pharmacological aspects of cardiovascular disease in the elderly erin beth hays, pharmd white river...
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Pharmacological Aspects of Cardiovascular Disease
in the Elderly Erin Beth Hays, PharmD
White River Medical Center
Batesville, AR
Objectives
Discuss blood pressure goals and first-line treatment recommendations in the geriatric population for orthostatic hypotension and hypertension.
Discuss the benefits vs. risks in managing hyperlipidemias in elderly patients.
Discuss the barriers and issues regarding medications for heart failure in the geriatric population.
Describe the benefits vs. risks of anticoagulation in elderly patients for stroke prevention and venous thromboembolism prevention and management.
Discuss barriers to treating cardiovascular disease in the elderly population as they relate to medications
Orthostatic Hypotension
DefinitionDecrease in SBP of ≥ 20 mmHg orDecrease in DBP of ≥ 10 mmHg
Within 3 minutes of standing
Prevalence of OH in Relationship to Age
Orthostatic Hypotension- Epidemiology Prevalence
Increasing age Increasing vascular stiffness Diminishing baroreflex sensitivity Decreasing β-adrenoreceptor-mediated responses
Risk Factors Acute illness # of medications Types of medications Hypertension Diabetes Smoking Carotid artery stenosis/carotid artery intimamedia thickness Neurologic diseases
Orthostatic Hypotension
Causes Sicknesses: Dehydration, diarrhea, extreme heat, MI,
adrenal insufficiency, vomiting, sepsis Medications: short-acting, vasodilators, or volume
depleting Centrally acting α-receptor agonist, peripheral α-antagonists,
nitrates, hydralazine, minoxidil, loop diuretics. Others: antipsychotic, dopamine agonists, levodopa,
marijuana, narcotics, sedatives, sildenafil, and tricyclic antidepressants
Orthostatic Hypotension
TreatmentDiscontinue causative agentNon-pharmacologic treatmentsPharmacologic treatments
Fludrocortisone Midodrine
Fludrocortisone
Synthetic mineralocorticoid MOA:
Promotes increased reabsorption of sodium and loss of potassium from renal distal tubules promoting fluid retention
0.1-0.3 mg daily Adverse effects:
Suprine hypertension, ankle edema, headache, hypokalemia, heart failure
Midodrine
Peripheral selective α-receptor agonist 2.5-10 mg TID Adverse effects: suprine hypertension,
pruritus, paresthesias, piloerection, bradycardia, and urinary retention
Avoid in patients with hx of CAD, HF, urinary retention, acute kidney disease or thyrotoxicosis
Hypertension Goals
General population: <140/90 mmHgDiabetes or CKD: <130/80 mmHgStudy: mortality of 140/90 vs 180
Initial treatment (no compelling indications):140-159/ or 90-99 mmHg: thiazide diuretic≥ 160/ or ≥ 100 mmHg: thiazide + ACEI/ARB/
β-blocker/calcium channel blocker
HTN Tx for Compelling IndicationsCompelling Indication
Diuretic BB ACEI ARB CCB Aldosterone antagonist
Post-MI X X X
High risk for CHD
X X X X
Heart Failure X X X X X
Diabetes X X X X X
Chronic Kidney Disease
X X
Recurrent Stroke
Prevention
X X
HTN Medication Concerns for the Elderly Elderly are predisposed to orthostatic
hypotensionAlpha blockersCentral alpha agonistsDiuretics
Overall treatment should be the same as with younger adults except with lower starting doses
HTN Medication Concerns for the Elderly Renal function
Concern only when initiating and titrating therapy
Increased monitoring i.e. ACEI more vulnerable in developing
hyperkalemia
Thiazides lose efficacy when Clcr < 40 mL/min
Hyperlipidemias
Risk Category
LDL Goal (mg/dL)
LDL at which to initiate TLC
LDL at which to initiate Drug therapy
CHD or CHD risk equivalents (10-yr risk > 20%)
<100 ≥100 ≥130 (100-129) drug optional
2+ risk factors
(10 yr risk 10-20%)
<130 ≥130 ≥130
2+ risk factors
(10-yr risk < 10%)
<130 ≥130 ≥160
0-1 risk factor <160 ≥160 ≥190 (160-189 drug optional)
Hyperlipidemias
Concern in the ElderlyMay be at increased risk of developing statin-
induced myopathy. Polypharmacy, reduced renal function, and female
sex
Should be counseled regarding the symptoms of statin-induced myopathy
Palliative-only interventions are often a reason to defer or discontinue drug therapy
Simvastatin
New Safety and Dosing Information – FDA June 2011
Amiodarone, diltiazem or verapamil: Simvastatin dose should not exceed 10 mg/day
Amlodipine or ranolazine: Simvastatin dose should not exceed 20 mg/day
Limited Dosing: 80 mg use only in patients that have taken for > 12 months w/o evidence of myopathy
Simvastatin – Updated Labeling
Contraindicated with simvastatin: Itraconazole Ketoconazole Posaconazole (New) Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Nefazodone Gemfibrozil * Cyclosporine * Danazol *
Do not exceed 10 mg simvastatin daily dose with Amiodarone † Verapamil †
Diltiazem ¶
Do not exceed 20 mg simvastatin daily dose with Amlodipine (New) Ranolazine (New)
* Moved from 10 mg max simvastatin dose to contraindicated
† Moved from 20 mg max simvastatin dose to 10 mg max
¶ Moved from 40 mg max simvastatin dose to 10 mg max
Heart Failure
β-blockersDecrease mortality and hospitalizationWell-tolerated
ACE InhibitorsUse if toleratedARBs may be tried if ACEIs are not tolerated
Heart Failure
Digoxin Reduces hospitalization (independent of age) Age is a predictor of hospitalization for digoxin toxicity
and withdrawal of digoxin therapy Does not reduced mortality Should only be used in patients with left ventricular
systolic dysfunction who remain symptomatic despite maximally tolerated doses of a β-blocker, ACE inhibitor, and diuretic.
Heart Failure Barriers
Diagnosis of HF Hesitation to attempt titration of HF medications due to
risk for adverse effects Start at lowest dose β-blockers: titrate every 2-4 weeks ACE Inhibitors: titrate every 1-2 weeks
Monitoring of SCr and potassium with dose increases Diuretics can cause volume depletion and kidney
function may reduce diuretic efficacy Digoxin toxicity Drug interactions – counsel against use of NSAIDs
Anticoagulation
Stroke prophylaxis in patients with AFib
VTE prophylaxis
Atrial Fibrillation
CHAD2 ScoreCongestive heart failure = 1 pointHypertension = 1 pointAge ≥ 75 years = 1 pointDiabetes = 1 pointStroke or TIA history = 2 points
Atrial Fibrillation
CHAD2 Score
Degree of Risk
Recommended Stroke Prevention Strategy
0 Low Aspirin 325 mg daily
1 Moderate Aspirin 325 mg daily or
Warfarin (INR 2-3)
≥ 2 High Warfarin (INR 2-3)
Atrial Fibrillation – a new option Dabigatran
Indication: VTE and stroke prophylaxis in nonvalvular AFib
150 mg BIDRenally adjusted
15-30 mL/min: 75 mg BID
Adverse Rxns Dyspepsia 11% Bleeding (8% to 33%; major: ≤6%)
VTE Prophylaxis
Mechanical methods Medications
Total Knee & Hip LMWH, fondaparinux, warfarin
Hip fracture LWMH, fondaparinux, warfarin, LDUH
Medically ill patients LWMH, fondaparinux, LDUH
No evidence for use of prophylaxis in NH or homebound geriatrics
VTE Treatment
LMWH, fondaparinux, heparin Bridge with warfarin
Target INR = 2-3
Enoxaparin
LMWH Prophylaxis doses
40 mg daily 30 mg BID for hip and knee patients Renal adjustment
<30 mL/min = 30 mg daily
Treatment doses 1 mg/kg BID Renal Adjustment
<30 mL/min = 1 mg/kg daily
Dalteparin
LMWH Prophylaxis doses
2500-5000 int. units daily Renal adjustment
Treatment doses Cancer patient
Initial: 200 int. units/kg daily for 30 days Maintenance (after 30 days): 150 int. units daily
Renally adjustment if Clcr <30 mL/minute: monitoring anti-Xa levels
Fondaparinux
Factor Xa Inhibitor Prophylaxis doses
2.5 mg once daily Treatment doses
<50 kg: 5 mg once daily 50-100 kg: 7.5 mg once daily >100 kg: 10 mg once daily
Renal adjustment Clcr 30-50 mL/minute: Use caution Clcr <30 mL/minute: Contraindicated
Warfarin
Initial dose ≤5 mg daily Pros
Well studied
Cons Monitoring burden Drug-drug and drug-food interactions Compliance High sensitivity
Hypoalbuminemia Decreased dietary vitamin K intake
Counsel patients and caregivers/family about signs & symptoms of stroke
Medications in the Elderly
Start LOW and titrate SLOW More frequent monitoring Polypharmacy concerns
Drug-drug interactionsCompliance
Do all medications have an indication? Are the directions practical?
Renal function Nutrition status
Medication Appropriateness Index
Questions to Ask About Each Individual Medication1. Is there an indication for the medication?2. Is the medication effective for the condition?3. Is the dosage correct?4. Are the directions correct?5. Are the directions practical?6. Are there clinically significant drug–drug interactions?7. Are there clinically significant drug–disease/condition interactions?8. Is there unnecessary duplication with other medication(s)?9. Is the duration of therapy acceptable?10. Is this medication the least expensive alternative compared with
others of equal utility?
Medication Adherence
Simplify regimenMedication appropriatenessDosing intervals
Reduce cost Dosage forms Pill boxes, calendars, etc Family involvement
References Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al.
Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358(18):1887-98.
Benvenuto LJ, Krakoff LR. Morbidity and Mortality of OH: Implications for Management of Cardiovascular Disease. Am J of Hypertension. 2011; 24: 135-144.
Cohen DL, Townsend RR. Update on Pathophysiology and Treatment of Hypertension in the Elderly. Curr Hypertens Rep. Pub online June 18, 2011. DOI 10.1007/s11906-011-0215-x
Connolly SJ, Ezekowitz MB, Yusuf S, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2009; 361(12):1139-1152.
Cook K, Tisdale JE. Cardiovascular. In L. Hutchison & R.B. Sleeper (eds), Fundamentals of Geriatric Pharmacotherapy: An Evidence-Based Approach, 1st edn, American Society of Health-System Pharmacists: Bethesda, Maryland, 2010, pp. 121-161
FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Accessed online Jun 27, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm
All drug dosing and adverse effects were obtained from Lexicomp Online. Accessed Jun 26, 2011.