Applying MTM to the Geriatric Cardiovascular Patient
June 1, 2017
June 30, 2019
Donna M. Lisi, PharmD, BCPS, BCPP
MTM Certified Clinical Pharmacist
Somerset, New Jersey
FACULTY DISCLOSURE STATEMENTS:
Dr. Lisi has no actual or potential conflict of interest in relation to this activity.
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Credits: 2.0 hours (0. 20 ceu)
Type of Activity: Knowledge
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Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.
To educate the medication therapy management pharmacist about tools and resources available to perform an effective medication review for the older cardiovascular patient.
After completing this activity, the participant should be able to:
- Identify Medicare Part D criteria for performing medication therapy management (MTM).
- Recognize age-related changes in the cardiovascular (CV) system as well as altered disease presentation and pharmacodynamics in the older CV patient.
- List how renal and hepatic dysfunction and drug interactions affect the management of the older CV patient.
- Develop an MTM plan for the management of patients with chronic heart failure, dyslipidemia, or hypertension.
ABSTRACT: Medication therapy management (MTM), which is mandated under Medicare Part D, provides the pharmacist with an opportunity to optimize the drug therapy of patients with cardiovascular disease (CVD). Heart failure, dyslipidemia, and hypertension are three core chronic CVDs targeted by MTM. By having knowledge of age-related CV changes; alterations in CVD presentation and pharmacodynamics in the elderly; medications requiring dosage adjustments in renal and hepatic impairment; CV drug-drug interactions; and clinical guidelines and tools, and by using clinical data sets, MTM pharmacists can help to ensure safe and effective medication regimens for their CVD patients.
Medication therapy management (MTM) offers unique opportunities for pharmacists caring for older cardiovascular (CV) patients. By understanding age-related alterations in CV function, disease presentation, and drug therapy in the older CV patient, the MTM pharmacist can help promote safe and effective pharmacotherapy. This article discusses clinical tools to help MTM pharmacists better serve their CV patients.
Definition of MTM
MTM is defined as “a distinct service or group of services that optimize therapeutic outcomes for individual patients. MTM services are independent of, but can occur in conjunction with, the provision of a medication product.”1
Principles of MTM
MTM was mandated by Congress under the Medicare Prescription Drug Improvement and Modernization Act of 2003, or Medicare Modernization Act (MMA). The MMA includes provisions for a prescription-drug benefit under Medicare Part D and requires sponsoring insurers to provide MTM services to a defined subset of beneficiaries (based on disease states, number of medications, and medication expenditures) to help improve therapeutic outcomes, control costs, and reduce adverse drug events.2,3
These are the Medicare MTM Part D eligibility criteria in 20174:
Multiple Chronic Diseases: Sponsors may set the minimum threshold for the number of multiple chronic diseases present in an older subscriber at two or three, but they cannot require more than three chronic diseases as the minimum number of chronic conditions that a beneficiary must have to be eligible for the MTM program. Sponsors have the option of either targeting beneficiaries with any chronic disease or with specific chronic diseases. However, if a sponsor chooses to target beneficiaries with specific chronic diseases, the sponsor should include conditions from at least five of the following nine core chronic conditions: Alzheimer’s disease; chronic heart failure (CHF); diabetes mellitus (DM); dyslipidemia; end-stage renal disease; hypertension (HTN); respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease, or chronic lung disorders); bone diseases (e.g., osteoarthritis, rheumatoid arthritis or osteoporosis); or mental health conditions (e.g., depression, schizophrenia, bipolar disorder, or chronic/disabling mental health conditions). This list is not all-inclusive, and sponsors are encouraged to include additional diseases in their targeting criteria in order to meet the needs of their patient populations and improve therapeutic outcomes.
This article will focus on three of the nine core chronic conditions that involve CV diseases (CVDs)—CHF, dyslipidemia, and HTN. Additional cardiac diseases or related areas that may also be targeted for patient review as identified in the MTM program guidance and submission instructions of the Center for Medicare and Medicaid Services’ (CMS) include anticoagulation, atrial fibrillation (AF), and stroke; “CVDs in general” are included in CMS’s chronic disease list. Sponsors may target beneficiaries with any combination of the chronic diseases included in the criteria.
Multiple Part D Drugs: Eight Part D drugs are the maximum number of drugs a Part D plan sponsor may require as the minimum number of Part D drugs that a beneficiary must be taking for targeted enrollment; i.e., sponsors cannot require more than eight Part D drugs as the minimum number of Part D prescription drugs that a beneficiary must have filled to be eligible for the MTM program. However, sponsors may set this minimum threshold at any number equal to, or between, two and eight.
Annual Costs: Beneficiaries must incur annual costs for covered Part D drugs equal to or greater than the specified MTM cost threshold; the MTM program annual cost threshold in 2017 is $3,919. Drug costs are calculated based on the ingredient cost, dispensing fee, sales tax, and vaccine administration fee, if applicable. This projection may be based on claims within the program year or based on historical claims from the previous year.
If an enrollee meets all three of the required criteria, the enrollee should automatically be enrolled into an MTM program.
The goal of MTM is to provide patient-centered care to help optimize a patient’s health. MTM consists of the following core elements: a comprehensive medication review (CMR); personal medication list (PML); medication action plan (MAP); intervention and/or referral; and documentation of the encounter.5
CVD is the number-one cause of morbidity and mortality in the United States.6,7 The pharmacist, through the MTM process, can have a significant impact on reducing the consequences of CVD, including hospitalization and rehospitalization, in an aging population.
Age-Related Cardiovascular Changes
There are age-related changes that affect the CV system. (TABLE 1).8-11 Changes that make the older adult predisposed to arrhythmias can be exacerbated by electrolyte abnormalities or by drugs that prolong the QT interval. This change is coupled with changes in other organ systems, such as the renal, respiratory, and hepatic, which can further alter the effects of medications.12 Pharmacists need to be familiar with these age-related changes in function because they may potentially impact drug therapy.13
Altered Cardiovascular Disease Presentation in the Elderly
CVD often goes unrecognized in older adults due to an altered disease presentation, which can lead to misdiagnosis and delays in treatment. In women, persons aged ≥85 years, and those with multiple comorbidities, coronary artery disease (CAD) may present as dyspnea instead of chest pains; this may occur in approximately one-half of those aged ≥85 years. Other manifestations of CAD in the older adult may be more subtle and may consist of fatigue, weakness, or decreased functional status.15 Confusion, which occurs less frequently in younger patients, is a more common presentation in the elderly.16 AF is more prevalent in older adults due to left ventricular stiffness. Orthostasis is common and is due to a decrease in baroreflex sensitivity, placing older adults at risk for falls from their antihypertensive or psychotropic regimens. Heart failure (HF) with preserved ejection fraction is frequently seen and is due to a delay in early left ventricular filling, an increase in central arterial stiffness, and altered neurohormonal regulation. Isolated systolic HTN, which is due to increased arterial stiffness, especially in the large arteries, contributes to morbidity and mortality in the elderly.17
Pharmacist’s Role in Managing the Geriatric CV Patient
The pharmacist’s role in the management of the CV patient has expanded tremendously in recent years. In a joint council perspective paper from the Cardiovascular Team and Prevention Councils of the American College of Cardiology, the contribution of pharmacists in managing the cardiac patient was validated and strongly encouraged.18
In an attempt to standardize the MTM process, data sets have been developed to help assist the pharmacist in performing a medication review. An MTM data set is a stand-alone disease-based guide to help conduct the CMR. When put into practice, these data sets can help pharmacists focus on the minimum amount of information that should be gathered while performing MTM, as well as identify key information that should be conveyed to the patient.19
HF is “a clinical syndrome characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral edema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.”16 HF in patients with a normal left ventricular ejection fraction (LVEF), i.e., ≥50%, is called HF with preserved ejection fraction (HFpEF); HF that is associated with a reduced LVEF (i.e., <40%) is referred to as HF with reduced ejection fraction (HFrEF). HF with an LVEF in the range of 40% to 49% is now defined as HF with midrange ejection fraction (HFmrEF). It is important to distinguish between the various types of HF because underlying etiologies, demographics, comorbidities, and response to therapy may differ.16
The goals of therapy in the management of HF are to improve or maintain a patient’s quality of life; minimize or eliminate signs or symptoms of disease; prevent hospitalizations and rehospitalizations; and improve survival by slowing the trajectory of the disease.20
HF is a disease state/condition targeted by CMS because it is the primary reason for 30-day hospital readmission among Medicare recipients.21 HF costs Medicare over $17.4 billion annually, and this figure is only expected to rise as the population ages.22
Numerous studies have demonstrated the benefits of pharmacist involvement in the management of patients with HF.23-34
Pharmacists counseling the older adult with HF should be familiar with the subtypes and causes of HF, including medications.20 A useful tool is the scientific statement issued by the American Heart Association in August 2016 on drugs that may cause or exacerbate HF.35
Pharmacists should also be knowledgeable about the underlying pathophysiology and clinical manifestations of HF, including compensatory mechanisms as well as the beneficial and detrimental effects of such compensation.20
Comprehensive Medication Review
In performing MTM in the patients with chronic HF, the pharmacist should initially perform a CMR, which is the first core element. He or she should ascertain the following information during the interview process: identification and control of chronic HF symptoms; general medication use and adherence; presence of additional risk factors for HD; and prevention strategies and assessment of how to deal with medical emergencies.
Identify and Control Symptoms: In order to evaluate the patient’s ability to recognize symptoms of HF and to gauge how well they are controlled, the pharmacist should ask about symptoms of HF that the patient may be manifesting (including activities that precipitate symptoms; activities that make symptoms better; whether symptoms are present during rest; frequency with which symptoms occur; change in the severity/frequency of symptoms in the recent past; and limitations in activities and function due to HF symptoms); the duration of HF since diagnosis; whether the patient has other cardiac manifestations, including myocardial infarction (MI), coronary artery bypass surgery (CABG), or percutaneous coronary intervention (PCI); the current HF medication regimen; whether the patient is also on antihypertensives or antiarrhythmics for other cardiac disease manifestations; and any recent fluctuations in body weight.
Assess Medication Use/Adherence: In assessing medication use and adherence, the pharmacist should inquire as to what time patients are taking their medications; how often they miss a dose and what to do if that occurs; whether they have ever discontinued a medication without their provider’s knowledge and the reason for this; any OTC medications or herbal products or dietary supplements (HDS) they may also be using; and how much sodium and liquid they consume during the course of a day.
Identify Additional Risk Factors: To identify additional risk factors that can worsen or precipitate HF, the pharmacist should ask patients about their tobacco use (including e-cigarettes), how often they check their blood pressure (BP), lipid profile, and blood glucose parameters, and whether they know their results.
Prevent Future Exacerbations: Prevention of future exacerbations of HF is key to improved outcomes. Patients should also be familiar with the warning signs of acute HF and what to do should they occur; if any new symptoms have recently developed while at rest; if the patient has experienced hypotensive or bradycardic episodes, confusion, is refractory to diuretic use; and, if the patient has a defibrillator, if it has ever fired. The patient should be advised to seek medical attention if experiencing new symptoms at rest; dizziness; change in mental status; chest pains; defibrillator firings; or other symptoms indicative of either hypotension, acute coronary syndrome, or arrhythmias.20
Answer Patient Questions: In addition to educating patients about the above, pharmacists should also be prepared to answer any questions that the patient may have, such as what HF is; what causes HF; whether an MI can precipitate HF; how comorbidities such as diabetes and HTN affect HF; the importance of medications to manage HF and what can occur if medications are discontinued inappropriately; what the patient should do if he or she experiences an adverse drug effect; when to seek medical attention; and whether there is a cure for HF.20
Personal Medication List
The second core element in MTM is the development of a PML. The PML informs the patient about the name of the medication; how to use the medication; the indication for the medication; the date the medication was started; and the date the medication was stopped, if applicable, and the reason why. This should all be explained in lay terms.20
Medication Action Plan
Once the PML is developed, the third core element is writing the MAP. The MAP reiterates what was discussed with the patient about HF and its management and identifies actions that the patient needs to take: for example, medication adherence, limiting sodium and fluid intake, and checking daily weight, BP, and heart rate. Patients record what they did and when they took action. The MAP should be limited to crucial initial actions that should be taken so as not to overwhelm the patient. With subsequent follow-ups, less urgent actions the patient needs to perform to enhance HF control can be reviewed.20
Intervention and/or Referral
In performing the fourth core element of MTM, the intervention and/or referral, pharmacists should use evidence-based medicine to make their recommendations.20
The 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines on the management of HF were recently updated to include newer therapies, such as the angiotensin receptor–neprilysin inhibitor valsartan/sacubitril and the sinoatrial node modulator ivabradine.36,37 Additionally, in 2016 the European Society of Cardiology (ESC) disseminated updated guidelines on the treatment of acute and chronic HF.16
During the course of recommending interventions, pharmacists should identify modifiable risk factors (e.g., smoking, HTN, dyslipidemia, DM, obesity, alcohol consumption, lack of physical activity, stress, anxiety or depression) that may be present and can worsen HF. Patient factors, including the presence of compelling indications, comorbidities, concomitant medications, cost, and adherence should be considered. Medications for HF should be introduced at low doses in the older adult but should be titrated to a target dose.20
Hospitalization or rehospitalization is common among HF patients and is one of the strongest prognostic factors for increased mortality. While the prognosis has significantly improved for patients with CHF over the years, for unstable patients who require hospitalization, the mortality rate within 30 to 60 days post-discharge is around 15%. The main reasons for HF readmission are congestion and fluid overload.22 Pharmacists can assist their patients by encouraging adherence to salt and fluid restrictions and by the proper use of diuretic therapy.
Dyslipidemia is defined as an elevation in total cholesterol, low-density lipoprotein cholesterol (LDL-C); or triglycerides; a low high-density lipoprotein cholesterol level (HDL-C): or a combination of these lipid abnormalities.38
The goals of therapy in the management of dyslipidemia are primary or secondary prevention of complications from atherosclerotic cardiovascular disease (ASCVD), cerebrovascular disease, and peripheral vascular disease (PVD).39
Patients often do not achieve target management for their dyslipidemia. The role of the pharmacist in managing patients with dyslipidemia has been studied both in the U.S. and abroad.40-49 The pharmacist can assist with improving the success of treatment and reducing adverse vascular outcomes.50-53
Before counseling the older adult with dyslipidemia, the pharmacist should be familiar with the types of lipid abnormalities (including familial hypercholesterolemia, hyperlipidemia, hypertriglyceridemia); primary and secondary prevention strategies for atherosclerotic events; risk factors for dyslipidemia such as gender and age (males aged >45 years, females aged >55 years); smoking history; family history; HTN and low HDL-C (<40 mg/dL); secondary causes of dyslipidemia; complications (e.g., CV, cerebrovascular, peripheral vascular); and other complications associated with lipid abnormalities (e.g., pancreatitis from hypertriglyceridemia, nonalcoholic steatohepatitis).38
When exploring secondary causes of dyslipidemia, it is important to note that medications can cause druginduced hyperlipidemia by altering LDL-C, triglyceride, or HDL-C levels.38,54-57
During the CMR, the pharmacist should inquire about the duration of dyslipidemia; family history of HD or dyslipidemia; patient’s knowledge about the risks associated with hyperlipidemia; history of CVD or cerebrovascular disease (e.g., MI, angina, CAD, PVD, stroke, transient ischemic attack [TIA]) and any surgeries associated with these conditions (e.g., CABG, PCI); co-occurrence of DM or HTN; and smoking history. The pharmacist should also inquire about goals of therapy based on a discussion with the patient’s prescriber; medications being used to manage the lipid disorder; how these medications are being taken; how long the patient has been on the current medication regimen; what medications have been used in the past and why they were discontinued; whether the patient is experiencing any adverse effects from these medications; how often doses are missed and how this is handled; use of OTC medications, HDS, and any nonpharmacologic interventions that have been tried, including dietary restrictions and exercise. In addition, the patient should be cautioned about avoiding statin-OTC drug interactions.
The pharmacist should also determine whether the patient knows the warning signs of an MI and a stroke, and if he or she knows what to do should either occur. Asking about falls, dizziness, blurred vision, memory changes, unilateral weakness, sudden abdominal pains, muscle pains, muscle weakness, or changes in urine color may also identify the presence of an undetected adverse drug event.38
PML, MAP, and Intervention
Once the CMR is completed, the pharmacist will develop a PML. This step is followed by the completion of a MAP. In the MAP, the pharmacist can provide information to help enhance the effectiveness of medications, such as counseling patients to take their statin prior to bedtime (especially simvastatin, since it has a short half-life); suggesting use of compliance aids; and recommending limiting saturated fats and cholesterol in their diet, eating more fruits, vegetables, and fiber, and exercising.38,58
During the intervention and referral phase, medications are selected based on weighing risk versus benefit in the older adult, as well as on treatment goals, concomitant disease states, and concurrent medications. Common and severe side effects or the presence of a contraindication should be relayed to the patient’s provider, as should any concern over the potential for serious drug interactions, including statin drug interactions. Pharmacists are encouraged to use drug-interaction checkers for the latest drug-interaction information. Recently, a clinician’s guide to statin-drug interactions was published, which is also useful.59
Documentation and Follow-up
During the documentation and follow-up phase, the pharmacist should assess for medication-related problems such as nonadherence; unnecessary medications (e.g., use of two statins concurrently); need for additional medication (e.g., persistently and markedly elevated triglyceride levels); ineffective medications (e.g., use of statin monotherapy in patients with severe or very severe hypertriglyceridemia); subtherapeutic or supratherapeutic doses (e.g., failure to titrate to maximally tolerated doses); excessive dosing in renal or hepatic dysfunction (e.g., renal dose adjustment needed for rosuvastatin); and adverse drug events (e.g., muscle pain, increased liver function tests).38 A fasting lipid panel should be performed within 4 to 12 weeks after initiation or dose adjustment of a statin and every 3 to 12 months thereafter.39 Other parameters to monitor include creatinine kinase levels (e.g., at baseline and if muscle complaints appear) and the occurrence of adverse drug events.38
Unlike previous guidelines on hyperlipidemia, which focused on achieving targeted total cholesterol, LDL-C, HDL-C, and triglyceride goals, the 2013 ACCF/AHA guidelines are based on the degree of ASCVD risk and achieving maximally tolerated statin doses. An ASCVD risk calculator is included in the guidelines. An online version of the ASCVD risk estimator can be found at http://tools.acc.org/ASCVD-Risk-Estimator.60
The 2016 ESC guidelines have still retained an LDL target structure and factor in total CV risk, based on the SCORE (Systematic Coronary Risk Estimation) System. SCORE is used to calculate risk in patients who do not have either known CVD or DM, very high levels of individual risk factors, or chronic kidney disease (CKD); patients who have these conditions are already at very high or high total CV risk.61
The 2013 ACCF/AHA dyslipidemia guidelines identify four groups that would benefit from the use of a statin: those with clinical ASCVD; those with primary elevations of LDL-C ≥190 mg/dL; those aged 40 to 75 years with DM who have LDL-C of 70 to 189 mg/dL; and those without clinical ASCVD or DM who are aged 40 to 75 years with LDL-C of 70 to 189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher. The guidelines caution that a discussion of the potential ASCVD risk-reduction benefits should be tempered by the risk of possible adverse effects and drug-drug interactions (DDIs), as well as patient preferences, prior to the initiation of statin therapy for primary prevention in older people. In those patients aged >75 years with clinical ASCVD, this discussion should also occur, but the Expert Panel considers it reasonable to continue statin therapy in these patients if there are no issues with tolerance.39
These guidelines have generated much controversy.39 Many clinicians did not want to abandon target LDL-C levels. In response to this debate, the National Lipid Association released guidelines in 2015 that are based on expert opinion and still use a target lipid level. 62-64
The 2016 ESC guidelines on the management of dyslipidemia in the older adult recommend that statins be used in patients with established CVD in the same way as in younger patients; that lipid-lowering agents should be started at a lower dose and titrated cautiously to target lipid levels because of comorbidities and altered pharmacokinetics in this population compared with younger persons; and that statin therapy should be considered in older adults who do not have CVD but who have risk factors (e.g. HTN, smoking, DM, and dyslipidemia).61
The American Heart Association has issued a scientific statement on the secondary prevention of atherosclerotic CVD in older adults. An emphasis is placed on lifestyle modifications.65
Additionally, older patients with DM are at increased risk of CVD.66 Pharmacists can help improve major CV risk factors in patients with DM.67
Primary or essential HTN is defined as persistently elevated arterial BP in the absence of identifiable causes.68 Uncontrolled HTN is a leading cause of MI, stroke, renal failure, and death.69
Pharmacists have been engaged in managing BP elevations of hypertensive patients for many years.70 Others, both in the U.S. and internationally, have also demonstrated benefit with respect to improved outcomes, increased adherence, and/or decreased cost.71-93 Pharmacists have achieved this by being involved in collaborative practice agreements or by being part of an interdisciplinary team.71
When performing MTM, pharmacists should be familiar with the classification of BP readings and the terms hypertensive crisis (i.e., hypertensive emergency versus hypertensive urgency); isolated systolic HTN; masked HTN; orthostatic hypotension (which is common in the elderly); pseudohypertension; white coat HTN; and secondary HTN (e.g., due to CKD, Cushing syndrome, coarctation of the aorta, obstructive sleep apnea, parathyroid disease, pheochromocytoma, primary aldosteronism, renovascular disease, thyroid disease).68,94 Medications can be a cause of secondary HTN. Pharmacists should be familiar with which medications can alter BP.68,95 Nicotine and narcotic withdrawal can also result in elevations of BP.68
Pharmacists should be aware of the complications associated with long-standing HTN, which include CV (e.g., angina, atherosclerosis, AF, CHD, left ventricular hypertrophy [LVH], HF, MI, sudden death); cerebrovascular (e.g., cognitive decline, intracerebral hemorrhage, ischemic stroke, TIA, vascular dementia); ophthalmologic (e.g., age-related macular degeneration, retinopathy, atherosclerosis); PVD (e.g., edema, peripheral arterial disease, arteriosclerosis); and renal disease (e.g., CKD, microalbuminuria/proteinuria).68
The Joint National Committee 8 (JNC8) advises that in those aged >60 years, treatment should be initiated when the systolic blood pressure (SBP) is >150 mmHg and the diastolic blood pressure (DBP) is >90 mmHg. Goal BP in this age group is an SBP of <150 mm Hg and a DBP of <90 mmHg. However, if an older adult has already achieved a BP that is lower than recommended and it is not associated with any adverse effects, treatment should not be adjusted.69
In 2015, the U.S. Preventive Services Task Force (USPSTF) disseminated guidelines on screening for HTN in adults. The USPSTF supports the JNC8 recommendations for those >60 years because moderate-to-high quality evidence has demonstrated efficacy in reducing the incidence of stroke, HF, and CHD. However, the guidelines do acknowledge that some experts are recommending lower treatment goals, i.e., <140/90.96
Pharmacists should be cognizant of the steps involved in measuring BP with either a manual or an automated sphygmomanometer, and be able to counsel patients on ambulatory or self-(home) monitoring. Pharmacists should be able to identify reasons for inaccurate BP readings as well as the occurrence of the J-curve phenomenon (i.e., as DBP decreases, coronary perfusion becomes compromised and can result in death) and reasons for treatment failure, which may include nonadherence.68
In performing the CMR, the pharmacist should inquire about the duration of HTN; family history; the patient’s knowledge about the risks of uncontrolled HTN; how and when the patient checks his or her BP and what these readings have been; how elevated BPs are handled; the patient’s goal BP as discussed with his or her provider; whether the patient has experienced any signs or symptoms of hypotension (i.e., blurry vision, confusion, dizziness, lightheadedness, falling, fainting, fatigue, nausea, weakness); the patient’s current and past medication regimens; reasons for discontinuing medications, if applicable; whether doses are missed and how that is handled; whether the patient has discontinued medications without his or her provider’s knowledge; any OTC or HDS products the patient may be taking; any nonpharmacologic interventions that have been tried to lower BP (e.g., salt restriction, exercise) and their success; whether the patient knows the warning signs of an MI or stroke and what to do if either should occur; and if the patient has ever been hospitalized for BP-related problems.68
The pharmacist should also be prepared to answer patients’ questions, which may include explaining what BP is; causes of HTN; what abnormal BP readings are; what resultant health problems are associated with HTN; how a patient would know if his or her BP were high; importance of adherence; if and when the patient can stop taking antihypertensives; what would happen if treatment were discontinued; when the provider should be notified; and how adverse effects should be handled.68
PML and MAP
Once this interview is conducted, the pharmacist should develop the patient’s PML and MAP. The MAP includes the actions that the patient needs to take at home in order to be adherent to his or her antihypertensive regimen. The MAP may also address how to handle any problems that may have been discovered during the CMR, such as orthostasis. The patient’s responsibility, including checking and recording his or her BP readings, should be clearly spelled out.68
Intervention and Referral
During the intervention and referral phase, lifestyle modifications should be encouraged, including dietary interventions, weight loss, exercise, and restricting alcohol intake.68,97 Many patients are not aware of the sodium in processed foods and are unfamiliar with how to read food labels.98
Pharmacists should work with providers to try to achieve target antihypertensive doses.69 The presence of compelling indications may help guide drug selection.94 As MTM continues to evolve, telehealth is offering pharmacists opportunities to be involved in the management of HTN.99,100
Altered Dosing in Renal and Hepatic Dysfunction
The glomerular filtration rate decreases by approximately 8 mL/min/decade after age 40.101 Dosing alterations for selected renally eliminated cardiac medications based on the Beer’s Criteria, as well as a consensus guideline developed for oral medications that are renally cleared in older adults, have recently been published.101,102 A review of drug management in the elderly with CKD was also recently published.103 MTM pharmacists are encouraged to check prescribing information or renal dosing databases such as GlobalRPh (www.globalrph.com/index_renal.htm) or the University of Louisville Kidney Disease Program (https://kdpnet.kdp.louisville.edu/drugbook/adult) prior to dispensing or writing prescriptions. KidneyCalc is an iPhone app designed to help clinicians make decisions about dosage adjustments in patients with renal dysfunction (https://itunes.apple.com/us/app/kidneycalc-dosage-adjustment/id3453 99703?mt=8).104-106
Altered response to drugs in liver disease may be due to impairment in function or lack of hepatocytes, resulting in decreased intrinsic metabolizing capacity; reductions in biliary elimination or hepatic blood flow; alterations in volume of distribution; decreased protein binding; reduced first-pass metabolism; and decreased bioavailability due to malabsorption of fats as occurs in cholestatic liver injury.107 There are no evidence-based guidelines for the use of drugs in patients with liver cirrhosis. However, in general, liver disease in the absence of cirrhosis only results in mild alterations in drug pharmacokinetics, and most drugs can be used safely. However, drug-induced liver injury is poorly tolerated in this population.108
CV medications that have been found to have significantly increased oral bioavailability in patients with cirrhosis include carvedilol, labetalol, metoprolol, nifedipine, nisoldipine, propranolol, and verapamil. Among the CV agents, the effects of beta-blockers and diuretics are impacted the most in cirrhosis.109 In advanced cirrhosis, there is a decrease in beta-receptor density, which may help explain the decreased therapeutic effect observed with beta-adrenergic antagonists (e.g., propranolol, metoprolol).109 However, all beta-blockers undergo first-pass metabolism, which is reduced in cirrhosis, allowing for higher active drug concentrations.110
Altered Pharmacodynamics of CV Medications
Age-related pharmacodynamic changes can result in altered sensitivity or response to a drug for a given drug concentration in older patients compared with a younger population. Mechanisms that may contribute to this altered response include variations in receptor number and receptor affinity and changes in secondary messengers and cellular responses to drugs in the older adult.111 TABLE 2 includes information on age-related pharmacodynamic changes involving CV medications.
Significant Drug Interactions Involving CV Medications
CV medications account for 25% of all preventable adverse drug reactions.113 It has recently been recognized that DDIs that were solely attributed to CYP3A4 interactions may also involve permeability glycoprotein (P-glycoprotein), as there may be overlap between the two systems or the DDIs may have been misclassified. P-glycoprotein, which can be found in the small intestine, brain, liver, and renal proximal tubule, regulates the transport of drugs in and out of cells. Many CV drugs are substrates at the P-glycoprotein receptor (e.g., bepridil, digoxin, quinidine, verapamil; all the direct oral anticoagulants; warfarin, aliskiren, diltiazem, labetalol, losartan, nadolol, propranolol, timolol, clopidogrel, ticagrelor, atorvastatin, lovastatin), and several are strong inhibitors of P-glycoprotein (amiodarone, dronedarone, quinidine, verapamil, carvedilol, nicardipine, atorvastatin). The concomitant use of strong inhibitors should be avoided in patients taking CV drugs that are also substrates of P-glycoprotein. An excellent review of P-glycoprotein interactions involving cardiac drugs has been published.114
In 2016, the American Heart Association published a scientific statement on recommendations for the management of clinically significant DDIs with statins and selected agents used in patients with cardiovascular disease.115
Another area of concern is DDIs involving medications that can prolong the QTc interval and facilitate the development of torsades de pointes. For the latest information on this topic, pharmacists are encouraged to visit Crediblemeds.org (www.crediblemeds.org). A comprehensive overview of clinical trials involving QT-prolonging drugs was recently published.116,117 A thorough review of all CV medication drug interactions is beyond the scope of this article. The reader is advised to consult a reputable druginteractions checker program such as Medscape (http://reference.medscape.com/drug-interactionchecker), Drugs. com (www.drugs.com/drug_interactions.html), RxList (www.rxlist.com/drug-interaction-checker.htm), and WebMed (www.webmd.com/interaction-checker/).118-121 Additionally, a detailed list of CYP enzyme substrates, inducers, and inhibitors can be found at http://medicine. iupui.edu/clinpharm/ddis/main-table.122
Other Resources for Pharmacists
Other resources for the MTM pharmacist include the use of clinical practice guidelines, the Beer’s Criteria on potentially inappropriate medications, the START/STOPP criteria, and Healthy People 2020.102,123-125
The Medicare Modernization Act, which resulted in the formation of Medicare Part D and the development of mandatory MTM programs for selected Medicare beneficiaries, has opened the door for pharmacists to utilize their clinical skills to enhance patient care. Evidence-based medicine is guiding this care. As the focus in healthcare has shifted away from a fee-for-service model to a qualitybased reimbursement structure, pharmacists can play a vital role in helping to contain costs by actively participating in drug selection; preventing and monitoring for adverse drug reactions and drug interactions; and promoting adherence. The cardiac patient has the most to gain from this expanded pharmacist’s role, as heart disease is the number-one cause of mortality in this country and is expected to continue to increase with the graying of society.
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