In my patient on oral anticoagulation about to undergo coronary stenting, will triple therapy (an oral anticoagulant plus two antiplatelet agents) be necessary or can I get away with double therapy (an oral anticoagulant plus a single antiplatelet agent)?

 

Patients with atrial fibrillation (AF) who need percutaneous coronary intervention (PCI) after acute coronary syndrome or for stable angina pose a treatment challenge as oral anticoagulants (OACs) and dual antiplatelet therapy (DAPT) are often used concurrently to decrease the risk of systemic thromboembolism and stent thrombosis. However, “triple therapy”, including aspirin, a P2Y12 inhibitor, and an OAC (eg, warfarin or a direct oral anticoagulant-DOAC), also increases the risk of bleeding, necessitating several recent landmark trials to better address the subject.

Two modest-sized RCTs (WOEST and ISAR-TRIPLE) reported that when compared to triple therapy (DAPT plus warfarin), double therapy (single antiplatelet agent plus INR-targeted warfarin) is associated with reduced risk of bleeding complications without an increased risk of thrombotic events. 1,2

Two larger RCTs, PIONEER AF-PCI and RE-DUAL PCI, studied rivaroxaban and dabigatran, respectively, in patients with non-valvular AF undergoing PCI and found a reduction in bleeding events in patients receiving double therapy (single antiplatelet agent plus DOAC) compared to triple therapy (DAPT plus warfarin), without an increased risk of thrombotic complications. 3,4

Collectively, these studies suggest that it may be safe to treat patients with increased risk of bleeding with double therapy (even immediately following PCI) without an increase in thrombotic events. If triple therapy is elected, duration should be minimized, clopidogrel should be preferred over more potent P2Y12 inhibitors, and a PPI should be considered.

 

References:

  1. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107-15. https://www.ncbi.nlm.nih.gov/pubmed/23415013
  2. Fiedler KA, Maeng M, Mehilli J, et al. Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015;65:1619-29. https://www.ncbi.nlm.nih.gov/pubmed/25908066
  3. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423-2434. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1611594
  4. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. Published online, Aug, 27, 2017. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1708454

 

Contributed by Amulya Nagarur, MD, Mass General Hospital, Boston, MA

In my patient on oral anticoagulation about to undergo coronary stenting, will triple therapy (an oral anticoagulant plus two antiplatelet agents) be necessary or can I get away with double therapy (an oral anticoagulant plus a single antiplatelet agent)?

What pharmacological options should I consider when treating neurogenic orthostatic hypotension in my elderly patient with supine hypertension?

Treating symptomatic neurogenic orthostatic hypotension (nOH) in patients with supine hypertension can be challenging.

Before adding new agents, consider discontinuation or dose reduction of medications that can potentially aggravate orthostatic symptoms (eg, diuretics, vasodilators, negative chronotropic agents, including beta blockers).

Midodrine (an α1-adrenoreceptor agonist) and droxidopa (a norepinephrine pro-drug) are the only 2 FDA-approved drugs for the treatment of OH.

  • Midodrine is typically dosed between 2.5 mg-15 mg 1-3x/d during waking hours (prior to getting out of bed, before lunch, mid-afternoon).
  • Droxidopa is dosed from 100-600 mg 3x/day during waking hours (eg, 8 AM, noon, 4PM).
  • To reduce the risk of supine hypertension, these agents are not recommended to be taken within 5 h of bedtime, and should be used with caution in patients with congestive heart failure and chronic renal failure.

Fludrocortisone and pyridostigmine are used off-label for treatment of nOH.

  • Fludrocortisone (typical dose 0.1-0.2 mg/day) expands intravascular blood volume by increasing renal sodium and water reabsorption, with an attendant risk of exacerbating supine hypertension, hypokalemia, and edema.
  • Pyridostigmine (typical dose 30-60 mg 1-3x/day) is an acetylcholinesterase inhibitor that potentiates neurotransmission in the sympathetic ganglia and has the advantage of not worsening supine hypertension. Side effects include abdominal cramps, diarrhea, excessive sweating and urinary incontinence.

In practice,  1 or more of these agents are often used along with non-pharmacological measures.

Go to a related pearl at https://pearls4peers.com/2017/09/18/which-non-pharmacological-approaches-may-help-symptoms-of-orthostatic-hypotension-in-my-patient-with-autonomic-insufficiency/.

 

Reference

Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a concensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017;264:1567-82.https://www.ncbi.nlm.nih.gov/pubmed/28050656

 

What pharmacological options should I consider when treating neurogenic orthostatic hypotension in my elderly patient with supine hypertension?

Which non-pharmacological approaches may help symptoms of orthostatic hypotension in my patient with autonomic insufficiency?

A number of simple measures to help reduce the symptoms of neurogenic orthostatic hypotension (nOH) in susceptible patients have been recommended.1

  • Blood volume repletion (a minimum of 64 oz or 2L of water intake daily), depending on cardiac status. In addition, rapid consumption (within 5 min) of 16 oz or 500 ml of water can raise blood pressure by 30 mmHg for about an hour. It’s worth noting that liquids other than water (eg, water plus salt) do not provide the same BP response, likely due to water-induced hypo-osmolar reflex in the portal circulation.2,3
  • Increase salt intake if possible (eg, add 1-2 teaspoons or 2.3-4.6 g of salt per day), as many patients with nOH have an inadequate salt intake.
  • Improve physical conditioning that is not gravitationally challenging (eg, stationary recumbent bicyle, rowing machine).
  • Avoid increased core body temperature (eg hot tubs, prolonged hot showers).
  • Head-up position while sleeping through use of a wedge under the mattress or blocks under the head of the bed so that the head is 6-9 inches (15-23 cm) higher than the feet. This is to minimize nocturnal supine hypertension which can cause pressure diuresis and volume depletion.
  • Compressive garments, preferably either an abdominal binder or thigh high stockings when erect; knee high stocking are not likely to be effective.
  • Smaller, more frequent,  meals not high in carbohydrates in patients with postprandial hypotension.
  • Dietary supplementation with B12 or iron, if deficient.

 

References

  1. Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017;264:1567-1582. https://www.ncbi.nlm.nih.gov/pubmed/28050656
  2. Jordan J, Shannon JR, Black BK, et al. The pressor response to water drinking in humans: a sympathetic reflex? Circulation 101:504-9. http://circ.ahajournals.org/content/101/5/504.long
  3. Raj SR, Biaggioni I, Black BK, et al. Sodium paradoxically reduces the gastropressor response in patients with orthostatic hypotension. Hypertension 2007;48:329-334. https://www.ncbi.nlm.nih.gov/pubmed/16785332
Which non-pharmacological approaches may help symptoms of orthostatic hypotension in my patient with autonomic insufficiency?

My patient with a thrombosed hemodialysis access is found to have an asymptomatic segmental pulmonary embolism following a vascular access declotting procedure. Does he need systemic anticoagulation?

There is no firm evidence either for or against the use of systemic anticoagulants (ACs) in patients with asymptomatic pulmonary embolism (PE) following hemodialysis vascular access declotting (HVAD).  

However, despite the common occurrence of asymptomatic PE following HVAD procedures (~40%), symptomatic PE—at times fatal—has also been reported in these patients1,2.

In the absence of hard data and any contraindications, anticoagulation can be justified in our patient for the following reasons:

  • Asymptomatic segmental PE is commonly treated as symptomatic PE irrespective of setting2,3
  • Hemodialysis patients are often considered hypercoagulable due to a variety of factors eg, platelet activation due to extracorporeal circulation, anti-cardiolipin antibody, lupus anticoagulant, decreased protein C or S activity, and/or reduced anti-thrombin III activity4-7
  • Overall, chronic dialysis patients have higher incidence of PE compared to the general population8
  • There is no evidence that asymptomatic PE following HVAD has a more benign course compared to that in other settings
  • Untreated PE may be associated with repeated latent thrombosis or progression of thrombosis in the pulmonary artery5

 

References

  1. Calderon K, Jhaveri KD, Mossey R. Pulmonary embolism following thrombolysis of dialysis access: Is anticoagulation really necessary? Semin Dial 2010:23:522-25. https://www.ncbi.nlm.nih.gov/pubmed/21039878
  2. Sadjadi SA, Sharif-Hassanabadi M. Fatal pulmonary embolism after hemodialysis vascular access declotting. Am J Case Rep 2014;15:172-75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004792/pdf/amjcaserep-15-172.pdf
  3. Chiu V, O’Connell C. Management of the incidental pulmonary embolism. AJR 2017;208:485-88. http://www.ajronline.org/doi/pdf/10.2214/AJR.16.17201
  4. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: Chest guideline and expert panel report. CHEST 2016;149:315-52. http://journal.chestnet.org/article/S0012-3692(15)00335-9/fulltext
  5. Yamasaki K, Haruyama N, Taniguchi M, et al. Subacute pulmonary embolism in a hemodialysis patient, successfully treated with surgical thrombectomy. CEN Case Rep 2016;5:74-77 https://link.springer.com/article/10.1007/s13730-015-0195-9
  6. Nampoory MR, Das KC, Johny KV, et al. Hypercoagulability, a serious problem in patients with ESRD on maintenance hemodialysis, and its correction after kidney transplantation. Am J Kidney Dis 2003;42:797-805. https://www.ncbi.nlm.nih.gov/pubmed/14520631
  7. O’Shea SI, Lawson JH, Reddan D, et al. Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis. J Vasc Surg 2003;38: 541-48. http://www.jvascsurg.org/article/S0741-5214(03)00321-5/pdf
  8. Tveit DP, Hypolite IO, Hshieh P, et al. Chronic dialysis patients have high risk for pulmonary embolism. Am J Kidney Dis 2002;39:1011-17. https://www.ncbi.nlm.nih.gov/pubmed/11979344
My patient with a thrombosed hemodialysis access is found to have an asymptomatic segmental pulmonary embolism following a vascular access declotting procedure. Does he need systemic anticoagulation?

Does hypertension cause epistaxis?

Although traditionally we think of epistaxis as a potential sign of hypertension, particularly when severe, whether hypertension causes epistaxis is unclear and even the association of these 2 conditions has been challenged in recent years.

A 2014 systematic review found that although the majority of studies reported an association between these 2 conditions, many did not include a control group, were of poor methodological quality and did not adjust for confounding variables such as age, sex, and anticoagulation1.  Indeed, a larger study that controlled for many potential confounding factors failed to confirm such an association2.  A small prospective study also found no correlation between the severity of hypertension and epistaxis3.

Even when an association between hypertension and epistaxis has been found, it is unclear how much of the stress of bleeding itself and white coat syndrome may affect the readings1. However, an interesting 2017 study found masked hypertension (normal blood pressure in office, abnormal on ambulatory measurements) in 33.3% of patients with epistaxis with night time blood pressures that were significantly higher among patients with epistaxis4.

So the data is all over the place! It makes sense that long standing hypertension through its effects on blood vessels such as atherosclerosis and endothelium dysfunction may set the stage for epistaxis1,5, particularly in our ever-aging population on anticoagulants.  But whether hypertension by itself is enough to cause epistaxis is likely to be debated for years to come.  

 

References

  1. Kikidis D, Tsioufis K, Papanikolaou V, et al. Is epistaxis associated with arterial hypertension? A systematic review of the literature 2014;271:237-243. https://www.ncbi.nlm.nih.gov/pubmed/23539411
  2. Fuchs FD, Moreira LB, Pires CP, et al. Absence of association between hypertension and epistaxis: a population-based study. Blood Press 12:145-48. http://www.tandfonline.com/doi/abs/10.1080/08037050310001750
  3. Knopfholz J, Lima-Junior E, Précoma-Neto D, et al. Association between epistaxis and hypertension: A one year follow-up after an index episode of nose bleeding in hypertensive patients. Internat J Cardiol 2009;134:e107-e109. https://www.ncbi.nlm.nih.gov/pubmed/18499285
  4. Acar B, Yavuz B, Yildiz E, et al. A possible cause of epistaxis: increased masked hypertension prevalence in patients with epistaxis. Braz J Otorhinolaryngol 2017;83:45-49. http://www.scielo.br/pdf/bjorl/v83n1/1808-8694-bjorl-83-01-0045.pdf
  5. Celik T, Iyisoy A, Yuksel UC, et al. A new evidence of end-organ damage in the patients with arterial hypertension: epistaxis? Internat J Cardiol 2008;141:105-107. https://www.ncbi.nlm.nih.gov/pubmed/19138805
Does hypertension cause epistaxis?

What complication of Behçet’s syndrome carries the highest mortality?

Behçet’s syndrome may cause life-threatening hemoptysis due to pulmonary artery aneurysms.1 In a cohort of 387  patients with such syndrome followed for over 20 years, massive hemoptysis was the leading cause of death, found most commonly early in the course of the disease among young men.2 Conversely, the one-year mortality of pulmonary artery aneurysm in Behçet’s may be greater than 50%.1 Behçet’s syndrome is the only vasculitic disease with a proclivity for large pulmonary vessels, while its less frequent pulmonary manifestations, such as fibrosis and thrombosis, overlap with other small vessel vasculitides.3 Beware that the initial presentation of pulmonary aneurysm rupture may be confused with that of pulmonary embolism, with potential for fatal complications from anticoagulation.1 CT angiogram should help in distinguishing the two conditions.

 

References 

  1. Uzun O, Akpolat T, Erkan L. Pulmonary vasculitis in behcet disease: a cumulative analysis. Chest. 2005;127(6):2243-2253.
  2. Kural-Seyahi E, Fresko I, Seyahi N, et al. The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore). 2003;82(1):60-76.
  3. Hamuryudan V, Er T, Seyahi E, et al. Pulmonary artery aneurysms in Behçet syndrome. Am J Med. 2004;117(11):867-870.

 

Contributed by Sam Slavin, Harvard Medical Student

What complication of Behçet’s syndrome carries the highest mortality?

Is there a seasonal variation in the incidence of cardiovascular (CV) events or venous thromboembolism (VTE)?

Seasonal variation, primarily characterized by a winter peak, has been reported for acute CV events, such as acute myocardial infarction (AMI) and sudden death, aortic rupture or dissection, and ischemic or hemorrhagic stroke, and VTE (1). A meta-analysis involving patients with VTE, primarily with a diagnosis of pulmonary embolism, revealed a 20% absolute increase in the incidence of VTE during January (1).  

Potential physiological mechanisms for these observations include increased sympathetic activity, decreased loss of fluids and sodium, increase in LDL cholesterol, increase in serum fibrinogen levels and other coagulation markers, and C-reactive protein, and lower vitamin D levels due to shorter daylight hours during winter months (1,2). At least in the case of AMI in the U.S., the higher incidence in winter is not affected by climate (2).  Respiratory virus infections as a cause of acute inflammation leading to  CV or VTE events is an intriguing hypothesis (3).

 

References

  1. Dentali F, Ageno W, Rancan E, et al. Seasonal and monthly variability in the incidence of venous thromboembolism. A systematic review and a meta-analysis of the literature. Thromb Haemost 2011;106:439-447.
  2. Spencer FA, Goldberg RJ, Becker RC, et al. Seasonal distribution of acute myocardial infarction in the Second National Registry of Myocardial Infarction. J Am Coll Cardiol 1998;31:1226-33.
  3. 3. Woodhouse PR, Khaw KT, Plummer M, et al. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994;343:435-39.

 

 

 

 

Is there a seasonal variation in the incidence of cardiovascular (CV) events or venous thromboembolism (VTE)?