over the past year , multiple noteworthy trials with the potential to evolve current clinical practice and guidelines have been presented at international meetings including the american college of cardiology ( acc , san diego , usa , march 2015 ) , european association for percutaneous cardiovascular interventions ( europcr , paris , france , may 2015 ) , american diabetes association ( ada , ma , usa , june 2015 ) , european society of cardiology ( esc , london , uk , august 2015 ) , transcatheter cardiovascular therapeutics ( tct , san francisco , usa , october 2015 ) , heart rhythm congress ( hrc , birmingham , uk , october 2015 ) , and the american heart association scientific sessions ( aha , florida , the authors describe new clinical data placed in the context of acute coronary syndrome ( acs ) , interventional cardiology , heart failure , atrial fibrillation , electrophysiology , and coronary prevention . the results of major clinical trials in cardiology presented at major conferences in 2015 were reviewed by the authors . search terms included  acute coronary syndrome  ,  atrial fibrillation  ,  coronary prevention  ,  electrophysiology  ,  heart failure  , and  interventional cardiology  . trials were selected based on relevance to the cardiovascular ( cv ) community , the potential to change clinical practice , and the potential to guide further phase 3 research . this article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors . advances in heart failure ( hf ) have featured prominently in many 2015 conferences with particular focus on addressing the side effects of currently used drug classes . mineralocorticoid antagonists ( mras ) have a class 1a recommendation for reduction in mortality and hospitalization in patients with heart failure with reduced ejection fraction ( ef ) . however , this drug class is typically under - prescribed due to concerns regarding hyperkalemia and renal impairment in high - risk patients . finerenone is a novel non - steroidal mra with greater receptor selectivity than spironolactone and better receptor affinity than eplerenone in vitro [ 1 , 2 ] , which may have the potential to reduce side effects of hyperkalemia and renal impairment . the arts - hf ( mineralocorticoid receptor antagonist tolerability study - heart failure ) double - blind controlled phase 2b trial ( clinicaltrials.gov # nct01807221 ) randomized 1060 patients with heart failure ( hf ) , type 2 diabetes mellitus ( t2 dm )    chronic kidney disease ( ckd ) to finerenone ( titrated from one of five doses from 2.5 to 20  mg ) or eplerenone ( titrating from 25 to 50  mg ) [ 1 , 2 ] . although the proportion of patients with a relative decrease of 30% in 90-day nt - probnp ( primary endpoint ) was similar in all groups , the measurement of nt - probnp to predict clinical outcome is not well established , and the subgroup of patients receiving finerenone 1020  mg showed a 44% reduction the secondary clinical composite endpoint of 90-day all - cause death , cv death , hospitalization , or emergency presentation for worsening chronic hf [ 1 , 2 ] . finerenone 1020  mg appeared better tolerated than eplerenone with a smaller increase in potassium ( 0.119 vs. 0.262 mmol / l ; p  =  0.016 ) and lower incidence of estimated glomerular filtration rate ( egfr ) decrease > 40% ( 4.2% vs. 9.4% ) [ 1 , 2 ] . hyperkalemia is a common concern in hf patients using renin - angiotensin - aldosterone ( raas ) inhibitors . in a previous trial , opal - hk ( clinicaltrials.gov # nct01810939 ) , investigators showed a short - term sustained decrease in potassium in patients with hf taking the potassium binder patiromer with raas inhibitors . the phase 2 amethyst dn trial ( clinicaltrials.gov # nct01371747 ) assigned 304 patients with ckd , hypertension ( htn ) , t2 dm , serum potassium above 5  meq / l and who were taking raas inhibitors to patiromer ( starting dose stratified by baseline potassium ) . meq / l in patients with hf ( n  =  105 ) or without hf ( n  =  199 ) for up to 1  year ( p  <  0.001 ) . in total , 74% of the hf subgroup completed the trial , 7% withdrew consent , and a further 7% had adverse effects such as diarrhea , hypokalemia , and hypomagnesemia . further studies are planned to assess if improved control of hyperkalemia will translate into survival benefit . renal dysfunction is another common issue with raas inhibitors . a combination of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan ( lcz696 ) was previously shown to decrease the primary endpoint of cv death or hf hospitalization , cv death , and a reduction in all - cause mortality compared with enalapril in the 2014 paradigm - hf study ( prospective comparison of arni with acei to determine impact on global mortality and morbidity in hf ) ( clinicaltrials.gov # nct01035255 ) [ 3 , 6 ] . the renal tolerability of sacubitril / valsartan was presented at the esc congress 2015 . over a 48-month period , egfr decreased by 0.14  ml / min/1.73  m in the enalapril group and 0.11  ml / min/1.73  m in the sacubitril / valsartan groups , respectively ( p  =  0.001 ) . although , it should be noted that patients with an acute initial decline in egfr were excluded from the paradigm - hf study , cv death or hf hospitalization was reduced similarly in the ckd group ( 36% of the study population ) compared to those without baseline ckd ( hr 0.790 vs. 0.799 ; p  =  0.90 for interaction ) ,   suggesting a favorable cardiorenal profile . the value of mra treatment in mild heart failure has already been established by the prior emphasis - hf study ( eplerenone in mild patients hospitalization and survival study in heart failure ) ( clinicaltrials.gov # nct00232180 ) in which eplerenone reduced the rate of cv death or hf hospitalization ( 18.3% vs. 25.9% ; hr 0.63 ) among patients with new york heart association ( nyha ) class ii symptoms and an ef 35% . the potential for extension of mra use to patients without previously diagnosed hf was investigated by the open label albatross ( aldosterone lethal effects blockade in acute myocardial infarction treated with or without reperfusion to improve outcome and survival at six months follow - up ) ( clinicaltrials.gov # nct01059136 ) trial in which 1600 patients without known hf were randomized to spironolactone or control within 72  h of mi ( myocardial infarction ) . although there was a suggestion of benefit in the st elevation subgroup ( 1229 ) , overall , no significant difference was found in the primary composite endpoint of death , resuscitated cardiac death , ventricular fibrillation / ventricular tachycardia , hf , or indication for implantable cardiac defibrillator at 6  months [ hr 0.97 ; 95% confidence interval ( ci ) 0.731.28 ; p  =  0.81 ]   and thus results do not justify extension of mra use at present . the prevention of cardiac dysfunction during adjuvant cancer therapy ( prada ) trial ( clinicaltrials.gov # nct01434134 ) randomized 126 breast cancer patients with a baseline ef of > 50% being treated with anthracycline    trastuzumab and radiation to a protective strategy of candesartan or metoprolol vs. placebo . patients receiving candesartan had a significantly smaller decline in ef from baseline vs. placebo ( 0.8% vs. 2.6% ; p  =  0.026 ) . although small in size , this study suggests potential benefit from candesartan therapy in this patient group . previous studies have yielded conflicting conclusions regarding the mortality effect of digoxin among patients with congestive heart failure ( chf ) [ 11 , 12 ] . thus conducted an observational study using a danish nationwide registry of patients discharged from hospital with both hf and atrial fibrillation ( af ) , excluding those receiving antiarrhythmic therapy ( e.g. , amiodarone ) , those who died within 30  days of discharge , and those not taking a vitamin - k antagonist , then matching the 8078 digoxin - treated patients with 8078 control patients , based on age , sex , comorbidities , cha2ds2vasc score , medication , and heart - failure severity . the risk of death was reduced [ hazard ratio ( hr ) 0.92 ; ( ci 95% 0.860.98 ) and risk of readmission increased hr 1.07 ; 95% ci 1.011.12 ] with digoxin users . when death was considered as a competing risk , the collective incidences of readmission were similar at 64.9% in digoxin users and 64.4% in non - users . the authors concluded that in digoxin - naive patients with af , digoxin use was associated with a slightly reduced risk of death . a novel heart failure strategy may be attenuation of myocyte sodium overload by beta 3 agonists . in the beta 3 agonists treatment in hf ( beat - hf ) trial ( clinicaltrials.gov # nct01876433 ) [ 14 , 15 ] , 70 patients with hf were randomized to the beta 3 agonist mirabegron or placebo for 6  months [ 14 , 15 ] . while mirabegron was not associated with improvement in patients with a baseline ef > 40% ( mean difference 0.4% ; 95% ci 3.5 to 3.8 ; p  =  0.82 ) an exploratory analysis of patients with a baseline ef 40% noted a 5.5% increase in ef ( 95% ci 0.610.4 ; p  <  0.03 ) [ 14 , 15 ] . further studies are thus planned in patients with severe heart failure . since some diabetes therapies including some thiazolidinediones and some dpp-4 inhibitors have been associated with an increased risk of hf events , new diabetes therapies require rigorous evaluation of cv safety . tecos ( trial evaluating cardiovascular outcomes with sitagliptin ) ( clinicaltrials.gov # nct00790205 ) randomized 14,671 patients with diabetics and cv disease ( history of major coronary artery disease , ischemic cerebrovascular disease , or atherosclerotic peripheral arterial disease ) to sitagliptin vs. placebo . at 3  years , there was no difference in the primary endpoint of cv death , non - fatal mi , non - fatal stroke , or hospitalization for unstable angina for with sitagliptin vs. placebo ( 11.4% vs. 11.6% ; p  <  0.001 for noninferiority ) , no difference in total hf hospitalization events ( 345 vs. 347 placebo ; p =  0.996 ) [ 16 , 17 ] and in the subgroup of patients with hf at baseline , no significant difference in hospitalization for hf ( 7.4% vs. 7.0% hr 1.03 ; 95% ci 0.771.36 ; p  =  0.86 ) . thus , in contrast to some previous gliptin data , no signal to increased hf was seen , which could reflect differences in clinical or patient factors , or a potential intrinsic pharmacologic difference among the dpp-4 inhibitors [ 18 , 19 ] . the sodium glucose cotransporter 2 ( sglt2 ) is responsible for 90% of reabsorption of urinary glucose . inhibition of sglt2 has been found to significantly reduce hba1c , weight , and blood pressure and may augment natriuresis [ 20 , 21 ] . empa - reg outcome ( clinicaltrials.gov # nct01131676 ) randomized 7020 patients with t2 dm and at high cv risk to the highly selective sglt2 inhibitor empagliflozin ( 10 or 25  mg ) or placebo [ 20 , 21 ] . hf was not an exclusion although most patients did not have hf at baseline [ 20 , 21 ] . empagliflozin was associated with a 14% reduction in the primary composite outcome of cv death , nonfatal mi , or nonfatal stroke ( 10.5% vs. 12.1% ; hr 0.86 ; 95% ci 0.740.99 ; p  =  0.0382 for superiority ) largely driven by a 38% reduction in cv death ( 3.67% vs. 5.87% ; hr 0.62 ; 95% ci 0.490.77 ; p  <  0.0001 ) . empagliflozin was also associated with a 34% reduction in hf hospitalization or cv death ( hr 0.66 ; 95% ci 0.550.79 ; p  <  0.0001 ) and 39% reduction in hospitalization for , or death from , hf ( hr 0.61 ; 95% ci 0.470.79 ; p  =  0.0002 ) . although these findings were consistent in both patients with and without hf at baseline , numerically there were very few events in patients without baseline hf . augment - hf ( clinicaltrials.gov # nct01311791 ) assessed the clinical impact of an alginate - hydrogel lv epicardial implant placed during open thoracotomy ( fig .  1 ) , of 78 patients with advanced hf and lef 35% randomized to the alginate implant or placebo , 58 patients completed 1-year follow - up . peak vo2 was significantly improved in the alginate group ( mean increase 2.10  ml / kg / min ; 95% ci 0.963.24 ; p  <  0.001 ) with significantly improved nyha status and 6-min walk test distance ( p  <  0.001 ) . while a note of caution is needed given nine ( 22.5% ) deaths in the alginate vs. four ( 10.5% ) deaths in the control group ( p  =  ns ) , the trial was not powered to assess mortality and further clinical trials are planned for this novel approach .fig . 1augment - hf alginate - hydrogel lv epicardial implantation at the mid - ventricular level ( a ) with equal spacing from the antero - septal groove and ending at the postero - septal groove ( b ) . a prospective comparison of alginatehydrogel with standard medical therapy to determine the impact on functional capacity and clinical outcomes in patients with advanced heart failure ( augmenthf trial ) . eur heart j. 2015 , 36 : 22972309 
  augment - hf alginate - hydrogel lv epicardial implantation at the mid - ventricular level ( a ) with equal spacing from the antero - septal groove and ending at the postero - septal groove ( b ) . reproduced with permission from anker , coats & christian , et al . a prospective comparison of alginatehydrogel with standard medical therapy to determine the impact on functional capacity and clinical outcomes in patients with advanced heart failure ( augmenthf trial ) . eur heart j. 2015 , 36 : 22972309 large infarcts are associated with degradation of extracellular matrix . previous preclinical studies and a small human pilot trial have shown that bioabsorbable cardiac matrix ( bcm ) ik-5001 ( an aqueous mixture of sodium alginate and calcium gluconate ) when given as an intracoronary bolus can flow to the extracellular space where it forms a flexible hydrogel matrix , thickening the infarct zone , reducing lv wall stress , and potentially reducing adverse remodeling . in preservation i ( clinicaltrials.gov # nct01226563 ) , 303 patients with moderate to large stemis ( ef < 35% or mi size > 20% ) were randomized to intracoronary injection of 4  ml bcm ( n  =  201 ) vs. saline control ( n  =  102 ) 25  days after their primary pci . injection of bcm was not associated with any difference vs. saline in the primary endpoint ( change in lv end diastolic volume index ( lvedvi ) from baseline to 6  months ) , or in secondary endpoints including 6-min walk test , nyha grade , cv hospitalization , or death . bcm injection was associated with five temporary angiographic occlusions vs. one with saline . the disappointing discrepancy between pre - clinical data and preservation i findings may have been related to microvascular obstruction and edema preventing entry of bcm into the myocardium . hf may be complicated by sleep - disordered breathing and early treatment may improve outcomes . seventy patients with acute hf diagnosed with sleep apnea by overnight polysomnography within 4  weeks of discharge were treated with continuous positive airway pressure ( cpap ) treatment . of these , 37 ( 53% ) met the definition of good compliance with the cpap device . patients with good cpap compliance showed a significant decrease in 6-month readmission rates after therapy compared with the 6-month readmission rates pre - therapy ( mean    se : 1.5    0.2  events ; p  <  0.0001 ) . better effectiveness after transition  heart failure ( beat hf ) ( clinicaltrials.gov # nct01360203 ) assessed care transition intervention involving pre - discharge education , regular scheduled telephone coaching , and telemonitoring of weight , blood pressure , heart rate , and symptoms in hf patients . overall , there was no significant effect on 30- and 180-day readmission ( 50.8% vs. 49.2% , hr 1.03 ; 95% ci 0.881.20 ; p  =  0.74 ) or 180-day mortality . however , in post hoc analysis , adherence rates with the telephone call and monitoring schedules was noted to be variable . patients with good telephone call adherence ( > 50% calls completed ) had lower 180-day mortality compared to non - adherent patients ( 8.3% vs. 26% ; p    0.001 ) [ 25 , 26 ] . patients with good remote monitoring adherence ( > 50% days ) had lower 180-day mortality ( 6.6% vs. 21.4% ; p    0.001 ) and lower 180-day readmission rates ( 41.3% vs. 61.1% ; p    0.001 ) [ 25 , 26 ] . while good adherence to a telephone and telemonitoring program appears to be of clinical benefit , as this was a post hoc observation , further prospective investigation is needed . until recently , the absence of a specific reversal agent for non - vitamin k antagonist oral anticoagulants ( noacs ) has been seen as a limitation . in late 2015 , the first specific reversal agent  idarucizumab  was approved for reversal of the direct thrombin inhibitor dabigatran . approval was based on interim results of reverse - ad ( clinicaltrials.gov # nct02104947 ) [ 28 , 29 ] in 90 patients51 with serious bleeding ( group a ) and 39 requiring an urgent procedure ( group b ) . the anticoagulant effects of dabigatran were rapidly ( within minutes ) and completely reversed in 88 to 98% of the patients who had had elevated clotting times at baseline . unbound dabigatran concentration at 24  h remained below 20  ng / ml in 79% of patients . one thrombotic event occurred within 72  h of idarucizumab in a patient who had not received anticoagulant re - initiation . factor xa oral anticoagulants do not yet have an approved reversal agent but andexanet alfa  a recombinant engineered version of human factor xa with the ability to bind factor xa inhibitors  has been tested in healthy older ( aged 5075 ) volunteers receiving apixaban 5  mg twice daily or rivaroxaban 20  mg once daily . in apixaban participants , andexanet alfa reduced anti - xa activity by 94% ( vs. 21% receiving placebo ; p  <  0.001 ) and thrombin generation was fully restored in 100% ( vs. 11% receiving placebo ; p  <  0.001 ) within 2 to 5  min . among the rivaroxaban participants , andexanet alfa reduced anti - factor xa activity by 92% ( vs. 18% receiving placebo ) and thrombin generation was fully restored in 96% ( vs. 7% receiving placebo ; p  <  0.001 ) . a phase iiib / iv trial is now recruiting patients with active bleeding , treated with andexanet . balancing antithrombotic efficacy with bleeding safety regulate - pci ( clinicaltrials.gov # nct01848106 ) , randomized patients undergoing pci to the novel anti ixa anticoagulant pegnivacogin ( n  =  1616 ) prior to pci with administration of the specific reversal agent anivamersen at the end of the pci , or to bivalirudin ( n  =  1616 ) ( standard bolus , plus infusion for the duration of the pci ) . the trial was halted early as 10/1605 ( 0.6% ) patients had severe allergic reactions with the novel regimen ( including one fatality ) compared to one severe allergic reaction with bivalirudin and had higher rates of bleeding ( p  =  0.002 ) . however , the primary efficacy outcomes were similar between the two groups , thus suggesting that factor ixa could be a potential target if the allergy issues could be addressed . the assessment of an education and guidance programme for eliquis adherence in non - valvular atrial fibrillation ( aegean ) ( clinicaltrials.gov # nct01884350 ) study assessed the impact of an educational program on adherence to apixaban for stroke prevention in af . adherence and persistence were measured by an electronic monitoring device , with non - adherence defined as a 24-h period where two tablets were missed and non - persistence a 30-day period of discontinuation . adherence was 88.51% for standard care and 88.34% for the educational programme ( p  =  0.89 ) at week 24 . persistence at 24  weeks was 90.5% with standard care and 91.1% with an educational programme ( p  =  0.7 ) . the authors concluded there was no additional value found so far with an educational programme in the first 6  months of treatment . currently , transcatheter aortic valve replacement ( tavr ) is indicated principally in patients at high surgical risk . in the nordic aortic valve intervention trial ( notion ) ( clinicaltrials.gov # nct01057173 ) , 280 patients with severe aortic stenosis , an age over 70 but otherwise deemed low risk by the sts ( society of thoracic surgeons ) score ( 81% with a score < 4 ) , and deemed suitable for either procedure at a multidisciplinary conference , were randomized to tavr ( corevalve medtronic n  =  145 ) or surgical aortic valve replacement ( savr n  =  135 ) . tavr compared with savr 
 was associated with a similar incidence in the primary endpoint of composite death , stroke , or mi ( 13.1% vs. 16.3% , p  =  0.43 . ) , less major bleeding ( 11.3% vs. 20.9% p  =  0.03 ) , less cardiogenic shock ( 10.4% vs. 4.2% ( p  =  0.05 ) , less acute kidney injury ( 0.7% vs. 6.7% p  =  0.01 ) and less new / worsening af at 1  year ( 21.2% vs. 59.4% ; p  < 0.001 ) although a higher incidence of pacemaker requirement ( 38% vs. 2.4% ; p  <  0.001 ) and higher incidence of moderate to severe aortic regurgitation at 1  year ( 15.7% vs. 0.9% ; p  <  0.001 ) . echocardiography rather than computed tomography ( ct ) was routinely used for pre - procedure measurements , and low tavr placement was felt to contribute to conduction abnormalities . although underpowered , notion suggests tavr may be a reasonable alternative to surgical intervention even in low - risk patients . deflect 3 ( clinicaltrials.gov # nct02070731 ) was a small ( n  =  85 ) randomized trial investigating the use of the triguard embolic deflecting device vs. control in patients undergoing tavr . complete three - vessel cerebral coverage was achieved in 88.9% of patients assigned to triguard . no significant difference in macce ( major adverse cardiac or cerebrovascular events ) defined as death , stroke , life - threatening or disabling bleeding , acute kidney injury , or major vascular complications was noted ( triguard 21.7 vs. control 30.8% subjects p  =  0.34 ) . however , patients with full three - vessel coverage had greater freedom from new brain lesions on magnetic resonance imaging ( 3.1% vs. 15.4% ) ( fig . 2 ) , fewer new neurological deficits ( national institutes of health stroke scale 3.1% vs. 15.4% ) , and a greater than twofold increase in cognitive recovery at 30  days ( assessed by montreal cognitive assessment scores ) .fig .  2deflect iii ( a)% patients with complete freedom from ischemic brain lesions in the intention - to - treat and per - treatment analysis populations . b per - subject median single and maximum lesion volumes in the intention - to - treat and per - treatment analysis populations . c proportion of subjects experiencing a total lesion volume by diffusion - weighted magnetic resonance imaging in the given size range . reproduced with permission from lansky , schofer and tchetche , et al . a prospective randomized evaluation of the triguard hdh embolic deflection device during transcatheter aortic valve implantation : results from the deflect iii trial . eur heart j. 2015 ; 36 : 20702078 
  deflect iii ( a)% patients with complete freedom from ischemic brain lesions in the intention - to - treat and per - treatment analysis populations . b per - subject median single and maximum lesion volumes in the intention - to - treat and per - treatment analysis populations . c proportion of subjects experiencing a total lesion volume by diffusion - weighted magnetic resonance imaging in the given size range . reproduced with permission from lansky , schofer and tchetche , et al . a prospective randomized evaluation of the triguard hdh embolic deflection device during transcatheter aortic valve implantation : results from the deflect iii trial . eur heart j. 2015 ; 36 : 20702078 the partner ii ( placement of aortic transcatheter valves ) trial ( clinicaltrials.gov # nct01314313 ) evaluated use of valve - in - valve tavr using the edwards sapien xt among 197 patients with severe aortic stenosis or regurgitation , a previous surgical bioprosthetic aortic valve and high operative risk . patients had to be suitable for 23-mm or 26-mm valve and patients with surgical valves < 21  mm were excluded . at 1  year , the primary endpoint of all - cause mortality was 13.4% , cardiac mortality was 8.9% , stroke rate was 3.7% , and rehospitalization rate was 11.8% . significant clinical benefit compared with baseline was noted for nyha status , 6-min walk test , and quality of life . although non - randomized and sizing issues restrict the applicable population , partner ii suggests sapien xt is a potential alternative to corevalve for valve - in - valve procedures . in contrast to aortic valve disease , conventional surgery remains the primary treatment for mitral regurgitation in most patients . two - year results of a randomized trial ( clinicaltrials.gov # nct00807040 ) comparing surgical mitral - valve repair with surgical mitral - valve replacement in 251 patients with severe ischemic mitral regurgitation were presented at aha 2015 . there was no significant difference in mean left ventricular end - systolic volume index at 2  years ( 52.6 vs. 60.6  ml / m ) for repair vs. replacement , and no difference in 2-year mortality ( 19.0% vs. 23.2% hr 0.79 ; 95% ci 0.461.35 ; p  =  0.39 ) . however , repair was associated with a higher rate of moderate or severe mitral regurgitation ( 58.8% vs. 3.8% ; p  <  0.001 ) , serious adverse events related to hf ( p  =  0.05 ) and cv readmissions ( p  =  0.01 ) . ten - year data from the respect trial , investigating the amplatzer pfo ( patent foramen ovale ) ( st jude medical ) ( clinicaltrials.gov # nct00465270 ) in preventing recurrent stroke in patients with previous cryptogenic ischemic stroke ( n  =  499 ) vs. guideline - directed therapy ( n  =  481 ) were presented at tct 2015 . pfo closure was not associated with significant reduction in all - cause strokes in the overall intention - to - treat analysis ( 18 vs. 24 ; p  =  0.16 ) but was associated with a significant reduction in cryptogenic stroke ( 10 vs. 19 ; hr 0.46 ; p  =  0.042 ) . in patients < 60  years , pfo closure was associated with a 52% reduction in all - cause stroke ( p  =  0.035 )   and in those with atrial septal aneurysmal or substantial shunts , pfo closure was associated with a 75% reduction in all - cause stroke ( p  =  0.007 ) . there was no intra - procedure stroke , no device embolization , no device thrombosis , no device erosion , a very low rate of major vascular complications ( 0.9% ) and device explants ( 0.4% ) . despite use of high - dose statin and ezetimibe , patients with elevated ldl cholesterol can remain at elevated cv risk . proprotein convertase subtilisin - kexin type 9 ( pcsk9 ) reduces ldl - receptor recycling , resulting in a decrease of ldl - c receptors on the surface of hepatocytes and an increase of plasma ldl - c . inhibition of pcsk9 leads to an increase in surface ldl - c receptors with subsequent lowering of plasma levels of ldl - c ( fig . the ldlr is a cell - surface glycoprotein that is synthesized in the er and processed in the golgi apparatus , and transported to the cell surface . the resulting receptor  ligand complex is then internalized by endocytosis , which involves the ldlrap1 . ldl complex extracellularly and prevents it from dissociating within the vesicle , thus targeting the whole complex for degradation in the lysosomal compartment . b antibody to pcsk9 prevents the binding of pcsk9 to the ldlr  ldl complex . the receptor is recycled to the cell surface , whereas the ldl particle is degraded in the lysosomal compartment . accumulation of free cholesterol released by hydrolysis of cholesteryl esters in the core of ldl inactivates srebp . ldl , low - density lipoprotein ; apob , apolipoprotein b ; er , endoplasmic reticulum ; ldlr , ldl receptor ; ldlrap1 , ldl receptor adaptor protein 1 ; pcsk9 , pro - protein convertase subtilisin / kexin type 9 ; srebp , sterol regulatory element - binding protein . reproduced with permission from hovingh , davidson and kastelein , et al eur heart j. 2013 ; 34 : 962971 
  catabolism of the ldl particle ; the role of pcsk9 and antibody to pcsk9 . the ldlr is a cell - surface glycoprotein that is synthesized in the er and processed in the golgi apparatus , and transported to the cell surface . the resulting receptor  ligand complex is then internalized by endocytosis , which involves the ldlrap1 . pcsk9 binds the ldlr  ldl complex extracellularly and prevents it from dissociating within the vesicle , thus targeting the whole complex for degradation in the lysosomal compartment . b antibody to pcsk9 prevents the binding of pcsk9 to the ldlr  ldl complex . the receptor is recycled to the cell surface , whereas the ldl particle is degraded in the lysosomal compartment . accumulation of free cholesterol released by hydrolysis of cholesteryl esters in the core of ldl inactivates srebp . ldl , low - density lipoprotein ; apob , apolipoprotein b ; er , endoplasmic reticulum ; ldlr , ldl receptor ; ldlrap1 , ldl receptor adaptor protein 1 ; pcsk9 , pro - protein convertase subtilisin / kexin type 9 ; srebp , sterol regulatory element - binding protein . reproduced with permission from hovingh , davidson and kastelein , et al . diagnosis and treatment of familial hypercholesterolemia . eur heart j. 2013 ; 34 : 962971 in an open - label extension study of osler-1 ( clinicaltrials.gov # nct01439880 ) and osler-2 ( clinicaltrials.gov # nct01854918 ) patients were randomly assigned in a 2:1 ratio to receive the pcsk9 inhibitor evolocumab ( 140  mg every 2  weeks or 420  mg monthly ) plus standard therapy ( n  =  2976 ) or standard therapy alone ( n  =  1487 ) . at 1  year , evolucamab reduced ldl by 61% from a median 12048  mg / dl ; p  <  0.001 ) . evolucamab was not associated with an increase in serious adverse events ( 7.5% vs. 7.5% ) although neurocognitive side effects were more frequent ( 0.9% vs. 0.3% ) . exploratory analysis suggested evolucamab was associated with a reduction in the endpoint of combined cv events ( 0.95% vs. 2.18% ; hr 0.47 ; 95% ci 0.280.78 ; p  =  0.003 ) which will be further assessed in the fourier ( further cardiovascular outcomes research with pcsk9 inhibition in subjects with elevated risk ) study ( clinicaltrials.gov # nct01764633 ) . a second pcsk9 inhibitor , alirocumab , was evaluated in the odyssey long term study ( clinicaltrials.gov number # nct01507831 ) in which 2341 patients with ldl cholesterol > 1.8 mmol / l despite maximum tolerated statin were randomized in 2:1 ratio to alirocumab ( 150  mg ) or placebo subcutaneous injection every 2  weeks for 78  weeks . at week 24 , ldl - c in the alirocumab group had dropped 62% more from baseline than with placebo ( p  <  0.001 ) ; an effect that remained consistent over 78  weeks . patients receiving alirocumab reported higher rates of myalgia ( 5.4% vs. 2.9% ) , neurocognitive events ( 1.2% vs. 0.5% ) , and ophthalmologic events ( 2.9% vs. 1.9% ) . in exploratory post hoc analysis , mace events ( chd death , mi , ischemic stroke , or unstable angina requiring hospitalization ) were 48% lower with alirocumab ( 1.7% vs. 3.3% ; hr 0.52 ; 95% ci 0.310.90 ; nominal p  =  0.02 ) , which will be further assessed in the ongoing 18,000-patient , 5-year odyssey outcomes study ( clinicaltrials.gov number # nct01663402 ) . less than one - third of smokers hospitalized with an acute coronary syndrome remain abstinent following discharge , but the safety of varenicline in this setting remained to be established . the evaluation of varenicline in smoking cessation for patients post - acute coronary syndrome ( evita ) study ( clinicaltrials.gov # nct00794573 ) randomized smokers ( 10 cigarettes per day ) with acute coronary syndrome ( acs ) to varenicline or placebo . the primary endpoint ( self - reported cessation at 24  weeks confirmed by carbon monoxide testing ) was achieved in 47.3% of those receiving varenicline vs. 32.5% receiving placebo ( p  =  0.012 ; number needed to treat 6.8 ) . at follow - up , continuous abstinence was reported in 35.8% vs. 25.8% ( p  =  0.081 ) and rates of 50% reduction in cigarettes were 67.4% vs. 55.6% ( p  =  0.05 ) . there was no significant difference in adverse events except for a higher incidence of abnormal dreams with varenicline ( 15.2% vs. 4.6% ) . blood pressure targets were relaxed in most recent guidelines . the systolic blood pressure intervention trial ( sprint ) ( clinicaltrials.gov # nct01206062 ) randomized 9361 patients aged over 50 with systolic blood pressure 130  mmhg , increased cv risk , but without diabetes , to a target systolic pressure < 120  mmhg ( intensive treatment ) or a target < 140  mmhg ( standard treatment ) . the population was typical of a hypertensive population with 28% of patients over 75  years of age and 28% with ckd . a mean systolic blood pressure of 121.4  mmhg was reached in the intensive group ( achieved on average with 2.8 medications ) and 136.2  mmhg ( 1.8 medications ) and standard groups , respectively . the study was stopped early at 3.26  years at which point intensive treatment associated with a 25% reduction in the primary endpoint of mi , acs , stroke , heart failure , or death from cv causes ( 1.65  % /year vs. 2.19  % /year ; hr 0.75 ; 95  % ci 0.640.89 ; p  <  0.001 ) and a 27  % reduction in all - cause mortality ( 3.3% vs. 4.5% ; hr 0.73 ; 95  % ci 0.600.90 ; p  =  0.003 ) . there was a higher rate of hypotension ( 2.4% vs. 1.4% ; hr 1.67 ; p  =  0.001 ) , syncope , electrolyte abnormalities , and acute kidney injury / failure , but not of falls leading to injury . diuretics remain important treatment options in blood pressure guidelines although they may have adverse effects on blood glucose and potassium . the prevention and treatment of hypertension with algorithm based therapy 3 ( pathway 3 ) ( clinicaltrials.gov # nct00797862 ) randomized 441 patients with systolic blood pressure > 140  mmhg , eligible for diuretic use and with 1 other component of metabolic syndrome to therapy with amiloride alone , to combination amiloride plus hydrochlorothiazide , or to hydrochlorothiazide alone . two - hour glucose concentrations after an oral glucose tolerance test , averaged at 12 and 24  weeks ( the primary endpoint ) , were significantly lower with amiloride alone than hydrochlorothiazide alone ( 0.55  mmol / l , 95% ci 0.96 to 0.14 ; p  =  0.0093 ) and in the combination group compared to hydrochlorothiazide alone [ 0.42  mmol / l ( 0.84 to 0.004 ) ; p  =  0048 ] . mean home systolic blood pressure was reduced similarly with single treatments , but combination therapy led to an additional 3.4  mmhg reduction compared with hydrochlorothiazide ( 95% ci 0.95.8 ; p  =  0.007 ) . hyperkalemia occurred in seven ( 4.8% ) amiloride patients compared to three ( 2.3% ) in the combination group . in summary , combination therapy appeared to be a favorable treatment option being neutral for glucose and potassium but with greater effects on blood pressure . lower fasting glucose and hba1c levels with ranolazine have been suggested by previous trials in the setting of coronary disease [ 45 , 46 ] . a prospective randomized study presented at the american diabetes association ( ada ) 2015 scientific sessions ( clinicaltrials.gov # nct01472185 ) evaluated the effect of ranolazine on type 2 diabetics with a hba1c of 710% ( 5386  mmol / mol ) compared with placebo . ranolazine compared with placebo was associated with a greater reduction in the primary end point of fall in hba1c from baseline at 24  weeks [ mean difference 0.56% ( 6.1  mmol / mol ) ; p  <  0.0001 ] and a greater number of patients achieved hba1c < 7.0% at week 24 ( 41.2% vs. 25.6% ; p  =  0.0004 ) . thus , ranolazine may be of particular benefit in patients with coronary disease and diabetes . the biomarkers in acute cardiovascular care ( bacc ) study ( clinicaltrials.gov # nct02355457 ) investigated the different cut - off values for high - sensitivity troponin i and testing at 1 vs. 3  h for early detection of acute mi among 1045 patients presenting with acute ischemic - type chest pain of whom 184 were ultimately diagnosed with acute mi . a cut - off of 6  ng / l was found to be optimal rather than a conventional 99th percentile value for the assay ( 27  ng / l ) . for rule - out mi , using the 6  ng / l cut off , there was no difference in negative predictive values between the 1-h [ npv 99.7 95% ci ( 98.6100.0 ) ] and 3-h measurements [ negative predictive value ( npv ) 100.0 95% ci ( 98.5100.0 ) ] . for rule in mi ( defined as levels of 6  ng / l rising to at least 12  ng / l ) there was no significant difference in positive predictive at 1 or 3  h [ 82.8 95% ci ( 73.290.0 ) vs. 78.6 95% ci ( 69.885.8 ) ] . the bacc findings are in keeping with other studies suggesting that an accelerated high - sensitivity troponin protocol may enable earlier rule in / rule out of acute mi . use of additional early biomarkers may improve diagnosis further at this early time point and are under investigation . the optimal duration of dual antiplatelet therapy ( dapt ) after stenting has been widely debated . the dual antiplatelet therapy ( dapt ) study ( clinicaltrials.gov # nct00977938 ) randomized 11,648 subjects who were able to tolerate initial 12  months of dapt to an extended further 18  months of dapt ( total 30  months ) vs. dapt discontinuation ( total 12  months ) . a comparison of subgroups with and without mi was presented at the acc 2015 scientific sessions . extended dapt was associated with reduced in - stent thrombosis ( primary endpoint ) in those with mi ( 0.5% vs. 1.9% ; p  <  0.001 ) and without mi ( 0.4% vs. 1.1% , p  < 0.001 ) ( interaction p  =  0.69 ) , reduced new mi in both post mi and non - mi subgroups , and reduced macce ( co - primary endpoint ) in those with mi ( 3.9% vs. 6.8% ; p  < 0.001 ) although only a trend to reduced macce in those without mi ( 4.4% vs. 5.3% ; p  =  0.08 ; interaction p  =  0.03 ) . however , extended dapt was associated with increased moderate to severe gusto bleeding in both mi ( 1.9% vs. 0.8% ; p  =  0.005 ) and non - mi ( 2.6% vs. 1.7% ; p  =  0.007 ) patients ( interaction p  =  0.21 ) . long - term dapt was also explored in pegasus - timi 54 trial ( prevention of cardiovascular events in patients with prior heart attack using ticagrelor compared to placebo on a background of aspirin - thrombolysis in myocardial infarction 54 ) ( clinicaltrials.gov # nct01225562 ) . pegasus randomized 21,162 patients with a history of mi during the previous 13  years to extended standard dose ticagrelor ( 90  mg bd ) , extended low dose ( 60  mg bd ) ticagrelor , or placebo . at a median of 33  months , both ticagrelor groups showed a significant reduction in the incidence of the primary endpoint ( cv death , mi or stroke ) compared with placebo ( 7.85% standard dose ticagrelor ( hr 0.85 ; 95% ci 0.740.96 ; p  =  0.008 ) ; 7.77% reduced dose ticagrelor ( hr 0.84 ; 95% ci 0.740.95 ; p  =  0.004 ) ; vs. 9.04% placebo ) . timi major bleeding rates were significantly ( p  <  0.001 ) increased in both ticagrelor groups compared with placebo ( 2.60% standard dose ticagrelor , 2.30% reduced dose ticagrelor vs. 1.06% placebo ) although the incidence of intracranial hemorrhage or fatal bleeding was similar in all three groups . dyspnea was significantly more frequent with ticagrelor ( 18.93% standard dose 15.84% low dose vs. 6.38% placebo ) . the dapt and pegasus trials suggest that patients at high ischemic risk but low bleeding risk are most likely to benefit from extended therapy a dapt score has been developed from the dapt study dataset to help identify patients who may derive net benefit and this , or a similar strategy , is likely to be addressed in future acs guidelines . the requirement for at least 36  months of dapt has limited use of drug eluting stents ( des ) in patients at high baseline risk of bleeding . the biofreedom stainless - steel stent incorporates a novel microporous abluminal surface ( fig . 4 ) that enables controlled release of biolimus a9 , with therapeutic concentrations in local tissue sustained up to 28  days post - implantation . previous angiographic studies have reported similar late loss to conventional des while the absence of surface polymer may facilitate early stent healing and a shorter course of dapt . the leaders - free trial ( clinicaltrials.gov # nct01623180 ) randomized 2466 patients at high baseline bleeding risk undergoing pci to biofreedom or a bare metal stent with dapt discontinuation after 1  month . at 390  days , biofreedom was associated with a 50% reduction in the primary efficacy endpoint of clinically driven tlr ( 5.1% vs. 9.8% ; hr 0.50 ; 95% ci 0.370.69 ; p  <  0.001 ) , a 29% reduction in the primary safety endpoint of cv death , stent thrombosis or mi ( 9.4% vs. 12.9% ; hr 0.71 ; 95% ci 0.560.91 ; p  =  0.005 ) ( fig . 5 ) , and a 32% reduction in secondary endpoint of mi ( 6.1% vs. 8.9% ; hr 0.68 ; 95% ci 0.500.91 ; p  =  0.01 ) . biofreedom appears a logical stent choice ( rather than bare metal stent or conventional des ) for patients requiring short - course dapt or at increased risk of bleeding requiring early dapt discontinuation.fig . 4biofreedom stainless - steel stent that incorporates a novel microporous abluminal surface . reproduced with permission from biosensors 
 fig . 5primary efficacy and safety endpoints from the leaders - free trial for the biofreedom drug - coated stent vs. bare metal stenting . reproduced with permission from biosensors 
  biofreedom stainless - steel stent that incorporates a novel microporous abluminal surface . reproduced with permission from biosensors primary efficacy and safety endpoints from the leaders - free trial for the biofreedom drug - coated stent vs. bare metal stenting . reproduced with permission from biosensors the role of pci vs. cabg for treatment of left main coronary disease is the ongoing focus of several large studies . the premier of randomized comparison of bypass surgery vs. angioplasty using sirolimus - eluting stent in patients with left main coronary artery disease ( precombat ) ( clinicaltrials.gov # nct00422968 ) trial examined patients with left main coronary stenosis receiving pci ( n  =  300 ) compared to cabg ( n  =  300 ) . at 5  years , there was no difference in macce ( 17.5% pci vs. 14.3% cabg ; hr 1.27 ; 95% ci 0.841.90 ; p  =  0.26 ) or the composite of death , mi or stroke ( 8.4% pci vs. 9.6% cabg ; hr 0.89 ; 95% ci 0.521.52 ; p  =  0.66 ) . of note , there was higher rate of ischemia - driven target vessel revascularization ( tvr ) with pci ( 11.4% pci vs. 5.5% cabg ; hr 2.11 ; 95% ci 1.163.84 ; p  =  0.012 ) and 2 pci patients developed stent thrombosis . however , precombat used first - generation des , which are associated with higher rates of tvr and late stent thrombosis than latest - generation stents . results of noble ( nordic - baltic - british left main revascularization study ) ( clinicaltrials.gov # nct01496651 ) comparing biomatrix flex with cabg and excel ( evaluation of xience everolimus eluting stent vs. coronary artery bypass surgery for effectiveness of left main revascularization ) ( clinicaltrials.gov # nct01205776 ) are expected in later 2016 . while the thrombus aspiration during percutaneous coronary intervention in acute myocardial infarction study ( tapas ) ( current controlled trials # isrctn16716833 ) suggested a benefit for routine thrombectomy in primary pci , the thrombus aspiration in st - elevation myocardial infarction in scandinavia trial ( taste ) ( clinicaltrials.gov # nct01093404 ) failed to demonstrate a reduction in death , mi , or stent thrombosis . given concerns that taste was underpowered to detect smaller event rates , the large trial of routine aspiration thrombectomy with pci vs. pci alone in patients with stemi ( total ) ( clinicaltrials.gov # nct01149044 ) was undertaken in which patients with stemi undergoing primary pci were randomized to routine thrombectomy ( n  =  5372 ) vs. primary pci alone ( n  =  5360 ) . while , like in tapas , routine thrombectomy was associated with greater st segment resolution and less distal embolization , this did not translate into clinical benefit . there was no reduction in the primary outcome ( cv death , recurrent mi , cardiogenic shock or nyha class iv hf at 180  days ) ( 6.9% vs. 7.0% respectively , hr 0.99 ; 95% ci 0.851.15 ; p  =  0.86 ) , no reduction in the secondary outcome ( primary endpoint plus stent thrombosis or tvr within 180  days ) ( 9.9% thrombectomy vs. 9.8% pci alone , hr 1.00 ; 95% ci 0.891.14 ; p  =  0.95 ) , and no reduction in cv mortality at 180  days ( 3.1% thrombectomy vs. 3.5% pci alone , hr 0.90 ; 95% ci 0.731.12 ; p  =  0.34 ) . although numerically low , stroke rates were increased in the thrombectomy compared to pci alone at both 30  days ( 0.7% vs. 0.3% respectively , hr 2.06 ; 95% ci 1.133.75 ; p  =  0.02 ) and 180  days ( 52 ( 1% ) vs. 25 ( 0.5% ) respectively hr 2.08 ; 95% ci 1.293.35 ; p  =  0.02 ) . thus routine thrombectomy is no longer recommended in primary pci , although may have a  bail out  role for selected patients . danami-3 primulti ( the third danish study of optimal acute treatment of patients with st - segment elevation myocardial infarction primary pci in multivessel disease ) ( clinicaltrials.gov # nct01960933 ) compared complete revascularization ( with staged pressure wire - guided pci of non - culprit lesions during index admission ) ( n  =  314 ) vs. culprit artery intervention alone ( n  =  313 ) . the complete revascularization strategy was associated with a 44% reduction in the primary endpoint of death , reinfarction , or ischemia - driven non - culprit artery revascularization ( 13% vs. 22% ; hr 0.56 ; 95% ci 0.380.83 ; p  =  0.004 ) , driven by a 69% reduction in repeat revascularization ( 5 vs. 17% ; hr 0.31 ; 95% ci 0.180.53 ; p  < thus , while complete revascularization should usually be undertaken , since there was no difference in death or reinfarction , danami-3 suggests a conservative approach to non - culprit pci is reasonable if such pci appears of high risk . no - reflow following pci may be associated with adverse cardiac outcomes and reduced myocardial salvage ( the final infarct size indexed to the initial area at risk ) . no reflow , if it occurs , is most often observed following stent deployment . the single korean center innovation trial ( nct02324348 ) randomized 102 stemi patients deemed at higher baseline risk of no - reflow following initial thrombectomy and/or balloon angioplasty to deferred stenting at 37  days vs. immediate stenting . deferred stenting was associated with less no - reflow or slow - reflow ( 6%  vs. 29% ; p  =  0.006 ) , less no reflow ( 2%  vs. 14% ; p  =  0.052 ) , less intra - procedural thrombotic events ( 10% vs. 33% ; p  =  0.010 ) and increased myocardial salvage at 6  months ( 19.7% vs. 14.7% ; p  =  0.027 ) . the study is too small to be conclusive but a larger european deferred stent study is ongoing with results expected in 2016 . fully bioresorbable stent scaffolds could offer potential long - term vascular advantages over conventional des although appropriate patient types and safety are still being evaluated . absorb japan ( clinicaltrials.gov # nct01844284 ) presented at esc 2015 , randomized 400 patients undergoing pci to the absorb everolimus - eluting bioresorbable vascular scaffold or the xience everolimus - eluting permanent cobalt - chromium stent . absorb was non - inferior to xience for the primary endpoint of target lesion failure [ cardiac death , mi attributable to target vessel , or ischemia - driven target lesion revascularization ( tlr ) ] at 12  months ( 4.2%  vs. 3.8% ; p non - inferiority < 0.0001 ) . there was no difference in the rate of 12-month device thrombosis ( although the study was underpowered for this endpoint ) , 12-month tlr , or 13-month angiographic late lumen loss . the absorb iii trial ( clinicaltrials.gov # nct01751906 ) randomized 2008 patients undergoing pci to one or two de novo lesions to absorb or xience ( in 2:1 fashion ) . absorb was non - inferior to xience for the primary endpoint of target lesion failure at 1  year ( 7.8% vs. 6.1% ; p non - inferiority  =  0.007 ) with no difference in individual endpoint components . of note , absorb was associated with a higher rate of subacute ( > 24  h to 30  days ) device thrombosis ( 0.9% vs. 0.1% ; rr 6.26 ; 95% ci 0.8248.04 ; p  =  0.04 ) although the relative difference was less at 1  year ( 1.5% vs. 0.7% ; rr 2.08 ; 95% ci 0.785.51 ; p  =  0.13 ) . intravascular imaging is usually recommended to guide optimal b vs. deployment but a surprisingly low use was noted in absorb iii . the first - generation absorb b vs. has relatively thick struts and device thrombosis was less prevalent in vessels > 2.25  mm . nevertheless , a meta - analysis of six trials including absorb japan and absorb iii did confirm a small but significant increase in device thrombosis . thus , appropriate patient / lesion selection , careful lesion preparation , optical coherence tomography to guide sizing    post dilatation and extended dapt ( to 2  years ) is recommended minimize risk of device thrombosis . reducing bleeding complications following pci is an important goal given the association of bleeding with adverse clinical outcomes . the matrix ( minimizing adverse haemorrhagic events by transradial access site and systemic implementation of angiox ) ( clinicaltrials.gov # nct01433627 ) study randomized 8404 patients with acs , undergoing urgent angiography ( and 80% with follow - on pci ) to radial or femoral access [ 62 , 63 ] . radial access was associated with a significant reduction in non - cabg major bleeding ( 1.6% vs. 2.3% , rr 0.67 ; 95% ci 0.490.92 ; p  =  0.013 ) , a 14.6% trend to reduction in the primary endpoint of mace ( death , mi or stroke ; 8.8% vs. 10.3% ; 95% ci 0.740.99 ; p  =  0.0307 although not - significant at an  of 0.025 )   and significant reductions in secondary endpoints of all - cause mortality ( 1.6% vs. 2.2% , rr 0.72 ; 95% ci 0.530.99 ; p  =  0.045 ) and nace ( net composite of death , mi , stroke , or major bleeding ; 9.8% vs. 11.7% ; hr 0.83 ; 95% ci 0.730.96 ; p  =  0.0092 ) . such results strongly support radial access being preferred as the default access site . a separate randomization within the matrix study to bivalirudin vs. unfractionated heparin    bail out glycoprotein iib / iiia inhibition did not show any difference in mace or nace . in some patients with poor radial access , the ulnar artery route , although technically more challenging , may be a useful alternative to avoid femoral cannulation . the single - center ajmer ulnar artery working group study ( ajular ) presented at acc2015 randomized 2533 patients undergoing pci by experienced operators ( > 50 ulnar procedures ) to ulnar or radial access . there was no significant difference in the primary endpoint ( composite mace , site cross - over , major vascular events during hospital stay ; 14.6% tua vs. 14.4% tra 95% ci ; p  =  0.92 ) , or individual components of the composite endpoint . requirement for creation of a subcutaneous pacemaker pocket and insertion of a transvenous lead in conventional pacing systems can be associated with important complications such as pocket hematoma or infection , pneumothorax , or hemothorax . the micra transcatheter pacing system study ( clinicaltrials.gov # nct02004873 ) evaluated use of a leadless pacemaker ( fig . 6 ) implanted in the right ventricular apex via femoral vein implantation and secured by small tines in 725 patients ( 719 successfully implanted ) . the primary safety endpoint ( freedom from system or procedure related major complications ) was achieved in 96% and the primary efficacy endpoint ( percentage of patients with low and stable pacing capture thresholds at 6  months ) in 98.3%both of which were higher than the minimum performance goals from conventional pacing historical control data . major complications , which were less common than in the historical control dataset , included cardiac perforation or effusion / tamponade ( 1.6% ) , groin site complication ( 0.7% ) , and pacing issues ( 0.3% ) but no ( 0% ) dislodgments .fig . reproduced with permission of medtronic , inc 
  traditional pacemaker vs. micra . reproduced with permission of medtronic , inc another leadless pacemaker  the nanostim lp ( st . jude medical)was evaluated among 300 patients in the leadless ii study ( clinicaltrials.gov # nct02030418 ) . the primary safety endpoint ( 6-month freedom from device - related serious adverse events ) was met in 93.3% and primary efficacy endpoint ( acceptable 6-month pacing threshold and sensing amplitude ) was met in 90%both also exceeding minimum performance goals from conventional pacing historical control data . in total , 6.7% had serious adverse events ( 1.7% device dislodgement with percutaneous retrieval , 1.3% cardiac perforation and 1.3% pacing - threshold elevation requiring percutaneous retrieval and device replacement ) . as each of the leadless pacemaker studies are observational , larger randomized studies with longer term data including safety and retrieval data is required . current guidelines suggest it is reasonable to perform af ablation in selected patients undergoing cardiac surgery but acknowledge that supporting data are limited . thus , in a cardiothoracic surgical trials network ( ctsn ) study ( clinicaltrials.gov # nct00903370 ) 260 patients with persistent including longstanding persistent af requiring mitral valve surgery were randomized to ablation or no - ablation groups . patients assigned to ablation were further randomized to pulmonary vein isolation ( pvi ) or the more complex biatrial maze . those receiving concomitant af ablation were over twice as likely to be free from af on 72-h holter at both 6 and 12  months ( 63.2% vs. 29.4% ; p  < 0.001 ) although there no difference whether performed by pvi or biatrial maze ( 61% vs. 66% ; p  =  0.6 ) . ablation was associated with increased need for permanent pacemaker implantation ( 21.5 vs. 8.1 per 100 patient - years , p  =  0.01 ) . there was no difference in major cardiac or cerebrovascular adverse events at 12  months but the study was not powered to show benefit in this respect . although the ctsn study did not find an advantage for the more complex biatrial maze over pvi , with a transcatheter approach , persistent af may benefit more extensive ablation . the belief trial ( clinicaltrials.gov # nct01362738 ) randomized 173 patients with long - standing persistent af undergoing pulmonary vein antrum and non - pulmonary vein trigger ablation to additional left atrial appendage ( laa ) electrical isolation ( n  =  85 ) or no laa isolation ( n  =  88 ) . those undergoing laa electrical isolation had significantly higher freedom from af at 1-year ( 56% vs. 28% ; hr , 1.92 ; p  =  0.001 ) . there was no significant difference in secondary endpoints including mortality , stroke , or re - hospitalization . anticoagulation strategy was assessed in the randomized active - controlled multi - center study with blind - adjudication designed to evaluate the safety of uninterrupted rivaroxaban and uninterrupted vitamin k antagonists [ vka ] in subjects undergoing catheter ablation for non - valvular atrial fibrillation ( venture - af ; clinicaltrials.gov # nct01729871 , n  =  248 patients ) . no adverse safety endpoints were reported for rivaroxaban and only rarely for vka ( major bleeding 0.4% ; composite of stroke / systemic embolism / mi / vascular death / bleeding 0.8% ) . while the trial was too small to assess superiority , it suggests rivaroxaban is a reasonable alternative to vitamin k antagonists in patients undergoing catheter ablation in the setting of uninterrupted anticoagulation . the legacy study ( long - term effect of goal directed weight management on af cohort : a 5-year follow - up study ) ( actrn12614001123639 ) evaluated the long - term impact of weight loss and weight fluctuation on rhythm control in obese individuals with symptomatic paroxysmal or persistent af . all patients received weight loss counseling with optional participation in a weight management clinic or self - managed program . those achieving 10% vs. < 10% weight loss had reduced af burden and symptom severity ( p  <  0.001 ) and a sixfold greater likelihood of arrhythmia - free survival ( p  < multivariate analyses found weight loss and weight fluctuation to be independent predictors of outcomes ( p  <  0.001 ) . the trial of continuous or interrupted chest compressions during cpr conducted by the resuscitation outcomes consortium ) ( clinicaltrials.gov # nct01372748 ) assessed whether outcomes with non - trauma related cardiac arrest after continuous compressions with positive - pressure ventilation ( intervention group ) differed from those after compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations ( control group ) . however , there was no significant difference in survival to hospital discharge ( 8.9% vs. 9.7% , 95% ci 1.5 to 0.1 ; p  =  0.07 ) or recovery of favorable neurologic function at discharge ( 7.0% vs. 7.7% , 95% ci 1.4 to 0.1 ; p  =  0.09 ) . the prospective multicenter imaging study for evaluation of chest pain ( promise ) study ( clinicaltrials.gov # nct01174550 ) randomized 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography ( cta ) or to functional testing ( nuclear stress testing 68% , stress echocardiography 22% or exercise electrocardiography 10% ) . median cumulative radiation exposure per patient was lower with cta ( driven by significantly higher exposure with nuclear imaging vs. cta ) . those assigned to cta vs. functional testing were more likely to undergo cardiac catheterization ( 12.2% vs. 8.1% ) but of these , most patients in the cta group ( 72.1% ) had obstructive coronary disease , whereas less than half in the functional group ( 47.5% ) had obstructive coronary disease ) . revascularization < 90  days was undertaken in 6.2% of the cta group vs. 3.2% in the functional group ( p  <  0.001 ) , including 72 patients and 38 patients , respectively , who underwent cabg . over a median follow - up of 25  months there was no difference in the incidence of the primary end - point ( death , mi , hospitalization for unstable angina , or major procedural complication ; 3.3% vs. 3.0% ; adjusted hr 1.04 ; 95% ci 0.831.29 ; p  =  0.75 ) . thus , cta appears to identify coronary disease more accurately than functional testing although the clinical impact in promise was unclear . a second large multicenter cta study ( the scot - heart trial ) scot - heart randomized 9849 patients with an initial clinical diagnosis of coronary heart disease ( chd ) in 47% and angina due to chd in 36% to usual care plus cta at ~6  weeks or to usual care alone ( clinicaltrials.gov # nct01149590 ) . use of cta reclassified diagnosis of chd in 27% and angina in 23% ( vs. 1% and 1% , respectively , with usual care p  <  0.0001 ) and led to a change in planned investigation in 15% ( cancellation of 121 functional tests , cancellation of 29 invasive angiograms , but scheduling of an additional 94 invasive angiograms , 88% of which showed obstructive disease requiring revascularization ) . at a median follow - up of 1.7  years , there was a 38% trend to reduction in fatal and non - fatal mi ( 26 vs. 42 , hr 0.62 , 95% ci 0.381.01 ; p  =  0.0527 ) . scot - heart thus confirmed that cta helps clarify diagnosis , enables more appropriate use of invasive angiography / intervention and may reduce the future risk of mi . in this paper , we have highlighted and summarized numerous important studies in the field of cardiology that have been presented to major international cardiology meetings throughout 2015 . many of these studies will contribute to updating of current practice guidelines and others will play an integral role in the advancement and development of new therapeutic strategies . ian menown has received grants to institution , honoraria and/or conference sponsorship from : boston scientific , sanofi aventis , biosensors , meril life , orbus neich , menarini , astra zeneca , bayer , boehringer ingelheim , daichii sankyo , lilly , bristol myers squibb , and pfizer . this article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors . this article is distributed under the terms of the creative commons attribution - noncommercial 4.0 international license ( http://creativecommons.org/licenses/by-nc/4.0/ ) , which permits any noncommercial use , distribution , and reproduction in any medium , provided you give appropriate credit to the original author(s ) and the source , provide a link to the creative commons license , and indicate if changes were made .