Ramyashree Tummala

Specific antidotes against direct oral anticoagulants: A comprehensive review of clinical trials data

The Vitamin K antagonist warfarin was the only oral anticoagulant available for decades for the treatment of thrombosis and prevention of thromboembolism until Direct Oral Anticoagulants (DOACs); a group of new oral anticoagulants got approved in the last few years. Direct thrombin inhibitor: dabigatran and factor Xa inhibitors: apixaban, rivaroxaban, and edoxaban directly inhibit the coagulation cascade. DOACs have many advantages over warfarin. However, the biggest drawback of DOACs has been the lack of specific antidotes to reverse the anticoagulant effect in emergency situations. Activated charcoal, hemodialysis, and activated Prothrombin Complex Concentrate (PCC) were amongst the nonspecific agents used in a DOAC associated bleeding but with limited success. Idarucizumab, the first novel antidote against direct thrombin inhibitor dabigatran was approved by US FDA in October 2015. It comprehensively reversed dabigatran-induced anticoagulation in a phase I study. A phase III trial on Idarucizumab also complete reversal of anticoagulant effect of dabigatran. Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively. It is currently being studied in ANNEXA-4, a phase IV study. Aripazine (PER-977), the third reversal agent, has shown promising activity against dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH. This review article summarizes pharmacological characteristics of these novel antidotes, coagulations tests affected, available clinical and preclinical data, and the need for phase III and IV studies.

Failure Mechanisms and Neoatherosclerosis Patterns in Very Late Drug-Eluting and Bare-Metal Stent Thrombosis

Background—There are few clinical studies on the pathophysiological mechanisms of very late stent thrombosis (VLST). We report optical coherence tomography findings in patients with VLST and compare the findings between bare-metal stents (BMS) and drug-eluting stents (DES). Methods and Results—We conducted a registry of stent thrombosis at 4 North American centers with optical coherence tomography imaging programs SAFE registry (The Study of Late Stent Failure Evaluated by OCT). Images were acquired in 61 patients (42 DES and 19 BMS) presenting with definite VLST. The median duration from implantation to VLST presentation was 51.4 months in the DES and 69.9 months in the BMS group (P=0.011). Uncovered and malapposed struts were observed in 70.5% (43/61) and 62.3% (38/61) of patients, respectively, whereas neoatherosclerosis was revealed in 49.2% (30/61). Stent underexpansion was observed in 42.4% of patients. Malapposed struts and stent underexpansion were more frequently demonstrated in DES than in BMS patients, whereas neoatherosclerosis was frequently observed in BMS (40.5% in DES and 68.4% in BMS; P=0.056). The percentage of frames with neoatherosclerosis was lower in DES than in BMS (15.56% [12.24–28.57] versus, 56.41% [40.74–70.00], respectively; P<0.001). Maximum consecutive lipid neointima length was shorter in DES than in BMS (2.4 [1.2–3.6] and 5.3 [3.0–7.0] mm; P=0.011). Conclusions—Optical coherence tomography imaging demonstrated that VLST in DES and BMS had a wide variety of abnormal findings, such as neoatherosclerosis, uncovered strut, and malapposed strut. Neoatherosclerosis and lipid neointima were more frequently observed and had more longitudinal extension in BMS compared with DES.

Combined Neprilysin and RAS Inhibition in Cardiovascular Diseases: A Review of Clinical Studies.

Abstract: The aim of this comprehensive review article is to emphasize on the possible exploration of a new therapeutic approach in the management of heart failure (HF) and other cardiovascular diseases: the renin–angiotensin–aldosterone system–neprilysin combination inhibitors, also called angiotensin receptor neprilysin inhibitor, valsartan/sacubitril (LCZ696). Sacubitril is an inhibitor of neutral endopeptidase (NEP) which degrades vasoactive peptides such as atrial natriuretic peptide and brain natriuretic peptide. Valsartan is an angiotensin receptor blocker which is usually used in hypertension. Although HF has been a global health burden, for decades there has been lack of novel therapeutic options as many trials failed due to potential side effects. With the published results of the landmark trial Prospective comparison of ARNI with ACEI to Determine the Impact on Global Mortality and morbidity in HF (PARADIGM-HF), a new direction in the treatment of HF is anticipated. This trial showed that LCZ696 was able to reduce the primary composite end point of cardiovascular death or HF hospitalization, and similar reduction was observed for cardiovascular death. This review article also highlights the results of 4 published trials of LCZ696 in both HTN and HF. After the results of PARADIGM-HF trial, the major challenge will be outcome in regular clinical practice, as subjects in the trial were mostly stable New York Heart Association class II patients with no comorbidities. In addition, many trials are simultaneously in progress regarding the use of LCZ696 in patients with diabetes, renal failure, and hepatic impairment. To conclude, sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HF, but it will need meticulous attention when used in real outpatient practice.

Peripheral vascular interventional advances in 2017

Aim of this review is to inform major clinical trials in peripheral vascular interventions in the year of 2017.

Clinical and procedural outcomes with the SAPIEN 3 versus the SAPIEN XT prosthetic valves in transcatheter aortic valve replacement: A systematic review and meta-analysis

The SAPIEN 3 valve (S3V) was designed to overcome the shortcomings of its predecessor, the SAPIEN XT (SXT) valve. We conducted a meta‐analysis to compare their clinical outcomes and procedural characteristics.

Leriche’s syndrome: a rare complication following anterior approach lumbar spinal surgery

Leriche’s syndrome is an aortic occlusive disease, which is due to obliteration of distal aorta above the site of bifurcation of common iliac arteries. The classic triad of symptoms include claudication, impotence, and absent or decreased femoral pulses. It may be acute or chronic in onset. Most of the cases are chronic in nature due to baseline pathophysiology involving atherosclerotic changes in the aorta. There are many causes of acute leriche’s syndrome like surgical manipulation, trauma, thromboembolic disease, hypercoagulability, atrial fibrillation, neoplasm, intraplaque hemorrhage in an aneurysm. Post-surgical Leriche’s syndrome is rare and needs a strong index of suspicion to diagnose. The authors highlight a case of Leriche’s syndrome, as a post-surgical complication and its clinical importance.

A Case of Typical Chest Pain: Takotsubo Cardiomyopathy FollowingRhabdomyolysis

Takotsubo cardiomyopathy (TCM) is a reversible disorder characterized by left ventricular wall apical ballooning precipitated by stressful event. Clinical presentation of this disorder mimics acute coronary syndrome (ACS). We are presenting a case of TCM, which is unique as rhabdomyolysis being the triggering factor. Although, our patient presented with features of NSTEMI on EKG and elevated troponins, diagnosis of TCM was made by echocardiography which showed left ventricular apical wall hypokinesis with Left ventriculogram showing the apical ballooning. The unique feature of the case was the triggering factor being rhabdomyolysis.

Utility of ankle-brachial index in screening for peripheral arterial disease in rural India: A cross-sectional study and review of literature

Background Peripheral arterial disease (PAD) is an underdiagnosed illness often affecting the elderly population. Ankle brachial index (ABI) is a good diagnostic tool for PAD in outpatient practice, but remains underused. Materials and methods Patients were recruited from an outpatient medical camp in rural India, and assessed for symptoms and pre-existing risk factors. Measured ABI ≤ 0.9 was considered abnormal and considered PAD. Results Out of 100 patients recruited, PAD was diagnosed in 57 patients. Associated risk factors were like age >55 years (67%), hypertension (66%), smoking (69%) and diabetes mellitus (35%) were common. Conclusion PAD is a very common and underdiagnosed illness in rural India. A simple tool like ABI can help diagnosis in underserved areas.