Stent selection among patients with chronic kidney disease: Results from the NCDR CathPCI Registry.

OBJECTIVES: This study sought to define contemporary rates of drug eluting stent (DES) usage in patients with chronic kidney disease (CKD). BACKGROUND: Among patients with CKD undergoing percutaneous coronary interventions (PCIs), outcomes are superior for those who receive DES compared to those who receive bare metal stents (BMSs). However, perceived barriers may limit the use of DES in this population. METHODS: All adult PCI cases from the NCDR CathPCI Registry involving coronary stent placement between July 1, 2009 and December 31, 2015 were analyzed. The rate of DES usage was then compared among four groups, stratified by CKD stage (I/II, III, IV, and V). Subgroup analysis was conducted based on PCI status and indication. Cases were linked to Medicare claims data to assess 1-year mortality. RESULTS: A total of 3,650,333 PCI cases met criteria for analysis. DES usage significantly declined as renal function worsened (83.0%, 79.9%, 75.6%, and 75.6%, respectively, in the four CKD stages; p < .001). DES usage was universally lower across the four groups in the setting of ST-Elevation Myocardial Infarction (STEMI) (70.6%, 66.5%, 58.7%, 58.0%; p < .001) and higher in the setting of elective PCI (87.6%, 84.9%, 82.3%, 77.9%; p < .0001). DES was associated with improved 1-year survival, and usage increased over time across each group. CONCLUSIONS: DESs are underutilized in patients with advanced renal dysfunction. Although DES usage has increased over time, variation still exists between patients with normal renal function and those with CKD.

Cost-Effectiveness of Strategies to Personalize the Selection of P2Y12 Inhibitors in Patients with Acute Coronary Syndrome.

PURPOSE: Perform a cost-effectiveness analysis comparing strategies for selecting P2Y12 inhibitors in acute coronary syndrome (ACS). METHODS: Six strategies for selection of P2Y12 inhibitors in ACS were compared from the US healthcare system perspective: (1) clopidogrel for all (universal clopidogrel); (2) ticagrelor guided by platelet reactivity assay (PRA; clopidogrel + phenotype); (3) ticagrelor use only in CYP2C19 poor metabolizers (genotype + conservative ticagrelor); (4) ticagrelor use in both CYP2C19 intermediate and poor metabolizers (genotype + liberal ticagrelor); (5) ticagrelor use only in patients with CYP2C19 polymorphisms and clopidogrel nonresponse by PRA (genotype + phenotype); and (6) ticagrelor for all (universal ticagrelor). A decision model was developed to model major adverse cardiovascular events and bleeding during 1 year of treatment with a P2Y12 inhibitor. Model inputs were identified from the literature. Lifetime costs were adjusted to 2017 US dollars; quality-adjusted life-years (QALYs) were projected using a Markov model. The primary endpoint was the incremental cost-effectiveness compared to the next best option along the cost-effectiveness continuum. Sensitivity analyses were performed on all model inputs to assess their influence on the incremental cost-effectiveness. RESULTS: In the base case analysis, incremental cost-effectiveness ratios (ICER) for the clopidogrel + phenotype, genotype + liberal ticagrelor, and universal ticagrelor strategies were $12,119/QALY, $29,412/QALY, and $142,456/QALY, respectively. Genotype + conservative ticagrelor and genotype + phenotype were not cost-effective due to second-order dominance. Genotype + liberal ticagrelor compared to clopidogrel + phenotype demonstrated the highest acceptance (97%) at a willingness to pay (WTP) threshold of $100,000/QALY. CONCLUSION: Cost-effective strategies to personalize P2Y12 inhibition in ACS include clopidogrel +phenotype and genotype + liberal ticagrelor. Universal ticagrelor may be considered cost-effective at a higher WTP threshold ($150,000/QALY). Genotype + liberal ticagrelor exhibited the highest acceptability compared to clopidogrel + phenotype over the widest range of WTP thresholds and may be preferred.

Current medical management of stable coronary artery disease before and after elective percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) is not superior to optimal medical therapy. It remains unclear if patients who receive PCI for stable CAD are receiving appropriate medical therapy. METHODS: We evaluated the medical management of 60,386 patients who underwent PCI for stable CAD between 2004 and 2009. We excluded patients with contraindications to aspirin, clopidogrel, statins, or ß-blockers (BBs). We defined essential medical therapy of stable CAD as treatment with aspirin, statin, and BB before PCI and treatment with aspirin, clopidogrel, and statin after PCI. RESULTS: Essential medical therapy was used in 53.0% of patients before PCI and 82.1% at discharge. Aspirin was used in 94.8% patients before PCI and 98.3% of after PCI. Statins were used in 69.5% of patients before PCI and 84.5% after PCI. ß-Blockers were used in 72.8% of patients before PCI. Clopidogrel was used in 97.3% of patients after PCI. Patients with a history of myocardial infarction or revascularization before PCI had better medical therapy compared with patients without such a history (62.8% vs 34.3% [P < .001] before PCI and 83.6% vs 79.1% [P < .001] after PCI). After adjusting for confounders and clustering, women (odds ratio 0.74, 95% CI 0.71-0.78) and patients on dialysis (odds ratio 0.68, 95% CI 0.57-0.80) were less likely to receive a statin at discharge. CONCLUSIONS: Medical therapy remains underused before and after PCI for stable CAD. Women are less likely to receive statin therapy. There are significant opportunities to optimize medical therapy in patients with stable CAD.

Coronary Stent Placement in an Interarterial Anomalous Right Coronary Artery: An Alternative Approach in a Multimorbid High-risk Surgical Patient.

Anomalous aortic origin of a coronary artery is a rare congenital anomaly and potential aetiology for sudden cardiac death. However, the mere presence of this anomaly does not portend clinical significance, and there are many factors that contribute to limiting coronary blood flow in these patients. The standard of care for symptomatic individuals is surgical management with coronary unroofing although not all cases are amenable to surgery. We report the case of an anomalous right coronary artery with interarterial course managed by percutaneous coronary intervention due to surgical contraindication secondary to comorbidities. The proposed mechanism of action culminating in aborted sudden cardiac death is unique and involves aggravated pulmonary hypertension in an individual with severe comorbid pulmonary disease.

Comparison of 6-Month Costs Between Oral Antiplatelet Agents Following Acute Coronary Syndrome.

BACKGROUND: In patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), newer antiplatelet agents prasugrel and ticagrelor have lower rates of cardiovascular events when compared with clopidogrel. However, it is unclear whether there are differences in economic outcomes when comparing these agents in ACS-PCI patients. OBJECTIVE: To assess aggregated costs and medical resource utilization among ACS-PCI patients prescribed prasugrel, ticagrelor, or generic clopidogrel, using a large commercial insurance claims database. METHODS: Costs attributable to any medical and pharmacy service and resource utilization including number of admissions, length of hospital stay, emergency room visits, and office visits over the 180-day postdischarge period were compared. All-cause and cardiovascular health care costs and resource utilization were separately analyzed for patients enrolled in the data over the continuous follow-up (CFU) period, and for patients continuously taking their initial treatment for 6 months (CTX). Potential confounders collected over a 6-month baseline assessment period were controlled for, using a generalized linear model. RESULTS: Over the 180-day follow-up, prasugrel and ticagrelor patients underwent fewer admissions (rate ratio [RR] = 0.87, 95% CI = 0.80-0.95) from CFU and RR = 0.81, 95% CI = 0.71-0.89 from CTX) compared with clopidogrel patients. The newer agent cohort incurred more overall health care costs than the generic clopidogrel group, with added costs of $957 (95% CI = $236-$1,725) in the CFU group and $1,122 (95% CI = $455-$1,865) in the CTX group, which were smaller than the increase in all-cause outpatient pharmacy costs associated with the newer agents versus clopidogrel (CFU: $1,175, 95% CI = $1,079-$1,278 and CTX: $1,360, 95% CI = $1,256-$1,487). Overall, there was no statistically significant difference in the economic outcomes associated with prasugrel and ticagrelor. There were, however, significant correlations between all-cause and cardiovascular-related outcomes. CONCLUSIONS: The higher price of prasugrel and ticagrelor was partially offset by a decrease in hospital admission compared with generic clopidogrel over a 6-month postdischarge period. Aggregated medical costs and resource utilization were not significantly different between prasugrel and ticagrelor patients. DISCLOSURES: No funding was received for this study. DiDomenico has received an honorarium from Amgen for preparation of a heart failure drug monograph for Pharmacy Practice News and serves as an advisory board member for a heart failure program at Otsuka America Pharmaceuticals and for Novartis Pharmaceuticals. Touchette has received unrestricted grant funding from Cardinal Health, Sunovion Pharmaceuticals, and Takeda and has served as a consultant to and director of the American College of Clinical Pharmacy Practice-Based Research Network on a study funded by Pfizer. Walton has served as a paid consultant for Bristol-Myers Squibb, Baxter, Merck, Genentech, Primus, Takeda, and Abbott. The other authors have nothing to disclose.

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Small cell lung cancer presenting as a paraneoplastic syndrome characterized by recurrent episodic hypotension and bradycardia: case report.

A 56-year-old man presenting with a 6-month history of recurrent episodic hypotension and bradycardia was found to have limited-stage small cell lung cancer. During both quiescence and episodes of hemodynamic embarrassment, extensive evaluations were conducted. Possible explanations included the following: intermittent great vessel obstruction; baroreceptor failure/hypersensitivity; and autonomic dysfunction. His clinical course favored an antibody-negative dysautonomic paraneoplastic syndrome.

Comparative Effectiveness of Oral Antiplatelet Agents in Patients with Acute Coronary Syndrome.

OBJECTIVE: In randomized controlled trials, prasugrel and ticagrelor reduced cardiovascular complications in patients with acute coronary syndrome (ACS) compared with clopidogrel. However, limited head-to-head comparisons have been conducted across the three antiplatelet agents using real-world data. The aim of this study was to compare clinical outcomes of three strategies during a 1-year period after percutaneous coronary intervention (PCI). METHODS: Rates of all-cause and acute myocardial infarction (AMI) hospitalizations were compared retrospectively using an insurance claims database. Patients who filled a prescription for an oral antiplatelet agent between September 2011 and December 2013 for post ACS-PCI care were identified. Time to all-cause and AMI hospitalization for a 365-day postdischarge period was compared using Cox proportional hazard models controlling for potential confounders within a propensity score matched cohort. RESULTS: A matched cohort of 9504 clopidogrel, 7128 prasugrel, and 2376 ticagrelor patients was analyzed. The 1-year hazard ratio (HR) for the two newer agents versus clopidogrel was 0.84 (0.78-0.91). The HR for the newer agents versus clopidogrel of admission with AMI as the primary diagnosis was 0.78 (0.61-1.03), and for AMI as any diagnosis during a hospitalization was 0.88 (0.77-1.00). The HR of all-cause admission for ticagrelor versus prasugrel was 0.97 (0.84-1.13), and the HRs of AMI-related admission were not statistically significant between the two agents. Robustness checks across statistical methods to control for potential confounders did not influence the conclusion. CONCLUSION: This real-world study demonstrated that use of the newer agents following PCI was associated with a decrease in all-cause and AMI-related hospitalizations. However, no significant difference was found in the rate of admission between ticagrelor versus prasugrel. Due to concerns regarding statistical power, future studies should examine larger cohorts to obtain more precise estimates for AMI hospitalization for ticagrelor and prasugrel.

Contemporary Trends in Oral Antiplatelet Agent Use in Patients Treated with Percutaneous Coronary Intervention for Acute Coronary Syndrome.

BACKGROUND: Recent trials demonstrated the efficacy of prasugrel and ticagrelor compared with clopidogrel in the reduction of cardiovascular complications in patients with acute coronary syndrome (ACS). However, it is unclear how use of the 3 antiplatelet medications has changed in commercially insured patients since the advent of the new agents. OBJECTIVES: To (a) describe the adoption of prasugrel and ticagrelor in patients who received percutaneous coronary intervention (PCI) for the onset of ACS and (b) explore patient factors associated with the selection of the drug to provide insight into utilization patterns of these antiplatelet agents. METHODS: Patients who received a new dispensing of an antiplatelet agent following a hospitalization for a PCI administered for ACS were identified from insurance claims between 2009 and 2013. Demographics and comorbid conditions were determined based on a 6-month period before the ACS event. Longitudinal trends in antiplatelet agent selection were illustrated using descriptive statistics segmented by month and quarter. Using logistic regressions with stepwise model selection, factors associated with use of the newer medications, as well as with the selection between ticagrelor and prasugrel, were identified. RESULTS: The analysis included 66,335 subjects. The use of clopidogrel decreased from 100% to roughly 65% of total antiplatelet agent use by the end of 2011 and leveled off thereafter. The introduction of ticagrelor in 2011 coincided with a drop in prasugrel initiation from 35%-18% by December 2013. The use of new agents as opposed to use of clopidogrel was associated with younger age (< 65 years), male gender, and a diagnosis of ST-elevation myocardial infarction. In addition, conditions increasing mortality and risk of cardiovascular complication were associated with higher odds of using clopidogrel. The odds of using ticagrelor over prasugrel increased with older age and history of a cerebrovascular event. CONCLUSIONS: In 2013, clopidogrel remained the most prescribed agent. Meanwhile, ticagrelor had gradually replaced a substantial portion of prasugrel initiation. Further investigation into outcomes associated with the newer agents, as well as reasons behind the conservative use of the antiplatelet agents, is warranted. DISCLOSURES: No funding was received for the conduct of this study. DiDomenico received an honorarium from Amgen for the preparation of a heart failure drug monograph for Pharmacy Practice News and was a co-investigator on funded research for the Patient-Centered Outcomes Research Institute. DiDomenico also serves as an advisory board member for a heart failure program at Otsuka America Pharmaceuticals and as an advisory board member at Novartis Pharmaceuticals. Touchette has received unrestricted grant funding from Cardinal Health and Sunovion Pharmaceuticals and has also served as a consultant to and director of the American College of Clinical Pharmacy Practice-Based Research Network on a study funded by Pfizer. None of the authors of this study are involved in financial or personal relationships with agencies, institutions, or organizations that inappropriately influenced the statistical analysis plan or interpretation of the results. Study concept and design were contributed by Kim, Lee, Touchette, and Walton, with assistance from DiDomenico and Ardati. Kim and Lee collected the data, and data interpretation was performed by Lee, DiDomenico, and Ardati, along with Kim and Walton and assisted by Touchette. The manuscript was written by Kim and Walton, with assistance from the other authors, and revised by Kim, Walton, and Lee, with assistance from the other authors.

Image noise reduction technology reduces radiation in a radial-first cardiac catheterization laboratory.

BACKGROUND: Transradial coronary angiography (TRA) has been associated with increased radiation doses. We hypothesized that contemporary image noise reduction technology would reduce radiation doses in the cardiac catheterization laboratory in a typical clinical setting. METHODS AND RESULTS: We performed a single-center, retrospective analysis of 400 consecutive patients who underwent diagnostic and interventional cardiac catheterizations in a predominantly TRA laboratory with traditional fluoroscopy (N=200) and a new image noise reduction fluoroscopy system (N=200). The primary endpoint was radiation dose (mGy cm2). Secondary endpoints were contrast dose, fluoroscopy times, number of cineangiograms, and radiation dose by operator between the two study periods. Radiation was reduced by 44.7% between the old and new cardiac catheterization laboratory (75.8mGycm2±74.0 vs. 41.9mGycm2±40.7, p<0.0001). Radiation was reduced for both diagnostic procedures (45.9%, p<0.0001) and interventional procedures (37.7%, p<0.0001). There was no statistically significant difference in radiation dose between individual operators (p=0.84). In multivariate analysis, radiation dose remained significantly decreased with the use of the new system (p<0.0001) and was associated with weight (p<0.0001), previous coronary artery bypass grafting (p<0.0007) and greater than 3 stents used (p<0.0004). TRA was used in 90% of all cases in both periods. Compared with a transfemoral approach (TFA), TRA was not associated with higher radiation doses (p=0.20). CONCLUSIONS: Image noise reduction technology significantly reduces radiation dose in a contemporary radial-first cardiac catheterization clinical practice.

Genotype- and phenotype-directed antiplatelet therapy selection in patients with acute coronary syndromes.

Although dual antiplatelet therapy (DAPT) has been a standard treatment in patients with acute coronary syndrome (ACS) for over a decade, only recently have therapeutic options beyond aspirin and clopidogrel become available. Additional treatment options are particularly useful because of the documented history of variability in antiplatelet response. This article reviews the current treatment options for DAPT in ACS, and reviews both genotype- and phenotype-guided methods for determining optimal antiplatelet therapy for patients with ACS. Additionally, recommendations from current guidelines as well as expert commentary are provided for the use of available testing methods to determine optimal DAPT for ACS patients.

The quality and impact of risk factor control in patients with stable claudication presenting for peripheral vascular interventions.

BACKGROUND: Peripheral arterial disease is a manifestation of systemic atherosclerosis and is predictive of future cardiovascular events. Clinical trial data have demonstrated that medical therapy can attenuate cardiovascular morbidity and mortality in patients with peripheral arterial disease. The utilization and impact of recommended medical therapy in a contemporary population of patients who undergo percutaneous interventions for lifestyle-limiting peripheral arterial disease is unknown. METHODS AND RESULTS: Using the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Peripheral Vascular Intervention (BMC2 PVI) database, we identified 1357 peripheral vascular intervention encounters between January 2007 and December 2009 for the purpose of treating claudication. Before the intervention, 85% of these patients used aspirin, 76% used statin, 65% abstained from smoking, and 47% did all 3. There was no difference in cardiovascular events among those taking an aspirin and a statin on admission and those who were not. However, in both an unadjusted and a multivariable analysis, the odds of an adverse peripheral vascular outcome (repeat peripheral intervention, amputation, or limb salvage surgery) within 6 months decreased by more than half in patients receiving aspirin and statin therapy before peripheral vascular intervention as compared with those who received neither (odds ratio, 0.45; 95% CI, 0.29-0.71). CONCLUSIONS: The fundamental elements of medical therapy in patients with lifestyle-limiting claudication are often underutilized before referral for revascularization. Appropriate medical therapy before percutaneous revascularization is associated with fewer peripheral vascular events at 6 months.