Oral Oncolytics and Cardiovascular Risk Management and Monitoring.

ABSTRACT: Oral oncolytic treatment options have expanded over the last decade and have brought to light the need to monitor and manage cardiovascular (CV) disease in patients being treated with these therapies. There is a need to assess CV risk before patients receive oral oncolytic therapy with known potential to cause negative CV sequelae such as left ventricular dysfunction, hypercholesterolemia, hypertension, and arrhythmias. The review highlights the need to evaluate traditional CV risk factors and their association with the development and progression of cancer. In addition, this review suggests approaches to monitor for CV adverse events and manage CV disease during and after treatment with oral oncolytic therapy. Key guideline recommendations are reviewed and highlight specific approaches to minimize CV harm for patients exposed to oral oncolytic therapy. Careful monitoring and patient-centered decision making are key in choosing appropriate therapies. A multidisciplinary approach between oncologists, cardio-oncologists, pharmacists, and other members of the health care team is essential in navigating cardiac toxicities.

Can Direct Oral Anticoagulants Be Used for Stroke Prevention Among Patients with Valvular Atrial Fibrillation?

PURPOSE OF REVIEW: To review the clinical evidence underlying the efficacy and safety of the use of direct oral anticoagulants (DOACs) for the treatment of patients with valvular atrial fibrillation (AF). RECENT FINDINGS: The recent focused update to the 2014 AHA/ACC/HRS Atrial Fibrillation Guidelines defines valvular AF as AF in the setting of moderate-to-severe mitral stenosis (MS) and/or in the presence of a mechanical heart valve. Landmark clinical trials of DOACs in patients with AF systematically excluded these patient populations. However, there are trial data in both animals and humans regarding the use of DOACs in patients with MS and in those with mechanical heart valves. Based on sub-analyses and meta-analyses of clinical trial data in patients with AF, the use of DOACs in valvular AF is not recommended. Patients with moderate-to-severe MS or a mechanical heart valve and AF should be anticoagulated with dose-adjusted warfarin. DOACs are reasonable alternatives to warfarin in patients with AF and other types of valvular disease, including mild MS and bioprosthetic valves.

Discontinuation of Statins: What Are the Risks?

The key benefits of statin therapy have been well established in both primary and secondary prevention cardiovascular patients. Many studies have shown a significant statin discontinuation rate within the first year of initiation whether for primary or secondary prevention. National guidelines for the management of dyslipidemia highlight the lack of benefit seen with statin therapy in patients with chronic kidney disease receiving dialysis, heart failure with reduced ejection fraction, and patients greater than 75 years of age without atherosclerotic cardiovascular disease. Available data outside of these patient populations do not support discontinuation of statin therapy. Recent studies support an association with statin discontinuation and increased risk of myocardial infarction and cardiovascular death. Based on the available data, discontinuation of statin therapy should be carefully considered.

Evaluation of Statin Prescribing for Secondary Prevention in Primary Care Following New Guideline Recommendations.

BACKGROUND: The American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Treatment of Blood Cholesterol recommends high-intensity statin therapy for most patients with established atherosclerotic cardiovascular disease (ASCVD) versus previously recommended low-density lipoprotein cholesterol targets. The impact of the ACC/AHA guidelines on prescribing patterns in primary care is uncertain. OBJECTIVE: To describe the prescribing habits of statin therapy in primary care patients with ASCVD before and after the ACC/AHA guidelines were published. METHODS: This retrospective observational study evaluated patients with ASCVD who were seen in at least 1 of 8 primary care clinics in the University of Colorado Health system. It received expedited approval by the Colorado Multiple Institutional Review Board. The primary outcome measure was the proportion of patients with established ASCVD prescribed high-intensity statin therapy within 1 year before or after guideline release. RESULTS: In total, 220 patients were included in the analysis with 110 in the before and 110 in the after cohort. For the primary outcome analysis, the rate of high-intensity statin utilization in the before versus after groups was significantly greater (25.5% vs 41.8%, P = 0.01). For ages 76 to 89 years, 36 of 37 and 29 of 30 patients in the before and after groups were receiving moderate- to high-intensity statin therapy (97.3% vs 96.7%, P = 0.99). Subgroup analysis in the after cohort for all ages showed no change in statin therapy for 77% of patients. CONCLUSIONS: High-intensity statin prescribing increased in patients with ASCVD after release of the ACC/AHA cholesterol guidelines. Our data indicate that national evidence-based guidelines may influence clinical practice in very high risk patients.

Evaluation of aspirin use in patients with diabetes receiving care in community health.

BACKGROUND: The American Diabetes Association (ADA) recommends low-dose aspirin therapy as a primary prevention strategy in patients with type 1 or type 2 diabetes mellitus (DM) at increased cardiovascular risk. However, not all patients who are indicated are taking aspirin therapy, and it is not routinely documented in the electronic health record (EHR). OBJECTIVE: To determine frequencies of appropriate aspirin use and documentation in the EHR in adult patients with DM. METHODS: Adult patients with DM were randomized and contacted for participation in a telephonic survey between January and October 2013. Patients who consented were administered a standardized oral telephone survey regarding aspirin use. Patient demographics, current medications, allergies, past medical history, and pertinent laboratory values were collected. Patients were then stratified by the ADA-defined indication for aspirin. The primary outcomes were rates of appropriate aspirin use and documentation of aspirin therapy in the EHR. RESULTS: Investigators contacted 276 patients for inclusion. Of the 81 patients surveyed, 74% were indicated for aspirin therapy. Nearly all (92.3%) patients reporting aspirin use were indicated for aspirin therapy compared with only 57.1% of patients who did not report aspirin but were indicated (P = 0.0003). Alternatively, 96.7% of patients with aspirin use documented in their EHR were indicated for aspirin therapy compared with only 60.8% of patients who did not have aspirin use documented in the EHR but had an indication (P = 0.0002). Approximately 20% of the patients indicated for and reporting aspirin use did not have aspirin documented in their EHR. CONCLUSIONS: Aspirin use in patients with DM who are indicated for therapy is significantly underutilized and underdocumented.

Probable Interaction Between Warfarin and Divalproex Sodium.

Objective: A potential interaction between warfarin and divalproex sodium is described. Case Summary: A 65-year-old Arabic-speaking Egyptian woman chronically anticoagulated with warfarin for atrial fibrillation and a history of stroke presented to the anticoagulation clinic with an elevated international normalized ratio (INR) of 3.2. This was an increase of 1.4 over her previous INR of 1.8 only 9 days prior. Discussion with the patient's daughter revealed the addition of divalproex sodium (a derivative of valproic acid) 250 mg twice daily to the patient's medication regimen 6 days prior. Other contributing factors that could cause an elevated INR were ruled out. The patient's total weekly dose (TWD) of warfarin was decreased from 22.5 mg to 20 mg, and the patient was instructed to return for a repeat INR in 1 week. On the day the patient was due to return for a repeat INR, she was admitted to the hospital and her INR was 2.2 on admission. Based on medication reconciliation information, the patient had decreased her warfarin TWD as instructed and had self-discontinued the divalproex sodium due to intolerable fatigue. During this time, the patient received no additional divalproex sodium. She was instructed to resume her previous TWD of warfarin of 22.5 mg on discharge and subsequently had a therapeutic INR (2.6) 11 days later. Discussion: Warfarin and divalproex sodium are commonly prescribed agents with few case reports to describe their interaction. Primary literature supports a multifactorial mechanism, including CYP450 metabolism inhibition and protein-binding displacement, both of which can result in an elevated INR. Use of the Drug Interaction Probability Scale indicated a probable interaction between warfarin and divalproex sodium. Conclusions: Patients receiving concurrent warfarin and divalproex sodium therapy should be monitored closely for changes in INR values as the combination may increase the INR and put the patient at increased risk for bleeding.

Tirzepatide for type 2 diabetes.

One in ten adults worldwide is living with diabetes, with 95% having type 2 diabetes (T2D). Sustained glycaemic control in people with T2D is difficult to achieve despite recent advances in T2D management with the advent of glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i). Tirzepatide represents a first-in-class agent as a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP1RA to be approved in the USA and Europe for the treatment of T2D. This narrative review intends to list and discuss the glycaemic efficacy, key safety and weight loss outcomes related to the treatment of T2D with tirzepatide. Tirzepatide has been evaluated in five published clinical trials (n=6278) within the SURPASS clinical trial programme, with a focus on glycaemic control and weight loss. These trials have demonstrated significant improvements in glycosylated haemoglobin (-1.24% to -2.11% versus placebo and -0.6% to -1.14% versus active comparator) and weight (up to 15.5 kg versus placebo or active comparator) in patients with T2D. Notably, tirzepatide exhibited superior glycaemic control and weight loss when compared directly with a GLP1RA. Adverse events with the use of tirzepatide are similar to other approved GLP1RA and are predominantly gastrointestinal (nausea, vomiting). The tirzepatide cardiovascular outcomes trial (SURPASS-CVOT) is in progress and is expected to be completed in the fall of 2024. Tirzepatide represents an attractive new option and first-in-class agent for the treatment of T2D in people unable to achieve their glycaemic or weight management goals.

Using Emotional Intelligence as a Framework for Students' Professional Identity Formation.

Emotional intelligence and professional identity formation (PIF) intersect at various levels. Professional identity formation requires acute observation of others in the profession and the ability to decipher intentionality in behaviors. The developing pharmacist must make a deliberate effort to emulate positive norms and values that coincide with those associated with the profession while deliberately ignoring those that are incongruent. To learn from others in the profession, social skills are required, so one can ask questions, determine the best course of action, set goals, grow, and maintain relationships, and ask for help. The ability to manage one's emotions regardless of external circumstances can be valuable for any profession. Self-regulation and self-assessment of one's emotions and motivations can be useful for reevaluating our perspectives and priorities as pharmacists. Emotional intelligence is a critical component of building, demonstrating, and improving PIF. This commentary will provide strategies to facilitate and solidify the connection between the two.

Impact of telehealth on the current and future practice of lipidology: a scoping review.

Telehealth services have been implemented to deliver care for patients living with many chronic conditions and have expanded greatly during the COVID-19 pandemic. Little is known about the current or future impacts of telehealth on lipid management practices. The PubMed database was searched from inception to June 25, 2021, with the keywords "lipids or cholesterol" and "telehealth," which yielded 376 published articles. Telehealth was defined as a synchronous visit between a patient and clinician that replaced an in-office appointment. Studies that solely used remote monitoring, mobile health technologies, or callbacks of results, were excluded. Articles must have measured lipid values. Review articles and protocol papers were not included. After evaluation, 128 abstracts were included for full text evaluation, with 55 full-text articles eventually included. Of the articles, 29 were randomized clinical trials, 15 were pre-post evaluations, and 11 were other study designs. Telehealth had positive to neutral impacts on lipid management. Reported facilitators include easier implementation of multidisciplinary approaches to care, and utilization of patient-centered programs. Reported barriers to telehealth services include technological barriers, such as various skill levels with technology; systems barriers, such as cost and reimbursement; patient-related barriers, including patient non-adherence; and clinician-related barriers, such as difficulty standardizing care. Clinicians reported improved satisfaction among patients but had mixed feelings regarding their ability to deliver quality care. Telemedicine use to provide care for individuals with lipid conditions has expanded during the COVID-19 pandemic, but more research is needed to determine its potential as a sustainable tool for lipid management.

Description of patient questions received by clinical pharmacists in the Nudge Study.

PURPOSE: The Nudge Study is a patient level-randomized trial testing different text message medication refill reminders sent to patients assigned to 4 arms: (1) usual care, (2) generic text, (3) optimized text, and (4) optimized text plus chatbot. This report describes the frequency and types of patient questions sent to clinical pharmacists (CPs) following text reminders. METHODS: Patients were enrolled from Denver Health and Hospital Authority (DHHA) and Veterans Affairs Eastern Colorado Health Care System (VA ECHCS) from October 1, 2019, through May 30, 2021. Included patients responded to at least 1 text or interactive voice response (IVR) message. Patients were dichotomized as those who posed at least 1 question to a CP and those who posed no questions. RESULTS: Of the 6,325 patients enrolled in an intervention arm, 3,323 (52.5%) responded to at least 1 text or IVR message, and among those responding, 305 (9.2%) responded with a pharmacist question. Patient factors associated with submitting a CP question included age (45-74 years), enrollment from DHHA, and receipt of the optimized text or optimized text plus chatbot message versus the generic text. Questions to CP were in the following categories: medication related (48.2%), refill logistics (38.4%), cost (9.2%), and other (17.7%). CONCLUSION: In a text messaging intervention focused on medication refills, there were few questions directed to the CP. Patients assigned to receive optimized texts were more likely to have questions. We hypothesize that this may suggest greater patient engagement regarding their condition, resulting in more questions.

Dapagliflozin for the treatment of type 2 diabetes.

OBJECTIVE: To review the literature and describe the pharmacologic, pharmacokinetic, and pharmacodynamic properties; clinical safety; and efficacy of dapagliflozin, a new drug currently under review by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes. DATA SOURCES: A MEDLINE (1995-November 2011) and ClinicalTrials.gov search was conducted using the terms dapagliflozin, sodium-glucose cotransporter 2 inhibitor, and SGLT2 inhibitor. Reference citations from publications identified were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language studies, including abstracts, evaluating dapagliflozin use in humans were included in this review. DATA SYNTHESIS: Dapagliflozin is the first-in-class oral sodium-glucose cotransporter 2 (SGLT2) inhibitor that represents a new potential therapeutic option for the treatment of type 2 diabetes mellitus. Its mechanism of action is insulin- and insulin-sensitivity independent. Preliminary data suggest that dapagliflozin decreases hemoglobin A(1c), fasting plasma glucose, and postprandial plasma glucose, while also promoting weight loss. In Phase 1, 2, and 3 clinical trials, dapagliflozin has exhibited a safety and tolerability profile similar to that of placebo. CONCLUSIONS: Dapagliflozin is a novel oral antihyperglycemic agent that has demonstrated promise as monotherapy and as synergistic combination therapy with currently available agents in Phase 3 clinical trials. On January 19, 2012, the FDA issued a complete response letter to AstraZeneca and Bristol-Myers Squibb regarding the new drug application for dapagliflozin. The FDA is requesting additional clinical data-from ongoing studies and potentially new clinical trials-to better describe the risk-benefit profile of the drug. Both manufacturers remain committed to the development of dapagliflozin, and there are currently 8 Phase 3 trials ongoing. Dapagliflozin has the potential to be the next new oral agent in the diabetes drug armamentarium.

Diabetes: how to manage cardiovascular risk in secondary prevention patients.

Atherosclerotic cardiovascular disease (ASCVD) commonly affects people with type 2 diabetes (T2D). Historically, traditional cardiovascular (CV) risk-lowering therapies in patients with T2D and ASCVD have included antiplatelet agents, blood pressure-lowering therapies, lipid-lowering therapies and healthy lifestyle modifications. In the past decade, multiple antihyperglycaemic agents have emerged as CV risk-lowering therapies in this population as well. This article provides a narrative review on the current non-glycaemic and glycaemic treatment options for CV risk reduction in patients with T2D and ASCVD. The FDA requirement that all new antihyperglycaemic agents undergo cardiovascular outcomes trials has demonstrated increasing evidence to support the role of glucagon-like peptide 1 (GLP1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors as first-line agents for both glycaemic control and CV risk reduction in this population.

Evidence and Strategies for Including Emotional Intelligence in Pharmacy Education.

Objective. This integrative review summarizes the literature addressing emotional intelligence among health care professionals and students to better define and incorporate it into the pharmacy curricula.Findings. Emotional intelligence is an essential attribute for relationship building, stress management, and self-regulation. Pharmacy students must develop and improve their emotional intelligence to support their development of successful relationships with patients, pharmacy colleagues, and other health care providers. In addition, awareness of one's own biases and emotions can help with behavioral regulation, which can facilitate enhanced communications with others. Increasing evidence suggests that emotional intelligence can influence academic success, the ability to provide compassionate and competent patient care, the ability to lead and influence others, and the ability to manage stress, all of which are important in pharmacy education. Educators can help learners develop emotional intelligence by designing activities that directly identify and target areas of weakness while leveraging areas of strength.Summary. This article discusses key background studies on emotional intelligence in the health professions literature and identifies specific methods and strategies to develop learners' emotional intelligence within the curriculum.

Clinical Pharmacist Outreach to Increase Statin Use for Patients with Cardiovascular Disease in a Safety-Net Healthcare System.

BACKGROUND: Statin Therapy for Patients with Cardiovascular Disease (SPC) is a Centers for Medicare & Medicaid Services Star measure added to Medicare Part C (Medicare Advantage) plans in 2019 to incentivize statin use for secondary prevention of cardiovascular disease (CVD). The measure assesses statin dispensing and adherence in patients with atherosclerotic CVD (ASCVD). Clinical pharmacists are well-positioned to affect positively a health system's performance on the SPC measure. OBJECTIVE: To assess the effect of telephone outreach by clinical pharmacists on moderate- or high-intensity statin prescribing in patients with ASCVD. METHODS: Patients in managed care health plans who meet the SPC measure criteria and are not currently receiving a moderate- to high-intensity statin therapy were contacted by a clinical pharmacist through telephone outreach. If appropriate, they were prescribed a statin by a clinical pharmacist. The primary outcome measure was the proportion of patients who meet the SPC measure classification and had 1 confirmed prescription fill for a moderate- or high-intensity statin after intervention by a clinical pharmacist. RESULTS: A total of 84 patients were identified for review and outreach, of whom 35 (41.7%) met the SPC measure criteria. Of these 35 patients, 16 (45.7%) were female and the mean age was 66 years. A total of 22 (62.9%) patients agreed to a statin prescription, and 16 (72.7%) of these patients picked up the prescription within 10 days of prescribing. An additional 4 patients, for a total of 20 (57.1%) of the 35 eligible patients, were eventually dispensed a statin. Healthcare Effectiveness Data and Information Set (HEDIS) vendor data available after the intervention showed a larger SPC measure population than was captured with the health plan's internal report. HEDIS data showed an increase in statin prescribing for patients meeting the SPC measure classification from 24.7% to 56.6% during the study period (P <.001). The mean time spent per patient for chart review and/or outreach by the clinical pharmacist was 27.7 (standard deviation, 9) minutes. CONCLUSION: These results indicate that clinical pharmacists who conduct a telephonic population health intervention can achieve a high rate of success in initiating a moderate- to high-intensity statin therapy in patients with ASCVD.

Antihypertensive prescribing patterns and hypertension control in females of childbearing age.

PURPOSE: The use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to treat hypertension (HTN) during pregnancy presents well-established risks to a developing fetus. A cross-sectional study was conducted to evaluate the current state of antihypertensive prescribing and contraceptive use in females of childbearing age within a large safety-net health system. METHODS: The retrospective cross-sectional study focused on females aged 18-49 years with a documented diagnosis of HTN. The proportion of patients prescribed an ACE inhibitor or ARB and using a documented form of contraception was calculated. Documented forms of contraception included oral contraceptives, intrauterine devices, injections, implants, and surgical intervention. RESULTS: A total of 4,187 patients were identified from the HTN registry; after application of exclusion criteria 3,045 patients were included in the study population. The mean age was 39 years (range, 18-49 years). The most frequently prescribed classes of antihypertensive medications were ACE inhibitors and ARBs (one or the other was used by 1,146 patients [37.6%]), followed by thiazide diuretics (n = 710, 23.3%) and calcium channel blockers (n = 599, 19.7%). Of the 1,146 patients prescribed an ACE inhibitor or ARB, 553 (48%) were using a documented form of contraception. CONCLUSION: Rates of ACE inhibitor or ARB prescribing to females of childbearing age were high despite the teratogenic risks, and fewer than half of patients had documented protection from pregnancy. Provider and patient education and potential creation of best practice alerts in the electronic medical record regarding the risks of using ACE inhibitors and ARBs in females of childbearing age are warranted.

Retrospective cohort study of statin prescribing for primary prevention among people living with HIV.

OBJECTIVE: To compare statin prescribing rates between intermediate-risk people living with human immunodeficiency virus (HIV; PLWH) and intermediate-risk patients without a diagnosis of HIV for primary prevention of atherosclerotic cardiovascular disease (ASCVD). METHODS: Retrospective cohort study . Electronic health record data were used to identify a cohort of PLWH aged 40-75 years with a calculated 10-year ASCVD risk between 7.5%-19.9% as determined by the Pooled Cohort Equation (PCE). A matched cohort of primary prevention non-HIV patients was identified. The primary outcome was the proportion of PLWH who were prescribed statin therapy compared to patients who were not living with HIV and were prescribed statin therapy. RESULTS: 81 patients meeting study criteria in the PLWH cohort were matched to 81 non-HIV patients. The proportion of patients prescribed statins was 33.0% and 30.9% in the PLWH and non-HIV cohorts, respectively (p = 0.74).Conclusion and relevance: This study evaluated statin prescribing in PLWH for primary prevention of ASCVD as described in the 2018 AHA/ACC/Multisociety guideline. Rates of statin prescribing were similar, yet overall low, among intermediate-risk primary prevention PLWH compared to those not diagnosed with HIV.

Report of the 2020-2021 Strategic Engagement Standing Committee.

EXECUTIVE SUMMARY For the American Association of Colleges of Pharmacy (AACP), strategic engagement is critical to the success of colleges and schools of pharmacy in expanding pharmacy and public health practice, meeting programmatic needs, and fulfilling institutional missions. The 2020-2021 Strategic Engagement Standing Committee was charged with identifying effective strategies to leverage the temporary expansion of pharmacist practice capabilities granted during the COVID-19 pandemic for sustained practice. The group was also tasked with looking at ways to partner with the Association of American Medical Colleges (AAMC), our medicine counterparts to develop a plan for collaborating with them to advance interprofessional practice. In this unique year, all standing committees were charged with reading all the reports last year to put President Lin's charges into perspective with the hopes of carrying over the overall theme and work of the previous years committee. Overall, throughout the COVID-19 pandemic, there have been several expansions on the scope of practice for pharmacists and vary by state. We hope to draw out some of those expansions to see how we can build upon efforts to make those permanent.

The NUDGE trial pragmatic trial to enhance cardiovascular medication adherence: study protocol for a randomized controlled trial.

BACKGROUND: Nearly half of patients do not take their cardiovascular medications as prescribed, resulting in increased morbidity, mortality, and healthcare costs. Mobile and digital technologies for health promotion and disease self-management offer an opportunity to adapt behavioral "nudges" using ubiquitous mobile phone technology to facilitate medication adherence. The Nudge pragmatic clinical trial uses population-level pharmacy data to deliver nudges via mobile phone text messaging and an artificial intelligent interactive chat bot with the goal of improving medication adherence and patient outcomes in three integrated healthcare delivery systems. METHODS: The Theory of mHealth, the Expanded RE-AIM/PRISM, and the PRECIS-2 frameworks were used for program planning, implementation, and evaluation, along with a focus on dissemination and cost considerations. During the planning phase, the Nudge study team developed and piloted a technology-based nudge message and chat bot of optimized interactive content libraries for a range of diverse patients. Inclusion criteria are very broad and include patients in one of three diverse health systems who take medications to treat hypertension, atrial fibrillation, coronary artery disease, diabetes, or hyperlipidemia. A target of approximately 10,000 participants will be randomized to one of 4 study arms: usual care (no intervention), generic nudge (text reminder), optimized nudge, and optimized nudge plus interactive AI chat bot. The PRECIS-2 tool indicated that the study protocol is very pragmatic, although there is variability across PRECIS-2 dimensions. DISCUSSION: The primary effectiveness outcome is medication adherence defined by the proportion of days covered (PDC) using pharmacy refill data. Implementation outcomes are assessed using the RE-AIM framework, with a particular focus on reach, consistency of implementation, adaptations, cost, and maintenance/sustainability. The project has limitations including limited power to detect some subgroup effects, medication complications (bleeding), and longer-term outcomes (myocardial infarction). Strengths of the study include the diverse healthcare systems, a feasible and generalizable intervention, transparent reporting using established pragmatic research and implementation science frameworks, strong stakeholder engagement, and planning for dissemination and sustainment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03973931 . Registered on 4 June 2019. The study was funded by the NIH; grant number is 4UH3HL144163-02 issued 4/5/19.

Spironolactone management of resistant hypertension.

OBJECTIVE: To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone in the treatment of resistant hypertension. DATA SOURCES: A literature search was conducted using MEDLINE (1966-July 2010), International Pharmaceutical Abstracts (1970-July 2010), and Cochrane database (2009) for the key words spironolactone or resistant hypertension. References cited in the articles were reviewed for additional information. STUDY SELECTION AND DATA EXTRACTION: English-language literature reporting pharmacology data from animal studies and clinical trials evaluating the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone were included. DATA SYNTHESIS: Spironolactone is a potassium-sparing diuretic with anti-aldosterone effects that are beneficial in the management of hypertension. Spironolactone has shown improvement in 5 prospective studies and 1 retrospective study evaluating its blood pressuring-lowering abilities in patients with resistant hypertension. Specifically, the average blood pressure lowering noted in these trials with the addition of spironolactone in patients with resistant hypertension was 22/10 mm Hg. Trials evaluating spironolactone's role in resistant hypertension treatment have identified hyperkalemia, gynecomastia, and renal insufficiency as the major adverse effects that warrant monitoring. CONCLUSIONS: Spironolactone is an appropriate antihypertensive medication to add to treatment of patients with resistant hypertension (≥3 antihypertensive medications at optimal doses) not at their blood pressure goal. In patients considered to have resistant hypertension, secondary causes should be ruled out.