Extent of coronary artery disease and outcomes after ticagrelor administration in patients with an acute coronary syndrome: Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial.

BACKGROUND: Extensive coronary artery disease (CAD) is associated with higher risk. In this substudy of the PLATO trial, we examined the effects of randomized treatment on outcome events and safety in relation to the extent of CAD. METHODS: Patients were classified according to presence of extensive CAD (defined as 3-vessel disease, left main disease, or prior coronary artery bypass graft surgery). The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS: Among 15,388 study patients for whom the extent of CAD was known, 4,646 (30%) had extensive CAD. Patients with extensive CAD had more high-risk characteristics and experienced more clinical events during follow-up. They were less likely to undergo percutaneous coronary intervention (58% vs 79%, P < .001) but more likely to undergo coronary artery bypass graft surgery (16% vs 2%, P < .001). Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD (14.9% vs 17.6%, hazard ratio [HR] 0.85 [0.73-0.98]) similar to its reduction in those without extensive CAD (6.8% vs 8.0%, HR 0.85 [0.74-0.98], Pinteraction = .99). Major bleeding was similar with ticagrelor vs clopidogrel among patients with (25.7% vs 25.5%, HR 1.02 [0.90-1.15]) and without (7.3% vs 6.4%, HR 1.14 [0.98-1.33], Pinteraction = .24) extensive CAD. CONCLUSIONS: Patients with extensive CAD have higher rates of recurrent cardiovascular events and bleeding. Ticagrelor reduced ischemic events to a similar extent both in patients with and without extensive CAD, with bleeding rates similar to clopidogrel.

Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: insights from the PLATelet inhibition and patient outcomes (PLATO) trial.

BACKGROUND: Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. METHODS: Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS: Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P(interaction) = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P(interaction) = .46) prior CABG. CONCLUSIONS: Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

Comparing the long-term outcomes in chronic coronary syndrome patients with prior ST-segment and non-ST-segment elevation myocardial infarction: findings from the TIGRIS registry.

OBJECTIVES: Compared with ST-segment elevation myocardial infarction (STEMI) patients, non-STEMI (NSTEMI) patients have more comorbidities and extensive coronary artery disease. Contemporary comparative data on the long-term prognosis of stable post-myocardial infarction subtypes are needed. DESIGN: Long-Term rIsk, clinical manaGement and healthcare Resource utilisation of stable coronary artery dISease (TIGRIS) was a multinational, observational and longitudinal cohort study. SETTING: Patients were enrolled from 350 centres, with >95% coming from cardiology practices across 24 countries, from 19 June 2013 to 31 March 2017. PARTICIPANTS: This study enrolled 8277 stable patients 1-3 years after myocardial infarction with ≥1 additional risk factor. OUTCOME MEASURES: Over a 2 year follow-up, cardiovascular events and deaths and self-reported health using the EuroQol 5-dimension questionnaire score were recorded. Relative risk of clinical events and health resource utilisation in STEMI and NSTEMI patients were compared using multivariable Poisson regression models, adjusting for prognostically relevant patient factors. RESULTS: Of 7752 patients with known myocardial infarction type, 46% had NSTEMI; NSTEMI patients were older with more comorbidities than STEMI patients. NSTEMI patients had significantly poorer self-reported health and lower prevalence of dual antiplatelet therapy at hospital discharge and at enrolment 1-3 years later. NSTEMI patients had a higher incidence of combined myocardial infarction, stroke and cardiovascular death (5.6% vs 3.9%, p<0.001) and higher all-cause mortality (4.2% vs 2.6%, p<0.001) compared with STEMI patients. Risks were attenuated after adjusting for other patient characteristics. Health resource utilisation was higher in NSTEMI patients, although STEMI patients had more cardiologist visits. CONCLUSIONS: Post-NSTEMI chronic coronary syndrome patients had a less favourable risk factor profile, poorer self-reported health and more adverse cardiovascular events during long-term follow-up than individuals post STEMI. Efforts are needed to recognise the risks of stable patients after NSTEMI and optimise secondary prevention and care. TRIAL REGISTRATION NUMBER: NCT01866904.

Does coronary artery bypass surgery improve survival?

OBJECTIVES: According to guide-lines, coronary bypass surgery improves survival in high risk patients. The evidence for this is more than 20 years old and may be questioned. Long waiting lists for coronary bypass surgery are detrimental but offer the possibility to compare the risk of death before and after surgery. We hypothesized that the risk of death is lower after bypass surgery than before the operation in high risk patients in a more recent cohort. DESIGN AND RESULTS: Death hazard functions were calculated by the use of Poisson regression scheduled for bypass surgery between 1 Jan 1995 and 31 July 2005. The analyses were performed in two states: 1) in the period after triage until admission for surgery during which optimal medication was intended and 2) after surgery and up to 11 years (corresponding to 57,548 patient years). The probability of death was calculated by entering individual risk profile data into the two multivariable functions. There were several significant differences between the hazard functions in the two states. All variables reflecting angiographic severity of coronary lesions indicated lower risk of death after bypass surgery. The risk associated with left ventricular impairment was lower after surgery (beta coefficients - 0.0546 vs. - 0.0234, p <0.001). Only one variable, age, indicated higher risk after surgery (which is also seen in a general population over time). The reduction of risk was dependent on preoperative risk with a large reduction when preoperative risk was high and vice versa. When preoperative risk was low, however, the risk increased due to surgical mortality. CONCLUSIONS: The risk of death is lower after bypass surgery than before the operation in high risk patients. This is most likely explained by a prognostic gain from bypass surgery. The gain is largest in high-risk patients but small or absent in low risk patients.

Determinants of long-term dual antiplatelet therapy use in post myocardial infarction patients: Insights from the TIGRIS registry.

BACKGROUND: Patterns of dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI) have not been well studied. METHODS: TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 24 countries), observational study of patients 1 to 3 years post-MI. We sought to identify the prevalence and determinants of DAPT use ≥1 year post-MI in patients enrolled in TIGRIS. We used multivariable logistic regression to identify determinants of DAPT use at 396 days post-MI (365 days plus a 31day overrun period to account for intended DAPT discontinuation at 1 year). Patients treated with an oral anticoagulant were excluded. RESULTS: Of 7708 patients (median age 67 years, women 25%, ST-elevation MI 50%), 39% and 16% were on DAPT at 396 days and 5 years post-MI, respectively. DAPT use at 396 days post-MI was more prevalent in patients <65 years of age, treated with percutaneous coronary intervention (versus coronary artery bypass grafting or medical therapy), and with multivessel disease or a history of angina. Additional clinical determinants of ischemic and/or bleeding events following MI (diabetes, second prior MI, hypertension, peripheral artery disease, heart failure, smoking, and renal insufficiency) were not independently associated with DAPT use at 396 days. There were geographic variations in the use of DAPT at 396 days (p<0.001), with the lowest use in Europe and the highest in Asia and Australia. CONCLUSION: In a contemporary patient cohort, DAPT use beyond 1 year post MI was prevalent and associated with patient and index event characteristics. There were marked geographical variations in DAPT use beyond 1 year post MI.

Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database.

The relationship between statin-induced increases in HDL cholesterol (HDL-C) concentration and statin-induced decreases in LDL cholesterol (LDL-C) is unknown. The effects of different statins on HDL-C levels, relationships between changes in HDL-C and changes in LDL-C, and predictors of statin-induced increases in HDL-C have been investigated in an individual patient meta-analysis of 32,258 dyslipidemic patients included in 37 randomized studies using rosuvastatin, atorvastatin, and simvastatin. The HDL-C raising ability of rosuvastatin, and simvastatin was comparable, with both being superior to atorvastatin. Increases in HDL-C were positively related to statin dose with rosuvastatin and simvastatin but inversely related to dose with atorvastatin. There was no apparent relationship between reduction in LDL-C and increase in HDL-C, whether analyzed overall for all statins (correlation coefficient = 0.005) or for each statin individually. Percentage increase in apolipoprotein A-I was virtually identical to that of HDL-C at all doses of the three statins. Baseline concentrations of HDL-C and triglyceride (TG) and presence of diabetes were strong, independent predictors of statin-induced elevations of HDL-C. Statins vary in their HDL-C raising ability. The HDL-C increase achieved by all three statins was independent of LDL-C decrease. However, baseline HDL-C and TGs and the presence of diabetes were predictors of statin-induced increases in HDL-C.

Diabetes association with self-reported health, resource utilization, and prognosis post-myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health-related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post-myocardial infarction (MI) patients with and without DM. HYPOTHESIS: In post-MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes. METHODS: The prospective, observational long-term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post-MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and <60 mL/min, and DM treated with medication. Self-reported health status was assessed at baseline, 1 and 2 years and converted to EQ-5D scores. The main outcome measures were baseline HRQoL and HRU during follow-up. RESULTS: DM at enrollment was 33% (2959 patients, 869 insulin treated). Mean baseline EQ-5D score (0.86 vs 0.82; P < .0001) was higher; mean number of hospitalizations (0.38 vs 0.50, P < .0001) and mean length of stay (LoS; 9.3 vs 11.5; P = .001) were lower in patients without vs with DM. All-cause death and the composite of CV death, MI, and stroke were significantly higher in DM patients, with adjusted 2-year rate ratios of 1.43 (P < .01) and 1.55 (P < .001), respectively. CONCLUSIONS: Stable post-MI patients with DM (especially insulin treated) had poorer EQ-5D scores, higher hospitalization rates and LoS, and worse clinical outcomes vs those without DM. Strategies focusing specifically on this high-risk population should be developed to improve outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01866904 (https://clinicaltrials.gov).

Symptoms of chest pain and dyspnea and factors associated with chest pain and dyspnea 10 years after coronary artery bypass grafting.

BACKGROUND: The purpose of the study is to describe (a) changes in physical activity and symptoms of chest pain and dyspnea during 10 years after coronary artery bypass grafting (CABG) and (b) risk indicators for chest pain and dyspnea 10 years after CABG. METHODS: This is a prospective observational study in Western Sweden. The study includes all patients who underwent CABG without simultaneous valve surgery and with no previous CABG between June 1, 1988, and June 1, 1991. All patients were prospectively followed up for 10 years. Evaluation of symptoms took place via postal inquiries before, 5, and 10 years after the operation. RESULTS: In all, 2,000 patients participated in a survey evaluating chest pain and dyspnea during 10 years after CABG. The overall 10-year mortality was 32%. The proportion of patients with no chest pain increased from 3% before surgery to 56% 5 years after the operation and 54% after 10 years. There was only one predictor for chest pain after 10 years and that was the duration of angina pectoris before surgery. The proportion of patients with no dyspnea increased from 12% before surgery to 40% after 5 years but decreased to 31% after 10 years. The most significant predictors for dyspnea after 10 years were female sex, obesity, diabetes mellitus, high age, duration of angina pectoris, functional class before CABG, and number of days in intensive care unit after CABG. CONCLUSION: During 10 years after CABG, one third died. After 10 years, 54% of the survivors were free from chest pain and 31% were free from dyspnea. Predictors for chest pain and dyspnea could be defined and reflected age, history, sex, obesity, preoperative complications, and symptom severity.

Short-term sinus rhythm predicts long-term sinus rhythm and clinical improvement after intraoperative ablation of atrial fibrillation.

AIMS: Our aim was to compare the long-term effects on rhythm and quality of life (QoL) after left atrial epicardial radiofrequency (RF) ablation vs. no ablation in patients undergoing cardiac surgery. METHODS AND RESULTS: Thirty-nine patients with ECG documented atrial fibrillation (AF) scheduled for coronary artery bypass grafting (CABG) with or without concomitant valve surgery were consecutively elected for epicardial RF ablation. Thirty-nine age- and gender-matched patients scheduled for CABG with or without concomitant valve surgery only and with documented AF served as controls. The follow-up after ablation was 32 +/- 11 months. The percentage of patients in sinus rhythm (SR) at long-term follow-up was 62 vs. 33% (P = 0.03) after ablation and no ablation, respectively. SR at 3 months was highly predictive of that at 32 months (sensitivity 95%, positive predictive value 86%). Long-term SR was associated with better QoL, fewer symptoms, higher ejection fraction, and smaller left and right atria than AF. CONCLUSION: SR at 3 months was highly predictive of long-term SR that was associated with clinical improvement when compared with patients still in AF. AF at 3 months did not preclude a later stabilization to SR.

Comparison of low and high initial tacrolimus dosing in primary heart transplant recipients: a prospective European multicenter study.

BACKGROUND: The purpose of this prospective, randomized, open-label, phase II, multicenter study was to optimize the initial oral dose of tacrolimus. METHODS: A total of 113 patients were randomly assigned to initial low-dose (0.075 mg/kg/day, n=55) or high-dose (0.15 mg/kg/day, n=58) oral tacrolimus and followed for 3 months. Target whole-blood trough levels were 10 to 20 ng/mL. Prophylactic use of corticosteroids and azathioprine was identical in both groups, and antibody induction was mandatory. The primary endpoint was the time to and incidence of the initial oral tacrolimus dose adjustment because of toxicity or rejection, or withdrawal before initial dose change. Efficacy was assessed by the occurrence of biopsy-proven rejection (International Society for Heart and Lung Transplantation grade > or =1B). RESULTS: In the primary endpoint, no significant difference was observed between the low- and high-dose groups. After 3 months, there was no difference in freedom from initial oral tacrolimus dose change because of rejection, toxicity, or withdrawal (89.0% vs. 87.6%; not significant [NS]). In both groups, dose adjustments were mainly required to achieve and maintain target blood levels (80.0% vs. 82.8%; NS). Patient survival was 92.7% and 98.3% (NS). There was no significant difference between groups regarding freedom from biopsy-proven acute rejection (57.1% vs. 66.3%; NS). The overall safety profiles indicated a tendency toward better tolerability in the low-dose group. CONCLUSIONS: Although low-dose and high-dose tacrolimus had similar efficacy, low-dose tacrolimus was associated with a more favorable safety profile. Therefore we recommend starting tacrolimus therapy after antibody induction at 0.075 mg/kg and adjust dose according to whole-blood trough levels.

Determinants for an impaired quality of life 10 years after coronary artery bypass surgery.

OBJECTIVE: To identify determinants of an inferior quality of life (QoL) 10 years after coronary artery bypass grafting (CABG). SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. PARTICIPANTS: All patients from Western Sweden who underwent CABG between 1988 and 1991 without simultaneous valve surgery and no previous CABG. MAIN OUTCOME MEASURES: Questionnaires for evaluating QoL 10 years after the operation. Three different instruments were used: The Nottingham health profile (NHP), the psychological general wellbeing index (PGWI), and the Physical Activity Score (PAS). RESULTS: 2000 patients underwent CABG, of whom 633 died during 10 years of follow-up. Information on QoL at 10 years was available in 976 patients (71% of survivors). A history of diabetes and chronic obstructive pulmonary disease were the two independent predictors for an inferior QoL with all three instruments. Furthermore, there were three predictors of an inferior QoL with two of the instruments: high age, female sex and a history of hypertension. A number of factors predicted an inferior QoL with one of the instruments. These were the duration of angina pectoris and functional class prior to CABG, renal dysfunction, a history of cerebrovascular disease, obesity, height, duration of respirator treatment and requirement of inotropic drugs postoperatively. In addition, when introducing preoperative QoL into the model a low QoL before surgery was a strong independent predictor also of an inferior QoL 10 years after CABG. CONCLUSION: Variables independently predictive of an impaired QoL 10 years after CABG, irrespective of the instrument used, were an impaired QoL prior to surgery, chronic obstructive pulmonary disease and a history of diabetes. However, other factors reflecting gender, the previous history as well as postoperative complications were also associated with the QoL 10 years later in at least one of these instruments.

Mortality on the waiting list for coronary artery bypass grafting: incidence and risk factors.

BACKGROUND: Insufficient capacity for coronary artery bypass grafting results in waiting times before operation, prioritization of patients and, ultimately, death on the waiting list. We aimed to calculate waiting list mortality and to identify risk factors for death on the waiting list. METHODS: The study included 5,864 consecutive patients accepted for elective coronary artery bypass grafting (78% male; mean age, 66 +/- 9 years). The patients were categorized at acceptance into three priority groups: imperative (39%), urgent (36%), or routine (25%). Waiting list mortality was calculated and compared between groups, and risk factors were identified by Poisson regression. RESULTS: Median waiting time for the whole population was 55 days. Seventy-seven patients (1.3%) died, corresponding to a mortality rate of 5.8 deaths per 100 patient-years. The mortality rate per 100 patient-years was highest for those in the imperative group, 15.1 deaths, compared with 5.3 deaths in the urgent group and 3.2 in the routine group (p < 0.001). Independent risk factors were male sex (p = 0.032), Cleveland Clinic risk score (p = 0.005), impaired left ventricular ejection fraction (p = 0.007), unstable angina pectoris (p = 0.001), concomitant aortic valve disease (p = 0.002), priority group (p < 0.001), and time after acceptance (p = 0.019). The mortality risk increased with time after acceptance by 11% a month. CONCLUSIONS: Long waiting lists for coronary artery bypass grafting are associated with considerable mortality. The risk of death increases significantly with waiting time. Sex, unstable angina, perioperative risk, impaired left ventricular function, and concomitant aortic valve disease are independent risk factors and should be considered at triage.

Improvement and factors associated with improvement in quality of life during 10 years after coronary artery bypass grafting.

AIM: To describe (1) the improvement in various aspects of quality of life (QoL) and (2) predictors of improvement, during 10 years after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: All patients who underwent CABG in western Sweden between June 1988 and June 1991 without simultaneous valve surgery and with no previous CABG were approached with an inquiry prior to and 5 and 10 years after the operation. QoL was measured with three different instruments: (1) Nottingham health profile (NHP), (2) psychological general well-being index (PGWBI) and (3) physical activity score (PAS). RESULTS: There was a significant improvement in QoL with all three instruments from before to 10 years after the operation. The mean improvements +/-SD were for NHP, - 4.2+/-17.0 (P<0.0001), for PGWBI, +9.7+/-17.6 (P<0.0001) and for PAS, -0.96+/-1.23 (P<0.0001). However, there was also a deterioration with all three instruments between 5 and 10 years after surgery. The mean deteriorations +/-SD were for NHP, +4.4+/-12.8 (P<0.0001), for PGWBI, -4.6+/-14.8 (P<0.0001) and for PAS, +0.44+/-0.94 (P<0.0001). Independent predictors for an improvement in QoL with at least one of the instruments were low preoperative QoL, a younger age, being a man, high functional class (New York Heart Association), no hypertension, proximal left anterior descending coronary artery stenosis, short extracorporeal circulation time, use of internal mammary artery and a short postoperative time in the intensive care unit. CONCLUSION: There is a higher estimated QoL 10 years after CABG than before, despite the fact that the patients are 10 years older. However, there is also a deterioration in QoL between 5 and 10 years after surgery. Predictors of improvement during the 10 years included age, sex, previous history, localization of stenosis, type of graft and preoperative and postoperative factors.

Predictors of death during 10 years after coronary artery bypass grafting with particular emphasis on age.

OBJECTIVES: To describe predictors of death during 10 years of follow-up after coronary artery bypass grafting (CABG); to evaluate whether age interacts with the influence of various predictors on outcome; and to compare the mortality during 10 years after CABG with the mortality in an age- and sex-matched control population. DESIGN: Prospective, observational study. SETTING: Department of Thoracic and Cardiovascular Surgery at Sahlgrenska University Hospital and Scandinavian Heart Centre in Göteborg, Sweden. PARTICIPANTS: All patients from western Sweden who underwent CABG between 1 June 1988 and 1 June 1991 without simultaneous valve surgery and with no previous CABG. MAIN OUTCOME MEASUREMENTS: All-cause mortality during 10 years but more than 30 days after CABG. RESULTS: In all, 2000 patients participated in the survey. The following factors appeared as independent predictors of death: preoperative factors-age, history of congestive heart failure, cerebrovascular disease, history of intermittent claudication, current smoking, degree of left ventricular impairment, valvular disease and duration of angina pectoris; peroperative factors-ventilator time and neurological complications; postoperative factors-arrhythmia, requirement of digitalis and requirement of antidiabetics. There was an interaction between age and history of cerebrovascular disease with a stronger impact on outcome in younger patients. The late (>30 days after CABG) 10-year mortality in the study cohort was 29.6% compared with 25.9% in the control population (P=0.02). CONCLUSION: Among patients who underwent CABG, 13 independent predictors for mortality were found, mainly among preoperative factors but also among peroperative factors, postoperative complications and medication requirement after CABG.

Gender and mortality risk on the waiting list for coronary artery bypass grafting.

OBJECTIVE: There are gender differences in clinical presentation, treatment and outcome of patients with coronary artery disease. We investigated whether there is also a gender difference in terms of mortality risk on the waiting list in patients accepted for coronary artery bypass grafting (CABG). METHODS: All our patients accepted for elective CABG 1995-1999 (1303 women and 4561 men) were included. Prospectively registered preoperative characteristics and mortality were compared between men and women. Hazard functions for death on the waiting list were calculated using Poisson regression. RESULTS: At acceptance, women were older (68+/-9 vs 65+/-9 years, P<0.001), had a higher Cleveland risk score (2.4+/-1.8 vs 1.8+/-1.8, P<0.001) and a better left ventricular ejection fraction (60+/-14 vs 57+/-14%, P<0.001). More women had unstable angina pectoris (33 vs 20%, P<0.001), diabetes mellitus (23 vs 17%, P<0.001), chronic obstructive pulmonary disease (8 vs 5%, P<0.001), hypertension (47 vs 37%, P<0.001) and planned concomitant aortic valve surgery (13 vs 4%, P<0.001) while more men had three vessel disease (70 vs 66%, P=0.001). Median waiting time (55 vs 54 days, P=0.19) and unadjusted mortality (1.4 vs 1.0%, P=0.25) on the waiting list did not differ significantly between men and women but in a multivariate hazard analysis, female gender was associated with a lower risk than men of death on the waiting list (risk ratio 0.42, 95% confidence interval 0.19-0.93, P=0.032). CONCLUSIONS: Women have a lower risk of death on the waiting list for CABG, in spite of more advanced age, more co-morbidity, and a higher percentage of unstable angina pectoris.

[Thoracic and abdominal aorta aneurysms demand an experienced team work]. / Aneurysm i bröst- och bukaorta kräver vältrimmat lagarbete.

Patients with combined aneurysms in the thoracic and abdominal aorta need to be treated at experienced centres. These complicated aneurysms are today treated with various combinations of open and/or endovascular techniques. The complexity of the interventions is associated with high morbidity and mortality. By forming a structured organisation for care of these patients a better outcome can be expected. In this article we present the approach taken in Göteborg to meet these challenges.

Ticagrelor enhances adenosine-induced coronary vasodilatory responses in humans.

OBJECTIVES: This study was undertaken to determine if ticagrelor augments adenosine-induced coronary blood flow and the sensation of dyspnea in human subjects. BACKGROUND: Ticagrelor is a P2Y(12) receptor antagonist that showed superior clinical benefit versus clopidogrel in a phase III trial (PLATO [Platelet Inhibition and Patient Outcomes]). Ticagrelor has been shown to inhibit cell uptake of adenosine and enhance adenosine-mediated hyperemia responses in a dog model. METHODS: In this double-blind, placebo-controlled study, 40 healthy male subjects were randomized to receive a single dose of ticagrelor (180 mg) or placebo in a crossover fashion. Coronary blood flow velocity (CBFV) was measured by using transthoracic Doppler echocardiography at rest after multiple stepwise adenosine infusions given before and after study drug, and again after the infusion of theophylline. RESULTS: Ticagrelor significantly increased the area under the curve of CBFV versus the adenosine dose compared with placebo (p = 0.008). There was a significant correlation between ticagrelor plasma concentrations and increases in the area under the curve (p < 0.001). In both treatment groups, the adenosine-induced increase in CBFV was significantly attenuated by theophylline, with no significant differences between subjects receiving ticagrelor or placebo (p = 0.39). Furthermore, ticagrelor significantly enhanced the sensation of dyspnea during adenosine infusion, and the effects were diminished by theophylline. CONCLUSIONS: Ticagrelor enhanced adenosine-induced CBFV and the sensation of dyspnea in these healthy male subjects via an adenosine-mediated mechanism. (Study to Assess the Effect of Ticagrelor on Coronary Blood Flow in Healthy Male Subjects; NCT01226602).

Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery.

OBJECTIVES: This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial. BACKGROUND: In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality. METHODS: In the 1,261 patients with CABG performed within 7 days after stopping study drug, reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death. RESULTS: Numerically more vascular deaths occurred in the clopidogrel versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively). CONCLUSIONS: The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications. (Platelet Inhibition and Patient Outcomes [PLATO]; NCT00391872).

Postoperative autotransfusion of mediastinal shed blood does not influence haemostasis after elective coronary artery bypass grafting.

OBJECTIVES: The rationale of using autotransfusion of mediastinal shed blood after cardiac surgery is to preserve haemoglobin levels and reduce the need for allogenic blood transfusions. However, the method is controversial and its clinical value has been questioned. We hypothesised that re-transfusion of mediastinal shed blood instead impairs haemostasis after routine coronary artery bypass grafting and thus increases postoperative bleeding. METHODS: Seventy-seven consecutive elective coronary artery bypass surgery patients (mean age 67±9 years, 77% men) were included in a prospective, randomised controlled study. The patients were randomised to postoperative re-transfusion of mediastinal shed blood (n=39) or to a group where mediastinal shed blood was discarded (n=38). Primary end point was bleeding during the first 12 postoperative hours. Secondary end points were postoperative transfusion requirements, haemoglobin levels, thrombo-elastometric variables and plasma concentrations of interleukin-6, thrombin-anti-thrombin complex and D-dimer. RESULTS: Mean re-transfused volume in the autotransfusion group was 282±210 ml. There was no difference in postoperative bleeding (median 394 ml (interquartile range 270-480) vs 385 (255-430) ml, p=0.69), proportion of patients receiving transfusions of blood products (11/39 vs 11/38, p=0.95), haemoglobin levels 24h after surgery (116±13 vs 116±14 g l(-1), p=0.87), thrombo-elastometric variables, interleukin-6 (219±144 vs 201±144 pg ml(-1), p=0.59), thrombin-anti-thrombin complex (11.0±9.1 vs 14.8±15, p=0.19) or D-dimer (0.56±0.49 vs 0.54±0.44, p=0.79) between the autotransfusion group and the no-autotransfusion group. CONCLUSIONS: Autotransfusion of small-to-moderate amounts of mediastinal shed blood does not influence haemostasis after elective coronary artery bypass grafting.

Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER).

Statins are the most commonly prescribed agents for lowering levels of low-density lipoprotein (LDL) cholesterol. Although dose-dependent reductions in levels of atherogenic lipids are observed with all statins, the impact of increasing dose has not been fully elucidated. An individual patient data pooled analysis was performed of 32,258 patients in studies comparing the efficacy of rosuvastatin with that of atorvastatin or simvastatin. The impact of increasing dose on lowering LDL cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B was investigated. Doubling the dose of each statin was accompanied by a 4% to 7% greater degree of lowering of all atherogenic lipids. A stronger correlation was observed between changes in LDL cholesterol and non-HDL cholesterol (r = 0.92, p <0.001) or apolipoprotein B (r = 0.76, p <0.001) than triglycerides (r = 0.14, p <0.001). On multivariate analysis, baseline lipid level (p <0.0001) and increasing statin dose (p <0.0001) were strong predictors of achieving treatment goals in high-risk patients. Increasing age was a strong independent predictor of achieving goal for all atherogenic lipids (p <0.0001). Achieving LDL cholesterol goals was also more likely in women (p <0.0001), patients with diabetes (p <0.0001), and patients without atherosclerotic disease (p = 0.0002). In contrast, normal triglyceride levels were more often observed in men (p <0.0001) and patients without diabetes mellitus (p = 0.03). In conclusion, doubling statin dose was associated with greater lowering of LDL cholesterol by 4% to 6% and non-HDL cholesterol by 3% to 6%. Greater lipid goal achievement with increasing dose supports the use of high-dose statin therapy for more effective cardiovascular prevention.