The Clinical Debates

Transcription

1 The Clinical Debates ACPE UAN L01-P & L01-T Activity Type: Application-Based 0.1 CEUs/1.0 Hr. Program Objectives for Pharmacists: Upon completion of this program, participants should be able to: 1. Utilize scientific evidence to make decisions on current clinical controversies. 2. Distinguish the risk versus benefits of using aspirin therapy for the primary prevention of cardiovascular disease. 3. Identify the differences between drug therapy options to treat erosive esophagitis. 4. Compare and contrast the risks and benefits of various drug therapies to select the appropriate drug choice for a given patient. Program Objectives for Technicians: Upon completion of this program, participants should be able to: 1. Recognize the controversy over the use of aspirin for the prevention of cardiovascular disease. 2. Identify benefits and risks of the use of aspirin in patients. 3. Recognize medications to treat gastrointestinal disease. 4. Identify the different options about how best to treat gastrointestinal disease. Speakers: Round 1: Use of Aspirin for Primary Prevention of Cardiovascular Disease Michelle Bottenberg, PharmD, BCPS, is an Assistant Professor of Clinical Sciences at Drake University College of Pharmacy and Health Sciences in Des Moines, Iowa. Her clinical practice site is with the inpatient Internal Medicine Teaching Service at the VA Central Iowa Healthcare System in Des Moines. Her primary areas of interest include infectious disease, cardiology, and medication reconciliation. After graduating from Drake University College of Pharmacy and Health Sciences in 2005, Michelle completed a PGY-1 pharmacy practice residency with an emphasis in internal medicine at Iowa Methodist Medical Center in Des Moines. She earned her Board Certification in Pharmacotherapy (BCPS) in She is a member of ASHP, IPA, ACCP, and Rho Chi Honor Society, for which she currently serves as the chapter advisor at Drake. Karly Hegge, PharmD, BCPS, is an Assistant Professor of Pharmacy Practice at South Dakota State University s College of Pharmacy. Her ambulatory clinical practice site is at Center for Family Medicine clinic in Sioux Falls, and she also coordinates student pharmaceutical care opportunities in various community settings. Dr. Hegge received her Bachelor of Science in Pharmaceutical Sciences at South Dakota State University in 2003, followed by her Doctorate of Pharmacy from South Dakota State University in She completed an ASHP-accredited residency program at Iowa Methodist Medical Center in 2006 and spent two years as a faculty member at Drake University College of Pharmacy and Health Sciences. Speaker Disclosures: Michelle Bottenberg and Karly Hegge report they have no actual or potential conflicts of interest in relation to this program. The speakers have indicated that off-label use of medications will not be discussed during this presentation.

2 Speakers: Round 2: PPI vs. OTC Calcium Carbonate and H2 Blockers Carrie Koenigsfeld, PharmD, is an Associate Professor with the Department of Pharmacy Practice at Drake University College of Pharmacy. Dr. Koenigsfeld received her Doctor of Pharmacy from the University of Iowa in She completed an ASHP-accredited Pharmacy Practice Residency with emphasis in Community Care at the University of Iowa in She then joined the faculty at Drake in Her clinical practice site for precepting rotation students is Lakeview Internal Medicine in West Des Moines, Iowa. She currently teaches in the team taught Therapeutics course at Drake and is course coordinator of the Immunization course. She has participated in certificate training programs in the area of immunizations, diabetes, osteoporosis, and smoking cessation. Dr. Koenigsfeld has published peer-reviewed papers in the area of headache, asthma, gout, osteoporosis, smoking cessation, home screening and monitoring devices, and development of a community pharmacy rotation. She is one of the national speakers for the American Pharmacist Association Lipid Management Certificate Program and Immunization Certificate Program. In 2004 and in 2009, she was selected as the Drake University College of Pharmacy Faculty Preceptor of the Year. She was awarded the Distinguished Young Pharmacist of the Year by the Iowa Pharmacy Association in She is an active member of several local and national Pharmacy organizations, including the Iowa Pharmacy Association, American Association of Colleges of Pharmacy, and the American Pharmacists Association. Sally Haack, PharmD, BCPS, is an Assistant Professor of Pharmacy Practice at Drake University. She began this position in 2004 after working for 2 years at Hy-Vee Pharmacy in Pella, IA. Her clinical practice site is at the Community Access Pharmacy on E 14th St., which serves uninsured and underinsured patients. She precepts rotation students at the pharmacy and is involved with managing the diabetes education and smoking cessation services. The current courses that she teaches are Therapeutics Recitation and Patient Assessment Practicum. Speaker Disclosures: Carrie Koenigsfeld and Sally Haack report they have no actual or potential conflicts of interest in relation to this program. The speakers have indicated that off-label use of medications will be discussed during this presentation.

3 The Clinical Debates Use of Aspirin for Primary Prevention of Cardiovascular Disease Michelle M. Bottenberg, PharmD, BCPS Assistant Professor, Department of Clinical Sciences Drake University College of Pharmacy & Health Sciences Faculty Disclosure Michelle Bottenberg and Karly Hegge report they have no actual or potential conflicts of interest associated with this presentation. Michelle Bottenberg and Karly Hegge have indicated that off-label use of medication will not be discussed during this presentation. Karly A. Hegge, PharmD, BCPS Assistant Professor of Pharmacy Practice South Dakota State University College of Pharmacy Learning Objectives Upon completion of this program pharmacists (or pharmacy technicians) will be able to: Utilize scientific evidence to make decisions on current clinical controversies Distinguish the risk versus benefits of using aspirin (ASA) therapy for the primary prevention of cardiovascular disease (CVD) Pre-Assessment Questions What is the major safety concern with patients taking aspirin therapy? What dose of aspirin therapy should you recommend for primary prevention of CVD? What are the differences between males and females with regard to ASA benefits & harms? The Debate Should patients use aspirin for primary prevention of cardiovascular disease? PRO: Potential Benefit Karly says YES Michelle says NO An aspirin a day to keep a heart attack at bay 1

4 Audience Response True or False: Aspirin has been shown to be beneficial in primary prevention of cardiovascular disease in men and women. A. True B. False Aspirin: The Wonder Drug? Cardiovascular disease (CVD) Leading cause of death in US Affects 1 in 3 adults Underlying or contributing cause in ~58% of deaths Aspirin (ASA) Commonly used antiplatelet agent Many reported benefits Role in primary prevention of CVD? USPSTF, Ann Intern Med 2009;150: Bayer website. Accessed 1 January Aspirin in the Headlines Aspirin: The Wonder Drug (or Miracle Drug)? 1 potentially saving tens of thousands of lives perhaps wonder should be changed to miracle Aspirin: The Remarkable Story of a Wonder Drug 2 the seemingly ordinary pill is one of the most amazing creations in medical history Simple Aspirin Becoming the Wonder Drug 3 Aspirin is steadily becoming the wonder drug for everything from Alzheimer s disease to cancer 1. Accessed 1 January Accessed 1 January Accessed 1 January Cardiovascular Disease (CVD) Coronary Heart Disease (CHD) Cardiovascular disease is often not limited to one of the three components 40% 15% 9% 11% 6% Kirshner HS, et al. J Am Board Fam Pract 2005;18: % 16% Cerebrovascular Disease Peripheral Arterial Disease (PAD) Men Versus Women Cardiovascular Disease Mortality Trends for Males & Females AHA. Accessed 1 January

5 Symptoms of Myocardial Infarction (MI) Cardiovascular Disease Men Women Lifetime risk: 2 in 3 Lower life expectancy Typically develop CVD ~10 years earlier in life Higher proportion of CVD events due to CORONARY HEART DISEASE Lifetime risk: 1 in 2 More likely to die from CVD 64% of sudden deaths due to CHD no previous symptoms Higher proportion of CVD events due to ISCHEMIC STROKE Devon, et al. Amer J Critical Care 2008;17: AHA. Accessed 1 January ASA: Evidence in Primary Prevention Physicians Health Study The HOT study N Engl J Med 1988;318: Hypertension Optimal Treatment. J Hypertens 2000;18: Findings from the aspirin component of the ongoing Physicians Health Study. N Engl J Med 1988;318: Randomised trial of prophylactic daily aspirin in British male doctors. (British Doctor s Trial) Peto R, et al. Br Med J (Clin Res Ed) 1988;296: British Doctor s Trial Peto R, et al. Br Med J (Clin Res Ed) 1988;296: An overview of the British and American aspirin studies Hennekens CH, et al. N Engl J Med 1988;318: Thrombosis prevention trial The Medical Research Council s General Practice Research Framework. Lancet ;1998;351: Primary Prevention Project De Gaetano G, et al. Lancet 2001;357: Women s Health Study Ridker PM, et al. N Engl J Med 2005;352: Antithrombotic Trialists (ATT) Collaboration Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: N=22,071 healthy male physicians Compared ASA 325 mg QOD to no ASA Study stopped early after 5 years ASA: 44% reduction in first MI N=5139 male physicians Compared ASA 500 mg/d to no ASA After 6 years, no significant differences in MI, stroke, or CVD death Findings from the aspirin component of the ongoing Physicians Health Study. N Engl J Med 1988;318: Randomised trial of prophylactic daily aspirin in British male doctors. (British Doctor s Trial) Peto R, et al. Br Med J (Clin Res Ed) 1988;296: Thrombosis prevention trial: randomised trial of lowintensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council s General Practice Research Framework. Lancet ;1998;351: An overview of the British and American aspirin studies. Hennekens CH, et al. N Engl J Med 1988;318: ASA: 33% reduction in relative risk of MI N=5085 males with high risk of ischemic heart disease Evaluated ASA 75 mg/d and/or warfarin (target INR 1.5) ASA alone: 20% reduction in ischemic heart disease & 32% reduction in nonfatal MI ASA + warfarin: 34% reduction in ischemic heart disease but increased risk for hemorrhagic strokes and nonfatal strokes 3

6 Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study. Hypertension Optimal Treatment. J Hypertens 2000;18: N=18,790 (47% women) ASA 75 mg/d vs. placebo ASA: reduced first MI (36%) & major CV events (15%) Benefit limited to men Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. De Gaetano G, et al. Lancet 2001;357: N=4495 (55% women) ASA 75 mg/d +/- Vitamin E ASA: 23% reduction in CV events & 44% reduction in CV death A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. (Women s Health Study) Ridker PM, et al. N Engl J Med 2005;352: Double-blind RCT comparing ASA 100 mg QOD to placebo in female health professionals (N=39,876) Mean follow-up: 10.1 years Aspirin therapy: Reduction in stroke (RR 0.83, 95% CI ) No reduction of combined CV events, MI, death from CV cause, or all-cause mortality Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Antithrombotic Trialists (ATT) Collaboration, BMJ 2002;324: Meta-analysis of 287 studies comparing antiplatelet therapy vs. control N=135,000 individuals at high risk of occlusive vascular events Antiplatelet therapy: reduced CV risk Serious vascular events: reduced by ~1/4 Non-fatal MI: reduced by ~1/3 Non-fatal stroke: reduced by ~1/4 Vascular mortality: reduced by ~1/6 Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: Meta-analysis of 6 primary prevention trials comparing long-term ASA vs. control N=95,000 individuals at low average risk ASA dose: ranged from 100 mg every other day to 500 mg/d Mean age: years 3 trials studied health professionals Assessment specific to gender Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: Aspirin use in men & women: Reduction in serious vascular events (0.51 vs. 0.57% per year, p=0.0001) Reduction in non-fatal MI (0.18 vs. 0.23% per year, p<0.0001) No reduction in total mortality Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: Aspirin use in men: Reduction in CV events (OR 0.86, 95% CI ) Reduction in MI (OR % CI ) No reduction in ischemic stroke or CV disease mortality 4

7 Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: Aspirin use in women: Reduction in CV events (OR 0.88, 95% CI ) Reduction in ischemic strokes (OR 0.76, 95% CI ) No reduction in MI or CV disease mortality Recommendations for ASA American Diabetes Association / American Heart Association 1 ASA mg/d in diabetics >age 40 or risk factors American Heart Association 2 ASA if 10-year risk for CV events 6-10% American Stroke Association 2 ASA for primary prevention in women American College of Chest Physicians 3 ASA mg/d for moderate risk of coronary event 1. Buse JB, et al, AHA/ADA. Circulation 2007;115: Goldstein LB, et al; AHA; ASA Stroke Council. Circulation 2006;113:e Becker RC, et al. Chest 2008;133:776S-814S. Aspirin Dosing Optimum dose not known Primary prevention trials various regimens: 75 mg daily 100 mg daily 100 mg every other day 325 mg every other day Risk for GI bleeding may increase with dose ~75 mg daily seems as effective as higher doses CON: Potential Harm An aspirin a day increases your gastroenterologist s pay USPSTF, Ann Intern Med 2009;150: Audience Response True or False: Aspirin can increase risk for bleeding when used for the primary prevention of cardiovascular disease. A. True B. False Aspirin in the Headlines Aspirin is 80 times more deadly than terrorism 1 aspirin and related drugs kill far more people in the US and Canada every year than terrorism kills in the entire world Study shows that aspirin might do more harm than good 2 it's much more dangerous than some other drugs that people get concerned about, like statins Not for Everyone: Aspirin Risks 3 may increase the risk of excessive bleeding, including the possibility of bleeding in the brain 1. Accessed 1 January Accessed 1 January Accessed 1 January

8 Aspirin and Bleeding Risk Main adverse effect increased risk of bleeding Gastrointestinal tract Intracranial vessels Low dose aspirin for cardiovascular prophylaxis More than 30% of all major GI hemorrhage in patients over age of 6 years 1 Current guidelines largely ignore any differences in bleeding risk Aspirin and Bleeding Risk Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: Findings: Aspirin used for primary prevention may reduce the risk of nonfatal ischemic events Benefits offset by higher bleeding 1. Weil J, et al. Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs. Gut 2000;46: Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: Aspirin use in men & women: Reduction in serious vascular events (0.51 vs. 0.57% per year, p=0.0001) Reduction in non-fatal MI (0.18 vs. 0.23% per year, p<0.0001) No reduction in total mortality Increased rate of major gastrointestinal (GI) and extracranial bleeding (0.10 vs. 0.07% per year, p<0.0001) Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: Aspirin use in men: Reduction in CV events (OR 0.86, 95% CI ) Reduction in MI (OR % CI ) No reduction in ischemic stroke or CV disease mortality Increased risk for hemorrhagic stroke (OR 1.69, 95% CI ) Increased risk for major bleeding (OR 1.72, 95% CI ) Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Antithrombotic Trialists (ATT) Collaboration, Lancet 2009;373: Aspirin use in women: Reduction in CV events (OR 0.88, 95% CI ) Reduction in ischemic strokes (OR 0.76, 95% CI ) No reduction in MI or CV disease mortality Increased risk for major bleeding (OR 1.68, 95% CI ) No difference in incidence of hemorrhagic stroke A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. (Women s Health Study) Ridker PM, et al. N Engl J Med 2005;352: Double-blind RCT comparing ASA 100 mg QOD to placebo in female health professionals (N=39,876) Mean follow-up: 10.1 years Aspirin therapy: Reduction in stroke (RR 0.83, 95% CI ) No reduction of combined CV events, MI, death from CV cause, or all-cause mortality Increased risk for serious GI bleeding (RR 1.40, 95% CI ) Increased risk for GI bleeding, peptic ulcers, self-reported hematuria, easy bruising, and epistaxis 6

9 Safety Concerns GI bleeding & ulceration Hemorrhagic strokes ACCF/ACG/AHA 2008 expert consensus document reducing the GI risks of antiplatelet therapy & NSAID use 1 Increase in use of proton pump inhibitors (PPIs)? 1. Bhatt DL, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Circulation 2008;118: Need for Antiplatelet Therapy Assess GI Risk Factors History of ulcer complication History of ulcer disease (non-bleeding) GI Bleeding Dual Antiplatelet Therapy Concomitant Anticoagulant Therapy More than 1 risk factor Age > 60 years Corticosteroid use Dyspepsia or GERD symptoms YES Adapted from figure 1 in Bhatt DL, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Circulation 2008;118:1900. PPI Assessment of Bleeding Risk Risk factors for GI bleed Increased age Sex (M>W) Upper GI pain GI ulcers Use of non-steroidal anti-inflammatory drugs (NSAIDs) Uncontrolled hypertension Concomitant anticoagulant use Prevention, NOT Causation Drug safety important in public health recommendations Particularly for large, disease-free populations Benefits should exceed the risks by an appropriate margin Enteric-coated or buffered aspirin No clear reduction in adverse GI effects A Possible Diversion? Diverts attention away from proven beneficial treatments Angiotensin converting enzyme (ACE) inhibitors Beta blockers Statins A False Gold Standard? Media influence advocated widely in newspapers, magazines, television & the Internet 7

10 PRO Rebuttal An aspirin a day, for whom is it ok? Aspirin for the Prevention of Cardiovascular Disease: U.S. Preventative Services Task Force Recommendation Statement USPSTF, Ann Intern Med 2009;150: Summary of recommendations Men age encourage ASA when potential benefit in myocardial infarction reduction outweighs potential harm Women age encourage ASA when potential benefit in ischemic stroke reduction outweighs potential harm Men & women age >80 insufficient evidence Men age <45 & women age <55 do not encourage ASA Net Benefit? Cardiac Risk Factors Assessing Potential Benefit MEN: 10-year CHD risk WOMEN: 10-year stroke risk Assessing Potential Harm MEN & WOMEN: GI bleeding risk Non-Modifiable Age Gender Heredity AGE & GENDER: increased focus in clinical trials assessing role of ASA in primary prevention of CVD Modifiable Tobacco Use Cholesterol Blood pressure Diabetes Physical inactivity Overweight condition USPSTF, Ann Intern Med 2009;150: Wilson PW, et al. Circulation1998;97: Variable Estimated Myocardial Infarctions Prevented with Aspirin Therapy for 10 years (per 1000 Men), n Variable Estimated Myocardial Infarctions Prevented with Aspirin Therapy for 10 years (per 1000 Women), n 10-year CHD risk Age Age Age % % % % % % % % % % % % % % % % % % % % Estimated Harms, n GI bleeding year stroke risk Age Age Age % % % % % % % % % % % % % % % % % % % % Estimated Harms, n GI bleeding Hemorrhagic stroke US Preventive Services Task Force. Ann Intern Med 2009;150: US Preventive Services Task Force. Ann Intern Med 2009;150:

11 Audience Response Patient Case: A 58-year-old male with hypertension asks a pharmacist whether he should begin taking a daily aspirin for heart protection. He is a smoker with the following measurements: SBP 122 mmhg, TC 212 mg/dl, HDL 33 mg/dl True or False: The potential benefit of ASA exceeds the potential harm in this patient. A. True B. False 10-year CHD Risk Levels at Which the Number of Cardiovascular Disease Events Prevented is Closely Balanced to the Number of Serious Bleeding Events Men Women Age 10-Year CHD Risk, % Age 10-year Stroke Risk, % years years years years years years 11 US Preventive Services Task Force. Ann Intern Med 2009;150: Other Patient Populations Younger patients limited evidence Men < 45 years Women <55 years Older patients (age > 80 years) Insufficient evidence Large potential benefit AND large potential harm Net balance between benefit and harm? Best patient: no risk factors for GI bleeding and could tolerate GI bleed CON Rebuttal An aspirin a day, what does the evidence really say? Patient education essential! Diabetes and Aspirin Therapy Diabetes Increased risk of serious vascular event Increased risk for bleeding Routine ASA recommended by many organizations AHA, ACC, ESC, EASD, ADA, AACE Exception: Canadian Diabetes Association Reasons for aspirin resistance? Diabetes Treatment Guidelines Aspirin mg/d as primary prevention in patients with diabetes who are at increased CV risk 40 years or older Family history of heart disease, HTN, smoking, dyslipidemia, or albuminuria Level C recommendation (was level A ) Secondary prevention level A American Diabetes Association. Standards of medical care in diabetes Diabetes Care 2009;32:S12-S54. 9

12 Diabetes and Aspirin Therapy Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. Ogawa H, et al. JAMA 2008;300: The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: Factorial randomized placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. Belch J, et al. BMJ 2008;337:a1840 (doi: /bmj.a1840). Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials De Berardis G, et al. BMJ 2009;339:b4531 (doi: /bmj.b4531). Effect of aspirin compared with placebo or no aspirin on relative risk of clinical events in patients with diabetes End Point Relative Risk 95% CI p-value Major cardiovascular events MI Stroke Cardiovascular death All-cause mortality Any bleeding NS De Berardis G, et al. BMJ 2009;339:b4531 (doi: /bmj.b4531). Diabetes and Aspirin Therapy Conclusion: uncertainty until more evidence becomes available Stay tuned A Study of Cardiovascular Events in Diabetes (ASCEND) Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial (ACCEPT-D) Aspirin for Asymptomatic Atherosclerosis (AAA) Presented at European Society of Cardiology (ESC) 2009 Congress 30 August 2009 Patient population: low ankle-brachial index (ABI) (N=3350) Randomized to ASA 100 mg daily or placebo Mean follow-up: 8.2 years Results: No reduction in cardiovascular or cerebrovascular events with aspirin Higher risk of adverse events with ASA Limitations: lack of power Haynes R, et al. BMJ 2009;DOI: /bmj.b4596. Estimating Benefit Versus Harm Closing Thoughts Complex decision Benefit of ASA in primary prevention likely lower compared to secondary prevention Primary & secondary: similar overall bleeding risk USPSTF guidelines 2002 ASA strongly recommended if increased CHD risk 2009 consider potential benefit and harm of ASA Re-assess benefit vs. harm on regular basis Shared decision making patient & provider 10

13 Summary Aspirin: many benefits, but not always Wonder Drug Primary prevention: consistent evidence demonstrates reduction in CVD events Men reduced MI risk Women reduced ischemic strokes risk ASA use increases bleeding risk Must consider benefit vs. harm when considering ASA for primary prevention of CVD Post-Assessment Questions What is the major safety concern with patients taking aspirin therapy? What dose of aspirin therapy should you recommend for primary prevention of CVD? What are the differences between males and females with regard to ASA benefits & harms? Continuing Pharmacy Education (CPE) To receive your CPE Statement of Credit: Log-on to the CEI Website Enter your user name/password or click on New to CEI to create a portfolio; Click on MY PORTFOLIO Enter the Access Code: (case sensitive) Pharmacists - Technicians - The Clinical Debates Use of Aspirin for Primary Prevention of Cardiovascular Disease Michelle M. Bottenberg, PharmD, BCPS Michelle.Bottenberg@drake.edu Karly A. Hegge, PharmD, BCPS Karly.Hegge@sdstate.edu 11

14 The Clinical Debates-Round 2: PPI vs OTC Calcium Carbonate and H 2 -Blockers Carrie Koenigsfeld, PharmD Associate Professor Drake College of Pharmacy Faculty Disclosure Carrie Koenigsfeld reports she has no actual or potential conflicts of interest associated with this presentation. Sally Haack reports she has no actual or potential conflicts of interest associated with this presentation. Carrie and Sally have indicated that off-label use of medication will not be discussed during this presentation. Sally Haack, PharmD, BCPS Assistant Professor Drake College of Pharmacy Learning Objectives Upon completion of this program pharmacists (or pharmacy technicians) will be able to: Pharmacists Identify the differences between drug therapy options to treat erosive esophagitis Compare and contrast the risks and benefits of various drug therapies to select the appropriate drug choice for a given patient Technicians Recognize medications to treat gastrointestinal disease Identify the different opinions about how best to treat gastrointestinal disease A Case for Debate A 42 yo female comes into your pharmacy seeking your advice. She complains of heartburn once a week, primarily on Friday evenings which is date night for she and her husband. She standardly orders Mexican of some sort as she loves jalapenos. This is also her night to indulge, where she orders a margarita and whatever chocolate item they have on the menu. She has tried Tums OTC and wants your opinion. Do you recommend Prilosec OTC or Zantac OTC? Categories of GERD Erosive Esophagitis Non-erosive GERD Barrett s esophagus

15 Goals of Therapy Proton Pump Inhibitors Quick Convenient Effective Minimize ADR s Cost Aliment Pharmcol Ther 1998; 12: Mechanism of Action: suppresses gastric basal and stimulated acid secretion by inhibiting the parietal cell proton pump Products: Dexlansoprazole (Kapidex) Esomeprazole (Nexium) Lansoprazole (Prevacid-available OTC) Omeprazole (Prilosec- available OTC) Omeprazole with sodium bicarbonate (Zegrid) Pantoprazole (Protonix) Rabeprazole (Aciphex) PPI s - Quick & Convenient Level I Evidence that PPI s provide more rapid relief of symptoms compared to H2RA s in patients with moderate to severe GERD Am J Gastroenterol 2005: 100: PPI s heal damage to the esophagus in 4-8 weeks; relief of GERD sxs within 4 weeks Omeprazole Antisecretory onset ~1 hour (omeprazole) Peak effect 2 hours 50% max effect at 24 hours Prevacid and Prilosec available OTC PPI s - Effective American Gastroenterological Association Medical Position Statement on the Management of Gastroesophageal Reflux Disease Grade A evidence: PPI s are more effective than H2RA s which are more effective than placebo Gastroenterology 2008; 135: The Management of acid-related dyspepsia in general practice: a comparison of an omeprazole versus an antacid-alginate/ranitidine 725 patients; Randomized, open parallel group comparison over 16 weeks yo; 131 clinics in UK and Ireland Step up as needed Omeprazole 10mg, 20mg, 40mg Gaviscon up to 150mg ranitidine BID Both groups could use antacids Complete relief: 61% omeprazole, 40% antacid/ranitidine (p<0.0001) Sufficient relief: 70% omeprazole, 51% antacid/ranitidine (p<0.0001) Patients assessment of omeprazole treatment was better than alternative therapy at 16 wks (p=0.0001) Aliment Pharmacol Ther 1998; 12: Medical treatments in the short term management of reflux esophagitis Meta-analysis of 136 randomized, controlled trials; 35,978 pts with esophagitis Rate of healing 83% PPI s 52% H2RA s 8% placebo Resolution of heartburn PPI vs H2RA (77% vs 48%) at 4-12 wks PPI vs H2RA (61% vs 40%) at 7 days (patients without known esophagitis) Cochrane Database Syst Rev 2007; 2:CD003244

16 PPI s - Minimize ADRs Most common side effect are: Headache Diarrhea Constipation Abdominal pain PPI s - Cost Prilosec 20mg OTC #28 $18 Prevacid 15mg OTC #28 $19.99 Walgreens.com (Accessed Dec 16, 2009) Prescription only options ~$ /month Generics available for Prevacid, Prilosec, and Protonix Antacids Mechanism of Action: neutralize gastric acidity to raise ph; results in decreased activation of pepsinogen & increased lower esophageal sphincter pressure Calcium-, aluminum-, and magnesiumbased products Rapid onset Inexpensive Additive benefits NOT appropriate for healing established esophageal erosions Histamine 2 -Receptor Antagonists Mechanism of Action: Reversibly inhibit histamine at the H 2 -receptors of the gastric parietal cells Products (all available OTC): Cimetidine (Tagamet) Famotidine (Pepcid) Nizatidine (Axid) Ranitidine (Zantac) H 2 RA s - Quick and Convenient Peak effect achieved in 1-3 hours Lasts up to hours H 2 RA s - Effective On-demand therapy for intermittent mildmoderate GERD symptoms Preventative dosing before meals or exercise Higher prescription doses often required for more severe symptoms or maintenance dosing Am J Gastroenterol 2005;100: Hemstreet BA. Gastrointestinal Disorders ACCP Updates in Therapeutics: The Pharmacotherapy Preparatory Course.

17 H 2 RA s - Minimize ADRs Most common side effects: Headache Diarrhea Dizziness Fatigue Confusion Generally well tolerated H 2 RA s - Cost Ranitidine 150mg OTC #50 $12.79 Pepcid AC 10mg OTC #30 $9.99 Walgreens.com (Accessed Dec 16, 2009) Pharmacy clinic for GERD patients: Patients stepped-down therapy if free of symptoms while on PPI therapy (> 8 weeks) 41 of 71 patients (58%) were asymptomatic off PPI therapy after 1 year of follow-up Total cost savings > $16,000 per year Gastroenterology 2001;121: PPI Concerns Osteoporosis Nested case-control study (UK from ) Adjusted OR for hip fracture with > 1 yr of PPI was 1.44 (95% CI, ) Interferes with calcium absorption through hypochlorhydria? Inhibits osteoclastic proton transport system? PPI Concerns C. difficile colitis Retrospective case-control study Cases more likely than controls (76.6% vs. 42.6%) to receive acid suppressive therapy during hospitalization, p=0.030 Am J Gastroenterol Sep;103(9): JAMA 2006;296(24): PPI Concerns Community-Acquired Pneumonia Reduction of gastric acid secretion allows pathogen colonization from the upper GI tract Case-control analysis: incidence rates for pneumonia for unexposed and exposed individuals Adjusted relative risk for pneumonia 1.89 (95% CI, ) A significant positive dose-response relationship was observed JAMA. 2004;292: PPI Concerns Clopidogrel (Plavix) Randomized, double-blind, placebo-controlled study of aspirin + clopidogrel patients: Omeprazole 20 mg daily Placebo Found platelet reactivity index (related to platelet activation) poorer in PPI group Retrospective claims review examined MI rates Control: 1.38%* Exposure to PPI < 6 months: 3.08% Exposure to PPI 6 months: 5.03%* *Statistically significant (p<0.05) J Am Coll Cardiol 2008;51: J Am Coll Cardiol 2008;52:1038-9

18 The Missing Pieces. Osteoporosis Adjust OR for hip fracture with >1 yr H2RA was 1.23 (95% CI, ) Population >50 yrs; high risk population > or < 1.75 doses; not representative of standard QD dosing Lower doses gastric acid suppression balanced with osteoclastic proton pump inhibition May be less impact from dietary sources C. difficile colitis Retrospective study design Lacking cause/effect relationship Odds with H2 s two fold increased The Missing Pieces. Community-Acquired Pneumonia H2RA s also had an increased risk: 1.63 (95%CI, ) PPI s and Clopidogrel (Plavix) PPI s that inhibit 2C19 Esomeprazole (Nexium) Omeprazole (Prilosec) Pantoprazole (Protonix)- minimal Dexlansoprazole (Kapidex)- minimal Lansoprazole (Prevacid) minimal Rabeprazole (Aciphex)- NONE COGENT event rates End point Placebo, n PPI, n p All CV events NS MI NS Revascularization NS GI events Bhatt D. TCT 2009; September 24, 2009; San Francisco, CA. A Case for Debate A 42 yo female comes into your pharmacy seeking your advice. She complains of heartburn once a week, primarily on Friday evenings which is date night for she and her husband. She standardly orders Mexican of some sort as she loves jalapenos. This is also her night to indulge, where she orders a margarita and whatever chocolate item they have on the menu. She has tried Tums OTC and wants your opinion. Do you recommend Prilosec OTC or Zantac OTC? Continuing Pharmacy Education (CPE) To receive your CPE Statement of Credit: Log-on to the CEI Website Enter your user name/password or click on New to CEI to create a portfolio; Click on MY PORTFOLIO Enter the Access Code: (case sensitive) Pharmacists - Technicians -