Management of Acute Coronary Syndrome in the Older Adult Population: A Scientific Statement From the American Heart Association.

Diagnostic and therapeutic advances during the past decades have substantially improved health outcomes for patients with acute coronary syndrome. Both age-related physiological changes and accumulated cardiovascular risk factors increase the susceptibility to acute coronary syndrome over a lifetime. Compared with younger patients, outcomes for acute coronary syndrome in the large and growing demographic of older adults are relatively worse. Increased atherosclerotic plaque burden and complexity of anatomic disease, compounded by age-related cardiovascular and noncardiovascular comorbid conditions, contribute to the worse prognosis observed in older individuals. Geriatric syndromes, including frailty, multimorbidity, impaired cognitive and physical function, polypharmacy, and other complexities of care, can undermine the therapeutic efficacy of guidelines-based treatments and the resiliency of older adults to survive and recover, as well. In this American Heart Association scientific statement, we (1) review age-related physiological changes that predispose to acute coronary syndrome and management complexity; (2) describe the influence of commonly encountered geriatric syndromes on cardiovascular disease outcomes; and (3) recommend age-appropriate and guideline-concordant revascularization and acute coronary syndrome management strategies, including transitions of care, the use of cardiac rehabilitation, palliative care services, and holistic approaches. The primacy of individualized risk assessment and patient-centered care decision-making is highlighted throughout.

Pharmacotherapy in the heart transplant recipient: A primer for nurse clinicians and pharmacists.

Heart transplantation (HT) is the definitive treatment for eligible patients with end-stage heart disease. A major complication of HT is allograft rejection which can lead to graft dysfunction and death. The guiding principle of chronic immunosuppression therapy is to prevent rejection of the transplanted organ while avoiding oversuppression of the immune system, which can cause opportunistic infections and malignancy. The purpose of this review is to describe immunosuppressive management of the HT recipient-including agent-specific pharmacology and pharmacokinetics, outcomes data, adverse effects, clinical considerations, and recent guideline updates. We will also provide recommendations for medical prophylaxis of immunosuppressed patients based on the most recent clinical guidelines. Additionally, we highlight the importance of medical therapy adherence and the effect of social determinants of health on the long-term management of HT. HT recipients are a complex and high-risk population. The objective of this review is to describe basic pharmacotherapy in HT and implications for nurses and pharmacists.

Safety and efficacy of IV theophylline for regadenoson-associated side effect reversal.

BACKGROUND: Aminophylline injection has been on an intermittent nation-wide shortage due to manufacturing delays leaving a need for an alternative reversal agent for regadenoson-associated side effects. Intravenous theophylline should be a logical acceptable pharmacological alternative; however, data regarding its safety and efficacy as a reversal agent are lacking. METHODS: Utilizing electronic medical records at the University of Colorado hospital, we identified patients ≥ 18 years of age who had a pharmacologic stress test using regadenoson during periods of aminophylline shortage (3/1/2013 to 5/31/2013 and 4/1/2018 to 8/30/2018) in which theophylline was used as an alternative antidote for side effect reversal. Intravenous theophylline was prepared by the inpatient pharmacy to a concentration of 0.8 mg/mL in a total volume of 100 mL D5W. Specific side effects and side effect resolution were evaluated. RESULTS: Of the 122 patients evaluated, theophylline was administered in doses ranging from 40 to 75 mg with the majority receiving 40 mg. Complete resolution of regadenoson side effects occurred in 98 patients with 12 experiencing partial resolution and 1 without resolution. No adverse effects or events were reported. CONCLUSION: Due to limited availability of aminophylline, theophylline may be a safe and effective alternative to reverse regadenoson-associated side effects.

Evaluation of an opioid pain teleconsultation service to address the opioid overdose epidemic in Colorado: A Health First Colorado demonstration project.

BACKGROUND: Since the mid-1990s, more than 500,000 deaths have been attributed to the opioid overdose epidemic, which has created a serious national crisis affecting public health and social and economic welfare. To mitigate these opioid-related overdoses and deaths, interventions targeted at both the patient and community level are needed. OBJECTIVE: This demonstration project sought to determine whether implementation of a provider-to-provider opioid pain teleconsultation service with a pain specialist was correlated with a reduction in inappropriate opioid use and improve health outcomes. METHODS: Individual-level claims data for Health First Colorado Medicaid members were collected between March 1, 2017, and September 30, 2021, for individuals who triggered a provider-to-provider pain management teleconsultation based on receipt of a prescription for an opioid where the member was receiving a high-dose opioid (n = 125) or was opioid-naive (n = 819). The primary outcome measures were a patient's opioid dose less than 200 morphine milligram equivalent (MME) by 6 months after the consult if consult was triggered for high-dose use or discontinuation of an opioid by 12 weeks after consult if the consult was triggered for opioid naivety. Secondary opioid-related health outcomes were also assessed. RESULTS: In the high-dose opioid cohort, 87% of the members had their monthly average MME reduced to less than 200 by 180 days after their consult. More than half of the opioid-naive group had discontinued their opioid by 90 days after their consult. CONCLUSION: Results indicate that provider-to-provider teleconsultation services with a pain specialist can be an effective intervention at reducing total inappropriate opioid use.

An Electronically Delivered Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure With Reduced Ejection Fraction: The EPIC-HF Trial.

BACKGROUND: Major gaps exist in the routine initiation and dose up-titration of guideline-directed medical therapies (GDMT) for patients with heart failure with reduced ejection fraction. Without novel approaches to improve prescribing, the cumulative benefits of heart failure with reduced ejection fraction treatment will be largely unrealized. Direct-to-consumer marketing and shared decision making reflect a culture where patients are increasingly involved in treatment choices, creating opportunities for prescribing interventions that engage patients. METHODS: The EPIC-HF (Electronically Delivered, Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure with Reduced Ejection Fraction) trial randomized patients with heart failure with reduced ejection fraction from a diverse health system to usual care versus patient activation tools-a 3-minute video and 1-page checklist-delivered electronically 1 week before, 3 days before, and 24 hours before a cardiology clinic visit. The tools encouraged patients to work collaboratively with their clinicians to "make one positive change" in heart failure with reduced ejection fraction prescribing. The primary endpoint was the percentage of patients with GDMT medication initiations and dose intensifications from immediately preceding the cardiology clinic visit to 30 days after, compared with usual care during the same period. RESULTS: EPIC-HF enrolled 306 patients, 290 of whom attended a clinic visit during the study period: 145 were sent the patient activation tools and 145 were controls. The median age of patients was 65 years; 29% were female, 11% were Black, 7% were Hispanic, and the median ejection fraction was 32%. Preclinic data revealed significant GDMT opportunities, with no patients on target doses of ß-blocker, sacubitril/valsartan, and mineralocorticoid receptor antagonists. From immediately preceding the cardiology clinic visit to 30 days after, 49.0% in the intervention and 29.7% in the control experienced an initiation or intensification of their GDMT (P=0.001). The majority of these changes were made at the clinician encounter itself and involved dose uptitrations. There were no deaths and no significant differences in hospitalization or emergency department visits at 30 days between groups. CONCLUSIONS: A patient activation tool delivered electronically before a cardiology clinic visit improved clinician intensification of GDMT. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03334188.

Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association.

Cannabis, or marijuana, has potential therapeutic and medicinal properties related to multiple compounds, particularly Δ-9-tetrahydrocannabinol and cannabidiol. Over the past 25 years, attitudes toward cannabis have evolved rapidly, with expanding legalization of medical and recreational use at the state level in the United States and recreational use nationally in Canada and Uruguay. As a result, the consumption of cannabis products is increasing considerably, particularly among youth. Our understanding of the safety and efficacy of cannabis has been limited by decades of worldwide illegality and continues to be limited in the United States by the ongoing classification of cannabis as a Schedule 1 controlled substance. These shifts in cannabis use require clinicians to understand conflicting laws, health implications, and therapeutic possibilities. Cannabis may have therapeutic benefits, but few are cardiovascular in nature. Conversely, many of the concerning health implications of cannabis include cardiovascular diseases, although they may be mediated by mechanisms of delivery. This statement critically reviews the use of medicinal and recreational cannabis from a clinical but also a policy and public health perspective by evaluating its safety and efficacy profile, particularly in relationship to cardiovascular health.

Older Adults in the Cardiac Intensive Care Unit: Factoring Geriatric Syndromes in the Management, Prognosis, and Process of Care: A Scientific Statement From the American Heart Association.

Longevity is increasing, and more adults are living to the stage of life when age-related biological factors determine a higher likelihood of cardiovascular disease in a distinctive context of concurrent geriatric conditions. Older adults with cardiovascular disease are frequently admitted to cardiac intensive care units (CICUs), where care is commensurate with high age-related cardiovascular disease risks but where the associated geriatric conditions (including multimorbidity, polypharmacy, cognitive decline and delirium, and frailty) may be inadvertently exacerbated and destabilized. The CICU environment of procedures, new medications, sensory overload, sleep deprivation, prolonged bed rest, malnourishment, and sleep is usually inherently disruptive to older patients regardless of the excellence of cardiovascular disease care. Given these fundamental and broad challenges of patient aging, CICU management priorities and associated decision-making are particularly complex and in need of enhancements. In this American Heart Association statement, we examine age-related risks and describe some of the distinctive dynamics pertinent to older adults and emerging opportunities to enhance CICU care. Relevant assessment tools are discussed, as well as the need for additional clinical research to best advance CICU care for the already dominating and still expanding population of older adults.

Comparative effectiveness of direct oral anticoagulants and warfarin for the treatment of left ventricular thrombus.

Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis, resulting in increased risk of thromboembolic complications. Observational studies support the general safety and efficacy of warfarin for this indication. Limited data exists regarding the use of direct oral anticoagulants (DOACs) for LV thrombus. This retrospective cohort study sought to compare the incidence of thromboembolic events, bleeding rates, and blood product administration in patients receiving a DOAC versus warfarin. A total of 949 patients met inclusion, 180 (19%) received a DOAC and 769 (81%) warfarin. For the primary endpoint of new onset thromboembolic stroke, no difference existed between treatments (DOAC: 7.8% vs warfarin: 11.7%, p = 0.13). When compared to warfarin, no difference existed in the composite of thromboembolic events (33% vs 30.6%, p = 0.53, respectively) or in GUSTO bleeding (10.9% vs 7.8%, p = 0.40, respectively). More patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p < 0.001).DOACs may be an alternative to warfarin for the treatment of LV thrombus based on a retrospective assessment of thromboembolic events and GUSTO bleeding events within 90 days of diagnosis of LV thrombus. However, further prospective studies are warranted.

A systematic review and meta-analysis of randomized controlled trials of cardiovascular toxicity of medical cannabinoids.

BACKGROUND: Several systematic reviews (SRs) have summarized the potential effectiveness of medical cannabinoids, but it is unclear to what extent safety-related outcomes were incorporated. OBJECTIVE: The objective of this study was to evaluate the cardiovascular toxicity associated with medical use of cannabinoids. METHODS: A 2-stage systematic review (SR) approach was undertaken to assess the current evidence on cannabinoid-associated cardiovascular events reported among randomized controlled trials (RCTs). First, we searched for SRs in multiple sources until June 2019. Second, RCTs identified from the SRs were included if they assessed medical cannabis and reported cardiovascular events. The outcomes of interest were all types of cardiovascular events. Data were extracted by 2 independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios (RRs) and 95% CIs were calculated using a random-effects model. RESULTS: A total of 47 studies involving 2800 patients were included. The median duration of cannabinoid use was 15.8 days (range 1 to 322), and 45% of the studies excluded patients with underlying cardiovascular diseases. Cannabinoid use was significantly associated with increased risks of orthostatic hypotension (RR 3.16 [95% CI 2.27-4.40], I2 = 2.3%) and hypotension (3.55 [1.45-8.71], I2 = 31.8%), with a trend of increased risk of tachycardia (1.94 [0.81-4.64], I2 = 48.6%). No study reported serious cardiovascular events. CONCLUSIONS: Cannabinoid use was associated with tachycardia, hypotension, and orthostatic hypotension. There is a paucity of data for other cardiovascular events among medical cannabis users. More data, especially regarding long-term effects among patients with existing cardiovascular diseases, are needed.

An Electronically delivered, Patient-activation tool for Intensification of medications for Chronic Heart Failure with reduced ejection fraction: Rationale and design of the EPIC-HF trial.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) benefits from initiation and intensification of multiple pharmacotherapies. Unfortunately, there are major gaps in the routine use of these drugs. Without novel approaches to improve prescribing, the cumulative benefits of HFrEF treatment will be largely unrealized. Direct-to-consumer marketing and shared decision making reflect a culture where patients are increasingly involved in treatment choices, creating opportunities for prescribing interventions that engage patients. HYPOTHESIS: Encouraging patients to engage providers in HFrEF prescribing decisions will improve the use of guideline-directed medical therapies. DESIGN: The Electronically delivered, Patient-activation tool for Intensification of Chronic medications for Heart Failure with reduced ejection fraction (EPIC-HF) trial randomizes patients with HFrEF to usual care versus patient-activation tools-a 3-minute video and 1-page checklist-delivered prior to cardiology clinic visits that encourage patients to work collaboratively with their clinicians to intensify HFrEF prescribing. The study assesses the effectiveness of the EPIC-HF intervention to improve guideline-directed medical therapy in the month after its delivery while using an implementation design to also understand the reach, adoption, implementation, and maintenance of this approach within the context of real-world care delivery. Study enrollment was completed in January 2020, with a total 305 patients. Baseline data revealed significant opportunities, with <1% of patients on optimal HFrEF medical therapy. SUMMARY: The EPIC-HF trial assesses the implementation, effectiveness, and safety of patient engagement in HFrEF prescribing decisions. If successful, the tool can be easily disseminated and may inform similar interventions for other chronic conditions.

National survey of physicians' perspectives on pharmacogenetic testing in solid organ transplantation.

INTRODUCTION: Our objective was to evaluate physicians' perspectives on the clinical utility of pharmacogenetic (PGx) testing in kidney, liver, heart, and lung transplantation (KLHL-Tx). METHODS: A 36-question web-based survey was developed and administered to medical and surgical directors of US KLHL-Tx centers. RESULTS: There were 82 respondents (10% response rate). The majority were men (78%), non-Hispanic whites (70%), medical directors (72%), and kidney transplant physicians (35%). Although 78% of respondents reported having some PGx education, most reported lack of confidence in their PGx knowledge and ability to apply a PGx test. Participants reported mixed views about the clinical utility of PGx testing-most agreed with the efficacy of PGx testing, but not the benefits relative to the risks or standard of care. While 55% reported that testing was available at their institution, only 38% ordered a PGx test in the past year, most commonly thiopurine-S-methyltransferase. Physician-reported barriers to PGx implementation included uncertainty about the clinical value of PGx testing and patient financial burden. CONCLUSION: Together, our findings suggest prospective PGx research and pilot implementation programs are needed to elucidate the clinical utility and value of PGx in KLHL-Tx. These initiatives should include educational efforts to inform the use of PGx testing.

Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association.

One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. The review covers the general patient population, as well as demographic subgroups, including the elderly, children, pregnant women, East Asians, and patients with specific conditions such as chronic disease of the kidney and liver, human immunodeficiency viral infection, and organ transplants. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied. In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase. In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms. This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.

Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association.

Heart failure is a common, costly, and debilitating syndrome that is associated with a highly complex drug regimen, a large number of comorbidities, and a large and often disparate number of healthcare providers. All of these factors conspire to increase the risk of heart failure exacerbation by direct myocardial toxicity, drug-drug interactions, or both. This scientific statement is designed to serve as a comprehensive and accessible source of drugs that may cause or exacerbate heart failure to assist healthcare providers in improving the quality of care for these patients.

Thiocyanate Accumulation in Critically Ill Patients Receiving Nitroprusside Infusions.

PURPOSE: This study evaluated thiocyanate concentrations and factors associated with thiocyanate accumulation in intensive care unit patients receiving nitroprusside with and without sodium thiosulfate coadministration. MATERIALS AND METHODS: This retrospective study evaluated critically ill adults who received nitroprusside infusions and had at least one thiocyanate concentration. Patients with thiocyanate accumulation (concentrations ≥30 µg/mL) were compared to patients without accumulation. Factors associated with accumulation were determined by Spearman correlation and multivariate regression. RESULTS: Thiocyanate concentrations (n = 192) were obtained from 87 patients. Fourteen of the 87 (16%) patients experienced thiocyanate accumulation with a mean (SD) thiocyanate concentration of 44 ± 11 µg/mL. Patients with accumulation had received greater cumulative nitroprusside doses (28 vs 8.2 mg/kg, P < .01), greater cumulative sodium thiosulfate doses (16.8 vs 10.1 mg/kg, P < .01), and longer infusion durations (10.9 vs 6.0 days, P < .01), compared to patients without accumulation. Sodium thiosulfate coadministration resulted in greater thiocyanate concentrations (22.8 ± 16.7 vs 16.8 ± 14.9 µg/mL, P = .01), despite utilization of lower cumulative nitroprusside doses (10.2 vs 14.6 mg/kg, P = .03). Cumulative nitroprusside dose ( r2 .44, P < .001) and cumulative sodium thiosulfate dose ( r2 .32, P < .001) demonstrated a significant correlation with measured thiocyanate concentrations. Thiocyanate accumulation was independently associated with cumulative nitroprusside dose in mg/kg (regression coefficient 0.75, 95% CI 0.63-0.89; P < .01). No clinically significant adverse effects of cyanide or thiocyanate toxicity were observed. CONCLUSIONS: Cumulative nitroprusside dose was independently associated with thiocyanate accumulation. Despite elevated thiocyanate levels in 16% of patients, there was no clinical evidence of cyanide or thiocyanate toxicity. Routine monitoring of thiocyanate concentrations appears most warranted in patients receiving higher cumulative doses of nitroprusside.

The impact of drug shortages on patients with cardiovascular disease: causes, consequences, and a call to action.

Shortages of cardiovascular drugs have become increasingly common, representing an ongoing public health crisis. Given few therapeutic alternatives to many of the drugs in short supply, these shortages also pose a major challenge for cardiovascular care professionals. Although changes in the regulatory environment have led to some improvements in recent years, problems involving manufacturing processes remain the most common underlying cause. Because of the complex nature of drug shortages, sustainable solutions to prevent and mitigate them will require collaboration between regulatory agencies, drug manufacturers, and other key stakeholder groups. In this report, we describe the scope of the cardiovascular drug shortage crisis in the United States, including its underlying causes and the efforts currently being made to address it. Furthermore, we provide specific recommendations for how cardiovascular care professionals can be involved in efforts to limit the impact of drug shortages on patient care as well as policy changes aimed at preventing and mitigating them.

CYP3A pharmacogenetics and tacrolimus disposition in adult heart transplant recipients.

BACKGROUND: Cytochrome P450 (CYP) 3A polymorphisms are associated with variable CYP3A metabolizing enzyme activity and tacrolimus pharmacokinetics. We sought to determine the singular and combined impact of CYP3A4*22 and CYP3A5*3 variants on tacrolimus drug disposition in adult heart transplant recipients. METHODS: The retrospective study included 76 patients greater than one year post-heart transplant and receiving tacrolimus. Patients were genotyped for CYP3A4*22 and CYP3A5*3, and combined genotypes were classified as follows: extensive metabolizers (EM, CYP3A4*1/*1+CYP3A5*1 carriers), intermediate metabolizers (IM, CYP3A4*1/*1+CYP3A5*3/*3, or CYP3A4*22 carriers+CYP3A5*1 carriers), and poor metabolizers (PM, CYP3A4*22 carriers+CYP3A5*3/*3). The primary outcome was tacrolimus dose-adjusted trough concentration (C0 /D, ng/mL per mg/d). RESULTS: In singular analysis, tacrolimus C0 /D did not differ significantly between CYP3A4*22 genotype groups. However, tacrolimus C0 /D was 1.8-fold lower (P<.001) in CYP3A5 expressers vs non-expressers. When combined CYP3A genotypes were evaluated, tacrolimus C0 /D was 1.8-fold lower in EMs vs IMs (P<.001) and EMs vs PMs (P=.001). Tacrolimus C0 /D did not differ significantly between CYP3A IMs vs PMs. CONCLUSION: Combined CYP3A genotype was associated with tacrolimus drug disposition in adult heart transplant recipients, but the effect was largely driven by CYP3A5*3. These data suggest that CYP3A4*22 and combined CYP3A genotypes are unlikely to provide additional information beyond CYP3A5 genotype.

Evaluating Patient-Level Medication Regimen Complexity Over Time in Heart Transplant Recipients.

BACKGROUND: Medication regimen complexity describes multiple characteristics of a patient's prescribed drug regimen. Heart transplant recipients must comply with a lifelong regimen that consists of numerous medications. However, a systematic assessment of medication regimen complexity over time has not been conducted in this, or any other, transplant population. OBJECTIVE: The objective of this study was to quantify patient-level medication regimen complexity over time following primary heart transplantation and heart retransplantation, using the validated patient-level Medication Regimen Complexity Index (pMRCI) tool. METHODS: Medication lists were reviewed at transplant discharge and years 1, 3, and 5 post-primary heart transplant, and at transplant discharge and years 1 and 3 post-heart retransplantation. Medications were categorized as transplant-specific, other prescription, and over-the-counter (OTC). RESULTS: In primary heart transplant recipients (n = 60), mean total medication count was 14.3 ± 3.4 at transplant discharge and did not change significantly over time ( P = 0.64). Transplant-specific medication count decreased significantly from discharge (2.9 ± 0.4) to year 5 (2.3 ± 0.6); P = 0.02. However, 32% of patients were taking 16 or more total medications at year 5 posttransplant. More than 70% of the pMRCI score was attributed to other prescription and OTC medications, which was largely driven by dosing frequency in this cohort. Medication complexity did not differ significantly between heart retransplant recipients (n = 11) and matched primary heart transplant controls (n = 22). CONCLUSION: Together, these data highlight the substantial medication burden after heart transplantation and reveal opportunities to address medication regimen complexity in this, and other, transplant populations.

Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction: Evidence Meets Practice, Part II.

Pharmacologic treatment for systolic heart failure, otherwise known as heart failure with reduced ejection fraction, has been established through clinical trials and is formulated into guidelines to standardize the diagnosis and treatment. Since the introduction of angiotensin-converting enzyme inhibitors and vasodilators in the 1980s, many guideline-recommended therapies have emerged over the past 20 years targeting specific neurohormones, aldosterone, and catecholamines to treat heart failure. Part 2 of this series will describe ß-blockers, digoxin, and aldosterone antagonists in the context of the mechanism of action in heart failure, investigational trials that showed beneficial effects, and the practical applications for clinical use.

Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction: Evidence Meets Practice, Part I.

Pharmacologic treatment for systolic heart failure, otherwise known as heart failure with reduced ejection fraction, has been established through clinical trials and is formulated into guidelines to standardize the diagnosis and treatment. The premise of pharmacologic therapy in heart failure with reduced ejection fraction is aimed primarily at interrupting the neurohormonal cascade that is responsible for altering left ventricular shape and function. This is the first in a series of articles to describe the pharmacologic agents in the guidelines that impact the morbidity and mortality associated with heart failure. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and vasodilators will be presented in the context of the mechanism of action in heart failure, investigational trials that showed beneficial effects, and the practical application for clinical use.