Pontus Andell

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and Chronic Obstructive Pulmonary Disease: An Analysis From the Platelet Inhibition and Patient Outcomes (PLATO) Trial

Background Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients. Methods and Results In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1‐year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO‐defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non‐COPD patients (HR=1.85). No COPD status‐by‐treatment interactions were found, showing consistency with the main trial results. Conclusions In this post‐hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit‐risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Delay From First Medical Contact to Primary PCI and All-Cause Mortality: A Nationwide Study of Patients With ST-Elevation Myocardial Infarction

Background Early reperfusion in the setting of an ST‐elevation myocardial infarction (STEMI) is of utmost importance. However, the effects of early versus late reperfusion in this patient group undergoing primary percutaneous coronary intervention (PCI) have so far been inconsistent in previous studies. The purpose of this study was to evaluate in a nationwide cohort the effects of delay from first medical contact to PCI (first medical contact [FMC]‐to‐PCI) and secondarily delay from symptom‐to‐PCI on clinical outcomes. Methods and Results Using the national Swedish Coronary Angiography and Angioplasty Register (SCAAR) registry, STEMI patients undergoing primary PCI between the years 2003 and 2008 were screened for. A total of 13 790 patients were included in the FMC‐to‐PCI analysis and 11 489 patients were included in the symptom‐to‐PCI analyses. Unadjusted as well as multivariable analyses showed an overall significant association between increasing FMC‐to‐PCI delay and 1‐year mortality. A statistically significant increase in mortality was noted at FMC‐to‐PCI delays exceeding 1 hour in an incremental fashion. FMC‐to‐PCI delays in excess of 1 hour were also significantly associated with an increase in severe left ventricular dysfunction at discharge. An overall significant association between increasing symptom‐to‐PCI delays and 1‐year mortality was noted. However, when stratified into time delay cohorts, no symptom‐to‐PCI delay except for the highest time delay showed a statistically significant association with increased mortality. Conclusions Delays in FMC‐to‐PCI were strongly associated with increased mortality already at delays of more than 1 hour, possibly through an increase in severe heart failure. A goal of FMC‐to‐PCI of less than 1 hour might save patient lives.

Impact of chronic obstructive pulmonary disease on morbidity and mortality after myocardial infarction.

Aim To gain a better understanding of the impact of chronic obstructive pulmonary disease (COPD) on long-term mortality in patients with myocardial infarction (MI) and identify areas where the clinical care for these patients may be improved. Methods Patients hospitalised for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry. Patients with MI and a prior COPD hospital discharge diagnosis were compared to patients with MI without a prior COPD hospital discharge diagnosis for the primary endpoint of all-cause mortality at 1 year after MI. Secondary endpoints included rates of reinfarction, new-onset stroke, new-onset bleeding and new-onset heart failure at 1 year. Results A total of 81 191 MI patients were included, of which 4867 (6%) had a COPD hospital discharge diagnosis at baseline. Patients with COPD showed a significantly higher unadjusted 1-year mortality (24.6 vs 13.8%) as well as a higher rate of reinfarction, new-onset bleeding and new-onset heart failure post-MI. After adjustment for potential confounders, including comorbidities and treatment, the patients with COPD still showed a significantly higher 1-year mortality (HR 1.14, 95% CI 1.07 to 1.21) as well as a higher rate of new-onset heart failure (HR 1.35, 95% CI 1.24 to 1.47), whereas no significant association between COPD and myocardial reinfarction or new-onset bleeding remained. Conclusions In this nationwide contemporary study, patients with COPD frequently had an atypical presentation, less often underwent revascularisation and less often received guideline-recommended secondary preventive medications of established benefit. Prior COPD was associated with a higher 1-year mortality and a higher risk of subsequent new-onset heart failure after MI. The association seems to be mainly explained by differences in background characteristics, comorbidities and treatment, although a minor part might be explained by COPD in itself. Improved in-hospital MI treatment and post-MI secondary prevention according to the guidelines may lower the mortality in this high-risk population.

Use, patient selection and outcomes of P2Y12 receptor inhibitor treatment in patients with STEMI based on contemporary European registries

AIMS Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in patients with STEMI based on the data from contemporary European ACS registries. METHODS AND RESULTS Twelve registries provided data in a systematic manner on outcomes in STEMI patients overall, and seven of these also provided data for P2Y12 receptor inhibitor-based dual antiplatelet therapy. The registries were heterogeneous in terms of site, patient, and treatment selection, as well as in definition of endpoints (e.g. bleeding events). All-cause death rates based on the data from 84 299 patients (9612 patients on prasugrel, 11 492 on ticagrelor, and 27 824 on clopidogrel) ranged between 0.49 and 6.68% in-hospital, between 3.07 and 7.95% at 30 days (reported in 6 registries), between 8.15 and 9.13% at 180 days, and between 2.41 and 9.58% at 1 year (5 registries). Major bleeding rates were 0.09-3.55% in-hospital (8 registries), 0.09-1.65% at 30 days, and 1.96% at 1 year (only 1 registry). Fatal/life-threatening bleeding was rare occurring between 0.08 and 0.13% in-hospital (4 registries) and 1.96% at 1 year (1 registry). CONCLUSIONS Real-world evidence from European contemporary registries shows that death, ischaemic events, and bleeding rates are lower than those reported in Phase III studies of P2Y12 inhibitors. Regarding individual P2Y12 inhibitors, patients on prasugrel, and, to a lesser degree, ticagrelor, had fewer ischaemic and bleeding events at all time points than clopidogrel-treated patients. These findings are partly related to the fact that the newer agents are used in younger and less ill patients.

β-Blocker Use and Mortality in COPD Patients After Myocardial Infarction: A Swedish Nationwide Observational Study.

Background Patients with myocardial infarction (MI) and concomitant chronic obstructive pulmonary disease (COPD) constitute a high‐risk group with increased mortality. β‐Blocker therapy has been shown to reduce mortality, prevent arrhythmias, and delay heart failure development after an MI in broad populations. However, the effect of β‐blockers in COPD patients is less well established and they may also be less treated due to fear of adverse reactions. We investigated β‐blocker prescription at discharge in patients with COPD after MI. Methods and Results Patients hospitalized for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry. Patients with COPD who were alive and discharged after an MI were selected as the study population. In this cohort, patients who were discharged with β‐blockers were compared to patients not discharged with β‐blockers. The primary end point was all‐cause mortality. A total of 4858 patients were included, of which 4086 (84.1%) were discharged with a β‐blocker while 772 (15.9%) were not. After adjusting for potential confounders including baseline characteristics, comorbidities, and in‐hospital characteristics, patients discharged with a β‐blocker had lower all‐cause mortality (hazard ratio 0.87, 95% CI 0.78 to 0.98) during the total follow‐up time (maximum 7.2 years). In the subgroup of patients with a history of heart failure, the corresponding hazard ratio was 0.77 (95% CI 0.63 to 0.95). Conclusions Patients with COPD discharged with β‐blockers after an MI had a lower all‐cause mortality compared to patients not prescribed β‐blockers. The results indicate that MI patients with COPD may benefit from β‐blockers.

Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study

Objective Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based studies are lacking. Methods We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified incidence of each VHD and adjusted comorbidity profiles were assessed. Results In the Swedish population (n=10 164 211), the incidence of VHD was 63.9 per 100 000 person-years, with aortic stenosis (AS; 47.2%), mitral regurgitation (MR; 24.2%) and aortic regurgitation (AR; 18.0%) contributing most of the VHD diagnoses. The majority of VHDs were diagnosed in the elderly (68.9% in subjects aged ≥65 years), but pulmonary valve disease incidence peaked in newborns. Incidences of AR, AS and MR were higher in men who were also more frequently diagnosed at an earlier age. Mitral stenosis (MS) incidence was higher in women. Rheumatic fever was rare. Half of AS cases had concomitant atherosclerotic vascular disease (48.4%), whereas concomitant heart failure and atrial fibrillation were common in mitral valve disease and tricuspid regurgitation. Other common comorbidities were thoracic aortic aneurysms in AR (10.3%), autoimmune disorders in MS (24.5%) and abdominal hernias or prolapse in MR (10.7%) and TR (10.3%). Conclusions Clinically diagnosed VHD was primarily a disease of the elderly. Rheumatic fever was rare in Sweden, but specific VHDs showed a range of different comorbidity profiles . Pronounced sex-specific patterns were observed for AR and MS, for which the mechanisms remain incompletely understood.

Association between the use of fondaparinux vs low-molecular-weight heparin and clinical outcomes in patients with non-ST-segment elevation myocardial infarction.

IMPORTANCE Fondaparinux was associated with reduced major bleeding events and improved survival compared with low-molecular-weight heparin (LMWH) in a large randomized clinical trial involving patients with non-ST-segment elevation myocardial infarction (NSTEMI). Large-scale experience of the use of fondaparinux vs LMWH in a nontrial setting is lacking. OBJECTIVE To study the association between the use of fondaparinux vs LMWH and outcomes in patients with NSTEMI in Sweden. DESIGN, SETTING, AND PATIENTS Prospective multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry involving 40,616 consecutive patients with NSTEMI who received fondaparinux or LMWH between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010. EXPOSURES In-hospital treatment with fondaparinux or LMWH during the hospital stay. MAIN OUTCOMES AND MEASURES In-hospital severe bleeding events and death and 30- and 180-day death, MI, stroke, and major bleeding events. Logistic regression models adjusted for calendar time, admitting hospital, baseline characteristics, and in-hospital revascularization. RESULTS In total, 14,791 patients (36.4%) were treated with fondaparinux and 25,825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42-0.70). A total of 394 patients (2.7%) in the fondaparinux group died while in the hospital vs 1022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63-0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups. CONCLUSIONS AND RELEVANCE In routine clinical care of patients with NSTEMI, fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.

Intravascular Ultrasound Guidance is Associated with Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared with Angiography Guidance Alone

Background— Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study. Methods and Results— Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50–0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47–0.82). In 340 propensity score–matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37–0.80). Conclusions— IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Myocardial Infarction Patients With Renal Dysfunction

BACKGROUND There is no consensus whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) should be used for secondary prevention in all or in only high-risk patients after an acute myocardial infarction (AMI). OBJECTIVES This study sought to investigate whether ACEI/ARB treatment after AMI is associated with better outcomes across different risk profiles, including the entire spectrum of estimated glomerular filtration rates. METHODS This study evaluated discharge and continuous follow-up data on ACEI/ARB use among AMI survivors (2006 to 2009) included in a large Swedish registry. The association between ACEI/ARB treatment and outcomes (mortality, myocardial infarction, stroke, and acute kidney injury [AKI]) was studied using Cox proportional hazards models (intention-to-treat and as treated). RESULTS In total, 45,697 patients (71%) were treated with ACEI/ARB. The 3-year mortality was 19.8% (17.4% of ACEI/ARB users and 25.4% of nonusers). In adjusted analysis, significantly better survival was observed for patients treated with ACEI/ARB (3-year hazard ratio: 0.80; 95% confidence interval: 0.77 to 0.83). The survival benefit was consistent through all kidney function strata, including dialysis patients. Overall, those treated with ACEI/ARB also had lower 3-year risk for myocardial infarction (hazard ratio: 0.91; 95% confidence interval: 0.87 to 0.95), whereas treatment had no significant effect on stroke risk. The crude risk for AKI was in general low (2.5% and 2.0% for treated and nontreated, respectively) and similar across estimated glomerular filtration rate categories but was significantly higher with ACEI/ARB treatment. However, the composite outcome of AKI and mortality favored ACEI/ARB treatment. CONCLUSIONS Treatment with ACEI/ARB after AMI was associated with improved long-term survival, regardless of underlying renal function, and was accompanied by low rates of adverse renal events.

Cangrelor in combination with ticagrelor provides consistent and potent P2Y12-inhibition during and after primary percutaneous coronary intervention in real-world patients with ST-segment-elevation myocardial infarction

Abstract Patients pretreated with ticagrelor with less than 1 hour from percutaneous coronary intervention (PCI) or receiving ticagrelor in cath lab were prospectively included and received cangrelor. Cangrelor was infused for 2 hours and platelet function was assessed as P2Y12 reactivity units (PRU) with the VerifyNow P2Y12 function assay before start of infusion, 15 min after the start of infusion, and 30 min after the end of infusion. A total of n = 32 patients with an average age of 68 (±13) years with n = 22 (69%) males were included. The level of P2Y12 inhibition before cangrelor infusion was started was 249 PRU (IQR 221–271). After 15 min of cangrelor infusion the P2Y12 reactivity was markedly decreased to 71 PRU (IQR 52–104, p < 0.001). At 30 min after end of infusion PRU remained within the therapeutic range, 89 PRU (IQR 50–178; p < 0.001 for comparison with preinfusion) with only n = 4 (12.5%) patients with PRU >225. Results were consistent between patients receiving ticagrelor prehospital or in the cath lab and no statistical differences in PRU were noted between the two groups in any of the three measurements. In conclusion, cangrelor in combination with ticagrelor results in consistent and strong P2Y12 inhibition during and after infusion and cangrelor may bridge the gap until oral P2Y12 inhibitors achieve effect in real-world STEMI patients undergoing primary PCI.