prothrombin G20210A mutation, or protein S deficiency; they ders before 34 weeks gestational age, whereas 6 (8. Women treated with enoxaparin had a much development of recurrent hypertensive disorders, with 3 women higher chance of a live birth than those allocated to aspirin (86% and delivering at 19-22 weeks (risk difference 8. The recently finished TIPPS study, which included 95% CI 7–34). However, several methodological issues were thrombophilic women either at high risk for pregnancy-mediated raised, and the results of this single study have not been confirmed complications or at high risk of pregnancy-related venous thrombo- by other trials; therefore, this regimen was not endorsed by the embolism, randomized women between LMWH and no LMWH and ACCP guidelines for women with a single previous pregnancy loss 42 24,35 found no effect of the intervention. In the SPIN and ALIFE studies, small proportions of the study Why should we prescribe prudently? In the ALIFE reactions such as itching and swelling, and the rarer complications Hematology 2014 397 of heparin-induced thrombocytopenia and heparin-induced osteope- the Confidential Enquiries into Maternal Deaths in the United Kingdom. Does thrombophilia testing help type allergic skin reactions due to administration of LMWH occur in the clinical management of patients? International consensus with nadroparin in the ALIFE study. Finally, the use of statement on an update of the classification criteria for definite antithrombotic therapy raises specific issues with regard to planning antiphospholipid syndrome (APS). Antiphospholipid antibod- Conclusions, management of the clinical case, and ies prevent extravillous trophoblast differentiation. Neutrophil In my view, the body of evidence shown in the above-mentioned activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal intervention studies have not clearly and unequivocally shown the death in a mouse model of antiphospholipid syndrome. The thrombomodulin-protein C inherited thrombophilia and recurrent pregnancy loss. Women with system is essential for the maintenance of pregnancy. Heparin and aspirin attenuate recurrent severe placenta-mediated pregnancy complications in placental apoptosis in vitro: implications for early pregnancy failure. Nevertheless, we have to deal with clinical cases every day. The association between antiphospholipid antibodies and placenta mediated complica- summarized my approach in clinical practice in Table 3. For the tions: a systematic review and meta-analysis.

(

Once asthma control is achieved and maintained discount 150 mg bupron sr mastercard, assess the patient at regular intervals and step down therapy (e cheap bupron sr 150 mg online. Do not use FORADIL for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids discount 150mg bupron sr with visa. Controller medications for asthma 218 of 369 Final Update 1 Report Drug Effectiveness Review Project Trade name Active ingredient(s) Boxed warnings Long-acting beta2-adrenergic agonists (LABA), such as formoterol the active ingredient in CERTIHALER, increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including formoterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Because of this risk, use of CERTIHALER for the treatment of asthma without a concomitant long-term asthma control ® Certihaler Formoterol medication, such as an inhaled corticosteroid, is contraindicated. Use CERTIHALER only as additional therapy for patients with asthma who are currently taking but are inadequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e. Do not use CERTIHALER for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids. Long-acting beta2-adrenergic agonists (LABA), such as formoterol the active ingredient in FORADIL AEROLIZER, increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including formoterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Because of this risk, use of FORADIL AEROLIZER for the treatment of asthma without a concomitant long-term asthma ® Foradil Aerolizer Formoterol control medication, such as an inhaled corticosteroid, is contraindicated. Use FORADIL AEROLIZER only as additional therapy for patients with asthma who are currently taking but are inadequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e. Do not use FORADIL AEROLIZER for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids. Data from a large placebo-controlled US study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving ® salmeterol. This finding with salmeterol is considered a class effect of LABA, including formoterol, the active Perforomist Formoterol ingredient in PERFOROMIST Inhalation Solution. The safety and efficacy of PERFOROMIST in patients with asthma have not been established. All LABA, including PERFOROMIST, are contraindicated in patients with asthma without use of a long-term asthma control medication. Controller medications for asthma 219 of 369 Final Update 1 Report Drug Effectiveness Review Project Trade name Active ingredient(s) Boxed warnings Data from a large placebo-controlled US study (Salmeterol Multi-center Asthma Research Trial) comparing the safety of the long-acting beta2-adrenergic agonist salmeterol to that of a placebo added to the original asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. Although the trial results were specific to salmeterol, one of the conclusions derived from this study is that long-acting beta2-adrenergic agonists may increase the risk of asthma exacerbation and possibly asthma-related death. Although available data Oxeze ® Formoterol for formoterol fumarate dihydrate do not suggest increased risk, it cannot be excluded that the findings with Turbuhaler salmeterol may apply to all longacting beta2-adrenergic agonists including formoterol fumarate dihydrate, the active ingredient in OXEZE TURBUHALER. When treating asthma patients, OXEZE TURBUHALER should be used only as additional therapy for patients whose conditions are not adequately controlled using low-to-medium dose inhaled corticosteroids or whose disease severity clearly warrants the initiation of treatment with two maintenance therapies, i. OXEZE TURBUHALER in addition to an inhaled corticosteroid. Data from a large placebo-controlled US study that compared the safety of another long-acting beta2 –adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients ® Brovana Arformoterol receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including arformoterol, the active ingredient in BROVANA. The safety and efficacy of BROVANA in patients with asthma have not been established. All LABA, including BROVANA, are contraindicated in patients with asthma without the use of a long- term asthma control medications Long-acting beta2-agonists (LABAs), such as salmeterol, the active ingredient in SEREVENT, increase the risk of asthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Because of this risk, use of SEREVENT for the treatment of asthma without concomitant use of a long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated. Use SEREVENT only as ® additional therapy for patients with asthma who are currently taking but are inadequately controlled on a long-term Serevent Salmeterol asthma control medication, such as an inhaled corticosteroid. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.

Benetos A proven 150mg bupron sr, Consoli S cheap bupron sr 150mg fast delivery, Safavian A discount bupron sr 150 mg otc, Dubanchet A, Safar M. Efficacy, safety, and effects on quality of life of bisoprolol/hydrochlorothiazide versus amlodipine in elderly patients with systolic hypertension. Metoprolol in angina pectoris complicated by essential hypertension. A clinical comparison of the antianginal efficacy of metoprolol slow- release tablets (durules(Reg. Quality of life among hypertensive patients with a diuretic background who are taking atenolol and enalapril. The effects of beta blockade with (epanolol) and without (atenolol) intrinsic sympathomimetic activity in stable angina pectoris. Bochkareva EV, Kokurina EV, Metelitsa VI, Pankina VA. Comparative efficacy of proxodolol and propranolol chosen on an individual basis for single and regular use in patients with angina pectoris. Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double- blind, placebo-controlled cross-over study. Betaxolol versus carvedilol in chronic heart failure (BETACAR study). Beta blockers Page 96 of 122 Final Report Update 4 Drug Effectiveness Review Project 52. A randomized comparison of the effect of four antihypertensive monotherapies on the subjective quality of life in previously untreated asymptomatic patients: field trial in general practice. Comparison of the effect of two metoprolol formulations on total ischaemic burden. Boquist S, Ruotolo G, Hellenius ML, Danell-Toverud K, Karpe F, Hamsten A. Effects of a cardioselective beta-blocker on postprandial triglyceride-rich lipoproteins, low density lipoprotein particle size and glucose-insulin homeostasis in middle-aged men with modestly increased cardiovascular risk. Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis. Assessment of metoprolol, a cardioselective beta- blocking agent, during chronic therapy in patients with angina pectoris. Discordance between effects of anti-ischemic therapy on ambulatory ischemia, exercise performance and anginal symptoms in patients with stable angina pectoris. Brady AR, Gibbs JSR, Greenhalgh RM, Powell JT, Sydes MR, investigators Pt. Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery: results of a randomized double-blind controlled trial. Bisoprolol and hypertension: effects on sexual functioning in men. A multicentre study of cardioselective metoprolol (Lopresor) and non-selective propranolol in the management of mild to moderate hypertension. Brunner HR, Waeber B, Ferguson RK, Turini GA, Gavras H. The position of beta- blockers in antihypertensive therapy. Comparison of verapamil versus propranolol therapy in syndrome X. Bisoprolol and nifedipine retard in elderly hypertensive patients: effect on quality of life. Maintainance of sinus rhythm after electrical cardioversion of persistent atrial fibrillation (multiple letters). Pharmacological therapy for portal hypertension: Rationale and results. Medical treatment of portal hypertension with metoprolol [EASL abstract]. Efficacy evaluation of carvedilol in the treatment of severe congestive heart failure. Beta blockers Page 97 of 122 Final Report Update 4 Drug Effectiveness Review Project 68. Campo C, Segura J, Fernandez ML, Guerrero L, Christiansen H, Ruilope LM. A prospective comparison of four antihypertensive agents in daily clinical practice. Carroll JD, Reidy M, Savundra PA, Cleave N, McAinsh J.