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4 inPHARMation November 2014 I © Pharmaceutical Society of Australia Ltd. John Bell says Low-dose aspirin By Jill Malek Learning objectives After reading this article, the pharmacist should be able to: • Discuss the use of low-dose aspirin in primary and secondary prevention of CVD • Recognise the significance of different doses of aspirin • Evaluate the adverse effects of low-dose aspirin and their role in limiting its use • Counsel consumers about low-dose aspirin therapy, with a focus on adverse effects. Competencies addressed (2010): 4.2, 6.1, 6.2, 6.3, 7.1, 7.2, 7.3. Aspirin has a dual action as an antiplatelet and anti-inflammatory agent. This education module is independently researched and compiled by PSA-commissioned authors and peer reviewed. 2 GROUP 2 UP TO CPD CREDITS Low-dose aspirin is used as an antiplatelet agent for secondary prevention of cardiovascular events such as myocardial infarction (MI), stroke and vascular death in patients with established cardiovascular disease (CVD).1 Its benefit for use in primary prevention is limited by the risk of bleeding (mostly gastrointestinal) and is currently not recommended.1,2 With one in six Australians currently affected by CVD3, research is continuing into the role of low-dose aspirin in primary CVD prevention. Facts Behind the Fact Card Low-dose aspirin Pharmacist CPD Module number 254 Richard (82 years old) had a coronary stent put in following an MI 3 months ago. He brings in a new prescription for CoPlavix (clopidogrel 75 mg, aspirin 100 mg) one daily. His other medications include Zinopril (lisinopril) 20 mg daily, Lopresor (metoprolol) 100 mg daily and Lipitor (atorvastatin) 80 mg daily. You explain to Richard that the new medicine is used to reduce the risk of heart attacks and strokes in people who have had a stent put in their heart. It helps to prevent blood clots from forming. You remind him that it is important to tell you and his doctor if he is taking any other medicines, including those bought without a prescription and herbal or complementary medicines. Action of low-dose aspirin Aspirin has a dual action as an antiplatelet and anti-inflammatory agent. Its effects are a result of its irreversible inhibition of the enzyme cyclo-oxygenase (COX). The two forms of COX are COX-1, which facilitates the production of prostaglandins, and COX-2, which regulates the pain and inflammation response when tissue is damaged.4–6 Aspirin’s effects on COX are dose-dependent: • Low doses of aspirin (75–300 mg per day) inhibit COX-1, reducing the synthesis of thromboxane A2 (an inducer of platelet aggregation synthesised in platelets), thereby preventing platelet aggregation.7 This action occurs almost immediately and at doses as low as 75 mg.5 • Higher doses of aspirin (≥325 mg per day) inhibit both COX-1 and COX-2, blocking prostaglandin production and producing analgesic and anti-inflammatory effects.4 The synthesis of prostacyclin is also inhibited, which can paradoxically lead to thrombotic effects.7 Inhibition of COX-1 by low-dose aspirin can also lead to damage and ulceration in the gastrointestinal tract (GIT). The enzyme is needed to maintain a thick stomach lining, and regular aspirin use can lead to a thinning of the mucosa that protects the stomach from gastric juices. Ulcers, bleeding and, in some cases, perforation of the stomach can occur.4 5inPHARMation November 2014 I © Pharmaceutical Society of Australia Ltd. Practice point 1 Low-dose aspirin and cancer Recent research has shown that low-dose aspirin may reduce the risk of cancer. Long-term daily use of low-dose aspirin may prevent certain types of cancer, including colorectal, oesophageal, stomach, prostate and breast cancer. The effect of aspirin on cancer risk appears not to become evident until a person has been taking aspirin for at least 5 years.27 As is the case with the use of aspirin to prevent cardiovascular events, its benefits in cancer risk reduction must be considered against the risk of bleeding.28 The use of aspirin to prevent cancer is still being investigated. Questions that need to be answered before aspirin can be recommended for cancer prevention include29: • What is the optimum dose to provide the best protection against cancer with the lowest risk of serious side effects? • Who is most likely to benefit from aspirin use? • Which cancers does aspirin protect against? • How long after stopping aspirin does its anticancer protective effect last? Until more definitive recommendations can be made, people considering taking aspirin to reduce the risk of cancer should be advised to consult their doctor first.29 Facts Behind the Fact CardLow-dose aspirin Pharmacist CPD Module number 254 Primary prevention Primary prevention involves taking measures to prevent the onset of a disease or health problem. Primary prevention strategies include immunisation, beneficial lifestyle changes (e.g. smoking cessation, exercise, healthy diet), and preventive pharmacotherapy (e.g. malaria prophylaxis).8 The aim of current primary prevention strategies for CVD (including MI, stroke, transient ischaemic attack (TIA), peripheral vascular disease, angina and heart failure6,9) is to reduce absolute CVD risk.2 The National Vascular Disease Prevention Alliance (NVDPA) guidelines for the management of absolute cardiovascular disease risk define absolute CVD risk as the likelihood (as a percentage) of a person experiencing a cardiovascular event within the next 5 years. Absolute CVD risk is categorised are low (<10%), moderate (10–15%) and high (>15%).1,9 Previously, primary prevention was based on managing single risk factors. Rather than assessing and managing a patient’s absolute CVD risk, individual risk factors such as hypertension or hyperlipidaemia were treated. Current guidelines recommend reducing absolute CVD risk by managing multiple risk factors. It has been shown that a moderate reduction in several risk factors is more effective in reducing absolute CVD risk than a major reduction in one factor. One aim of this approach is to avoid inappropriate treatment of patients, particularly those in the low-risk category.1,9 In earlier guidelines, low-dose aspirin was recommended for primary prevention in patients without CVD but who were at increased CVD risk.10 However, recent studies have raised doubts about whether the benefits of low-dose aspirin for primary prevention outweigh the risks of gastrointestinal (GI) and intracerebral bleeding.11 Meta-analyses of several primary prevention studies have demonstrated that low-dose aspirin reduces the relative risk of cardiovascular events by 14% in men and 12% in women, but that this is accompanied by up to a 70% increase in the relative risk of major bleeds. These meta-analyses also demonstrated that low-dose aspirin significantly reduces the risk of stroke in women (but not in men), and of non-fatal MI in men (but not in women). Absolute benefits were calculated to be 0.30% for women and 0.37% for men. Absolute risks were found to be 0.25% in women and 0.33% in men. In practical terms, this means that giving low-dose aspirin for primary prevention for an average of 6.4 years will prevent three cardiovascular events but cause 2.5 major bleeds per 1,000 women, and will prevent four cardiovascular events but cause three major bleeds per 1,000 men. The relatively small benefits need to be balanced against the potential risks. The increasing use of statins may have contributed to the apparent reduction in the benefits of aspirin in recent trials.1,5,7,12 Previously, patients with diabetes were routinely treated with low-dose aspirin, as it was believed that they had the same CVD risk as people with CVD but without diabetes. However, recent studies have found no evidence that primary prevention with low-dose aspirin reduces the risk of cardiovascular events in patients with diabetes.9 The risk of CVD increases with age, but elderly people are also at increased risk of GI bleeding. There is currently not enough information to draw definitive conclusions about the benefits vs. risks of low-dose aspirin for primary prevention in older people.12 The current NVDPA guidelines recommend that low-dose aspirin (and other antiplatelet therapy) should not be routinely recommended for primary prevention of CVD.1 This includes people at high CVD risk and those with type 2 diabetes.1 The use of low-dose aspirin in primary prevention continues to be researched. Many studies have been conducted Table 1. Low-dose aspirin in CVD prevention5,6 Prevention of CVD Diagnosis Antiplatelet treatment Duration of treatment Primary No established diagnosis of CVD Not routinely recommended n/a Secondary Established diagnosis of CVD • Start low-dose aspirin (75–150 mg daily) unless contraindicated • Consider alternative antiplatelet agent (e.g. clopidogrel 75 mg daily) if aspirin hypersensitivity Lifelong 6 inPHARMation November 2014 I © Pharmaceutical Society of Australia Ltd. John Bell says Practice point 2 Risk factors for gastrointestinal bleeding Aspirin directly damages the gastrointestinal epithelium, leading to gastric ulceration and bleeding. Factors associated with an increased risk of upper GI bleeding and perforation in people taking low-dose aspirin include5,12: • older age • history of peptic ulcer disease or upper GI bleeding • use of other medicines (e.g. anticoagulants, other antiplatelet agents, NSAIDs, selective serotonin reuptake inhibitors (SSRIs), corticosteroids) • Helicobacter pylori infection • significant comorbidity • smoking • excessive alcohol intake. Facts Behind the Fact Card reviewing its role and the impact of adverse effects.11–13 Studies are currently being conducted to clarify aspirin’s role in primary prevention in older people and people with diabetes. These include A Study of Cardiovascular Events iN Diabetes (ASCEND), which aims to provide further data on the effectiveness of aspirin for primary prevention in people with diabetes.14 Another trial, ASPirin in Reducing Events in the Elderly (ASPREE), is currently being conducted in Australian general practice to determine whether the benefits of low-dose aspirin outweigh the risks in healthy people aged ≥70 years. Results of the main ASPREE study should be known in 2018.15 Low-dose aspirin is increasingly being considered for use in the primary prevention of some cancers – particularly bowel cancer.11,16 See Practice point 1. Secondary prevention Secondary prevention involves preventing complications and slowing progression of established disease.11,12 The use of long-term low-dose aspirin in the secondary prevention of CVD is well established. Many trials have shown the effectiveness of low-dose aspirin in reducing the risk of future cardiovascular events such as non-fatal stroke, MI and TIA in patients with pre-existing CVD. In these patients, the benefits of low-dose aspirin outweigh the risks.10,12 Dosing The usual dose of aspirin for long-term antiplatelet therapy is 75–150 mg once daily. In acute situations (e.g. MI, acute ischaemic stroke, unstable angina, implantation of coronary stent), when an immediate antiplatelet effect is needed, a loading dose of 150–300 mg of aspirin can be given. This dose produces complete inhibition of thromboxane-mediated platelet aggregation within 30 minutes. The long-term use of aspirin in doses above 300 mg daily does not offer further antithrombotic benefits and increases the risk of clinically significant adverse effects.5,6 Aspirin and bleeding Bleeding (particularly GI bleeding) is a recognised adverse effect of aspirin. GI bleeding is associated with a higher risk of MI and death in patients with CVD. Treatment of CVD with aspirin must therefore be balanced against the risk of GI bleeding.12 See Practice point 2. The risk of bleeding (including fatal bleeds) is significantly higher with analgesic doses of aspirin (≥300 mg up to 4 times/day) than with lower antiplatelet doses (75–150 mg/ day). However, even at lower doses, the risk of GI bleeding is doubled compared with no aspirin.7,12 The risk of GI bleeding is not reduced by using enteric-coated tablets.6 For patients taking low-dose aspirin, concomitant use of a proton pump inhibitor may reduce the risk of aspirin-induced ulceration and bleeding.5,11 See Practice point 3. Pharmacists should advise patients who are taking low-dose aspirin to be alert for signs of bleeding. These include17: • easy bruising; bruises that take longer than normal to heal • red or dark-brown urine • red or black bowel motions • frequent or persistent nosebleeds • difficulty breathing or swallowing • coughing up blood • heavier than usual menstrual periods • prolonged bleeding from cuts and wounds • dark or blood-stained vomit Low-dose aspirin Pharmacist CPD Module number 254 Table 2. Aspirin dosage in CVD5,6 Aspirin dose Action Counselling 150–300 mg (loading dose) For immediate antiplatelet effect in MI, unstable angina or acute ischaemic stroke Full inhibition of platelet aggregation within 30 minutes Note: Without a loading dose, daily doses of 100 mg achieve maximal inhibition of thromboxane formation and platelet aggregation within 4–5 days Crushing, sucking or chewing a tablet may give more rapid absorption Avoid enteric-coated preparations 75–150 mg daily Continuous inhibition of thromboxane production from newly-formed platelets, while minimising GI adverse effects Take daily at the same time each day. Remove tablet from packaging just before use to avoid tablet degrading Take after food or use enteric-coated tablets to reduce GI adverse effects 7inPHARMation November 2014 I © Pharmaceutical Society of Australia Ltd. Practice point 3 Low-dose aspirin and proton pump inhibitors Proton pump inhibitors (PPIs) are recommended for use with low-dose aspirin in people who are at high risk of GI bleeding (see Practice point 2), to prevent and treat the upper GI adverse effects of aspirin.5,6 Low-dose aspirin use increases the risk of gastric ulceration. About 1 in 10 long-term users of low-dose aspirin will develop an ulcer, although most will not have any symptoms. Primary prevention with a PPI reduces the absolute risk of peptic ulceration by 6.3% after 6 months and, to a lesser extent, the risk of bleeding.5 Once-daily doses of PPIs (e.g. esomeprazole 20 mg, omeprazole 20 mg, pantoprazole 40 mg) are recommended. In patients who have developed a bleeding peptic ulcer while taking aspirin and still require antiplatelet therapy, PPI use reduces the risk of recurrent ulcer bleeding. Recurrent bleeding is less likely with continued aspirin use and PPI prophylaxis than with a switch from aspirin to clopidogrel.5,6 Facts Behind the Fact Card Related Fact Cards Exercise and the heart High blood pressure Weight and health Staying a non smoker • severe headache or dizziness • unexplained pain, swelling or discomfort. Aspirin and allergy Aspirin can (rarely) cause hypersensitivity characterised by rash, urticaria and angioedema. It can also cause bronchospasm and exacerbate asthma symptoms. People who experience sudden, severe asthma (e.g. admitted to intensive care with asthma), recurring nasal polyps, urticaria, or chronic nasal congestion/ rhinitis are at increased risk of developing aspirin-induced asthma.16–18 Symptoms of aspirin allergy may occur 1–3 hours after taking aspirin and include17,18: • swelling of the face, lips or tongue, making swallowing or breathing difficult • asthma, wheezing, shortness of breath • sudden or severe itching, skin rash, hives. Aspirin should be avoided by people who have previously experienced rhinitis or wheezing 1–3 hours after taking aspirin or an NSAID, and anyone who has been diagnosed with aspirin/NSAID-intolerant asthma (AIA).18 Combination therapy with aspirin Dual antiplatelet therapy (a combination of low-dose aspirin and another antiplatelet agent, e.g. clopidogrel, prasugrel or ticagrelor) provides more complete platelet inhibition by inhibiting platelet function via different pathways. Dual antiplatelet therapy is recommended after acute coronary syndrome (ACS). ACS is an acute cardiac event due to complete or partial obstruction of a coronary artery, and encompasses unstable angina and MI with or without elevation of the ST segment of the ECG. Dual therapy prevents more thrombotic events after ACS than aspirin alone, but increases the risk of bleeding.6,19–21 Low-dose aspirin can also be used in combination with the antiplatelet agent dipyridamole in the secondary prevention of stroke. The combination of dipyridamole 200 mg and aspirin 25 mg is slightly more effective than aspirin alone and has a comparable risk of bleeding to clopidogrel. Dipyridamole alone has similar antiplatelet efficacy to aspirin, and may be used if there is intolerance to aspirin and clopidogrel. Headache is a common adverse effect of dipyridamole, and may affect compliance.5,6 See Table 3. Aspirin resistance Aspirin resistance is not clearly defined. It is thought to be the inability of standard antiplatelet doses of aspirin (75–300 mg/day) to inhibit thromboxane A2 formation and reduce platelet aggregation. The prevalence of true pharmacological aspirin resistance is believed to be rare (about 1%). The occurrence of a cardiovascular event during low-dose aspirin therapy may not necessarily be due to aspirin resistance. Antiplatelet therapy reduces, but does not eliminate, the risk of cardiovascular events. In addition, treatment failure may be due to other factors, such as poor compliance, inadequate dose, or delayed and reduced absorption (which has been linked to the enteric coating on some formulations of aspirin). There are currently no reliable tests to confirm aspirin resistance.6,22,23 Role of the pharmacist As low-dose aspirin is available over- the-counter, pharmacists should advise customers on its use. • Risk of side effects: GI side-effects are common with aspirin. Uncoated tablets should be taken with or after food. Enteric-coated tablets may reduce the risk of GI upset (but not ulceration or bleeding). Advise customers to tell their doctor or pharmacist if they experience any abdominal pain, melaena (black, tarry faeces) or rectal bleeding. A serious fall or injury may result in internal bleeding. Therefore, suggest that customers report any injuries to their doctor, even if there are no obvious signs of bleeding.6,17 • Taking other medicines: if aspirin is being taken with another antiplatelet agent (e.g. clopidogrel) or an anticoagulant (e.g. warfarin) advise the patient to be extra careful about monitoring for any signs of bleeding.6 See also Practice point 4. • Take the correct dose: as aspirin is available in different strengths, determine the reason for use to avoid incorrect dosing and the risk of adverse effects. There is no advantage in taking higher analgesic doses of aspirin for preventing thrombotic events.17 • Encourage adherence: up to 40% of patients do not adhere to low-dose aspirin treatment.6 Poor adherence may increase Low-dose aspirin Pharmacist CPD Module number 254 8 inPHARMation November 2014 I © Pharmaceutical Society of Australia Ltd. John Bell says Facts Behind the Fact Card Practice point 4 Aspirin-drug interactions Medicines that can increase the risk of bleeding with low-dose aspirin include5,6,30: • anticoagulants (e.g. warfarin, enoxaparin, heparin, dabigatran, rivaroxaban) • other antiplatelet agents (e.g. clopidogrel, prasugrel, ticagrelor) • NSAIDs (may also reduce the antiplatelet activity of low-dose aspirin) • SSRIs (e.g. citalopram, fluoxetine, paroxetine, sertraline) • corticosteroids • anagrelide. Other medicines that can interact with low-dose aspirin include6,30: • methotrexate – increased risk of GI ulceration; possible increased serum levels of methotrexate (less likely with low-dose aspirin and low doses of methotrexate). the risk of adverse CV outcomes such as stroke, MI and death.24 The use of a dose administration aid may help to improve compliance. • Taking aspirin without medical advice: some people may believe that low- dose aspirin is ‘good for the heart’ or ‘prevents heart attacks’. Emphasise that low-dose aspirin does not prevent all cardiovascular events, but can lower the risk in people with pre-existing CVD. Low-dose aspirin should only be taken on the recommendation of a doctor.26 • Pain relief: if the customer needs pain relief (e.g. for a headache), advise the use of paracetamol rather than a non-steroidal anti-inflammatory drug (NSAID) or aspirin. Ensure that consumers are familiar with the names of medicines containing NSAIDs available OTC and in supermarkets.17 • Use in children: aspirin should not be used in children under 16 years of age who have fever and/or chicken pox or measles. There is an association between the use of aspirin in children and the development of Reye’s syndrome.6,25 • Pregnancy and breastfeeding: aspirin is pregnancy category C. Analgesic doses of aspirin are not recommended during the third trimester. However, low-dose aspirin is considered safe to take during pregnancy and breastfeeding.6 • Other medical conditions: aspirin is contraindicated in conditions associated with a high risk of bleeding i.e. bleeding disorders, erosive gastritis or peptic ulcer disease, severe hepatic disease. Aspirin is also contraindicated in aspirin-sensitive asthma.6 • Surgery: aspirin in analgesic/ anti inflammatory doses should, if possible, be stopped at least 7 days before surgery. However, low-dose aspirin can be continued for low-risk procedures (e.g. dental procedures). For high-risk procedures it may be stopped up to 7 days before surgery, but withdrawal of treatment may cause an increased risk of a cardiac event. The decision whether to cease aspirin therapy should be made by the surgeon.6 • When/how to take: advise the customer to take aspirin at about the same time each day. Aspirin breaks down quickly when exposed to air and moisture. The tablets or capsules should be removed from packaging immediately prior to use. If using dispersible tablets, mix with water and take immediately. Do not crush tablets or open capsules.6 A week later, Richard returns to the pharmacy. He asks the pharmacy assistant for a box of Astrix (aspirin 100 mg). He mentions that he forgot to get it last week. After questioning Richard, the pharmacy assistant asks you to speak to him. You explain that CoPlavix and Astrix both contain aspirin, and advise him to stop Low-dose aspirin Pharmacist CPD Module number 254 Table 3. Dual antiplatelet therapy with aspirin5,6 Antiplatelet therapy Use Dose Side effects Aspirin + clopidogrel Prevention of atherothrombotic events in ACS Prevention of thrombosis after coronary angioplasty Aspirin: 300 mg initially, then 75–150 mg daily Clopidogrel: 300 mg initially, then 75 mg daily Increased risk of bleeding, diarrhoea, GI ulceration, skin rash Aspirin + dipyridamole Secondary prevention of ischaemic stroke and TIA Aspirin: 25 mg twice daily Dipyridamole: 200 mg twice daily Headache, diarrhoea, nausea, vomiting, flushing, hypotension, dizziness Aspirin + prasugrel Prevention of atherothrombotic events in ACS Aspirin: 300 mg initially, then 75–150 mg daily Prasugrel: 60 mg initially then 10 mg daily (5 mg daily if >75 years or <60 kg) Bleeding Aspirin + ticagrelor Prevention of atherothrombotic events in ACS Aspirin: 300 mg initially, then 75–150 mg daily Ticagrelor: 180 mg initially, then 90 mg twice daily Bleeding (may be severe), rash, itch 9inPHARMation November 2014 I © Pharmaceutical Society of Australia Ltd. Facts Behind the Fact CardLow-dose aspirin Pharmacist CPD Module number 254 Practice point 5 Low-dose aspirin and complementary medicines Although evidence is limited, some complementary medicines may increase the risk of bleeding when taken with low-dose aspirin. They include31,32: • bilberry • dong quai • evening primrose oil • feverfew • fish oil (doses >3 g/day) • garlic • ginger • ginkgo • horse chestnut • saw palmetto • red clover • willow bark. taking Astrix. You tell him that if he takes both Astrix and CoPlavix, it will increase his risk of bleeding, which is a potentially dangerous side effect of aspirin. It is important for Richard to understand that he should not take any other medicines containing aspirin or any other NSAIDs unless they are recommended by his doctor. A detailed description (including showing him the boxes) of which products (including OTC products) contain aspirin or other NSAIDs may be helpful. You advise him that if he notices any unusual or unexplained bleeding, he should immediately return to the pharmacy or tell his doctor. You remind Richard that CoPlavix also has other side effects, such as stomach upset/pain and diarrhoea or constipation. He may also bruise more easily. If he experiences any of these side effects and they are severe, he should return to the pharmacy or contact his doctor. You remind Richard to take the CoPlavix once daily at the same time each day and tell him not to stop taking it unless instructed to by his doctor, as stopping it may increase the risk of a cardiac event. You also remind Richard that, if he has to have surgery, he should tell the surgeon that he is taking CoPlavix. References 1. National Vascular Disease Prevention Alliance. Guidelines for the management of absolute cardiovascular disease risk. National Stroke Foundation; 2012. At: http://strokefoundation. com.au/site/media/AbsoluteCVD_GL_webready.pdf 2. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373(9678):1849– 1860. At: www.thelancet.com/journals/lancet/article/ PIIS0140-6736%2809%2960503-1/fulltext 3. Heart Foundation. Cardiovascular disease fact sheet. 2012. At: www.heartfoundation.org.au/SiteCollectionDocuments/ Factsheet-Cardiovascular-disease.pdf 4. Interactive concepts in biochemistry. Aspirin. Wiley; 2006. At: www.wiley.com/legacy/college/boyer/0471661791/ cutting_edge/aspirin/aspirin.htm 5. Therapeutic guidelines: eTG complete. Melbourne: Therapeutic Guidelines; 2014. 6. Rossi S, ed. Australian medicines handbook 2014. Adelaide: Australian Medicines Handbook Pty Ltd; 2014. 7. Berger JS, Roncaglioni MC, Avanzini F et al. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006;295(3):306–313. At: http://jama. jamanetwork.com/article.aspx?articleid=202217 8. South Australia. Dept of Health. Statewide Service Strategy Division. Primary Prevention Plan 2011–2016. Government of South Australia; 2011. At: http://www.sahealth.sa.gov.au/ wps/wcm connect/fd31550046cd63e9937dfb2e504170d4/ PrimaryPreventionPlan20112016-SSS-HPB-1105. pdf?MOD=AJPERES&CACHEID=fd31550046 cd63e9937dfb2e504170d4 9. Nelson MR, Doust JA. Primary prevention of cardiovascular disease: new guidelines, technologies and therapies. Med J Aust 2013;198(11):606–610. At: www.mja.com.au/ journal/2013/198/11/primary-prevention-cardiovascular- disease-new-guidelines-technologies-and#15 10. Hung J. Aspirin for cardiovascular disease prevention. Med J Aust 2003;179(3):147–152. At: www.mja.com.au/journal/2003/179/3/ aspirin-cardiovascular-disease-prevention#Box6 11. Patrono C. Low-dose aspirin in primary prevention. Eur Heart J 2013;34(44):3403–3411. At: www.medscape.com/ viewarticle/815074_6 12. Park K, Bavry A. Aspirin: its risks, benefits, and optimal use in preventing cardiovascular events. CCJM 2013;80(5):318–326. At: www.ccjm.org/content/80/5/318.full.pdf+html 13. Clinical trial service unit and epidemiological studies unit. Antithrombotic trialists’ collaboration. University of Oxford. At: http://www.ctsu.ox.ac.uk/research/meta-trials/att/att-website 14. British heart Foundation. ASCEND – a study of cardiovascular events in diabetes. At: www.ctsu.ox.ac.uk/ascend/ 15. Aspirin in reducing events in the elderly. Monash University; 2010. At: http://www.aspree.org/AUS/aspree-content/aspree- study-details/about-aspree.aspx 16. Patient.co.uk. Antiplatelet drugs. 2012. At: www.patient.co.uk/ doctor/Anti-platelet-Drugs.htm 17. NPS MedicineWise. Low-dose aspirin to prevent stroke and heart problems. 2012. At: www.nps.org.au/medicines/heart-blood- and-blood-vessels/anti-clotting-medicines/for-individuals/ antiplatelets/for-individuals/active-ingredients/aspirin_low_dose 18. National Asthma Council. Aspirin/NSAID-intolerant asthma: pharmacy notes [revised April 2013]. National Asthma Council Australia; 2009. At: http://www.nationalasthma.org. au/uploads/content/199-2009_pain_relievers_and_asthma_ quick_reference_guide.pdf 19. Jayasinghe R, Markham R, Adsett G. Dual antiplatelet therapy - management in general practice. Aust Fam Phys 2013;42(10):702–705. At: www.racgp.org.au/afp/2013/october/ dual-antiplatelet-therapy/ 20. McCann A. Antiplatelet therapy after coronary occlusion. Aust Prescr 2007;30:92–6. At: www.australianprescriber.com/ magazine/30/4/92/6 21. NPS Radar. Prodigy study: duration of dual antiplatelet therapy under review. 2012. At: www.nps.org.au/__data/assets/pdf_ file/0003/159852/Brief-item-dual-antiplatelet-therapy.pdf 22. Schrör K. What is aspirin resistance? Br J Card 2010;17(Suppl 1): S5– S7. At: http://bjcardio.co.uk/2010/03/what-is-aspirin-resistance/ 23. Grosser T, Fries S, Lawson JA et al. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation 2013;127:377–385. At: http://circ.ahajournals.org/ content/127/3/377.full?sid=b172ac70-8fb9-45c1-a079-2c786a6625b6 24. Herlitz J, Tóth PP, Næsdal J. Low-dose aspirin therapy for cardiovascular prevention: quantification and consequences of poor compliance or discontinuation. Am J Cardiovasc Drugs 2010;10(2):125–141. At: http://link.springer.com/ article/10.2165%2F11318440-000000000-00000 25. The Royal Children’s Hospital Melbourne. Anticoagulation guidelines. 2014. At: http://www.rch.org.au/clinicalguide/ guideline_index/Anticoagulation_Therapy_Guidelines/ 26. The Pharmaceutical Society of Australia. Non-prescription medicines in pharmacy – guide to advice and treatment. Canberra: The Pharmaceutical Society of Australia; 2012. 27. Cuzick J, Thorat M.A, Bosetti et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol 2014;00:1–10. At: http://annonc.oxfordjournals.org/ content/early/2014/07/30/annonc.mdu225.full.pdf+html 28. Cancer Council Australia. Does an aspirin a day keep cancer away? 2013. At: www.cancer.org.au/news/blog/prevention/ does-an-aspirin-a-day-keep-cancer-away.html 29. National Cancer Institute. No easy answers about whether aspirin lowers cancer risk. 2014. At: http://www.cancer.gov/ cancertopics/research-updates/2014/aspirin 30. Interactions checker. eMIMS. St Leonards: UBM Medica Australia Pty Ltd; 2014. 31. Medline Plus. Herbs and supplements [revised August 2014]. National Institutes of Health; 2014. At: http://www.nlm.nih. gov/medlineplus/druginfo/herb_All.html 32. Complementary medicines monographs. In: Sansom LN, ed. Australian pharmaceutical formulary and handbook. 22nd edn. Canberra: Pharmaceutical Society of Australia, 2012. 11inPHARMation November 2014 I © Pharmaceutical Society of Australia Ltd. Circle one correct answer from each of the following questions. Before undertaking this assessment, you need to have read the Facts Behind the Fact Card article and the associated Fact Cards. This activity has been accredited by PSA as a Group 2 activity. Two CPD credits (Group 2) will be awarded to pharmacists with four out of five questions correct. PSA is accredited by the Australian Pharmacy Council to accredit providers of CPD activities for pharmacists that may be used as supporting evidence of continuing competence. Please submit your assessment by 31 December 2014 Submit answers Submit online at www.psa.org.au/selfcare Fax: 02 6285 2869 Mail: Self Care Answers Pharmaceutical Society of Australia PO Box 42 DEAKIN WEST ACT 2600 Accreditation number: CS140010 This activity has been accredited for 1 hour Group 2 CPD (or 2 CPD credits) suitable for inclusion in an individual pharmacist’s CPD plan. — — — — — —Personal ID number: Full name: ................................................................................................................................................................................ Pharmacy: ................................................................................................................................................................................ Address: ................................................................................................................................................................................... Suburb: .................................................................................State: ......................................Postcode: ................................... Low-dose aspirin Assessment questions for the pharmacist Please retain a copy for your own purposes. Photocopy if you require extra copies. Facts Behind the Fact CardLow-dose aspirin Pharmacist CPD Module number 254 1. Which of the following statements is CORRECT? a) Aspirin’s pharmacological effects are dose-dependent. b) Current guidelines recommend that low-dose aspirin should be routinely used for primary prevention in people at high risk of CVD. c) Secondary CVD prevention is the practise of treating people without CVD to avoid the development of disease. d) Current guidelines recommend that people with diabetes should be routinely treated with low-dose aspirin. 2. Which of the following statements is CORRECT? a) Treatment that aims to slow disease progression is known as primary prevention. b) Low-dose aspirin has been shown to reduce the risk of non-fatal myocardial infarction in patients with existing CVD. c) Low-dose aspirin significantly reduces the risk of stroke in men (but not in women). d) Without a loading dose, aspirin 100 mg/day produces maximal inhibition of platelet aggregation within 48 hours. 3. Which of the following statements is CORRECT? a) Doses of aspirin >300 mg/day are more effective than lower doses in reducing the risk of cardiovascular events. b) Enteric-coated low-dose aspirin tablets are associated with a reduced risk of GI bleeding. c) Low-dose aspirin is routinely recommended for primary prevention in people at high risk of bowel cancer. d) Cigarette smoking increases the risk of bleeding with low-dose aspirin. 4. Bleeding is an adverse effect of aspirin therapy. Of the following statements, which is CORRECT? a) Low-dose aspirin is not associated with an increased risk of GI bleeding. b) Aspirin use in older people is associated with an increased risk of GI bleeding. c) Recurrent bleeding from a peptic ulcer is less likely to occur with a switch from aspirin to clopidogrel than with continued low-dose aspirin and a PPI. d) The use of more than one antiplatelet drug lowers the risk of GI bleeding. 5. Mary, 70 years old, has been prescribed Astrix 100 mg daily. She also takes Zoloft 50 mg daily, Monopril 10 mg daily, Noten 50 mg daily and Anginine 600 mcg prn. Which of the following counselling points is MOST appropriate? a) Advise Mary that Astrix tablets are enteric-coated and are therefore less likely to cause gastrointestinal bleeding. b) Explain to Mary that she should avoid taking medicines such as Nurofen or Voltaren for pain relief while she is taking Astrix. c) Reassure Mary that the Astrix will not interact with any of her other medicines. d) Advise Mary to take the Astrix at the same time each day, preferably on an empty stomach. t of five questions correct. PSA is accredited by the Australian Pharmacy Council to accredit providers of CPD activities for pharmacists that may be used as supporting evidence of continuing competence. Please submit your assessment by 31 December 2014 Submit answers Submit online at www.psa.org.au/selfcare Fax: 02 6285 2869 Mail: Self Care Answers Pharmaceutical Society of Australia PO Box 42 DEAKIN WEST ACT 2600 Accreditation number: CS140010 This activity has been accredited for 1 hour Group 2 CPD (or 2 CPD credits) suitable for inclusion in an individual pharmacist’s CPD plan. — — — — — —Personal ID number: Full name: ................................................................................................................................................................................ Pharmacy: ................................................................................................................................................................................ Address: ................................................................................