Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + HYPERTENSION (HTN) Download Section PDF Listen +++ +++ Population ++ –Persons at risk for developing HTN.a +++ Recommendations ++ CHEPb 2015, JNC 8, 2014, ICSI 15th Ed 2014, ESC 2013 ++ –Recommend weight loss, reduced sodium intake, moderate alcohol consumption, increased physical activity, potassium supplementation, and modification of eating patterns. –Above the normal replacement levels, supplementation of K, Ca, and Mg is not recommended for the prevention or treatment of HTN. ++ Sources ++ –Hypertension Canada. –JAMA. 2014;311(5):507-520. –Kenning I, Kerandi H, Luehr D, et al. Institute for Clinical Systems Improvement. Hypertension Diagnosis and Treatment. 2014. –Eur Heart J. 2013;34:2159-2219. +++ Population ++ –Patients age >65 y. +++ Recommendation ++ ACCF/AHA 2011 ++ –Lifestyle management is effective in all ages. ++ Source ++ –J Am Coll Cardiol. 2011;57(20):2037-2114. +++ Comments ++ A 5 mm Hg reduction in systolic blood pressure in the population would result in a 14% overall reduction in mortality from stroke, a 9% reduction in mortality from CHD, and a 7% decrease in all-cause mortality. Weight loss of as little as 10 lb (4.5 kg) reduces blood pressure and/or prevents HTN in a large proportion of overweight patients. ++ Table Graphic Jump Location | Download (.pdf) | Print LIFESTYLE MODIFICATIONS FOR PREVENTION OF HYPERTENSION Maintain a healthy body weight for adults (BMI, 18.5–24.9 kg/m2; waist circumference <102 cm for men and <88 cm for women). Reduce dietary sodium intake to no more than 100 mmol/d (approximately 6 g of sodium chloride or 2.4 g of sodium/d). Per CHEP 2015: adequate intake 2000 mg daily (all >19-y-old) (80% in processed foods; 10% at the table or in cooking); 2000 mg sodium (Na) = 87 mmol sodium (Na)= 5 g of salt (NaCl) ~1 teaspoon of table salt. Engage in regular aerobic physical activity, such as brisk walking, jogging, cycling, or swimming (30–60 min per session, 4–7 d/wk), in addition to the routine activities of daily living. Higher intensities of exercise are not more effective. Weight training exercise does not adversely influence BP. Limit alcohol consumption to no more than 2 drinks (eg, 24 oz [720 mL] of beer, 10 oz [300 mL] of wine, or 3 oz [90 mL] of 100-proof whiskey) per day in most men and to no more than one drink per day in women and lighter-weight persons. Maintain adequate intake of dietary potassium (>90 mmol [3500 mg]/d). Above the normal replacement levels, supplementation of potassium, calcium, and magnesium is not recommended for prevention or treatment of hypertension. Daily K dietary intake >80 mmol. Consume a diet that is rich in fruits and vegetables and in low-fat dairy products with a reduced content of saturated and total fat (Dietary Approaches to Stop Hypertension [DASH] eating plan). Advice in combination with pharmacotherapy (varenicline, bupropion, nicotine replacement therapy) should be offered to all smokers with a goal of smoking cessation. Stress management should be considered as an intervention in hypertensive patients in whom stress may be contributing to BP elevation. Sources: CHEP 2015: http://guidelines.hypertension.caHypertension. 2003;42:1206-1252.ASH. J Clin Hypertens. 2009;11:358-368.2013 ACC/AHA Guideline on lifestyle management to reduce CV risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;01.cir.0000437740.48606.d1. + ++ aFamily history of HTN; African-American (black race) ancestry; overweight or obesity; sedentary lifestyle; excess intake of dietary sodium; insufficient intake of fruits, vegetables, and potassium; excess consumption of alcohol. ++ bCanadian Hypertension Education Program. + MYOCARDIAL INFARCTION (MI), ASPIRIN THERAPY Download Section PDF Listen +++ +++ Population ++ –Asymptomatic adults. +++ Recommendations ++ ACCP 2012, USPSTF 2016 ++ –Age 50–59 y: Initiate aspirin if 10-y CVD risk is >10%, life expectancy is >10 y, and willing to take low-dose aspirin consistently for 10 y. –Age 60–69 y: “Consider” aspirin if 10-y CVD risk is >10%, especially if at low risk for bleeding, have life expectancy >10 y, and are willing to take aspirin consistently for 10 y (fewer MIs are prevented and more GI bleeds are provoked compared to the 50–59 y age group). –Age <50 y: evidence insufficient, benefit likely less because CVD risk is likely lower. –Age >70 y: evidence insufficient, risk of bleeding increases significantly. ++ FDA 2016 ++ –Data do not support the general use of aspirin for primary prevention of a heart attack or stroke. Aspirin is associated with “serious risks,” including increased risk of intracerebral and GI bleeding. ++ Sources ++ –USPSTF. Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. 2016. –Chest. 2012;141(2 suppl):e637S-668S. –FDA. Use of Aspirin for Primary Prevention of Heart Attack and Stroke. 2016. +++ Comments ++ ACC/AHA “ABCS” of primary prevention presents risk reduction for ASCVD for mainstays of primary prevention: aspirin therapy in appropriate patients (RR 0.90), blood pressure control (RR 0.84 for CHD, 0.64 for Stroke), cholesterol management (RR 0.75), and smoking cessation (RR 0.73). (JACC. 2017;69(12):1617-1636) Risks of aspirin therapy: hemorrhagic stroke and GI bleeding (risk factors include age, male sex, GI ulcers, upper GI pain, concurrent NSAID/anticoagulant use, and uncontrolled hypertension). Establish risk factors by the ACC/AHA pooled cohort equation in all adults. In a report showing a 50% reduction in the population’s CHD mortality rate, 81% was attributable to primary prevention of CHD through tobacco cessation and lipid- and blood pressure–lowering activities. Only 19% of CHD mortality reduction occurred in patients with existing CHD (secondary prevention). (BMJ. 2005;331:614) + MYOCARDIAL INFARCTION (MI), DIETARY THERAPY Download Section PDF Listen +++ +++ Population ++ –All adults. +++ Recommendations ++ USPSTF 2017 ++ –Offer behavioral counseling to promote healthy diet and physical activity on an individualized basis, particularly to those interested and ready to make changes, even in the absence of obesity, abnormal blood glucose/diabetes, or dyslipidemia. ++ AHA/ACC 2013, ESC 2012, AHA/ACCF 2011 ++ –Dietary guidelines: Balance calorie intake and physical activity to achieve or maintain a healthy body weight. Consume diet rich in vegetables and fruits. Choose whole grain, high-fiber foods. Consume fish, especially oily fish, at least twice a week. Limit intake of saturated fats to <7% energy, trans fats to <1% energy, and cholesterol to <300 mg/d by: Choosing lean meats and vegetable alternatives. Selecting fat-free (skim), 1% fat, and low-fat dairy products. Minimizing intake of partially hydrogenated fats. Minimize intake of beverages and foods with added sugars. Choose and prepare foods with little or no salt. If you consume alcohol, do so in moderation. Follow these recommendations for food consumed/prepared inside and outside of the home. –Recommended diets: DASH, USDA Food Pattern, or AHA Diet. Avoid use of and exposure to tobacco products. ++ CCS 2012 ++ –The Mediterranean, Portfolio, or DASH diets are recommended to improve lipid profiles or decrease cardiovascular disease (CVD) risk. ++ Comments ++ There is a strong correlation between healthy diet, physical activity, and incidence of cardiovascular disease. Behavioral counseling has shown to have a small benefit in the absence of metabolic disorders. There is better data to support behavioral interventions for patients with obesity (USPSTF, 2016) and adults with abnormal blood glucose (USPSTF, 2018). ++ Sources ++ –Eckel RH, Jakicic JM, Ard JD, et al. 2013 ACC/AHA Guideline on lifestyle management to reduce CV risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S76-99. –Can J Cardiol. 2013;29(2):151-167. –JAMA. 2017:318:167-174. –https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/obesity-in-adults-screening-and-management –https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/screening-for-abnormal-blood-glucose-and-type-2-diabetes + MYOCARDIAL INFARCTION (MI), STATIN THERAPY Download Section PDF Listen +++ +++ Population ++ –Asymptomatic adults. +++ Recommendations ++ ACC/AHA 2013 ++ –10-y ASCVD risk score (updated ATP III guidelines): 3 high-risk groups identified, based on ASCVD score and LDL-C levels. –Lifestyle management and drug therapy recommended in all three categories. –Statin drugs remain the treatment of choice based upon outcome data. –For therapy see Chapter 3 (page 258). ++ Source ++ –Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014:24;129(25 suppl 2):S1-45. ++ Cochrane 2011 ++ –Statin therapy should be employed in primary prevention only in high-risk patients (Framingham risk >20%). –Restraint should be exercised in patients at low or intermediate 10-y risk (<10%; 10%–20%). –If low or intermediate 10-y risk, calculate lifetime risk to better assess benefit of statin therapy. ++ Sources ++ –Cochrane Database Syst Rev. 2011;(1):CD004816. –Am J Med. 2012;125:440-446. –Circulation. 2006;113:791-798. –N Engl J Med. 2012;366:321-329. ++ ACP 2004 ++ –Statins should be used for primary prevention of macrovascular complications if patient has type 2 DM and other CV risk factors (age >55 y, left ventricular hypertrophy, previous cerebrovascular disease, peripheral arterial disease, smoking, or HTN). +++ Comments ++ Short-term reduction in low-density lipoprotein (LDL) using dietary counseling by dietitians is superior to that achieved by physicians. (Am J Med. 2000;109:549) Statin therapy can safely reduce the 5-y incidence of major CVD events (coronary revascularization, stroke) by about one-fifth per mmol/L reduction in LDL cholesterol. (Lancet. 2005;366(9493):1267-1278) ++ CCS 2013 ++ –An increased risk of new-onset type 2 diabetes might apply to statin therapy. A recent review of the existing data suggests that potential mechanisms include increased insulin levels, reduced insulin sensitivity, and selection bias. However, the overall data strongly suggest that the reduction in CVD events outweighs the minor effect on glucose homeostasis. ++ Source ++ –Can J Cardiol. 2013;29(2):151-167. ++ Society of General Internal Medicine 2015 ++ –Statin use was associated with an increased likelihood of new diagnoses of DM, diabetic complications, and overweight/obesity in healthy people taking statin for primary prevention. ++ Source ++ –Mansi I, Frei CR, Wang CP, Mortensen EM. Statins and new-onset diabetes mellitus and diabetic complications: a retrospective cohort study of US healthy adults. J Gen Intern Med. 2015;30:1599. ++ FDA Warning 2012, CCS 2013 ++ –Statins may cause nonserious reversible cognitive side effects as well as increased blood sugar and HbA1c levels. ++ Sources ++ –N Engl J Med. 2012;366:321-329. –Ann Intern Med. 2004;140(8):644-649. +++ Population ++ –History of cerebrovascular accident (CVA). +++ Recommendation ++ AHA/ASA 2012 ++ –Large-vessel ischemic stroke is a CHD risk. Small-vessel disease may be considered CHD risk equivalent. ++ Source ++ –Stroke. 2012;43(7):1998-2027. +++ Comment ++ Meta-analysis concludes ASA prophylaxis reduces ischemic stroke risk in women (–17%) and MI events in men (–32%). No mortality benefit is seen in either group. Risk of bleeding is increased in both groups to a similar degree as the event rate reduction. Initiation of therapy based on a case by case basis. (JAMA. 2006;295:306-313) (Arch Intern Med. 2012;172:209-216) + MYOCARDIAL INFARCTION (MI), SPECIAL POPULATIONS Download Section PDF Listen +++ +++ Population ++ –Adults with HTN. +++ Recommendations ++ JNC 8, 2013 ++ –See Chapter 3, page 360 for JNC 8 treatment algorithms. ++ Source ++ –JAMA. 2014;311(5):507-520. ++ AHA/ACCF 2012, ACP 2007, AHA/ACC/ASH 2015 ++ –Goal: blood pressure (BP) <140/90 mm Hg for population with stable CAD. –BP target <140/90 mm Hg is reasonable for the secondary prevention of CV events in patients with HTN and CAD. Class IIa, level of evidence, B. –BP target <130/80 mm Hg may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack (TIA), or CAD risk equivalents (carotid artery disease, PAD, abdominal aortic aneurysm). Class IIb, level of evidence, B. –In patients with an elevated DBP and CAD with evidence of myocardial ischemia, BP should be lowered slowly, and caution is advised in inducing decreases in DBP <60 mm Hg in any patient with DM or who is >60 y. In older hypertensive patients with wide pulse pressures, lowering SBP may cause very low DBP values <60 mm Hg. This should alert clinicians to assess carefully any untoward signs or symptoms, especially those resulting from myocardial ischemia. Class IIa, level of evidence, C. –If ventricular dysfunction is present, lowering the goal to 120/80 mm Hg may be considered. ++ Sources ++ –Circulation. 2007;115:2761-2788. –Circulation. 2012;26:3097-3137. –Rosendorff C, Lackland DT, Allison M, et al. Treatment of HTN in patients with CAD. J Am Coll Cardiol. 2015;65(18):1998-2038. ++ CHEP 2015, ESC 2014 ++ –Recommends low-dose ASA for vascular protection, in hypertensive patients ≥ 50 y; caution should be exercised if BP is not controlled. –Give low-dose ASA to hypertensive patients with history of CV events; consider in hypertensive patients without prior history who are at higher risk. ++ Sources ++ –Hypertension Canada. https://guidelines.hypertension.ca/ –Eur Heart J. 2012;33(13):1635. ++ ESC/ECH 2013 ++ –<130/80 mm Hg goal in diabetics and other high-risk patients has not been supported by trials. No benefit and possible harm is suggested with SBP <130 mm Hg. –Elderly patients’ SBP goal is <160 mm Hg. ++ Source ++ –J Hypertens. 2013;31:1281-1357. +++ Population ++ –Diabetes mellitus. +++ Recommendation ++ ADA 2014 ++ –Lipid goals: Normal fasting glucose (≤130 mg/dL) and HbA1c (<7.5%), BP <140/80 mm Hg; low-density-lipoprotein cholesterol (LDL-C) <100 mg/dL (or <70 for high risk), high-density-lipoprotein cholesterol (HDL-C) >50 mg/dL and triglycerides <150 mg/dL. –Consider ASA (75–162 mg/d) if at increased CV risk (10-y >10%) based on Framingham risk score (see Appendix), and in men age >50 y or women age >60 y with one additional risk factor. ++ Sources ++ –N Engl J Med. 2008;358:2545-2572. –Diabetes Care. 2014;37(s1):S14-S80. +++ Population ++ –Smoking. +++ Recommendation ++ AHA 2006, ADA 2014 ++ –Advise all patients not to smoke. ++ Sources ++ –Diabetes Care. 2014;37(1). –Circulation. 2006;114:82-96. +++ Comments ++ Intensive glucose lowering should be avoided in patients with a history of hypoglycemic spells, advanced microvascular or macrovascular complications, long-standing DM, or if extensive comorbid conditions are present. DM with BP readings of 130–139/80–89 mm Hg that persist after lifestyle and behavioral therapy should be treated with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) agents. Multiple agents are often needed. Administer at least one agent at bedtime. No advantage of combining ACE inhibitor and ARB in HTN Rx (ONTARGET Trial). (N Engl J Med. 2008;358:1547-1559) +++ Recommendation ++ ESC 2012 ++ –Avoid passive smoking. ++ Source ++ –Eur Heart J. 2012;33:1635-1701. +++ Comment ++ New evidence on the health effects of passive smoking strengthens the recommendation on passive smoking. Smoking bans in public places, by law, lead to a decrease in incidence of myocardial infarction. +++ Population ++ –Women. +++ Recommendations ++ AHA 2011 ++ –Standard CVD lifestyle recommendations, plus: –Waist circumference <35 in. –Omega-3 fatty acids if high risk (EPA 1800 mg/d).a –BP <120/80 mm Hg. –Lipids: LDL-C <100 mg/dL, HDL-C >50 mg/dL, triglycerides <150 mg/dL. –ASA (75–325 mg/d) indicated only in high-risk women.a –In women age >65 y, consider ASA (81 mg daily or 100 mg every other day) if BP is controlled and the benefit of ischemic stroke and MI prevention is likely to outweigh the risk of a GI bleed and hemorrhagic stroke. ++ Source ++ –J Am Coll Cardiol. 2011;57(12):1404-1423. +++ Comments ++ Estrogen plus progestin hormone therapy should not be used or continued. Antioxidants (vitamins E and C, and β-carotene), folic acid, and B12 supplementation are not recommended to prevent CHD. ASA is not indicated to prevent MI in low-risk women age <65 y. +++ Population ++ –Adults at risk of CV disease. +++ Recommendations ++ ESC 2007, 2012 ++ –Smoking cessation. –Weight reduction if BMI >25 kg/m2 or waist circumference >88 cm in women and >102 cm in men. –No further weight gain if waist circumference 80–88 cm in women and 94–102 cm in men. –Thirty minutes of moderately vigorous exercise on most days of the week. –Healthy diet. –Antihypertensives when BP >140/90 mm Hg. Statins when total cholesterol >190 mg/dL or LDL >115 mg/dL. –In patients with known CV disease: ASA and statins. –In patients with DM: glucose-lowering drugs. –Psychosocial risk factor. –Low socioeconomic status, lack of social support, stress at work and in family life, depression, anxiety, hostility, and the type D personality contribute to both the risk of developing CVD and the worsening of clinical course and prognosis of CVD. These factors act as barriers to treatment adherence and efforts to improve lifestyle, as well as to promoting health and well-being in patients and populations. In addition, distinct psychobiologic mechanisms have been identified, which are directly involved in the pathogenesis of CVD. –Psychological interventions can counteract psychosocial stress and promote healthy behaviors and lifestyle. –Cognitive-behavioral methods are effective in supporting persons in adopting a healthy lifestyle. –More evidence on the impact of total diet/dietary patterns such as the Mediterranean type of diet has gained interest in recent years. –Antihypertensive treatment is beneficial in patients age >80 y. –Aspirin is no longer recommended for primary prevention in people with diabetes. –Nurse-coordinated prevention programs are effective across a variety of practice settings. ++ Sources ++ –Eur Heart J. 2007;28:2375. –Eur Heart J. 2012;33:1635-1701. +++ Comment ++ European Society of Cardiology recommends using the SCORE Risk System to estimate risk of atherosclerotic CV disease. + ++ aHigh risk: CHD or risk equivalent or 10-y absolute CHD risk >20% based on Framingham risk score (see Appendix VI, pages 536–539). + STROKE Download Section PDF Listen +++ +++ Population ++ –Adults. +++ Recommendations ++ AHA/ASA 2011 ++ –Treat known CV risk factors.a ++ FDA 2014 ++ –FDA does not support the general use of aspirin for primary prevention of strokes or heart attacks, given risk of cerebral and gastroenteral bleeding. ++ Sources ++ –FDA Consumer Updates 2014. https://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm390574.htm –Stroke. 2011;42:517-584. + ++ aMajor modifiable risk factors: hypertension, cigarette smoke exposure, diabetes, atrial fibrillation, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, obesity. + STROKE, ATRIAL FIBRILLATION Download Section PDF Listen +++ +++ Population ++ –Adults with atrial fibrillation. +++ Recommendations ++ AAFP 2017 ++ –Choose rate control, not rhythm control, for most patients. –Prefer lenient rate control (<110), not strict rate control (<80). –Discuss risk of stroke and bleeding with patients considering anticoagulation. –Prescribe chronic anticoagulation unless low stroke risk (CHADS2 <2) or specific contraindications. Options include warfarin, apixaban, dabigatran, edoxaban, or rivaroxaban. –Do not give dual treatment with anticoagulant and antiplatelet therapy. ++ Source ++ –Am Fam Physician. 2017;96(5):332-333. ++ AHA/ACC 2014, 2015 ++ –Prioritize rate control; consider rhythm control if this is the first event, and if it occurs in a young patient with minimal heart disease or if symptomatic. –Rate control goal is <110 beats/min in patients with stable ventricular function (ejection fraction [EF] >40%). –Antithrombotic therapy is required. Anticoagulation or antiplatelet therapy is determined by ACC/AHA or CHA2DS2VASc (nonvalvular atrial fibrillation) guidelines. –For patients with AF who have mechanical valves, warfarin is recommended with an international normalized ratio (INR) target of 2–3 or 2.5–3.5, depending on the type and location of prosthesis. –For patients with nonvalvular AF with a history of stroke, TIA or CHA2DS2VASc ≥2, oral anticoagulation is recommended: warfarin (INR: 2–3) or direct oral anticoagulants (DOACs) (novel oral anticoagulation agents)—see treatment. –In patients treated with warfarin, INR should be performed weekly until INR is stable and at least monthly when INR is in range and stable. –Renal function should be evaluated prior to initiation of direct thrombin or factor Xa inhibitors and should be reevaluated when clinically indicated and at least annually. –Initially clinicians should identify low-risk AF patients who do not require antithrombotic therapy (CHA2DS2VASc score, 0 for men, 1 for women). Patients with at least 1 risk factor (except when the only risk is being a woman) should be offered oral anticoagulant (OAC). The patient’s individual risk of bleeding should be addressed (BP control, discontinuing unnecessary medications such as ASA or nonsteroidal anti-inflammatory drugs). –In nonvalvular AF with CHA2DS2VASc = 0, no antithrombotic therapy or treatment with ASA or an OAC may be considered. –Following coronary revascularization (PCI or surgical) in patients with CHA2DS2VASc ≥2, it may be reasonable to use Clopidogrel with OAC but without ASA. ++ Sources ++ –Circulation. 2014;130(23):e199-267. –JAMA. 2015;313(19):1950-1962. +++ Comments ++ Strokes and nonfatal strokes are reduced in diabetic patients by lower BP targets (<130/80 mm Hg). In the absence of harm, this benefit appears to justify the lower BP goal. Average stroke rate in patients with risk factors is approximately 5% per year. Adjusted-dose warfarin and antiplatelet agents reduce absolute risk of stroke. Women have a higher prevalence of stroke than men. Women have unique risk factors for stroke, such as pregnancy, hormone therapy, and higher prevalence of hypertension in older ages. ++ ESC 2010, 2012 ++ –ESC recommends the CHA2DS2VASc score as more predictive for stroke risk, especially with a low CHADS2 score. DOACs offer better efficacy, safety, and convenience compared with OAC with VKAs. –In high-risk patient unsuitable for anticoagulation, dual antiplatelet therapy (ASA plus clopidogrel) is reasonable. ++ Sources ++ –Eur Heart J. 2010;31:2369-2429. –Eur Heart J. 2012;33:2719-2747. +++ Comments ++ Absolute CVA risk reduction with dual antiplatelet Rx is 0.8% per year balanced by increased bleeding risk 0.7% ACTIVE Trial. In high-risk patients with history of TIA/minor ischemic stroke, dual antiplatelet therapy (ASA+Plavix), started in the first 24 h, is superior to ASA alone in preventing stroke in the first 90 d, without having increased risk of hemorrhage. +++ FDA Warning 2011 ++ –Dronedarone should not be used in patients who have chronic AF with associated severe heart failure (HF) or LV systolic dysfunction. –See Management Algorithm. For therapy, see Chapter 3, page 194, pharmacologic and antithrombotic recommendations. –Dronedarone is contraindicated in patients with NYHA Class IV heart failure or NYHA Class II–III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. –Dronedarone reduces the incidence of AF recurrences, hospitalization, and death in patients with paroxysmal or persistent AF. However, dronedarone should not be used in high-risk patients with permanent AF or patients with unstable chronic HF due to safety concerns. J Clin Pharm Ther. 2014;39(2):112-117. ++ Source ++ –http://www.fda.gov/Drugs/DrugSafety/ucm240011.htm +++ Comment ++ Dronedarone doubles rate of CV death, stroke, and heart failure in patients with chronic atrial fibrillation. +++ Recommendations ++ HRS 2014, 2015 ++ –Given the impact of AF on stroke and the association of AF with cognitive dysfunction, brain imaging may improve the care of AF patients by helping to stratify stroke risk in AF patients. Presence of subclinical brain infarcts is robustly associated with the subsequent risk of stroke. Short-term risk of stroke after TIA was 3-fold higher in patients with a brain infarct on MRI compared to those without. –Compared to warfarin, DOACs offer relative efficacy, safety, and convenience. Warfarin efficacy and safety depend on the quality of anticoagulation control, as reflected by the average time in therapeutic range (TTR). Due to the difficulty of achieving therapeutic INRs quickly after starting warfarin, an increased risk of stroke has been observed in the 30 d after initiation of warfarin. –In patients with nonvalvular atrial fibrillation, a high SAMe-TT2R2 score (reflecting poor anticoagulation control with poor time in therapeutic range) was associated with more bleeding, adverse cardiovascular events, and mortality during follow-up. ++ Sources ++ –Heart Rhythm. 2015;12(1):e5-e25. –Am J Med. 2014;127(11):1083-1088. +++ Recommendations ++ CCS 2012 ++ –All patients should be stratified using CHADS2 and HASBLED risk scores. Patients with CHADS2 = 0 should have CHADS2-VaSc score calculated. All patients with CHADS2 = 2 and most of the ones with CHADS2 = 1 should have OAC therapy. –When OAC therapy is recommended, dabigatran and rivaroxaban are preferred over warfarin. Rate control goal is <100 beats/min. In stable CAD, ASA (75–325 mg) for CHADS2 = 0, OAC for most CHADS2 = 1. In high-risk patients with ACS, ASA + clopidogrel + OAC might be required (with adequate assessment of risk of stroke, recurrent CAD events, and hemorrhage). ++ Source ++ –Can J Cardiol. 2012;28:125-136. + STROKE, SPECIAL POPULATIONS Download Section PDF Listen +++ +++ Population ++ –HTN. +++ Recommendations ++ JNC 8 ++ –Treat to goal SBP <140 mm Hg. –If age ≥60 y, treat to <150/90 mm Hg. –If comorbid diabetes or chronic kidney disease, treat to <140/90 mm Hg. ++ ACC/AHA 2017 ++ –Treat to goal <130/80 mm Hg. –If ASCVD risk <10%, treat to goal <140/90. +++ Comment ++ See Chapter 3 (page 360) for JNC-8 treatment algorithms. ++ Sources ++ –JAMA. 2014;311(5):507-520. –Stroke. 2011;42:517-584. +++ Population ++ –DM. +++ Recommendations ++ AHA/ASA 2011 ++ –Six fold increase in stroke. –Short-term glycemic control does not lower macro vascular events. –HgA1c goal is <6.5%. –Goal is <130/80 mm Hg. –Statin therapy. –Consider ACE inhibitor or ARB therapy for further stroke risk reduction. ++ Source ++ –Stroke. 2011;42:517-584. +++ Population ++ –Asymptomatic CAS. +++ Recommendations ++ USPSTF 2014, AHA/ASA 2011 ++ –No indication for general screening for CAS with ultrasonography. –Screen for other stroke risk factors and treat aggressively. –ASA unless contraindicated. –Prophylactic carotid endarterectomy (CEA) for patients with high-grade (>70%) CAS by ultrasonography when performed by surgeons with low (<3%) morbidity/mortality rates may be useful in selected cases depending on life expectancy, age, sex, and comorbidities. –However, recent studies have demonstrated that “best” medical therapy results in a stroke rate <1%. –The number needed to treat (NNT) in published trials to prevent 1 stroke in 1 y in this asymptomatic group varies from 84 up to 2000. (J Am Coll Cardiol. 2011;57(8):e16-e94) ++ Sources ++ –USPSTF. Carotid Artery Stenosis. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/carotid-artery-stenosis-screening –Neurology. 2011;77:751-758. –Neurology. 2011;77:744-750. –Stroke. 2011;42:517-584. +++ Population ++ –Symptomatic CAS. +++ Recommendations ++ ASA/ACCF/AHA/AANN/AANS/ACR/CNS 2011 ++ –Optimal timing for CEA is within 2 wk of posttransient ischemic attack. –CEA plus medical therapy is effective within 6 mo of symptom onset with >70% CAS. –Intense medical therapy alone is indicated if the occlusion is <50%. –Intensive medical therapy plus CEA may be considered with obstruction 50%–69%. –Surgery should be limited to male patients with a low perioperative stroke/death rate (<6%) and should have a life expectancy of at least 5 y. ++ Sources ++ –J Am Coll Cardiol. 2011;57(8):1002-1038. –Neurology. 2005;65(6):794-801. –Arch Intern Med. 2011;171(20):1794-1795. –Stroke. 2011;42:227-276, 517-584. +++ Comments ++ –Medical treatment of asymptomatic CAS should be aggressive. –Surgical intervention should be individualized, guided by comparing comorbid medical conditions and life expectancy to the surgical morbidity and mortality. –Atherosclerotic intracranial stenosis: ASA should be used in preference to warfarin. –Warfarin—significantly higher rates of adverse events with no benefit over ASA. (N Engl J Med. 2005;352(13):1305-1316) –Qualitative findings (embolic signals and plaque ulceration) may identify patients who would benefit from asymptomatic CEA. +++ Populations ++ –Cryptogenic CVA. –Hyperlipidemia. +++ Recommendations ++ ASA/ACCF/AHA/AANN/AANS/ACR/CNS 2011 ++ –Carotid artery stenting is associated with increased nonfatal stroke frequency but this is offset by decreased risk of MI post-CEA. –Cryptogenic CVA with patent foramen ovale (PFO) should receive ASA 81 mg/d. ++ Sources ++ –J Am Coll Cardiol. 2011;57(8):1002-1044. –J Am Coll Cardiol.2009;53(21):2014-2018. –N Engl J Med. 2012;366:991-999. –N Engl J Med. 2013;368:1083-1091. +++ Comments ++ Consider referral to tertiary center for enrollment in randomized trial to determine optimal Rx. Closure I trial demonstrated no benefit at 2 y of PFO closure device over medical therapy. In 2013, the PC Trial also failed to demonstrate significant benefit in reducing recurrent embolic events in patients undergoing PFO closure compared to medical therapy, at 4 y follow-up. +++ Population ++ –Sickle cell disease. +++ Recommendations ++ ASA/ACCF/AHA/AANN/AANS/ACR/CNS 2011 ++ –Transfusion therapy (target reduction of hemoglobin S from a baseline of >90% to <30%) is effective for reducing stroke risk in those children at elevated stroke risk (Class I; level of evidence, B). –Begin screening with transcranial Doppler (TCD) at age 2 y. –Transfusion therapy is recommended for patients at high-stroke risk per TCD (high cerebral blood flow velocity >200 cm/s). –Frequency of screening not determined. ++ Sources ++ –J Am Coll Cardiol. 2011;57(8):1002-1044. ++ –ASH Education Book. 2013;2013(1):439-446. +++ Population ++ –Primary prevention in women. +++ Recommendations ++ ACC/ASA 2014 ++ –Higher lifetime risk, third leading cause of death in women, 53.5% of new recurrent strokes occur in women. –Sex-specific risk factors: pregnancy, preeclampsia, gestational diabetes, oral contraceptive use, postmenopausal hormone use, changes in hormonal status. –Risk factors with a stronger prevalence in women: migraine with aura, atrial fibrillation, diabetes, hypertension, depression, psychosocial stress. ++ Source ++ –Circulation. 2011;123:1243-1262. +++ Population ++ –Oral contraceptives/menopause, postmenopausal hormone therapy. +++ Recommendations ++ ACC/ASA 2014 ++ –Stroke risk with low-dose OC users is about 1.4–2 times that of non-OC users. –Measurement of BP is recommended prior to initiation of hormonal contraception therapy. –Routine screening for prothrombotic mutations prior to initiation of hormonal contraception is not useful. –Among OC users, aggressive therapy of stroke risk factors may be reasonable. –Hormone therapy (conjugated equine estrogen with or without medroxyprogesterone) should not be used for primary or secondary prevention of stroke in postmenopausal women. –Selective estrogen receptor modulators, such as raloxifene, tamoxifen, or tibolone, should not be used for primary prevention of stroke. ++ Source ++ –Stroke. 2014;45:1545-1588. ++ Table Graphic Jump Location | Download (.pdf) | Print SAMETT2R2 SCORE Sex (female) 1 Age >60 1 Medical history (>2 comorbidities: HTN, DM, CAD/MI, PAD, CHF, history of stroke, pulmonary disease, hepatic or renal disease) 1 Treatment (rhythm control strategy) (interacting medications, eg, beta-blocker, verapamil, amiodarone) 1 Tobacco use (within 2 y) 2 Race (non-white) 2 Maximum points 8 Interpretation Score >2 = DOAC Score 0–2 = VKA with TTR >65%–70% Source: Fauchier L, Angoulvant D, Lip GY. The SAME-TT2R2 score and quality of anticoagulation in atrial fibrillation: a simple aid to decision-making on who is suitable (or not) for vitamin K antagonists. doi: http://dx.doi.org/10.1093/europace/euv088.aAssess risk of stroke in all patients. See Appendix VII, pages 540–543 for risk assessment tool. + VENOUS THROMBOEMBOLISM (VTE) PROPHYLAXIS IN NONSURGICAL PATIENTS Download Section PDF Listen +++ +++ Populations ++ –Medical patients with low risk (Padua Prediction score—see Table I). –Medical patients with high risk (JAMA. 2012;307:306) (Padua Prediction score—see Table I). ++Table Graphic Jump LocationTABLE I:RISK FACTORS FOR VTE IN HOSPITALIZED MEDICAL PATIENTS—PADUA PREDICTIVE SCALEView Table||Download (.pdf) TABLE I: RISK FACTORS FOR VTE IN HOSPITALIZED MEDICAL PATIENTS—PADUA PREDICTIVE SCALE Risk Factor Points Active cancera 3 Previous VTE 3 Reduced mobilityb 3 Underlying thrombophilic disorderc 3 Recent (<1 mo) trauma or surgery 2 Age (>70 y) 1 Congestive heart failure (CHF) or respiratory failure 1 Acute MI or stroke 1 Acute infection or inflammatory disorder 1 Obesity (BMI >30) 1 Thrombophilic drugs (hormones, tamoxifen, erythroid stimulating agents, lenalidomide, bevacizumab) 1 High risk: >4 points—11% risk of VTE without prophylaxis Low risk: <3 points—0.3% risk of VTE without prophylaxis aLocal or distant metastasis, chemotherapy, or radiation within last 6 mo.bBed rest for >3 d.cHereditary thrombophilia (see Table III) and antiphospholipid antibody syndrome, nephrotic syndrome, hemolytic anemia. +++ Recommendations ++ ACCP 2016, ACP 2011 ++ –Recommend against the use of pharmacologic prophylaxis or mechanical prophylaxis in low-risk patients. –Recommend anticoagulant in high-risk patients Thromboprophylaxis with low-molecular-weight heparin (LMWH)—equivalent of enoxaparin 40 mg SQ daily; fondaparinux 2.5 mg SQ daily. Low-dose unfractionated heparin (UFH) 5000 units bid or tid should be used only in patients with significant renal disease. UFH has a 10-fold increased risk of heparin-induced thrombocytopenia (HIT). Women are 2.5 times likely to develop HIT compared to men. If patient is bleeding or at high risk of bleeding (see Table II), mechanical prophylaxis with graduated compression stockings (GCS) or intermittent pneumatic compression (IPC) is recommended. When bleeding risk decreases, substitute pharmacologic thromboprophylaxis for mechanical prophylaxis. Continue thromboprophylaxis for duration of hospital stay. Extended prophylaxis after discharge not recommended for medical patients but should be considered if patient has underlying thrombotic risk (see Table III). ++ Sources ++ –Ann Intern Med. 2011;155:625-632. –Chest. 2016;149:315-352. –http://www.uwhealth.org/files/uwheath/docs/anticoagulation/VTE ++Table Graphic Jump LocationTABLE II:RISK FACTORS FOR BLEEDING (CHEST. 2011;139:69-79)View Table||Download (.pdf) TABLE II: RISK FACTORS FOR BLEEDING (CHEST. 2011;139:69-79) Risk Factora,b N = % of Patients Overall Risk Active gastroduodenal ulcer 2.2 4.15 GI bleed <3 mo previous 2.2 3.64 Platelet count <50 K 1.7 3.37 Age ≥85 y (vs. 40 y) 10 2.96 Hepatic failure (INRc >1.5) 2 2.18 Renal failure (GFRd <30 mL/min) 11 2.14 ICU admission 8.5 2.10 Current cancer 10.7 1.78 Male sex 49.4 1.48 aAlthough not studied in medical patients, antiplatelet therapy would be expected to increase risk of bleeding.bGo to www.outcomes-umassmed.org/IMPROVE/risk_score/vte/index.html to calculate the risk of bleeding for individual patients.cInternational normalized ratio.dGlomerular filtration rate. ++Table Graphic Jump LocationTABLE III:HEREDITARY THROMBOPHILIC DISORDERSView Table||Download (.pdf) TABLE III: HEREDITARY THROMBOPHILIC DISORDERS Disorder % of US Population Increase in Lifetime of Risk of Clot Resistance to activated protein C (factor V Leiden mutation) 5–6 3× Prothrombin gene mutation 2–3 2.5× Elevated factor 8 (>175% activity) 6–8 2–3× Elevated homocysteine 10–15 1.5–2× Protein C deficiency 0.37 10× Protein S deficiency 0.5 10× Antithrombin deficiency 0.1 25× Homozygous factor V Leiden 0.3 60× +++ Comments ++ Clinical perspective Routine ultrasound screening for DVT is not recommended in any group. 150–200,000 deaths from VTE in the United States per year. Hospitalized patients have a VTE risk which is 130-fold greater than that of community residents. (Mayo Clin Proc. 2001;76:1102) Neither heparin nor warfarin is recommended prophylactically for patients with central venous catheters. In higher risk long-distance travelers, frequent ambulation, calf muscle exercises, aisle seat, and below-the-knee graduated compression stockings (GCS) are recommended over aspirin or anticoagulants. Hospitalized inpatients with solid tumors without additional risk factors for VTE (history of DVT, thrombophilic drugs, immobilization) should be treated with prophylactic dose LMWH. Be cautious in patients with Ccr <20–30 mL/min—UFH or dalteparin (half dose) preferred. Consider adjusted LMWH dose in patients <50 kg or >110 kg in weight. Monitor with heparin anti 10a activity testing. Inferior vena cava (IVC) filter indicated in patients with diagnosed DVT with or without pulmonary embolism (PE) who cannot be anticoagulated because of bleeding. There are no other situations where a filter has been proven to be beneficial. IVC filter should not be used prophylactically. Although several studies have shown survival benefit for VTE prophylaxis in surgical patients, this has not been proven in medical patients. (N Engl J Med. 2011;365:2463) (N Engl J Med. 2007;356:1438) In patients with cancer and VTE use LMWH. The new OACs are being tested and will probably have a role in cancer-related VTE in the near future. Warfarin is inferior to LMWH. (Lancet Oncol. 2008;9:577) (Thromb Res. 2012;130:853) In patients with mechanical heart valves, use warfarin for anticoagulation. The direct oral anticoagulants (DOACs) are inferior. (N Engl J Med. 2013;369:1206) + VENOUS THROMBOEMBOLISM (VTE) IN SURGICAL PATIENTS Download Section PDF Listen +++ +++ Populations ++ –Risk stratification –SURGICAL Low risk—<40 y, minor surgery, no risk factor, Caprini score <2 (see Table IV). Intermediate risk—minor surgery plus risk factors, age 40–60 y, major surgery with no risk factorsa,b ; Caprini score 3–4. High risk—major surgery plus risk factors,a,b high-risk medical patient, major trauma, spinal cord injury, craniotomy, total hip or knee arthroplasty (THA, TKA), thoracic, abdominal, pelvic cancer surgery. ++Table Graphic Jump LocationTABLE IV:CAPRINI RISK STRATIFICATION MODELView Table||Download (.pdf) TABLE IV: CAPRINI RISK STRATIFICATION MODEL 1 Point 2 Points 3 Points 5 Points Age 41–60 y Minor surgery BMI >251 g/m2 Swollen legs Varicose veins Pregnancy or postpartum History of recurrent spontaneous abortion Sepsis (<1 mo) Lung disease History of acute MI Congestive heart failure (CHF) (<1 mo) History of inflammatory bowel disease Medical patient at bed rest Age 61–74 y Arthroscopic surgery Major open surgery >45 min Laparoscopic surgery Malignancy Confined to bed Immobilizing cast Central venous catheter Age >75 y History VTE Family history of VTE Factor V Leiden Prothrombin gene mutation Lupus anticoagulant Elevated homocysteine Other congenital or acquired thrombophilia Stroke (<1 mo) Elective arthroplasty; hip, pelvis, or leg fracture Acute spinal cord injury (<1 mo) Caprini score <3: low risk Caprini score 3–4: intermediate risk Caprini score >5: high risk +++ Recommendation ++ ACCP 2016 ++ –Preventive measures Early ambulation—consider mechanical prophylaxis and intermittent pneumatic compression, graduated compression stocking (IPC or GCS). UFH 5000 U SQ q 8–12 h should ONLY be used in patients with renal disease with a Ccr <20–30 mL/min. LMWH equivalent to enoxaparin 40 mg SQ 2 h before surgery then daily or 30 mg q12h SQ starting 8–12 h postop. Fondaparinux 2.5 mg SQ daily starting 8–12 h postop. LMWH—equivalent to enoxaparin 40 mg SQ 2 h preoperative then daily or 30 mg SQ q12h starting 8–12 h postop and also use mechanical prophylaxis with IPC or GCS. Extend prophylaxis for as long as 28–35 d in high-risk patients. In THA, TKA ortho patients, acceptable VTE prophylaxis also includes rivaroxaban 10 mg/d, dabigatran 225 mg/d, adjusted dose warfarin, and aspirin, although LMWH is preferred. DOACs are likely to play a larger role in the future as trials continue to show superiority over warfarin. (Ann Int Med. 2013;159:275) (Thromb Haemot. 2011;105:444) If high risk of bleeding, use IPC alone. (Ann Intern Med. 2012;156:710, 720) (JAMA. 2012;307:294) Do not use UFH for prophylaxis if Ccr is >20 cc/min. There is a 10-fold increased risk of HIT compared to LMWH. ++ Source ++ –Chest. 2016;149:315. ++ –http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm390574.htm +++ Comments ++ Clinical points 75%–90% of surgical bleeding is structural. VTE prophylaxis adds minimally to risk of bleeding. With creatinine clearance <20 to 30 cc/min UFH with partial thromboplastin time (PTT) monitoring is preferred (decrease dose if PTT prolonged). In all other situations LMWH or DOACs are preferred to reduce the risk HIT. Patients with liver disease and prolonged INR are still at risk for clot. Risk-to-benefit ratio of VTE prophylaxis should be individualized. Epidural anesthesia—to place catheter wait 18 h after daily prophylactic dose of LMWH, and 24 h after prophylactic dose of fondaparinux. For patients on BID therapeutic LMWH anticoagulation or once daily LMWH wait more than 24 h before placing epidural catheter. Patients on DOACs should hold their anticoagulation for 3-5 days. After placing or removing an epidural catheter hold on starting anticoagulation for 6–8 h. Prophylactic IVC filter for high-risk surgery is not recommended. For cranial and spinal surgery patients at low risk for VTE use mechanical prophylaxis—high-risk patients should have pharmacologic prophylaxis added to mechanical prophylaxis once hemostasis is established and bleeding risk decreased. Patients at high risk of bleedinga with major surgery should have mechanical prophylaxis (IPC, GCS)—initiate anticoagulant prophylaxis if risk lowered. Surgical patients receive indicated prophylaxis 60% of the time compared to 40% in medical patients. + ++ aEye, ear, laparoscopy, cystoscopy, and arthroscopic operations. ++ bPrior VTE, cancer, stroke, obesity, congestive heart failure pregnancy, thrombophilic medications (tamoxifen, raloxifene, lenalidomide, thalidomide, erythroid-stimulating agents). ++ aSELECTED FACTORS IN THE RISING RISK OF MAJOR BLEEDING COMPLICATIONS: General Risk Factors: Active bleeding, previous major bleed, known untreated bleeding disorder, renal or liver failure, thrombocytopenia, acute stroke, uncontrolled high BP, concomitant use of anticoagulants, or antiplatelet therapy. Procedure-Specific Risk Factors: Major abdominal surgery—extensive cancer surgery, pancreatic-duodenectomy, hepatic resection, cardiac surgery, thoracic surgery (pneumonectomy or extended resection). Procedures where bleeding complications have especially severe consequences: craniotomy, spinal surgery, spinal trauma.