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.     

Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: Implications for immunoadjuvant potential

Ethnopharmacological relevance

Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations.

Aim of the study

To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals.

Materials and methods

We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside^®) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls.

Results

Treatment with ARE (100 mg/(kg b.w. p.o.)) resulted in significant increase of CD3⁺ and CD4/CD8⁺ percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes.

Conclusion

The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential.     

Insights into the assessment of myocardial perfusion offered by different cardiac imaging modalities

Myocardial perfusion may be very broadly defined as the tightly regulated nutrient delivery to cardiac tissue. The different components of perfusion are myocardial blood flow, oxygen delivery, myocardial oxygen consumption, and myocardial blood volume. Historically, focus has been placed mostly on the assessment of blood flow. In many instances, knowledge of flow without information about these other aspects is inadequate. This review discusses the various cardiac imaging techniques used for the assessment of myocardial perfusion that represent diverse physiologic measures of “perfusion.” Their strengths and limitations are discussed as is their relevance to specific clinicopathologic conditions. Significant work still needs to be performed before all the aspects of myocardial perfusion can be precisely measured in human beings. Supported in part by a grant (R01-HL48890) from the National Institutes of Health, Bethesda, Md. Dr. Lindner is the recipient of a Fellowship Training Grant from the Virginia Affiliate of the American Heart Association, Glen Allen, Va. Dr. Kaul is an Established Investigator of the National Center of the American Heart Association, Dallas, Texas.     

Transmyocardial revascularization ameliorates ischemia by attenuating paradoxical catecholamine-induced vasoconstriction

Background  The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates ischemia by reversing paradoxical catecholamine-induced vasoconstriction. Methods and Results  Chronic ischemic cardiomyopathy was created in 11 dogs by placing ameroid constrictors on the proximal coronary arteries and their major branches. Six weeks later, 35 channels were created percutaneously in the left circumflex artery region, with the left anterior descending artery region serving as control. At rest, wall thickening and myocardial blood flow did not change in the treated region, whereas they deteriorated in the control bed. Contractile and myocardial blood flow reserve increased in the treated region but deteriorated in the control region. There was diminished iodine 123 metaiodobenzylguanidine uptake and a significant reduction in noradrenergic nerves in the treated region compared with the control region, with a corresponding reduction in tissue tyrosine hydroxylase activity. Conclusions  We conclude that the absence of a catecholamine-induced reduction in MBF reserve and contractile reserve in the TMR-treated region with associated evidence of neuronal injury indicates that the relief of exercise-induced ischemia after TMR most likely results from reversal of paradoxical catecholamine-induced vasoconstriction. These findings may have implications in selecting patients who would benefit from TMR. Supported in part by grants from the National Institutes of Health (R01-HL66034 and K-08-HL074290-01). Bethesda. Md. The radio-labeled microspheres were provided by DuPont Pharmaceuticals, North Billerica. Mass, and the ultrasound equipment was supplied by Philips. Andover, Mass. Dr Leong-Poi was the recipient of a Fellowship Training Grant from the Canadian Institute of Health Research and the Heart and Stroke Foundation of Canada.     

A parallel group randomised comparative study of felodipine and nifedipine in hypertension.

We compared the antihypertensive effects and tolerability of a new calcium channel antagonist felodipine with nifedipine in an open randomised parallel group study in 49 patients with moderate hypertension (diastolic blood pressure 105-120 mm Hg). After two weeks run in period felodipine 5 mg and 10 mg once daily was compared with nifedipine 10 mg tid for an active treatment period of 4 weeks. Twenty three patients (mean age 42 +/- 10 years) received felodipine 5 mg once daily for first 2 weeks and 10 mg once daily for subsequent 2 weeks. Twenty six patients (mean age 45 +/- 9 years) received nifedipine 10 mg tid for 4 weeks. The mean reduction in supine diastolic blood pressure in two groups was 17 +/- 6 mm Hg (nifedipine) and 19 +/- 8 mm Hg (felodipine) (p = NS). The goal diastolic blood pressure of less than or equal to 90 mm Hg was achieved in 31 percent (nifedipine group) and 43.5 percent (felodipine group) of patients (p = NS). Side effects were common with both drugs; however, the tolerability was better with felodipine than with nifedipine. In conclusion felodipine was as effective as nifedipine and had the advantage of once a day dosage.     

Secondary left ventricular injury with haemopericardium caused by a rib fracture after blunt chest trauma

Trauma is the third most common cause of death in the West. In the US, approximately 90,000 deaths annually are traumatic in nature and over 75% of casualties from blunt trauma are due to chest injuries. Cardiac injuries from rib fractures following blunt trauma are extremely rare. We report the unusual case of a patient who fell from a height and presented with haemopericardium and haemothorax as a result of left ventricular and lingular lacerations and was sucessfully operated upon.     

SPIO标记间充质干细胞3TMR成像

目的：探讨小容积动物线圈3.0T临床磁共振扫描仪体外示踪磁标记间充质干细胞的可行性。方法：用GFP转染法将含有不同剂量铁（56ug／ml和560ug／m1）的超顺磁氧化铁（SPIO）标记间充质干细胞。细胞内铁的含量利用原子吸收谱来测量。磁共振扫描和显微镜可以观察培养试管中的磁标记间充质干细胞。     

In Vitro Stimulierung zytotoxischer T-Zellen von Patientinnen mit Mammakarzinom

Ohne Zusammenfassung     

Didanosine (ddl) and stavudine (d4T): Absence of peripheral neurotoxicity in rabbits

Some 20 male New Zealand White rabbits (five/group) were given either didanosine (ddl) or stavudine (d4T) at 750 and 1500 mg/kg body weight/day by oral intubation for 24 wk. An additional group was given 300 mg/kg body weight/day zidovudine (AZT) as a negative control. After 13 weeks the high dose of ddl was lowered from 1500 to 1000 mg/kg body weight/day following the death of one rabbit and continued inappetence in the dose group. The rabbits were observed daily, plasma drug levels were monitored, and electrophysiological measurements of peripheral nerve conduction were performed during the study. Additionally, body weight and food intake were recorded, and clinicopathological parameters were evaluated. Sections of selected peripheral nerves, and dorsal and ventral spinal nerve roots were examined by light and transmission electron microscopy. Although peripheral neuropathy has been reported in rabbits with the nucleoside analogue zalcitabine (ddC), based on clinical observations, electrophysiological measurements, and light and electron microscopy, no evidence of peripheral neurotoxicity was observed in rabbits given either ddl or d4T.