Robert L. Page

QT interval prolongation and the risk of torsades de pointes: essentials for clinicians

Abstract Objective: QT interval prolongation signifies an increased risk of the life-threatening arrhythmia torsades de pointes (TdP). The purpose of this paper is to review the diverse methods for assessing and monitoring the risk of TdP, discuss risk factors for TdP, and recommend interventions that may mitigate the risk of TdP. Methods: A non-systematic search of PubMed (through March 2013) was conducted to determine the optimal approach to assessing and monitoring QT interval, prevention of TdP, and to identify risks factors for TdP. Papers known to the authors were included, as were scientific statements. Articles were chosen based on the judgment of the authors. Results: Risk factors for drug-induced TdP include hypokalemia, female sex, drug–drug interactions, advancing age, genetic predisposition, hypomagnesemia, heart failure, bradycardia, and corrected QT (QTc) interval prolongation. Many risk factors, including hypokalemia, use of QT-interval-prolonging drugs, and drug interactions are potentially modifiable and should be corrected in persons at risk for QT interval prolongation. Given the variable onset of TdP following initiation of QT-interval-prolonging drugs, careful and regular monitoring of electrocardiography (EKG) and electrolytes are necessary. Patients at risk for QT interval prolongation should be educated to go directly to the emergency room if they experience palpitations, lightheadedness, dizziness or syncope. When the QTc interval is 470–500u2009ms for males, or 480–500u2009ms for females, or the QTc interval increases 60u2009ms or more from pretreatment values, dose reduction or discontinuation of the offending drug should be considered where possible, and electrolytes corrected as needed. Furthermore, if the QTc interval is ≥500u2009ms, the offending drug should be discontinued, and continuous EKG telemetry monitoring should be performed, or the 12-lead EKG should be repeated every 2–4 hours, until the QT interval has normalized. Conclusions: Close monitoring for QTc prolongation is necessary to prevent TdP. The recommendations in this paper are limited by the available evidence and additional studies are needed to better define the approach to monitoring.

Long-Term Anticoagulant Therapy in Coronary Atherosclerosis

Abstract We have presented a pooled clinical investigation in 1,091 patients with coronary atheroslcerosis treated with long-term anticoagulants for 3 to 100 months, for a total of 24,454 months. The average duration of therapy was 22.4 months. Four and four-tenths per cent developed non-fatal thromboembolism, and 131 patients, or 12.0 per cent, died on the regimen, mostly from cardiac disease. Three hundred nineteen patients, or 29.2 per cent, abandoned the regimen; an average 18.4 months follow-up of these showed that 28.2 per cent died within 4 years, chiefly with cardiac disease. These 319 patients serve as “controls”. Six hundred sixty-nine patients, or 61.3 per cent, continued the regimen an average of 27.6 months of therapy. Four hundred seventeen patients not given anticoagulants were used as additional “controls” and were followed by 5 of the authors for 3 to 120 months, averaging 38.1 months. Of these, 37.4 per cent died, the majority from cardiovascular disease.

Risk Factors of Prescription Opioid Overdose Among Colorado Medicaid Beneficiaries.

UNLABELLEDnThis study aims to determine risk factors of opioid overdose among the Colorado Medicaid population. A retrospective nested case-control study was undertaken. Medicaid beneficiaries who had ≥1 medical claim for an emergency department visit or a hospitalization associated with an opioid overdose from July 2009 to June 2014 were defined as cases. Controls were selected using a nearest neighbor matching without replacement. The matched controls were selected on the basis of age, sex, and opioid prescription. One case was matched with three controls. Multivariate conditional logistic regression was used to compare risk factors. A total of 816 cases with 2,448 controls were included. Six factors were associated with opioid overdose: mean morphine dose equivalent (>50xa0mg/d; odds ratio [OR]xa0=xa01.986 [95% confidence interval [CI], 1.509-2.614]), methadone use (switching opioid to methadone vs. no methadone use; ORxa0=xa07.230 [95% CI, 2.346-22.286]), drug/alcohol abuse (ORxa0=xa03.104 [95% CI, 2.195-4.388]), other psychiatric illness (ORxa0=xa01.730 [95% CI, 1.307-2.291]), benzodiazepine use (ORxa0=xa02.005 [95% CI, 1.516-2.652]), and the number of pharmacies used by the beneficiary (≥4 pharmacies vs. 1 pharmacy; ORxa0=xa01.514 [95% CI, 1.003-2.286]). In conclusion, several factors are associated with opioid overdose. States and communities should ensure the availability of at-home intranasal naloxone for overdose rescue on the basis of the presence of risk factors.nnnPERSPECTIVEnThis article presents the risk factors of opioid overdose among the Colorado Medicaid population. On the basis of study findings, Colorado Medicaid is currently working with physicians, hospitals, and other health system stakeholders to continue to develop policies to identify and assist this subset of our population. One such policy will be to provide at-home intranasal naloxone for overdose rescue.

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.

Automating and estimating glomerular filtration rate for dosing medications and staging chronic kidney disease

Objective The purpose of this paper is to serve as a review for primary care providers on the bedside methods for estimating glomerular filtration rate (GFR) for dosing and chronic kidney disease (CKD) staging and to discuss how automated health information technologies (HIT) can enhance clinical documentation of staging and reduce medication errors in patients with CKD. Methods A nonsystematic search of PubMed (through March 2013) was conducted to determine the optimal approach to estimate GFR for dosing and CKD staging and to identify examples of how automated HITs can improve health outcomes in patients with CKD. Papers known to the authors were included, as were scientific statements. Articles were chosen based on the judgment of the authors. Results Drug-dosing decisions should be based on the method used in the published studies and package labeling that have been determined to be safe, which is most often the Cockcroft–Gault formula unadjusted for body weight. Although Modification of Diet in Renal Disease is more commonly used in practice for staging, the CKD–Epidemiology Collaboration (CKD–EPI) equation is the most accurate formula for estimating the CKD staging, especially at higher GFR values. Automated HITs offer a solution to the complexity of determining which equation to use for a given clinical scenario. HITs can educate providers on which formula to use and how to apply the formula in a given clinical situation, ultimately improving appropriate medication and medical management in CKD patients. Conclusion Appropriate estimation of GFR is key to optimal health outcomes. HITs assist clinicians in both choosing the most appropriate GFR estimation formula and in applying the results of the GFR estimation in practice. Key limitations of the recommendations in this paper are the available evidence. Further studies are needed to better understand the best method for estimating GFR.

Impact of a Telehealth and Care Management Program on All-Cause Mortality and Healthcare Utilization in Patients with Heart Failure.

BACKGROUNDnTelehealth has the potential to improve chronic disease management and outcomes, but data regarding direct benefit of telehealth in patients with heart failure (HF) have been mixed. The objective of this study was to determine whether the Health Buddy Program (HBP) (Bosch Healthcare, Palo Alto, CA), a content-driven telehealth system coupled with care management, is associated with improved outcomes in Medicare beneficiaries with HF.nnnMATERIALS AND METHODSnThis was a retrospective cohort study of 623 Medicare beneficiaries with HF offered HBP enrollment compared with a propensity score-matched control group of Medicare beneficiaries with HF from the Medicare 5% sample. Associations between availability of the HBP and all-cause mortality, hospitalization, hospital days, and emergency department visits were evaluated.nnnRESULTSnBeneficiaries offered enrollment in the HBP had 24.9% lower risk-adjusted all-cause mortality over 3 years of follow-up (hazard ratio [HR] = 0.75; 95% confidence interval [CI], 0.63-0.89; p = 0.001). Patients who used the HBP at least once (36.9%) had 57.2% lower mortality compared with matched controls (HR = 0.43; 95% CI, 0.31-0.60; p < 0.001), whereas patients who did not use the HBP had no significant difference in survival (HR = 0.96; 95% CI, 0.78-1.19; p = 0.69). Patients offered the HBP also had fewer hospital admissions following enrollment (Δ = -0.05 admissions/quarter; p = 0.011), which was primarily observed in patients who used the HBP at least once (Δ = -0.10 admissions/quarter; p < 0.001).nnnCONCLUSIONSnThe HBP, a content-driven telehealth system coupled with care management, was associated with significantly better survival and reduced hospitalization in Medicare beneficiaries with HF. Prospective study is warranted to determine the mechanism of this association and opportunities for optimization.

CYP3A pharmacogenetics and tacrolimus disposition in adult heart transplant recipients

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.

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.

Assessment of chronic disease management among patients with diabetes and coronary artery disease receiving care in a cardiology clinic

Patients with coronary artery disease (CAD) often have multiple comorbidities (eg, diabetes, hypertension, and hyperlipidemia). It is unclear if these comorbidities are adequately managed among patients established in a cardiology clinic.

Pharmacokinetic Drug–Drug Interactions Between Immunosuppressant and Anti-Infective Agents: Antimetabolites and Corticosteroids

Infections account for 15–20% of deaths in transplant recipients, requiring rapid and appropriate therapeutic interventions. Many anti-infective agents interact with immunosuppressive regimens used in transplantation, placing patients at increased risk for adverse drug reactions and prolonged hospitalizations. There is established data regarding the level of evidence and magnitude of interactions between calcineurin inhibitors and mammalian target of rapamycin inhibitors with anti-infective agents. Less is known about the interactions with anti-proliferative agents and corticosteroids, with gaps in knowledge on the appropriate management of these interactions. The objective of this review was to highlight the pharmacokinetic drug–drug interactions between antimetabolites and corticosteroids with commonly used anti-infective agents.