Q Fever Endocarditis: A Review of Local and all Reported Cases in the Literature.

BACKGROUND: Q fever endocarditis by Coxiella burnetii is rare and presents a diagnostic challenge. With limited data available, the aim of this study was to review all reported cases together with unpublished local cases to understand risk factor profiles, diagnostic methods, clinical features, treatments and outcomes. METHODS: A search of the PubMed database using the term 'Q fever endocarditis' identified cases between 1950-2019. Included cases had positive polymerase chain reaction testing, valve culture or serology. Separately, to identify local cases meeting our criteria we queried the Western Australian Health Open Patient Administration System at two local hospitals for the ICD-10-AM diagnosis code A78 between 2013-2019. RESULTS: We identified 181 cases from 31 publications and four local cases to create a combined series of 185 cases. The majority 141 (76%) were male and only 11% had normal cardiac valves. Most (72%) of patients had a history of contact with animals or travel. Nearly all (98%) cases had positive serology and over half (56%) had surgery performed. Overall mortality was 17%, and mortality for native valve endocarditis and prosthetic valve endocarditis was 12% and 3% respectively. No patients treated with doxycycline and hydroxychloroquine died. Mortality prior to 1999 was 28%, compared with 5% for more recent cases. CONCLUSION: Serological diagnosis is key in Q fever endocarditis and possible risk factors exist such as male gender, pre-existing valvular conditions and contact with animals or travel. Native valve endocarditis and treatment with drugs other than doxycycline and hydroxychloroquine increase the risk of death.

A Practical Guide for Fractional Flow Reserve Guided Revascularisation.

The presence and extent of myocardial ischaemia is a major determinant of prognosis and benefit from revascularisation in patients with stable coronary artery disease. Fractional Flow Reserve (FFR) is accepted as the reference standard for invasive assessment of ischaemia. Its ability to detect lesion specific ischaemia makes it a useful test in a wide range of patient and lesion subsets, with FFR guided intervention improving clinical outcomes and reducing health care costs compared to assessment with coronary angiography alone. This article will review the basic principles in FFR, practical tips in FFR guided revascularisation and the role of emerging non-hyperaemic indices of ischaemia.

A Comparison of Radial and Femoral Coronary Angiography in Patients From SNAPSHOT ACS, a Prospective Acute Coronary Syndrome Audit in Australia and New Zealand.

BACKGROUND: There is wide variation in the use of radial over femoral access for patients with ACS. This study evaluates the factors associated with the selection of radial versus femoral angiography in Australia and New Zealand and the effect of access site on clinical events in acute coronary syndrome (ACS) patients. METHODS: An analysis of the SNAPSHOT ACS audit was conducted during May 2012 across 286 hospitals in Australia and New Zealand. Data collected included baseline patient characteristics, hospital site details, treatment received, clinical events in-hospital and mortality at 18 months. Univariate and multivariable analyses were performed. RESULTS: Of the 1621 patients undergoing coronary angiography, access was through the femoral artery in 1043 (63%), and the radial in 578 (36%) patients. Radial access dominated in New Zealand (241 out of 327, 73.7%), compared to Australia (337 out of 1293, 26.1%, p=<0.001), with interstate variation (6% to 54%, p=<0.001). Independent predictors of access site included country of admission (Odds of radial, Aus v NZ OR 0.14, 95% CI 0.08-0.24, p=<0.0001), prior CABG surgery (OR 0.16, 95% CI 0.09-0.31, p=<0.0001), high GRACE score (90th decile) (OR 0.44, 95% CI 0.21-0.91, p=0.026) and admission to a centre with high annual PCI volume (>209 cases per year) (OR 1.86, 95% CI 1.06-3.26, p=0.03). After adjustment, there was no difference in clinical events in-hospital or mortality at 18 months CONCLUSION: Coronary angiography in New Zealand rather than Australia is the strongest predictor of radial access in ACS patients. There was no difference in outcomes according to access site in this population based cohort study.

Characteristics and Clinical Course of STEMI Patients who Received no Reperfusion in the Australia and New Zealand SNAPSHOT ACS Registry.

BACKGROUND: Cohort studies of STEMI patients have reported that over 30% receive no reperfusion. Barriers to greater use of reperfusion in STEMI patients require further elucidation. METHODS: We collected data on STEMI patients with no reperfusion as part of the SNAPSHOT ACS Registry, which recruited consecutive ACS patients in 478 hospitals throughout Australia and New Zealand during 14-27 May 2012. RESULTS: Of 4387 patients enrolled, 419 were diagnosed with STEMI. Primary PCI (PPCI) was performed in 160 (38.2%), fibrinolysis was used in 105 (25.1%), and 154 (36.7%) had no reperfusion. Patients with no reperfusion had a mean age of 70.3±15.0 years compared with 63.1±13.5 in the reperfusion group (p<0.0001). There were more females in the no reperfusion group (37.1% v 23.0% p=0.002) and they were significantly more likely to have prior PCI or CABG, heart failure, atrial fibrillation, chronic kidney disease and other vascular disease, and to be nursing home residents (all p<0.05). Patients without reperfusion had a significantly higher mortality in hospital (11.7% v 4.9%, p=0.011). In 370 patients who presented within 12hours, 28 had early angiography without PCI, which was considered an attempt at reperfusion. Therefore reperfusion was attempted in 293 of 370 eligible patients (79.2%). CONCLUSION: Of consecutive STEMI patients, 36.7% did not receive any reperfusion and they had a higher risk of death in hospital. In eligible patients, reperfusion was attempted in 79.2%. National strategies to encourage earlier medical contact and greater use of reperfusion in eligible patients may lead to better outcomes.

Strategies for multivessel revascularization in patients with diabetes.

BACKGROUND: In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease. METHODS: In this randomized trial, we assigned patients with diabetes and multivessel coronary artery disease to undergo either PCI with drug-eluting stents or CABG. The patients were followed for a minimum of 2 years (median among survivors, 3.8 years). All patients were prescribed currently recommended medical therapies for the control of low-density lipoprotein cholesterol, systolic blood pressure, and glycated hemoglobin. The primary outcome measure was a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: From 2005 through 2010, we enrolled 1900 patients at 140 international centers. The patients' mean age was 63.1±9.1 years, 29% were women, and 83% had three-vessel disease. The primary outcome occurred more frequently in the PCI group (P=0.005), with 5-year rates of 26.6% in the PCI group and 18.7% in the CABG group. The benefit of CABG was driven by differences in rates of both myocardial infarction (P<0.001) and death from any cause (P=0.049). Stroke was more frequent in the CABG group, with 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=0.03). CONCLUSIONS: For patients with diabetes and advanced coronary artery disease, CABG was superior to PCI in that it significantly reduced rates of death and myocardial infarction, with a higher rate of stroke. (Funded by the National Heart, Lung, and Blood Institute and others; FREEDOM ClinicalTrials.gov number, NCT00086450.).

Kounis syndrome with Samter-Beer triad treated with intracoronary adrenaline.

Kounis syndrome is a well-described clinical condition characterized by the simultaneous occurrence of chest pain and an allergic reaction accompanied by clinical and laboratory findings of angina caused by inflammatory mediators released during an allergic insult. We present the case of a 50-year-old male with the Samter-Beer triad of asthma, nasal polyps, and salicylate intolerance with an ST elevation myocardial infarction complicated with cardiac arrest due to multi-vessel coronary artery spasm secondary to aspirin anaphylaxis. Adrenaline is recommended during anaphylaxis but is controversial in Kounis syndrome as it may worsen coronary spasm. We report the use of intracoronary adrenaline in successfully reversing coronary artery spasm in this hemodynamically unstable patient.

Age-specific gender differences in long-term recurrence and mortality following incident myocardial infarction: a population-based study.

BACKGROUND: Higher mortality following myocardial infarction (MI) is reported in women compared with men with short-term follow-up. Our study aim was to compare long-term gender- and age-specific outcomes following incident MI. METHODS: 30-day survivors of incident MI from 2003-2009 were identified from linked administrative data in Western Australia. Outcomes identified were recurrent MI, and cardiovascular and all-cause mortality. Follow-up data was available until 30(th) June 2011. Unadjusted risk out to eight-years was estimated from Kaplan-Meier survival curves, and multivariate Cox regression models were used to estimate relative risk in women compared with men by age group. RESULTS: There were 12,420 30-day survivors of incident MI from 2003-2009 (males 71.2%). Women had higher levels of comorbidities across all age groups compared with men. Unadjusted event risks were higher in women than men overall, underpinned by higher risk of recurrent MI in 55-69 year-old women and of cardiovascular mortality across all age groups in women. Gender differences were generally attenuated after adjustment for demographic factors and comorbidities. CONCLUSIONS: This study highlights the elevated risk of cardiovascular events in women compared with men with long-term follow-up, and demonstrates the need for improved long-term secondary prevention in this patient group.

Intra-aortic balloon pump: indications, efficacy, guidelines and future directions.

PURPOSE OF REVIEW: The intra-aortic balloon pump (IABP) has been used as a cardiac assist device in various clinical situations since 1968 on the basis of the physiological principles and observational data, with little randomized data until recently. RECENT FINDINGS: Recently published randomized controlled trials (RCTs) and meta-analyses have demonstrated acceptable safety for IABP but have raised doubt over efficacy in acute myocardial infarction (MI) both with and without cardiogenic shock. RCTs and meta-analyses have provided limited and qualified support for the efficacy of IABP in high-risk percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). There remains only observational data to support the efficacy of IABP in other niche indications, including mechanical complications of MI (acute severe mitral regurgitation and ventricular septal rupture) and refractory ventricular arrhythmia. SUMMARY: Current randomized trial data and meta-analyses support the safety of IABP, but provide limited or no support for its efficacy in the treatment of high-risk MI, MI complicated by cardiogenic shock or the use of prophylactic IABP in high-risk PCI and CABG. Further studies to inform optimal patient selection, timing and use of associated therapies are required to characterize the role of IABP in contemporary practice and optimize outcome in high-risk patient subsets.

Impact of the introduction of drug eluting stents on clinical outcomes in patients undergoing percutaneous and surgical coronary artery revascularisation procedures in Western Australia.

BACKGROUND: Increasing rates of percutaneous coronary intervention (PCI) and decreasing rates of coronary artery bypass graft (CABG) surgery followed the introduction of drug eluting stents in Western Australia in 2002. We assessed the impact of these changes on one-year outcomes for the total population of patients undergoing coronary artery revascularisation procedures (CARP) in Western Australia between 2000-2004. METHODS: Clinical and linked administrative data (inpatient admissions and death) were merged for all patients who had their first CARP with stent or CABG in Western Australia between 2000-2004. The clinical data were collected from all hospitals in Western Australia where CARP procedures are performed. We calculated the unadjusted (Kaplan-Meier) and adjusted (Cox) risks for one-year death (all-cause), death (all-cause) or admission for myocardial infarction (MI), target vessel revascularisation (TVR) and the composite outcome of death/MI/TVR (major adverse cardiac events, MACE). RESULTS: Over the study period, there were 14,118 index CARPs. The use of drug eluting stents increased from 0% to 95.8% of PCI procedures, and PCI procedures increased from 61.1% to 74.4% of all CARPS. There were no temporal changes in adjusted one-year mortality or death/MI. Overall, adjusted one-year MACE fell from 11.3% in 2000 to 8.5% in 2004 (p<0.0001) due to a significant reduction in TVR in the PCI group. CONCLUSION: The introduction of drug eluting stents and resulting changes in coronary revascularisation strategies were not associated with changes in the one-year risk of major clinical endpoints (death or death/MI), but were associated with a significant reduction in the risk of MACE, driven entirely by a reduction in TVR after PCI. This real world study supports the effectiveness of drug eluting stents in reducing repeat procedures in the total CARP population without increasing the risk of death or MI.

Primary care Adherence To Heart Failure guidelines IN Diagnosis, Evaluation and Routine management (PATHFINDER): a randomised controlled trial protocol.

INTRODUCTION: General practitioners (GPs) routinely provide care for patients with heart failure (HF); however, adherence to management guidelines, including titrating medication to optimal dose, can be challenging in this setting. This study will evaluate the effectiveness of a multifaceted intervention to support adherence to HF management guidelines in primary care. METHODS AND ANALYSIS: We will undertake a multicentre, parallel-group, randomised controlled trial of 200 participants with HF with reduced ejection fraction. Participants will be recruited during a hospital admission due to HF. Following hospital discharge, the intervention group will have follow-up with their GP scheduled at 1 week, 4 weeks and 3 months with the provision of a medication titration plan approved by a specialist HF cardiologist. The control group will receive usual care. The primary endpoint, assessed at 6 months, will be the difference between groups in the proportion of participants being prescribed five guideline-recommended treatments; (1) ACE inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor at least 50% of target dose, (2) beta-blocker at least 50% of target dose, (3) mineralocorticoid receptor antagonist at any dose, (4) anticoagulation for patients diagnosed with atrial fibrillation, (5) referral to cardiac rehabilitation. Secondary outcomes will include functional capacity (6-minute walk test); quality of life (Kansas City Cardiomyopathy Questionnaire); depressive symptoms (Patient Health Questionnaire-2); self-care behaviour (Self-Care of Heart Failure Index). Resource utilisation will also be assessed. ETHICS AND DISSEMINATION: Ethical approval was granted by the South Metropolitan Health Service Ethics Committee (RGS3531), with reciprocal approval at Curtin University (HRE2020-0322). Results will be disseminated via peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: ACTRN12620001069943.

Coronary computed tomographic angiography derived findings and risk score improves the allocation of lipid lowering therapy compared to clinical score.

ABSTRACT: The initiation of therapy for atherosclerotic cardiovascular disease (ASVCD) is currently guided by cohort-based risk scores. Coronary computed tomographic angiography (CCTA) offers more personalised risk assessments to optimise therapy allocation. This study investigates the utility of CCTA determined coronary stenosis (both obstructive and non-obstructive plaque) to guide allocation of lipid lowering therapy. A retrospective analysis of 450 patients with CCTA performed for the assessment of chest pain at a single centre was conducted. Baseline characteristics, investigations, treatments and clinical outcomes were recorded. The allocation of lipid lowering therapy was evaluated with three models, cohort-based risk score (pooled cohort equation), a previously validated CCTA based clinical risk score (pooled cohort equation and CCTA findings) and CCTA alone (without clinical characteristics). The reclassification analysis included 266 patients. Compared to the cohort-based risk score, CCTA based clinical risk score in total reassigned 23% of patients. CCTA alone compared to the CCTA based clinical risk score correctly reassigned 23% and incorrectly reassigned 10%. When comparing the performance of CCTA alone against the cohort-based risk score, both the additive NRI of 25.8 (95% CI 4.12-37.56) and absolute NRI of 13.2 (95% CI 5.88-19.77) was significant. Revascularisation was required in 3% with a low cohort-based risk, but no patients with low risk as per CCTA alone or CCTA based clinical risk score required revascularisation The use of a CCTA based clinical risk score or CCTA alone compared to cohort-based risk scores can improve the allocation of lipid lowering therapy.

Galactic Cosmic Rays Throughout the Heliosphere and in the Very Local Interstellar Medium.

We review recent observations and modeling developments on the subject of galactic cosmic rays through the heliosphere and in the Very Local Interstellar Medium, emphasizing knowledge that has accumulated over the past decade. We begin by highlighting key measurements of cosmic-ray spectra by Voyager, PAMELA, and AMS and discuss advances in global models of solar modulation. Next, we survey recent works related to large-scale, long-term spatial and temporal variations of cosmic rays in different regimes of the solar wind. Then we highlight new discoveries from beyond the heliopause and link these to the short-term evolution of transients caused by solar activity. Lastly, we visit new results that yield interesting insights from a broader astrophysical perspective.

Can we monitor heart attack in the troponin era? Evidence from a population-based cohort study.

BACKGROUND: Troponins (highly sensitive biomarkers of myocardial damage) increase counts of myocardial infarction (MI) in clinical practice, but their impact on trends in admission rates for MI in National statistics is uncertain. METHODS: Cases coded as MI or other cardiac diagnoses in the Hospital Morbidity Data Collection (MI-HMDC) in Western Australia in 1998 and 2003 were classified using revised criteria for MI developed by an International panel convened by the American Heart Association (AHA criteria) using information on symptoms, ECGs and cardiac biomarkers abstracted from samples of medical notes. Age-sex standardized rates of MI-HMDC were compared with rates of MI based on AHA criteria including troponins (MI-AHA) or traditional biomarkers only (MI-AHAck). RESULTS: Between 1998 and 2003, rates of MI-HMDC decreased by 3.5% whereas rates of MI-AHA increased by 17%, a difference largely due to increased false-negative cases in the HMDC associated with marked increased use of troponin tests in cardiac admissions generally, and progressively lower test thresholds. In contrast, rates of MI-AHAck declined by 18%. CONCLUSIONS: Increasing misclassification of MI-AHA by the HMDC may be due to reluctance by clinicians to diagnose MI based on relatively small increases in troponin levels. These influences are likely to continue. Monitoring MI using AHA criteria will require calibration of commercially available troponin tests and agreement on lower diagnostic thresholds for epidemiological studies. Declining rates of MI-AHA ck are consistent with long-standing trends in MI in Western Australia, suggesting that neither MI-HMDC nor MI-AHA reflect the true underlying population trends in MI.

Cardioprotective medication adherence in Western Australians in the first year after myocardial infarction: restricted cubic spline analysis of adherence-outcome relationships.

Adherence to cardioprotective medications following myocardial infarction (MI) is commonly assessed using a binary threshold of 80%. We investigated the relationship between medication adherence as a continuous measure and outcomes in MI survivors using restricted cubic splines (RCS). We identified all patients aged ≥65 years hospitalised for MI from 2003-2008 who survived one-year post-discharge (n = 5938). Adherence to statins, beta-blockers, renin angiotensin system inhibitors (RASI) and clopidogrel was calculated using proportion of days covered to one-year post-discharge (landmark date). Outcomes were 1-year all-cause death and major adverse cardiac events (MACE) after the landmark date. Adherence-outcome associations were estimated from RCS Cox regression models. RCS analyses indicated decreasing risk for both outcomes above 60% adherence for statins, RASI and clopidogrel, with each 10% increase in adherence associated with a 13.9%, 12.1% and 18.0% decrease respectively in adjusted risk of all-cause death (all p < 0.02). Similar results were observed for MACE (all p < 0.03). Beta-blockers had no effect on outcomes at any level of adherence. In MI survivors, increasing adherence to statins, RASI, and clopidogrel, but not beta blockers, is associated with a decreasing risk of death/MACE with no adherence threshold beyond 60%. Medication adherence should be considered as a continuous measure in outcomes analyses.

Invasive Coronary Angiography after Chest Pain Presentations to Emergency Departments.

We investigated patients presenting to emergency departments (EDs) with chest pain to identify factors that influence the use of invasive coronary angiography (ICA). Using linked ED, hospitalisations, death and cardiac biomarker data, we identified people aged 20 years and over who presented with chest pain to tertiary public hospital EDs in Western Australia from 1 January 2016 to 31 March 2017 (ED chest pain cohort). We report patient characteristics, ED discharge diagnosis, pathways to ICA, ICA within 90 days, troponin test results, and gender differences. Associations were examined with the Pearson Chi-squared test and multivariate logistic regression. There were 16,974 people in the ED chest pain cohort, with a mean age of 55.6 years and 50.7% males, accounting for 20,131 ED presentations. Acute coronary syndrome was the ED discharge diagnosis in 10.4% of presentations. ED pathways were: discharged home (57.5%); hospitalisation (41.7%); interhospital transfer (0.4%); and died in ED (0.03%)/inpatients (0.3%). There were 1546 (9.1%) ICAs performed within 90 days of the first ED chest pain visit, of which 59 visits (3.8%) had no troponin tests and 565 visits (36.6%) had normal troponin. ICAs were performed in more men than women (12.3% vs. 6.1%, p < 0.0001; adjusted OR 1.89, 95% CI 1.65, 2.18), and mostly within 7 days. Equal numbers of males and females present with chest pain to tertiary hospital EDs, but men are twice as likely to get ICA. Over one-third of ICAs occur in those with normal troponin levels, indicating that further investigation is required to determine risk profile, outcomes and cost effectiveness.

Coronary intervention for persistent occlusion after myocardial infarction.

BACKGROUND: It is unclear whether stable, high-risk patients with persistent total occlusion of the infarct-related coronary artery identified after the currently accepted period for myocardial salvage has passed should undergo percutaneous coronary intervention (PCI) in addition to receiving optimal medical therapy to reduce the risk of subsequent events. METHODS: We conducted a randomized study involving 2166 stable patients who had total occlusion of the infarct-related artery 3 to 28 days after myocardial infarction and who met a high-risk criterion (an ejection fraction of <50% or proximal occlusion). Of these patients, 1082 were assigned to routine PCI and stenting with optimal medical therapy, and 1084 were assigned to optimal medical therapy alone. The primary end point was a composite of death, myocardial reinfarction, or New York Heart Association (NYHA) class IV heart failure. RESULTS: The 4-year cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group (hazard ratio for death, reinfarction, or heart failure in the PCI group as compared with the medical therapy group, 1.16; 95% confidence interval [CI], 0.92 to 1.45; P=0.20). Rates of myocardial reinfarction (fatal and nonfatal) were 7.0% and 5.3% in the two groups, respectively (hazard ratio, 1.36; 95% CI, 0.92 to 2.00; P=0.13). Rates of nonfatal reinfarction were 6.9% and 5.0%, respectively (hazard ratio, 1.44; 95% CI, 0.96 to 2.16; P=0.08); only six reinfarctions (0.6%) were related to assigned PCI procedures. Rates of NYHA class IV heart failure (4.4% vs. 4.5%) and death (9.1% vs. 9.4%) were similar. There was no interaction between treatment effect and any subgroup variable (age, sex, race or ethnic group, infarct-related artery, ejection fraction, diabetes, Killip class, and the time from myocardial infarction to randomization). CONCLUSIONS: PCI did not reduce the occurrence of death, reinfarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up in stable patients with occlusion of the infarct-related artery 3 to 28 days after myocardial infarction. (ClinicalTrials.gov number, NCT00004562 [ClinicalTrials.gov].).

Randomized trial comparing 600- with 300-mg loading dose of clopidogrel in patients with non-ST elevation acute coronary syndrome undergoing percutaneous coronary intervention: results of the Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Coronary intervention in Acute coronary Lesions (PRACTICAL) Trial.

BACKGROUND: There is uncertainty about the benefit of a higher loading dose (LD) of clopidogrel in patients with non-ST elevation acute coronary syndrome (NSTEACS) undergoing early percutaneous coronary intervention (PCI). METHODS: We compared the effects of a 600- versus a 300-mg LD of clopidogrel on inhibition of platelet aggregation, myonecrosis, and clinical outcomes in patients with NSTEACS undergoing an early invasive management strategy. Patients with NSTEACS (n = 256, mean age 63 years, 81.6% elevated troponin) without thienopyridine for at least 7 days were randomized to receive 600- or 300-mg LD of clopidogrel. Percutaneous coronary intervention was performed in 140 patients, with glycoprotein IIb/IIIa inhibitor use in 68.6%. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by optical platelet aggregometry immediately before coronary angiography. RESULTS: Post-PCI myonecrosis was defined as a next-day troponin I greater than 5 times the upper limit of reference range and greater than baseline levels. Clopidogrel 600-mg LD compared with 300-mg LD was associated with significantly reduced ADP-induced platelet aggregation (49.7% vs 55.7% with ADP 20 micromol/L) but did not reduce post-PCI myonecrosis or adverse clinical outcomes to 6 months. There was no association between preprocedural platelet aggregation and outcome. CONCLUSIONS: These data confirm a modest incremental antiplatelet effect of a 600-mg clopidogrel LD compared with 300-mg LD but provide no support for a clinical benefit in patients with NSTEACS managed with an early invasive strategy including a high rate (69%) of glycoprotein IIb/IIIa inhibitor use during PCI.

Percutaneous coronary intervention in the Occluded Artery Trial: procedural success, hazard, and outcomes over 5 years.

BACKGROUND: The Occluded Artery Trial (OAT) was a 2,201-patient randomized clinical trial comparing routine stent-based percutaneous coronary intervention (PCI) versus optimal medical therapy alone in stable myocardial infarction (MI) survivors with persistent infarct-related artery occlusion identified day 3 to 28 post MI. Intent-to-treat analysis showed no difference between strategies with respect to the incidence of new class IV congestive heart failure, MI, or death. The influence of PCI failure, procedural hazard, and crossover on trial results has not been reported. METHODS: Study angiograms were analyzed and adjudicated centrally. Factors associated with PCI failure were examined. Time-to-event analysis using the OAT primary outcome was performed by PCI success status. Landmark analysis (up to and beyond 30 days) partitioned early hazard versus late outcome according to treatment received. RESULTS: Percutaneous coronary intervention was adjudicated successful in >87%. Percutaneous coronary intervention failure rates were similar in US and non-US sites, and did not significantly influence outcome at 60 months (hazard ratio for success vs fail 0.79, 99% CI 0.45-1.40, P = .29). Partitioning of early procedural hazard revealed no late benefit for PCI (hazard ratio for PCI success vs medical therapy alone 1.06, 99% CI 0.75-1.50, P = .66). CONCLUSIONS: Percutaneous coronary intervention failure and complication rates in the OAT were low. Neither PCI failure nor early procedural hazard substantively influenced the primary trial results.

Operationalization and validation of a novel method to calculate adherence to polypharmacy with refill data from the Australian pharmaceutical benefits scheme (PBS) database.

BACKGROUND: Electronic health care data contain rich information on medicine use from which adherence can be estimated. Various measures developed with medication claims data called for transparency of the equations used, predominantly because they may overestimate adherence, and even more when used with multiple medications. We aimed to operationalize a novel calculation of adherence with polypharmacy, the daily polypharmacy possession ratio (DPPR), and validate it against the common measure of adherence, the medication possession ratio (MPR) and a modified version (MPRm). METHODS: We used linked health data from the Australian Pharmaceutical Benefits Scheme and Western Australian hospital morbidity dataset and mortality register. We identified a strict study cohort from 16,185 patients aged ≥65 years hospitalized for myocardial infarction in 2003-2008 in Western Australia as an illustrative example. We applied iterative exclusion criteria to standardize the dispensing histories according to previous literature. A SAS program was developed to calculate the adherence measures accounting for various drug parameters. RESULTS: The study cohort was 348 incident patients (mean age 74.6±6.8 years; 69% male) with an admission for myocardial infarction who had cardiovascular medications over a median of 727 days (range 74 to 3,798 days) prior to readmission. There were statins (96.8%), angiotensin converting enzyme inhibitors (88.8%), beta-blockers (85.6%), and angiotensin receptor blockers (13.2%) dispensed. As expected, observed adherence values were higher with mean MPR (median 89.2%; Q1: 73.3%; Q3: 104.6%) than mean MPRm (median 82.8%; Q1: 68.5%; Q3: 95.9%). DPPR values were the most narrow (median 83.8%; Q1: 70.9%; Q3: 96.4%). Mean MPR and DPPR yielded very close possession values for 37.9% of the patients. Values were similar in patients with longer observation windows. When the traditional threshold of 80% was applied to mean MPR and DPPR values to signify the threshold for good adherence, 11.6% of patients were classified as good adherers with the mean MPR relative to the DPPR. CONCLUSION: In the absence of transparent and standardized equations to calculate adherence to polypharmacy from refill databases, the novel DPPR algorithm represents a valid and robust method to estimate medication possession for multi-medication regimens.

Impact of the Australian gender specific thresholds using the Abbott high sensitivity troponin I assay in clinical care.

The aim of this study was to ascertain the impact of gender specific hs-TnI thresholds in a clinical setting and determine the clinical characteristics and discharge diagnosis for individuals presenting to the Emergency Department (ED) with elevated troponin I with the Abbott high-sensitivity troponin I (hs-TnI) assay, but non-elevated troponin I on the previous generation assay (STAT TnI-II). Medical records of individuals presenting to the Royal Perth Hospital ED with elevated hs-TnI between 12 November 2013 and 24 December 2013 were retrospectively reviewed. The 99th percentile hs-TnI thresholds were ≥26 ng/L for males and ≥16 ng/L for females. TnI-II assays were performed concomitantly. In total, 1449 individuals [855 (59%) males] had 3580 troponin measurements. hs-TnI was elevated in 1569 (43.8%) measurements. Elevated hs-TnI with normal TnI-II was found in 120 (8.3%) individuals: 77 (64%) females and 43 (36%) males. Eight (6.7%) individuals were diagnosed with acute coronary syndrome (ACS): four (9.3%) males and four (5.2%) females. Other cardiac aetiologies were found in 33 (42%) females and 17 (40%) males. Individuals with elevated hs-TnI had high rates of hypertension (80%), diabetes mellitus (33%), cardiac failure (23%), aspirin use (53%) and lipid lowering therapy (52%). Significantly fewer females than males with discrepant troponin I results had previous ischaemic heart disease. The hsTnI assay identifies 8% more individuals with elevated troponin in an acute setting, with a female predominance (64%). However, only 6.7% of these individuals with multiple cardiovascular risk factors were diagnosed with ACS, a ∼0.5% increase overall. Outcome studies are required to determine if the Australian hs-TnI thresholds are clinically appropriate.