Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.

BACKGROUND: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. METHODS: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. RESULTS: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). CONCLUSIONS: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. CLINICALTRIALS: gov/study/NCT02270242.

Management of Coronary Disease in Patients with Advanced Kidney Disease.

BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

Rationale and design of the TUXEDO-2 India study: Ultra-Thin strUt Supraflex Cruz versus XiencE in a Diabetic pOpulation with multi-vessel disease-2.

BACKGROUND: The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease. AIMS: The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events. METHODS: In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%. CONCLUSIONS: The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).

Ticagrelor with or without Aspirin in High-Risk Patients after PCI.

BACKGROUND: Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).

Serial evaluation of vascular responses after implantation of everolimus-eluting coronary stent by optical coherence tomography.

AIM: To evaluate healing response at strut-level and cross-section level after implanting an ultra-thin strut, everolimus-eluting stent with biodegradable polymer (Tetrilimus) using optical coherence tomography (OCT) at 3 and 6 months. METHODS: This was prospective, multi-centre, single-arm, and investigator-initiated study performed at seven Indian sites between January, 2017 and September, 2018. OCT evaluations were performed in 57 patients who underwent Tetrilimus stent implantation. Follow-up OCT was scheduled at 3 months for first 16 patients and at 6 months for 41 patients. Primary outcomes included degree of strut coverage, malapposition and thickness of neointimal hyperplasia (NIH) over covered struts. RESULTS: Sixty one Tetrilimus stents were implanted to treat 59 lesions in 57 patients. Paired (baseline and follow-up) OCT data was available for 12 patients and 30 patients at 3 and 6 months, respectively. At 3 months, rapid early healing was indicated by 95.48% covered struts per lesion with very low (0.11 ± 0.06 mm) NIH. At 6 months, NIH accumulation was greater (0.21 ± 0.07 mm) as compared to 3 months. 99.77% of struts per lesion were covered at 6 months. There was a very symmetrical healing as shown by very low eccentricity index. There was no difference in vascular healing between stents with small to moderate size vessels (≤3.00 mm) and large size vessels (>3.00 mm). CONCLUSION: Present study demonstrated nearly complete endothelization and low NIH accumulation at 3 and 6 months following implantation of ultra-thin strut everolimus-eluting biodegradable polymer-coated Tetrilimus stent. Moreover, though being an ultra-thin strut stent, there was no difference in vascular healing and eccentricity after implantation of the Tetrilimus stents with smaller and larger diameters.

Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR.

AIMS: Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population. METHODS AND RESULTS: This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status. CONCLUSIONS: Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.

Ticagrelor monotherapy in patients with chronic kidney disease undergoing percutaneous coronary intervention: TWILIGHT-CKD.

AIMS: The aim of this study was to assess the impact of chronic kidney disease (CKD) on the safety and efficacy of ticagrelor monotherapy among patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In this prespecified subanalysis of the TWILIGHT trial, we evaluated the treatment effects of ticagrelor with or without aspirin according to renal function. The trial enrolled patients undergoing drug-eluting stent implantation who fulfilled at least one clinical and one angiographic high-risk criterion. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was a clinical study entry criterion. Following a 3-month period of ticagrelor plus aspirin, event-free patients were randomly assigned to aspirin or placebo on top of ticagrelor for an additional 12 months. Of the 6835 patients randomized and with available eGFR at baseline, 1111 (16.3%) had CKD. Ticagrelor plus placebo reduced the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding as compared with ticagrelor plus aspirin in both patients with [4.6% vs. 9.0%; hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.80] and without (4.0% vs. 6.7%; HR 0.59, 95% CI 0.47-0.75; Pinteraction = 0.508) CKD, but the absolute risk reduction was greater in the former group. Rates of death, myocardial infarction, or stroke were not significantly different between the two randomized groups irrespective of the presence (7.9% vs. 5.7%; HR 1.40, 95% CI 0.88-2.22) or absence of (3.2% vs. 3.6%; HR 0.90, 95% CI 0.68-1.20; Pinteraction = 0.111) CKD. CONCLUSION: Among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events as compared with ticagrelor plus aspirin.

Consensus document: management of heart failure in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a known predisposing factor for heart failure (HF). The growing burden of these two conditions and their impact on health of the individual and on society in general needs urgent attention from the health care professionals. Availability of multiple treatment choices for managing T2DM and HF may make therapeutic decisions more complex for clinicians. Recent cardiovascular outcome trials of antidiabetic drugs have added very robust evidence to effectively manage subjects with this dual condition. This consensus statement provides the prevalence trends and the impact of this dual burden on patients. In addition, it concisely narrates the types of HF, the different treatment algorithms, and recommendations for physicians to comprehensively manage such patients.

Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS.

AIMS: The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS AND RESULTS: We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36-0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54-1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74-1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61-1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96). CONCLUSION: Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02270242.

Safety and efficacy of a sirolimus-eluting coronary stent with ultra-thin strut for treatment of atherosclerotic lesions (TALENT): a prospective multicentre randomised controlled trial.

BACKGROUND: Supraflex is a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts. We aimed to compare Supraflex with the standard of care, Xience, an everolimus-eluting stent with a durable polymer coating, regarding clinical outcomes with a randomised trial in an all-comer population. METHODS: We did a prospective, randomised, single-blind, multicentre study (TALENT) across 23 centres in Europe (the Netherlands, Poland, the UK, Spain, Bulgaria, Hungary, and Italy). Eligible participants were aged 18 years or older, had one or more coronary artery stenosis of 50% or greater in a native coronary artery, saphenous venous graft, or arterial bypass conduit, and had a reference vessel diameter of 2·25-4·50 mm. Patients underwent percutaneous coronary intervention in an all-comer manner. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts (Supraflex) or an everolimus-eluting stent with a durable polymer coating (Xience). Randomisation was done by local investigators by use of a web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between groups at 12 months after the procedure, assessed in an intention-to-treat population. On assumption of 1-year composite endpoint prevalence of 8·3%, a margin of 4·0% was defined for non-inferiority of the Supraflex group compared with the Xience group. This trial is registered with ClinicalTrials.gov, number NCT02870140. FINDINGS: Between Oct 21, 2016, and July 3, 2017, 1435 patients with 1046 lesions were randomly assigned to Supraflex, of whom 720 received the index procedure, and 715 patients with 1030 lesions were assigned to Xience, all receiving the index procedure. At 12 months, the primary endpoint had occurred in 35 patients (4·9 %) in the Supraflex group and in 37 patients (5·3%) in the Xience group (absolute difference -0·3% [one-sided 95% upper confidence bound 1·6%], pnon-inferiority<0·0001). Definite or probable stent thrombosis prevalence, a safety indicator, was low in both groups and did not differ between them. INTERPRETATION: The Supraflex stent was non-inferior to the Xience stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. Supraflex seems a safe and effective alternative drug-eluting stent to other stents in clinical practice. FUNDING: European Cardiovascular Research Institute.

New dual peroxisome proliferator activated receptor agonist-Saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: integrated analysis of the real world evidence.

BACKGROUND: Saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) agonist, in clinical trials, has shown an improvement in lipid and glycemic parameters through the PPAR-α and γ agonist actions, respectively. It was granted marketing authorization in India in 2013 for diabetic dyslipidemia. This review was conducted to summarize the effects of Saroglitazar in patients with diabetic dyslipidemia in real world clinical studies conducted after marketing authorization in India. METHODS: In this review, we selected real world clinical studies of Saroglitazar published as manuscripts and abstracts presented at scientific conferences. In all these studies, patients with diabetic dyslipidemia were treated with Saroglitazar 4 mg once daily for at least 12 weeks and different lipid and glycemic parameters were measured at the baseline and end of the study. RESULTS: In 18 selected studies (5 published manuscripts and 13 abstracts), a total of 5824 patients with diabetic dyslipidemia were prescribed Saroglitazar 4 mg for a duration ranging from 12 to 58 weeks. Across all the studies, mean age of patients ranged from 49.6 to 59.1 years and the proportion of female patients ranged from 22% to 42%. Across all the studies, there was a consistent mean reduction in triglyceride levels (~ 45% to 62%), total cholesterol levels (~ 17% to 26%), non-high-density lipoprotein cholesterol levels (~ 21% to 36%), low-density lipoprotein cholesterol levels (~ 11% to 27%), and glycosylated hemoglobin levels (~ 0.7% to 1.6%) with an increase in mean high-density lipoprotein cholesterol levels (up to 9%) from baseline to end of the study. Saroglitazar also improved alanine aminotransferase levels and fatty liver (evaluated by FibroScan™) in non-alcoholic fatty liver disease patients with diabetic dyslipidemia. Body weight remained unchanged and no significant adverse events (AEs) were reported in the studies. CONCLUSION: Saroglitazar effectively improved lipid and glycemic parameters without significant AEs in patients with diabetic dyslipidemia in real-world clinical studies of up to 58 weeks duration.

Paclitaxel-Eluting versus Everolimus-Eluting Coronary Stents in Diabetes.

BACKGROUND: The choice of drug-eluting stent in the treatment of patients with diabetes mellitus and coronary artery disease who are undergoing percutaneous coronary intervention (PCI) has been debated. Previous studies comparing paclitaxel-eluting stents with stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) have produced contradictory results, ranging from equivalence between stent types to superiority of everolimus-eluting stents. METHODS: We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a noninferiority trial design with a noninferiority margin of 4 percentage points for the upper boundary of the 95% confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization at the 1-year follow-up. RESULTS: At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents with respect to the primary end point (rate of target-vessel failure, 5.6% vs. 2.9%; risk difference, 2.7 percentage points [95% confidence interval, 0.8 to 4.5]; relative risk, 1.89 [95% confidence interval, 1.20 to 2.99]; P=0.38 for noninferiority). There was a significantly higher 1-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P=0.005), spontaneous myocardial infarction (3.2% vs. 1.2%, P=0.004), stent thrombosis (2.1% vs. 0.4%, P=0.002), target-vessel revascularization (3.4% vs. 1.2%, P=0.002), and target-lesion revascularization (3.4% vs. 1.2%, P=0.002). CONCLUSIONS: In patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be noninferior to everolimus-eluting stents, and they resulted in higher rates of target-vessel failure, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. (Funded by Boston Scientific; TUXEDO-India Clinical Trials Registry-India number, CTRI/2011/06/001830).

Medical Management and Diagnostic Testing among Stable Angina Patients in India: The STable Angina obseRvational (STAR) Registry.

OBJECTIVE: To study the practice pattern in the management of patients with stable angina (SA) in India. METHODS: The Stable Angina obseRvational Registry (STAR) prospectively enrolled patients provisionally diagnosed with SA by non-interventional practicing internists in India. Patients were followed for 3 months after enrollment to assess medical treatment, diagnostic management, and interventional treatment of coronary artery disease (CAD). At the study conclusion, a statistical analysis retrospectively categorized patients not at risk of CAD by the Morise-Jalisi scale though this was not part of the study protocol. RESULTS: Between January and May 2012, 2079 patients were enrolled at 131 centres. Mean age was 57 ± 11 years, 62% were men, and 40% had a history of diabetes. Over 90% of patients completed follow-up visit, >85% received statins and antiplatelet medications, >70% received beta blockers, and >60% received angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers. Diagnostic testing rates were low: 93% for electrocardiogram, 44% echocardiogram, 42% chest radiography, 12% stress test, and 8% underwent noninvasive CT or invasive coronary angiography, of which, 86% had abnormal results. After the study, the Morise-Jalisi probability of CAD was intermediate in 42% and high in 51% of patients. Only 3.4% of all patients had coronary revascularization. CONCLUSIONS: In a large cohort of Indian patients with SA, disease severity and probability of CAD were high. Clinicians used evidence-based care for medical management, but underutilized diagnostic testing. Patients with SA in India need to be risk-stratified for probability and severity of CAD and, if indicated, receive additional diagnostic testing.

Hypothyroidism in acute coronary syndrome - A prospective Indian study.

BACKGROUND: Evidence suggests that hypothyroidism may be associated with an increased risk of acute coronary syndrome (ACS). The data regarding the influence of hypothyroidism on cardiovascular disease in the Asian population is conflicting. Therefore, we undertook this study to assess the overall prevalence of hypothyroidism in Acute Coronary Syndrome (ACS) patients and determine if there is a relationship between hypothyroidism, both sub-clinical and overt and other significant risk factors of ACS in an Indian population. METHODS: We studied 487 hospitalized patients between March 2018 and February 2021 with a diagnosis of ACS to determine the prevalence of hypothyroidism, both clinical and sub-clinical and their relationship with other known coronary risk factors. Thyroid function Tests - free T3, free T4 and TSH were collected from all the patients within 24 h of their admission to the coronary care unit (CCU) of 2 major hospitals in New Delhi and Imphal (Manipur). RESULTS: Subclinical hypothyroidism was prevalent in 44 (9 %), followed by overt hypothyroidism in 25 (5.2 %). Subclinical hypothyroidism was more common in females, whereas overt hypothyroidism was more common in males. ST Elevation Myocardial Infarction (STEMI) (52 %), followed by Non-ST-Elevation Myocardial Infarction (NSTEMI) (25 %), was the commonest diagnosis at presentation. Patients with overt hypothyroidism showed a higher proportion of increased triglyceride levels. Patients with hypothyroidism had no differences in the prevalence of concomitant diabetes hypertension and other coronary risk factors. CONCLUSIONS: Patients with ACS without known thyroid disorders should be screened for hypothyroidism since it is found frequently. There might be a case to treat their thyroid dysfunction appropriately.

Two-year outcomes after deployment of XIENCE V everolimus-eluting stents in patients undergoing percutaneous coronary intervention of bifurcation lesions: a report from the SPIRIT V single arm study.

The aim of this analysis was to analyze outcomes of patients undergoing Xience V EES treatment of bifurcation lesions, a subset in which treatment is particularly challenging. The SPIRIT V Study provided an evaluation of the Xience V everolimus eluting stent (EES) performance in complex patient and lesion population. The SPIRIT V Single Arm Study enrolled 2700 patients with de novo coronary artery lesions suitable to be optimally treated with a maximum of four planned Xience V EES. Lesion evaluation was by visual assessment. The outcomes of the 492 patients undergoing Xience V EES stenting of ≥1 bifurcation lesion were compared to those with no bifurcation lesion treated. Compared to those without bifurcation treatment, patients with bifurcation treatment were more likely to have multi-vessel disease (49% vs 40%), left main treatment (3.1% vs 0.9%), more lesions treated (1.5 vs 1.3), calcification (36.4% vs 27.5%), and ostial (17.1% vs 8.2%) and angulated lesions (29.3% vs 21.1%), all P < 0.001. The 30-day composite rate of death, myocardial infarction (MI), target vessel revascularization (TVR) was 4.3% in patients with bifurcation PCI and 2.2% in those with non-bifurcation PCI (P = 0.017). At 2 years, this composite event rate was 11.3% and 10.0% in these two groups, respectively (P = 0.403). Rates of cardiac death, MI, target lesion revascularization (TLR), TVR, and ARC defined definite or probable stent thrombosis (0.4% vs 0.9%, P = 0.402) were not significantly different between the two groups. Despite greater patient and lesion complexity, treatment of patients with bifurcation lesions using the Xience V EES in the SPIRIT V prospective Single Arm Study was safe and effective, with low overall event rates that were similar to those without bifurcation lesion treatment. © 2013 Wiley Periodicals, Inc.

Fractional flow reserve: intracoronary versus intravenous adenosine induced maximal coronary hyperemia.

BACKGROUND: Fractional Flow Reserve (FFR), a measure of coronary stenosis severity is based on the achievement of maximal hyperemia of coronary microcirculation. The most widely used pharmacological agent is adenosine which is administered either by intra coronary or intra venous routes. IV route is time consuming, has more side effects and expensive. This study is undertaken to compare the two routes of administration. METHODS: FFR was assessed in 50 patients with 56 intermediate focal lesions using both IV and intracoronary (IC) adenosine. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at maximal hyperemia. RESULTS: A total of 25 left anterior descending, 8 right, 21 circumflex, and 2 left main coronary arteries were evaluated. The mean percent stenosis was 63.91 ± 13.13 SD and, the mean FFR was 0.831 ± 0.0738 SD for IV and 0.832 ± 0.0707 SD for IC adenosine. There was a strong and linear correlation between 2 sets of observations with IV dose and IC adenosine dose (R = 0.964, y = 0.065 + 0.923x; p < 0.001) (y = IV dose, x = IC dose). The agreement between the two sets of measurements was also high, with a mean difference of: 0.001 ± 0.0197. The changes in heart rate and blood pressure were significantly higher in IV adenosine group. Different incremental doses were well tolerated, with fewer systemic adverse events with IC adenosine. Transient AV blocks were observed with both IV and IC adenosine. CONCLUSIONS: This study suggests that IC adenosine is equivalent to IV infusion for the determination of FFR. The administration of IC adenosine is easy to use, cost effective, safe and associated with fewer systemic events.

Angiotensin receptor blockers - advantages of the new sartans.

Advantages of the new angiotensin receptor blockers (ARBs) include once daily dosing, an absence of significant adverse reactions, well tolerated side effect profile and cost effectiveness. A growing realization is their beneficial pleotropic effects. Antihypertensive agents are widely used to reduce the risk of cardiovascular events partly beyond that of blood pressure-lowering. The RAAS, and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. For patients at high cardiovascular risk based on the results of the ONTARGET and TRANSCEND studies, telmisartan is indicated for cardiovascular prevention. Studies have shown that olmesartan medoxomil treatment may slow the progression of atherosclerosis and postpone albuminuria thereby potentially improving CV outcomes.

Post-marketing study of clinical experience of atorvastatin 80 mg vs 40 mg in Indian patients with acute coronary syndrome- a randomized, multi-centre study (CURE-ACS).

OBJECTIVE: To generate comparative clinical data in Indian patients with acute coronary syndrome (ACS) in terms of safety and efficacy of atorvastatin 80 mg vis-à-vis atorvastatin 40 mg MATERIALS AND METHODS: A total of 236 patients with diagnosed ACS (with TIMI Risk score > or = 3) within preceding 10 days were randomized to receive either atorvastatin 80 mg or atorvastatin 40 mg once daily for 12 weeks. Out of 236 patients, data for 173 was analyzed who had both baseline and post-baseline lipid assessment. The primary end point of the trial was percentage change in LDL-C at the end of treatment from baseline. Other end points were change in high sensitivity C reactive protein, incidence of increase in liver enzymes > or = 3 times upper limit of normal and incidence of myotoxicity (with or without elevation of creatinine phosphokinase) at the end of treatment. RESULTS: A dose-dependent response was observed with greater reduction of LDL -C in atorvastatin 80 mg (27.5% vs 19.04%) than that of atorvastatin 40 mg group. Both the treatment groups had a significant reduction (p < 0.001) in LDL-C at the end of 6 and 12 weeks in comparison to baseline. hs-CRP was also significantly reduced (p < 0.001) in both the treatment groups i.e. atorvastatin 80 mg (76.15%) and atorvastatin 40 mg (84.4%) from baseline at the end of 12 weeks. Both doses of atorvastatin were well tolerated. No patient had elevation of (> or = 3 times of upper limit of normal) liver enzymes or creatinine phosphokinase. One patient on atorvastatin 80 mg complained of myalgia. There were no dose-related differences in incidence of adverse events between two treatment groups. CONCLUSION: The CURE-ACS trial indicated that atorvastatin 80 mg was more effective than atorvastatin 40 mg in terms of reduction in LDL cholesterol and was as safe and well tolerated as 40 mg dose in Indian patients with ACS.