Summary Background Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to ...compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. Methods In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age <75 years vs ≥75 years and presence of cardiogenic shock yes vs no) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3–5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov , number NCT01519518. Findings Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients 13% in the bivalirudin group and 140 patients 15% in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk RR 1·52, 95% CI 1·09–2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70–1·89, p=0·59). Interpretation Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. Funding Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).
Alcohol septal ablation (ASA) is an established treatment option in hypertrophic obstructive cardiomyopathy (HOCM). ASA is ineffective in some: inaccurate infarct and inability to identify a vessel ...contribute. We aimed to improve accuracy of infarct using CT angiography guidance and provide a more predictable and satisfactory outcome.
Twenty-one successive patients with symptomatic LVOT obstruction refractory to medication underwent CT angiography planning to guide ASA. CT was performed using a dual-source CT system. Alcohol was delivered to the artery identified from CT: in 17/21 this was a sub-branch of a septal artery, in 2/21 the septal vessel was identified from the circumflex artery. Peak gradient improved from 98 (IQR 89.50-111.50) mmHg to 14 (IQR 8.50-22) mmHg (p=0.003). Systolic anterior motion (SAM) improved in 18/20 patients. NYHA class improved by ≥1 in 18/20. Peak VO2 improved from 79.19% of predicted value (±14.01) to 91.62% (±12.02) predicted (p<0.0001). Success at the first procedure is greater with CT guidance, 17/20 vs. 50/75 with traditional methods (pre-CT guidance) (p=0.02); 9/20 had six-month CMR with target septum infarct in all. ASA-related RBBB reduced from 62% to 13% (p=0.0004).
CT angiography planning improves localisation of infarct and procedural success at the first attempt in ASA when compared to traditional methods. Follow-up to six months suggests a symptomatic, functional and haemodynamic improvement.
Background Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, ...subsequent myocardial infarction (MI), and all-cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3-5, hazard ratio HR, 1.23; 95% CI, 0.90-1.68;
=0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98-1.74;
=0.07) except in the non-coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3-5, adjusted HR, 1.58; 95% CI, 1.09-2.31;
=0.017; and PLATO major HR, 1.67; 95% CI, 1.18-2.37;
=0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87-1.64;
=0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76-1.10;
=0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52-1.32;
=0.42). Conclusions This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02484924.
There is ongoing uncertainty regarding the safety and efficacy of unfractionated heparin and bivalirudin when used for systemic anticoagulation in patients undergoing primary percutaneous coronary ...intervention (PPCI). This paper reports 12-month mortality from the HEAT-PPCI randomised trial.
In this open-label, randomised controlled trial (RCT) we enrolled consecutive adults with suspected ST-elevation myocardial infarction (STEMI). Patients were randomised to heparin (bolus 70 U/kg) or bivalirudin (bolus 0.75 mg/kg followed by an infusion 1.75 mg/kg/h for the duration of the procedure). We report the pre-specified secondary outcome of all-cause mortality at 12 months.
Mortality was classified as cardiovascular or not, blinded to treatment allocation. Deaths in the first 28 days were classified by formal event adjudication and later events classified from death certificates.
Mortality status at 12 months was obtained for 1805/1812 = 99.6% of participants. Overall mortality was 160/1812 = 8.9%. There were more deaths in those randomised to bivalirudin (95/902 = 10.5% vs 65/903 = 7.2%; HR 1.48; 95% CI 1.08 to 2.03; p = 0.015).
Most deaths were classified as cardiovascular (71/902 = 7.9% in the bivalirudin group and 53/904 = 5.9% in the heparin group). The difference between the rates of cardiovascular deaths in each treatment group did not reach statistical significance: HR 1.35; 95% CI 0.95 to 1.93; p = 0.095.
At 12 months, treatment with bivalirudin, rather than heparin, was associated with a higher rate of all-cause mortality. Cardiovascular mortality was higher with bivalirudin although this difference was not statistically significant.
•Use of bivalirudin in PPCI was associated with a significantly higher risk of all-cause mortality at 12 months.•Cardiovascular causes of death at 12 months were not significantly different between the treatment groups.•There was a statistically significant difference in non-cardiovascular deaths that may have occurred by chance.
To determine the relative safety of heparin and bivalirudin in studies with differential use of glycoprotein (GP) IIb/IIIa inhibitor drugs is impossible.5 Observational data, such as from EUROMAX4 ...for patients treated with heparin, are interesting but cannot be regarded as definitive. The reported rate in HEAT-PPCI1 matches institutional and national norms, whereas in HORIZONS-AMI2 (2·6%), EUROMAX4 (3·0%) and BRIGHT3 (1·9%) it is less than half that declared in the national registries (UK 30-day mortality is 6·4% as per British Cardiovascular Intervention Society's audit data in 2012;7 USA inpatient mortality is 5·7% as per Diagnostic Catheterization and Percutaneous Coronary Intervention CathPCI Registry data in 2011).
Recent randomized controlled trials comparing femoral and radial access in primary percutaneous coronary intervention (PPCI) have shown conflicting results regarding the incidence of major adverse ...cardiovascular events (MACE) and major bleeding.
Using data from the HEAT-PPCI trial, we compared the primary efficacy (all-cause mortality, stroke, new myocardial infarction or unplanned repeat revascularization) and safety (major bleeding BARC 3–5) outcomes at 28 days, by final access site used (radial or femoral) and by default operator type. We then assessed outcomes in femoral cases performed by both operator types.
Radial access (RA) was associated with fewer MACE (91/1472 = 6.2% vs. 36/332 = 10.8% P = .003) and major bleeding events (38/1472 = 2.6% vs 22/332 = 6.6% P = .001) when compared to femoral access (FA). When analyzing outcomes by default operator type, there was a similar incidence of MACE (111/1575 = 7% vs 16/229 = 7% P = .97) and major bleeding events (49/1575 = 3.1% vs 11/229 = 4.8% P = .18). In cases where FA was performed by default radial operators, there was a higher rate of MACE (22/122 = 18% vs 14/210 = 6.7% P = .003) and major bleeding events (11/122 = 9% vs 11/210 = 5.2% P < .001), potentially explained by a higher risk profile in these cases.
Default femoral operators achieved comparable outcomes when compared to default radial operators. The less favorable outcomes observed in FA cases may result from its selective use by radial operators in high risk cases.
CT identifies target arteries from alternative epicardial arteries. 20 patients have received alcohol to target septal artery with follow up >=6 months.
Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. ...Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed.
To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin.
We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin.
From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin).
We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results.
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