Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

Malaria resurgence in India: a critical study

In 1953, the Indian National Malaria Control Programme (NMCP) was started. Encouraged by the results, and the fact that insecticide resistance in vector species may evolve and become an obstacle, in 1958 a control programme was converted to the National Malaria Eradication Programme (NMEP). By 1964, malaria was eradicated from 88% of the area and it was in the advanced stage of spraying in the remaining parts. At that time, focal outbreaks that occurred in 1965 and increased in later years, could not be contained due to the shortages of DDT. As a result, large areas in consolidation and maintenance phases were reverted to the attack phase. Besides, the infrastructure in general health services was not adequate and mature enough to take up surveillance and vigilance. This produced a large number of secondary cases due to the re-introduction and relapse of malaria. Added to this was the problem of urban malaria, the control of which was the responsibility of local bodies. Malaria cases increased in towns, and started diffusing to the rural areas, due to inadequate staff and the shortages of malarial larvicidal oil (MLO). Later, it turned out, that while it was technically feasible to eradicate malaria from 91% of the population, the strategy of indoor spraying of DDT to interrupt transmission did not succeed in 9.0% of the population, despite more than 12-14 years of regular spraying. During the years of resurgence, there was no research support to the programme, so that technical problems were not properly appreciated, understood and tackled. The reservoir of parasites that were present throughout the country started multiplying and spreading to newer areas due to the presence of vectors in high densities. Thus malaria resurged and re-established itself even in areas that were at one time freed from the disease. The analysis of the pattern of malaria resurgence revealed that malaria outbreaks preceded the true problem of insecticide resistance. It is noteworthy to mention that malaria resurgence occurred in towns where the control measures were non-insecticidal and in regions which were not under the influence of insecticide-resistant vectors. The study also revealed that resurgence occurred before the introduction of high-yielding varieties programme in the country, and had no relationship to either the cotton or rice growing or intensive agriculture.     

Effect of local mupirocin application on exit-site infection and peritonitis in an Indian peritoneal dialysis population.

BACKGROUND: Staphylococcus aureus-associated peritonitis and catheter exit-site infections (ESIs) are important causes of hospitalization and catheter loss in patients undergoing chronic peritoneal dialysis. Intranasal and topical use of mupirocin has been found to be an effective strategy in decreasing S. aureus-related infectious complications in persons who are carriers of S. aureus; however, there is no consensus regarding the prophylactic use of mupirocin irrespective of carrier status. We aimed to determine the potential effectiveness of application of mupirocin cream at the catheter exit site in preventing ESI and peritonitis irrespective of carrier status in a tropical country such as India. METHODS: This prospective historically controlled study was done in a total of 40 patients. From August 2003, all patients, incident and prevalent, were instructed to apply 2% mupirocin cream daily to the exit site instead of the older practice of povidone-iodine and gauze dressing. Patients were not screened to determine whether they were S. aureus carriers. The infection-related data for 1 year, until July 2004, were compared with the historical control, which was infection-related data for the year preceding the year of mupirocin application. RESULTS: Mean age of the study population was 62 years, with 61.8% being male and 64.3% being diabetic. Local application of mupirocin led to a significant reduction in the incidence density per patient-month of both ESI and peritonitis compared to controls (0.15 vs 0.37 and 0.37 vs 0.67, p = 0.01 for both). This amounted to a relative reduction of 60.5% and 55% respectively. ESI and peritonitis due to S. aureus were also significantly lower in the study group compared to controls (incidence density per patient-month 0.05 vs 0.13 and zero vs 0.17 respectively, p < 0.01 for both). There occurred no catheter removal due to infection-related complications during the study period compared to two during the control period. None of the patients reported a mupirocin-related adverse effect. CONCLUSIONS: Daily application of mupirocin at the exit site is a well-tolerated and effective strategy in reducing the incidence of ESI and peritonitis in a tropical country such as India. It can thus significantly reduce morbidity, catheter loss, and transfer to hemodialysis in peritoneal dialysis patients.     

CT19PTRICUSPID VALVE REPAIR IN ‘TORRENTIAL TRICUSPID REGURGITATION’ FOLLOWING PERMANENT PACEMAKER LEAD EXTRACTION – A CASE REPORT

Introduction Traumatic tricuspid regurgitation secondary to blunt chest trauma has been reported in literature. We report our experience with a case of ‘Torrential Tricuspid Regurgitation’ following permanent pacemaker lead extraction which was successfully treated with tricuspid valve repair and annuloplasty. Report A 67 year old woman was treated for Sick sinus syndrome with permanent pacemaker implant. She had three generator changes for end of life and repositioning.Erosion of generator, led cardiologist to plan lead and generator extraction with the surgical backup. During lead extraction a small piece of papillary muscle was avulsed. The patient remained hemodynamically stable in the theatre. However in ward she developed right sided cardiac failure not responding to conservative therapy. A transthoracic echo (TTE) revealed torrential tricuspid regurgitation with a freely mobile posterior leaflet with attached chordae and avulsed papillary muscle.During surgery the tricuspid valve was successfully repaired and transesophageal (TOE) images showed trivial to mild tricuspid regurgitation at the end of repair procedure. Additional procedure also included ligation of both atrial appendages and implantation of epicardial leads and pacemaker. Patient made good recovery from operation. Conclusion To the best of our knowledge this is first report of repair of tricuspid valve in ‘Torrential Tricuspid Regurgitation’ following pacemaker lead extraction. We share our experience with tricuspid valve repair technique and annuloplasty.     

ENDOSCOPY ASSISTED REMOVAL OF FERROMAGNETIC COINS WITH NOVEL MAGNETIC INSTRUMENT

Background: Ingestion of coins is a common clinical problem in children. Many of the coins are ferromagnetic and can be retrieved with the help of a magnet. We describe the use of a novel endoscopic accessory for removing ferromagnetic coins. Material and methods: Two magnet discs of 1.5 cm diameter were joined to a 200 cm steel wire of 0.75 mm thickness with a terminal 5 cm spring. A Teflon tube (160 cm, 7 F) was used along with this instrument as a sleeve. The use of this accessory was analyzed prospectively in subjects presenting with a history of coin ingestion. The time taken for removal of coins, complications during the procedure and failure rate was noted. Effect of the magnet on cardiac rhythm was also noted during the procedure. Results: A total of 55 children (mean age 5.1 ± 2.3 years) with coin ingestion presented over a period of 1 year. Forty‐four coins were ferromagnetic. All ferromagnetic coins were removed successfully. Mean time for removal was 68 ± 22 s. No complications were encountered. Conclusion: The novel magnetic instrument is precise, safe and quick for the removal of ferromagnetic coins under direct vision.     

Factors affecting the use of peritoneal dialysis among the ESRD population in India: a single-center study.

OBJECTIVES: Factors such as limited health-care budget allotment and poor accessibility of the majority of the population to hemodialysis (HD) facilities should favor the use of peritoneal dialysis (PD) in India. However, only 6% of end-stage renal disease patients undergoing dialysis in India are on PD. We undertook this prospective study to evaluate various factors that could contribute to this low rate of use of PD at a tertiary-care state-run hospital in Northern India. METHODS: All the patients who entered our HD or PD program from August 2001 to December 2003 were interviewed using a preset questionnaire. The questionnaire recorded their basic disease and comorbidity, social and demographic characteristics, awareness of the various modalities of renal replacement therapy (RRT), and the reasons for choosing their present modality of therapy. Treating nephrologists were also interviewed with respect to the factors that, in their opinion, were responsible for the limited use of PD at our institute. RESULTS: In total, 342 patients on HD, 66 patients on PD, and 24 nephrologists were interviewed. The rate of PD use was 16.2%. Mean age of patients on HD and PD was 34.6 +/- 11.8 years and 62.9 +/- 10.3 years respectively (p < 0.0001). The incidence of diabetes mellitus and coronary artery disease in the HD and PD populations was 2.5% and 62.5%, and 9.1% and 46.7% respectively (p < 0.0001 for both). Only 30.4% of patients on HD were aware of PD as a modality of RRT and 83.6% of them found PD to be expensive, 65.4% had low enthusiasm toward a domiciliary therapy such as PD, and 61.5% were not recommended PD by their nephrologist. Only 5 (7.6%) patients were initiated on PD directly, the remaining 61 patients were shifted from HD after a mean duration on HD of 185.3 +/- 15.4 days: 67.1% were shifted due to poor tolerance of HD, 29.4% were advised to shift to PD because of comorbidity and vascular access problems, and only 3.3% took up PD because of the independent lifestyle it offered. None of the interviewed nephrologists routinely discussed PD in predialysis counseling. They found financial constraints (100%), lack of patient enthusiasm (100%), doubtful patient compliance (83.2%), and lack of an organized PD program (79.2%) to be the main factors limiting more widespread use of PD at our institute. CONCLUSIONS: Peritoneal dialysis is an underused modality of RRT at our institute. The patients who are taken up for PD at our institute are elderly and have a higher incidence of other comorbid conditions, such as diabetes mellitus and coronary artery disease. Also, most patients who switch to PD do so due to their unsuitability for HD rather than by their own choice. The factors contributing to this low rate of use of PD are ignorance of PD, increased cost of therapy, low enthusiasm toward domiciliary therapy, and lack of adequate infrastructure for PD at our institute. Effective predialysis counseling, reduction in the cost of the therapy, and development of an adequate infrastructure can increase the rate of use of PD.