Cost-Effectiveness of 12-Month Treatment With Ticagrelor Compared With Clopidogrel in the Management of Acute Coronary Syndromes

Background

The PLATO (Platelet Inhibition and Patient Outcomes) randomized trial (NCT00391872) in patients with acute coronary syndromes (ACS) reported that ticagrelor (in addition to aspirin) reduced the rate of the composite end point of myocardial infarction (MI), stroke, or cardiovascular death compared with clopidogrel (in addition to aspirin) by 16% over 12 months (P < 0.001). No significant difference in the incidence of major bleeding was noted, but ticagrelor was associated with a higher rate of major bleeding not related to coronary artery bypass grafting.

Objective

By extrapolating the key findings of PLATO, we sought to assess the cost-effectiveness of ticagrelor compared with clopidogrel in the management of ACS in a contemporary Australian setting.

Methods

A Markov model with 4 health states (free from further ACS events, MI, stroke, and death) was developed to simulate the long-term costs and outcomes associated with ACS. Event risks were based on data derived directly from PLATO, and costs and utilities were drawn from published sources. A 10-year time horizon was simulated, and future costs and benefits were discounted at a 5% annual rate. However, treatment with ticagrelor and clopidogrel was only assumed for the first 12 months, with no benefits applied beyond drug cessation. Sensitivity analyses were undertaken based on variations to key data inputs. All costs for resource use applied in the analysis were based on published Australian prices (in 2010/2011 dollars [A$]).

Results

Over 10 years, the estimated quality-adjusted life-years lived per-patient were 5.74 and 5.68 for ticagrelor and clopidogrel, respectively. Net costs were A$19,132 for ticagrelor and A$18,428 for clopidogrel. These equated to an incremental cost-effectiveness ratio of A$9031 per quality-adjusted life-year gained for ticagrelor compared with clopidogrel. Sensitivity analyses indicated the result to be robust.

Conclusions

When assessed from the perspective of the Australian health care system, ticagrelor is likely to be cost-effective compared with clopidogrel in preventing downstream morbidity and mortality associated with ACS.     

Point-of-care Measurements of Platelet Inhibition After Clopidogrel Loading in Patients With Acute Coronary Syndrome: Comparison of Generic and Branded Clopidogrel Bisulfate

PurposePlatelet-function suppression with antiplatelet therapy is effective in preventing and treating cardiovascular disease. Clopidogrel is a thienopyridine derivative that blocks platelet activation by adenosine diphosphate receptor binding. This study demonstrates the effects of generic clopidogrel bisulfate in comparison to branded clopidogrel bisulfate in patients with acute coronary syndromes.MethodsThis prospective, 2-arm, single-center, open-label trial used 1:1 randomization to assign patients to receive generic or branded clopidogrel bisulfate. Patients with unstable angina or non–ST-segment elevation myocardial infarction and scheduled to undergo coronary angiography were enrolled. Platelet function was measured with a P2Y₁₂ assay and reported in P2Y₁₂ reaction units (PRU) and aspirin reaction units (ARU) after randomization. Platelet function was measured at 2, 4, 8, and 24 hours after 600-mg clopidogrel loading. The clinical outcome was checked at 1 month after coronary angiography.FindingsNinety-five patients were enrolled and randomized to the generic or branded group. Ninety patients (62 men [69%], 28 women [31%]; mean age, 58 years) completed the study protocol. The clinical characteristics were similar between the 2 groups. The difference in the baseline PRU measurements between the generic and branded groups was not significant (274.8 [59.7] vs 285.4 [62.4], respectively; P = 0.414). There were significant differences in 2-hour PRU (231.1 [71.3] vs 266.9 [67.4]; P = 0.017) and 4-hour PRU (227.3 [80.4] vs 265.7 [71.0]; P = 0.020); however, 24-hour PRU (200.5 [82.1] vs 220.6 [75.8]; P = 0.253) was similar. No death, myocardial infarction, target lesion revascularization, stent thrombosis, or Thrombolysis in Myocardial Infarction–defined major bleeding complications were reported during in-hospital stay or 1-month follow-up.ImplicationIn patients with ACS, loading of generic clopidogrel bisulfate was associated with an antiplatelet effect comparable to that of branded clopidogrel bisulfate. ClinicalTrials.gov identifier: NCT02060786.     

A Cost-effectiveness Analysis of Rabbit Antithymocyte Globulin Versus Antithymocyte Globulin-fresenius as Induction Therapy for Patients With Kidney Transplantation From Donation After Cardiac Death in China

Purpose

Induction immunosuppression therapy is used to support optimal outcomes in kidney transplantation. This study was to assess the cost-effectiveness of rabbit antithymocyte globulin (r-ATG) versus ATG-Fresenius (ATG-F) in kidney transplantation in the Chinese setting from the perspective of the health care payer.

Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy

ObjectiveTo evaluate the association between proton pump inhibitor (PPI) use and in-hospital gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) taking dual antiplatelet therapy (DAPT).Patients and MethodsThis study is based on the Improving Care for Cardiovascular Disease in China-ACS project, an ongoing collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. A total of 25,567 patients with ACS taking DAPT from 172 hospitals from July 1, 2017, through December 31, 2018, were included. Multivariable Cox regression and propensity score–matched analyses were used to evaluate the association between PPI use and in-hospital GI bleeding.ResultsOf these patients with ACS, 63.9% (n=16,332) were prescribed PPIs within 24 hours of admission. Patients using PPIs had a higher rate of GI bleeding compared with those not using PPIs (1.0% vs 0.5%; P<.001). In the multivariable Cox regression analysis, early PPI use was associated with a 58% higher risk of GI bleeding (hazard ratio, 1.58; 95% CI, 1.15 to 2.18; P=.005). Further propensity score matching attenuated the association but still showed that patients using PPIs had a higher rate of GI bleeding (0.8% vs 0.6%; P=.04).ConclusionIn China, PPIs are widely used within 24 hours of admission in patients with ACS taking DAPT. An increased risk of GI bleeding is observed in inpatients with early PPI use. Randomized trials on early use of PPIs in patients with ACS receiving DAPT are warranted.Trial Registrationclinicaltrials.gov Identifier: NCT02306616.     

Radiofrequency Catheter Ablation Versus Cryoballoon Ablation in the Treatment of Paroxysmal Atrial Fibrillation: A Cost-effectiveness Analysis in China

Purpose

The aim of this study was to evaluate the cost-effectiveness of radiofrequency catheter ablation (RFCA) compared with cryoballoon (CB) ablation in the treatment of patients with paroxysmal atrial fibrillation (PAF) from the payer's perspective in China.

Use of S-LANSS,a Tool for Screening Neuropathic Pain,for Predicting Postherpetic Neuralgia in Patients After Acute Herpes Zoster Events: A Single-Center, 12-Month,Prospective Cohort Study

Postherpetic neuralgia (PHN) is one of the most severe sequelae of herpes zoster events. Several risk factors have been reported for PHN, including old age, severe skin rash, and intense pain. This study therefore aims to evaluate the usefulness of the Self-completed Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) in conjunction with previously reported risk factors for predicting PHN. A group of herpes zoster patients (N = 305) were included in the cohort study. Subjects were asked for their demographic information, clinical symptoms and signs, intensity of pain by visual analog scale (VAS), and S-LANSS. They were followed up in clinical visits or via telephone for 12 months. Nineteen patients (6.2%) suffered from PHN in this study. Using logistic regression, 3 risk factors for PHN were identified: age ≥70 years, high VAS scores, and high S-LANSS scores. Prediction of PHN using VAS (≥8) and S-LANSS (≥15) criteria achieved a sensitivity of 78.9% and specificity of 78.0%. Prediction of PHN in elderly patients (≥70 years), using the criteria of VAS (≥6) and S-LANSS (≥15) as well, achieved 100% sensitivity and 57.1% specificity. S-LANSS could be a useful prediction tool for PHN, particularly if combined with previously well-known risk factors and VAS.PerspectiveAmong acute herpes zoster patients, subjects with characteristics of neuropathic pain showed high frequency of PHN. The tools for screening neuropathic pain like S-LANSS could be helpful for predicting PHN and enabling early intervention of pain management.     

The Evolving Face of Myocardial Reperfusion in Acute Coronary Syndromes: A Primer for the Internist

Acute coronary syndromes (ACSs) account for a large proportion of disease burden in the United States and worldwide, and our understanding of ACS management continues to evolve. In this review we take a practical approach to evaluating and treating a patient with ACS, focusing on the optimal timing and methods of coronary reperfusion. Beginning with initial assessment and risk stratification, a provider managing the patient with ACS must be able to expeditiously decide on and implement the correct guideline-directed pathway to optimize outcomes. With an ever-growing body and weight of knowledge in this field, the clinician is tasked with several challenges. First, there are a variety of pathways of care to be considered; second, adjunctive medical therapies are expanding; and third, when coupled with the multiple combinations of adjunctive supportive therapies for revascularization, the variety of potential therapeutic options can be overwhelming and confusing. Herein, we carefully review all the relevant guidelines and the contributing literature, taking a 4-step approach: (1) review the importance of risk stratification before engaging in a particular strategy of care, (2) define the reperfusion strategies available, (3) review the specific agents (antiplatelet and anticoagulant) that support reperfusion strategies, and (4) apply the strategies of care in the context of the clinical presentation.     

Newer P2Y12 Inhibitors vs Clopidogrel in Acute Myocardial Infarction With Cardiac Arrest or Cardiogenic Shock: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y₁₂ inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS).Patients and MethodsMEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y₁₂ inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y₁₂ inhibitors and clopidogrel in patients with AMI-CA/CS.ResultsEight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y₁₂ cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies).ConclusionIn patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y₁₂ inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.