Stratified medicine using invasive coronary function testing in angina: A cost-effectiveness analysis of the British Heart Foundation CorMicA trial.

AIM: Coronary angiography is indicated in many patients with known or suspected angina for the investigation of coronary artery disease (CAD). However, up to half of patients with symptoms of ischaemia have no obstructive coronary arteries (INOCA). This large subgroup includes patients with suspected microvascular angina (MVA) and/or vasospastic angina (VSA). Clinical guidelines relating to the management of patients with INOCA are limited. Uncertainty regarding the diagnosis of patients with INOCA presents a health economic challenge, both in terms of healthcare resource utilisation and of quality-of-life impact on patients. METHODS: A cost-effectiveness analysis of the introduction of stratified medicine into the invasive management of INOCA, based on clinical and resource-use data obtained in the CorMicA trial, from a UK NHS perspective. The intervention included an invasive diagnostic procedure (IDP) of coronary vascular function during coronary angiography to define clinical endotypes to target with linked medical therapy. Outcomes of interest were mean total cost and QALY gain between treatment groups, and the incremental cost-effectiveness ratio. We undertook probabilistic sensitivity and scenario analyses. RESULTS: The incremental cost per QALY gained at 12 months was £4500 (£2937, £33264). Compared with a willingness-to-pay (WTP) threshold of £20,000 per QALY, the use of the IDP test is cost-effective. At this WTP threshold there is a 96% probability of the IDP being cost-effective, based on the uncertainty described by bootstrap analysis. CONCLUSIONS: The burden of INOCA, particularly in women, is known to be significant. These findings provided new evidence to inform this unmet clinical need.

Abnormal haemoglobin levels in acute coronary syndromes.

BACKGROUND: Anaemia is an adverse prognostic marker in acute coronary syndromes (ACS), but the epidemiology of abnormal haemoglobin levels in such patients is uncertain. AIMS: To investigate the prevalence, nature and predictors of abnormal haemoglobin levels in ACS patients at admission. DESIGN: Observational study. METHODS: All emergency admissions from January to April 2005 were assessed within 24-48 h of hospital admission. ACS patients (unstable angina, non-ST-elevation or ST-elevation myocardial infarction) were enrolled (n = 320, 190 men). Clinical information was recorded. RESULTS: Overall, 71% had unstable angina; 18% non-ST-elevation myocardial infarction (MI), and 11% ST-elevation MI. Mean +/- SD haemoglobin was 14.3 +/- 1.7 g/dl in men and 13.2 +/- 1.5 g/dl in women. Abnormal haemoglobin was more common in men (65, 34%) than in women (34, 22%) (p = 0.013). Anaemia (haemoglobin <13 g/dl in men, or <12.0 g/dl in women) was recorded in 35 (18%) men and 24 (18%) women. All had admission haemoglobin >8 g/dl, and anaemia was usually normocytic. Multivariate predictors of anaemia (OR, 95%CI) were age (1.07, 1.04-1.1) and serum albumin (0.90, 0.81-1.00). Elevated haemoglobin (>16 g/dl) was recorded in 30 (16%) men and 4 (3%) women (p < 0.01), and was more common in ST-elevation MI patients (26%) than in unstable angina or non-ST elevation MI patients (9%) (p = 0.005). In patients who underwent invasive management with a post-procedure haemoglobin the following day (n = 85), 15 (18%) new cases of anaemia were detected. Admission duration correlated with haemoglobin (p < 0.01), creatinine (p < 0.01), troponin I (p < 0.01) and C-reactive protein (p < 0.01). Anaemia was more common in those who died in hospital (3, 60%) than in those who survived (56, 18%) (adjusted p = 0.0135). DISCUSSION: Abnormal haemoglobin levels were common in our ACS admissions. Anaemia was generally mild. Increasing age and interventional management were associated with anaemia, which in turn was associated with adverse in-hospital outcomes. Interventions to prevent and detect anaemia in this setting merit prospective testing.

Influence of socioeconomic status on clinical outcomes and quality of life after percutaneous coronary intervention.

OBJECTIVES: To determine whether socioeconomic status (SES) influences clinical outcomes and quality of life after percutaneous coronary intervention (PCI). DESIGN: Prospective observational study. SETTING: Two interventional cardiac centres. PARTICIPANTS: 1346 consecutive patients undergoing PCI over a 12-month period. OUTCOMES: Self reported health-related quality of life (HRQoL; EuroQol-5 Dimensions (EQ-5D); EuroQol Visual Analogue Scale (EQ-VAS)), repeat angiography, revascularisation, hospital admission, myocardial infarction and death within 12 months, by SES derived using postal address code. MAIN RESULTS: No significant differences were found between patients with high and low SES in the occurrence of repeat angiography (p = 0.55), repeat revascularisation (PCI, p = 0.81, CAEG, p = 0.27), total cardiac hospitalisation (p = 0.10), myocardial infarction (p = 0.97) or death 12 months after PCI (p = 0.88). Non-procedure-related readmissions were higher in patients with low SES (18.6% v 13.7%; p = 0.025). After adjustment for confounding factors, patients with low SES had lower HRQoL scores at baseline (95% CI for difference 0.01 to 0.14; p = 0.003) and at 12 months (95% CI 0.07 to 0.17; p<0.001) compared with those with high SES. CONCLUSIONS: Clinical outcomes were similar for patients in different SES groups. Patients with low SES had considerably more non-procedure-related readmissions and lower quality-of-life scores. Future studies on HRQoL after coronary revascularisation should take account of these important differences related to SES.

Limited clinical utility of CT coronary angiography in a district hospital setting.

BACKGROUND: Studies have demonstrated considerable accuracy of multi-slice CT coronary angiography (MSCT-CA) in comparison to invasive coronary angiography (I-CA) for evaluating coronary artery disease (CAD). The extent to which published MSCT-CA accuracy parameters are transferable to routine practice beyond high-volume tertiary centres is unknown. AIM: To determine the accuracy of MSCT-CA for the detection of CAD in a Scottish district general hospital. DESIGN: Prospective study of diagnostic accuracy. METHOD: One hundred patients with suspected CAD recruited from two Glasgow hospitals underwent both MSCT-CA (Philips Brilliance 40 × 0.625 collimation, 50-200 ms temporal resolution) and I-CA. Studies were reported by independent, blinded radiologists and cardiologists and compared using the AHA 15-segment model. RESULTS: Of 100 patients [55 male, 45 female, mean (SD) age 58.0 (10.7) years], 59 and 41% had low-intermediate and high pre-test probabilities of significant CAD, respectively. Mean (SD) heart rate during MSCT-CA was 68.8 (9.0) bpm. Fifty-seven per cent of patients had coronary artery calcification and 35% were obese. Patient prevalence of CAD was 38%. Per-patient sensitivity, specificity, positive and negative (NPV) predictive values for MSCT-CA were 92.1, 47.5, 52.2 and 90.6%, respectively. NPV was reduced to 75.0% in the high pre-test probability group. Specificity was compromised in patients with sub-optimally controlled heart rates, calcified arteries and elevated BMI. CONCLUSION: Forty-Slice MSCT-CA has a high NPV for ruling out significant CAD when performed in a district hospital setting in patients with low-intermediate pre-test probability and minimal arterial calcification. Specificity is compromised by clinically appropriate strategies for dealing with unevaluable studies. Effective heart rate control during MSCT-CA is imperative. National guidelines should be utilized to govern patient selection and direct MSCT-CA reporter training to ensure quality control.

Effects of changing clinical practice on costs and outcomes of percutaneous coronary intervention between 1998 and 2002.

AIM: To assess the effect of changing clinical practice on the costs and outcomes of percutaneous coronary intervention (PCI) between 1998 and 2002. SETTING: Two tertiary interventional centres. PATIENTS: Consecutive patients undergoing PCI over a 12-month period between 1998 and 2002. DESIGN: Comparative observational study of costs and 12-month clinical outcomes of consecutive PCI procedures in 1998 (n = 1047) and 2002 (n = 1346). Clinical data were recorded in the Scottish PCI register. Repeat PCI, coronary artery bypass graft and mortality were obtained by record linkage. Costs of equipment were calculated using a computerised bar-code system and standard National Health Service reference costs. RESULTS: Between 1998 and 2002, the use of bare metal stents increased from 44% to 81%, and the use of glycoprotein IIB/IIIA inhibitors increased from 0% to 14% of cases. During this time, a significant reduction was observed in repeat target-vessel PCI (from 8.4% to 5.1%, p = 0.001), any repeat PCI (from 11.7% to 9.2%, p = 0.05) and any repeat revascularisation (from 15.1% to 11.3%, p = 0.009) within 12 months. Significantly higher cost per case in 2002 compared with 1998 (mean (standard deviation) 2311 pounds (1158) v 1785 pounds (907), p<0.001) was mainly due to increased contribution from bed-day costs in 2002 (45.0% (16.3%) v 26.2% (12.6%), p = 0.01) associated with non-elective cases spending significantly longer in hospital (6.22 (4.3) v 4.6 (4.3) days, p = 0.01). CONCLUSIONS: Greater use of stents and glycoprotein IIb/IIIa inhibitors between 1998 and 2002 has been accompanied by a marked reduction in the need for repeat revascularisation. Longer duration of hospital stay for non-elective cases is mainly responsible for increasing costs. Strategies to reduce the length of stay could considerably reduce the costs of PCI.

Unemployment and deprivation are associated with a poorer outcome following percutaneous coronary angioplasty.

This prospective observational study aimed to assess the impact of employment status and deprivation on quality of life 12 months after percutaneous coronary intervention (PCI). Patients completed a questionnaire at baseline and at 1 year follow-up including a health utility score (EQ-5D), symptoms and employment status. Deprivation was assessed using the Carstairs' deprivation category based on area postcodes. The majority (79.6%) of patients of working age returned to work within 12 months. Unemployment was associated with a lower quality of life (QoL) at baseline (0.49 (0.32) vs 0.61 (0.27), p=0.002) and less improvement in QoL 1 year after PCI (0.15 (0.37) vs 0.26 (0.31), p<0.012). Furthermore, unemployed patients had significantly less improvement in chest pain score (p=0.002) and breathlessness (p<0.001). Unemployed patients from the most deprived areas had lowest QoL at follow-up and least improvement in QoL at 1 year. Unemployment and deprivation are associated with poorer outcomes following PCI.

Variations in clinical decision-making between cardiologists and cardiac surgeons; a case for management by multidisciplinary teams?

OBJECTIVE: To assess variations in decisions to revascularise patients with coronary heart disease between general cardiologists, interventional cardiologists and cardiac surgeons DESIGN: Six cases of coronary heart disease were presented at an open meeting in a standard format including clinical details which might influence the decision to revascularise. Clinicians (n = 53) were then asked to vote using an anonymous electronic system for one of 5 treatment options: medical, surgical (CABG), percutaneous coronary intervention (PCI) or initially medical proceeding to revascularisation if symptoms dictated. Each case was then discussed in an open forum following which clinicians were asked to revote. Differences in treatment preference were compared by chi squared test and agreement between groups and between voting rounds compared using Kappa. RESULTS: Surgeons were more likely to choose surgery as a form of treatment (p = 0.034) while interventional cardiologists were more likely to choose PCI (p = 0.056). There were no significant differences between non-interventional and interventional cardiologists (p = 0.13) in their choice of treatment. There was poor agreement between all clinicians in the first round of voting (Kappa 0.26) but this improved to a moderate level of agreement after open discussion for the second vote (Kappa 0.44). The level of agreement among surgeons (0.15) was less than that for cardiologists (0.34) in Round 1, but was similar in Round 2 (0.45 and 0.45 respectively). CONCLUSION: In this case series, there was poor agreement between cardiac clinical specialists in the choice of treatment offered to patients. Open discussion appeared to improve agreement. These results would support the need for decisions to revascularise to be made by a multidisciplinary panel.

Hospital volume of throughput and periprocedural and medium-term adverse events after percutaneous coronary intervention: retrospective cohort study of all 17,417 procedures undertaken in Scotland, 1997-2003.

OBJECTIVE: To determine whether percutaneous coronary intervention (PCI) hospital volume of throughput is associated with periprocedural and medium-term events, and whether any associations are independent of differences in case mix. DESIGN: Retrospective cohort study of all PCIs undertaken in Scottish National Health Service hospitals over a six-year period. METHODS: All PCIs in Scotland during 1997-2003 were examined. Linkage to administrative databases identified events over two years' follow up. The risk of events by hospital volume at 30 days and two years was compared by using logistic regression and Cox proportional hazards models. RESULTS: Of the 17,417 PCIs, 4900 (28%) were in low-volume hospitals and 3242 (19%) in high-volume hospitals. After adjustment for case mix, there were no significant differences in risk of death or myocardial infarction. Patients treated in high-volume hospitals were less likely to require emergency surgery (adjusted odds ratio 0.18, 95% confidence interval (CI) 0.07 to 0.54, p = 0.002). Over two years, patients in high-volume hospitals were less likely to undergo surgery (adjusted hazard ratio 0.52, 95% CI 0.35 to 0.75, p = 0.001), but this was offset by an increased likelihood of further PCI. There was no net difference in coronary revascularisation or in overall events. CONCLUSION: Death and myocardial infarction were infrequent complications of PCI and did not differ significantly by volume. Emergency surgery was less common in high-volume hospitals. Over two years, patients treated in high-volume centres were as likely to undergo some form of revascularisation but less likely to undergo surgery.

Coronary venous lipid peroxide concentrations after coronary angioplasty: correlation with biochemical and electrocardiographic evidence of myocardial ischaemia.

BACKGROUND: Raised lipid peroxide concentrations in coronary venous plasma have been reported after coronary angioplasty in humans. This may reflect increased free radical activity after myocardial ischaemia and reperfusion. If so, it may be possible to correlate lipid peroxide concentrations with the degree of myocardial ischaemia produced during angioplasty. METHODS: 15 patients (age range 42-70; 12 men) with stable angina pectoris undergoing angioplasty of a proximal left anterior descending coronary artery stenosis were studied. Plasma lipid peroxide and lactate concentrations were measured in sequential blood samples taken from the great cardiac vein before and immediately after one to five serial 60 second balloon inflations. The maximum ST segment shift during each balloon inflation was also measured. RESULTS: Lipid peroxide concentrations in coronary venous plasma were raised from pre-angioplasty values by more than 2 SDs of the relevant measurement error after 27 out of 46 (59%) balloon inflations. Lactate concentrations were raised after 43 out of 46 (93%) balloon inflations. No significant difference was found between the peak percentage change of either lipid peroxide or lactate concentrations after any of the first three serial inflations. The maximum ST segment shift after each of the first three serial inflations was also similar. Coronary venous lactate concentrations after balloon inflation correlated positively with the maximum ST segment shift, but did not correlate with lipid peroxide concentrations. CONCLUSIONS: Raised lipid peroxide concentrations in coronary venous plasma can be detected in humans after balloon angioplasty. There is no positive correlation between lipid peroxide concentrations in coronary venous plasma after angioplasty and the degree of preceding myocardial ischaemia as assessed by either ST segment shift or lactate production. These indices showed that one to three serial 60 second balloon inflations each produce a similar degree of myocardial ischaemia. The origin of the raised lipid peroxide concentrations in coronary venous plasma after angioplasty remains unknown.

Comparing performance between coronary intervention centres requires detailed case-mix adjusted analysis.

This study compares 12 month clinical outcomes and procedural costs at two interventional centres with significant differences in crude mortality and revascularization outcomes between 1997 and 1998. Percutaneous coronary intervention (PCI) registry data on 1046 consecutive patients treated contemporaneously at two university centres were linked to hospital discharge and death data to provide 12 month follow-up information on survival and repeat revascularization. Costs were determined by detailed analysis of equipment use, length of stay and staff from 100 contemporary cases at each centre to derive a procedural cost model. This model was then applied retrospectively to estimate cost per procedure. Stents were used more frequently at one centre (56 versus 26 per cent, chi(2) test, p < 0.001) resulting in greater procedural cost [mean (SE), pounds sterling 1970 (34) versus pounds sterling 1521 (39), t-test, p < 0.001). One year repeat target vessel PCI was significantly greater at the centre using more stents (10.3 versus 5.6 per cent, chi(2) test, p = 0.005) and the need for any repeat revascularization (PCI or coronary artery by-pass surgery) was also significantly greater at this centre (18.4 versus 10.8 per cent, chi(2) test, p < 0.001). Cox regression revealed that after correction for case-mix the difference in the need for repeat target vessel PCI between the two centres was no longer significant (p = 0.15). In the two centres studied, crude differences in cost per case, mortality and the need for revascularization were largely accounted for by significant differences in case-mix. Comparison of outcomes and costs between centres should not be published without careful adjustment for differences in case-mix.

Acute and chronic effects of once-daily isosorbide-5-mononitrate on the exercise capacity of patients with angina pectoris treated with a beta-blocking drug.

Forty-four patients with stable effort angina pectoris were included in a double-blind, randomised, placebo-controlled, parallel group study to compare the effect of two slow-release forms of isosorbide-5-mononitrate ('Ismo-Retard' 40 mg and 'Imdur' 60 mg) on exercise capacity when given as an adjunctive treatment to beta adrenoreceptor blocking therapy. In a symptom-limited exercise test performed three hours after the first dose, Ismo-retard increased the total duration of exercise by 92 seconds (confidence interval (CI) 5.1-116.9) p less than 0.006, and the time of onset to anginal pain by 117 seconds (CI 27.8, 156.1) p less than 0.004. A similar improvement in total duration of exercise (by 87 seconds) was noted three hours following 15 consecutive once-daily doses (CI 16.8-128) p less than 0.02, and in the time of onset to anginal pain by 101 seconds (CI 19.8-139.6) p less than 0.01. For Imdur the corresponding results were 53 seconds (CI 12.7-56.3), 84 seconds (CI 15.4-103.7), p less than .02, 54 seconds (CI 1.4-78.4) and 85 seconds (CI 6.9-120.5) respectively. These results would suggest that both active treatments were effective anti-anginal agents.

Comparison of survival following coronary artery bypass grafting vs. percutaneous coronary intervention in diabetic and non-diabetic patients: retrospective cohort study of 6320 procedures.

AIM: To determine whether mortality following percutaneous coronary intervention vs. coronary bypass grafting varies according to whether or not patients have diabetes. METHODS: We used the Scottish Coronary Revascularization Register to identify all patients undergoing revascularization in Scottish NHS hospitals since 1997. We excluded single-vessel disease, left main stem stenosis, and bypass grafting performed at the same time as other operations. We used death certificate data from the Registrar General to identify all subsequent deaths. RESULTS: Of the 6320 eligible procedures, 5042 (80%) were bypass grafts and 1278 (20%) angioplasties. Overall 831 (13%) patients had diabetes with no significant difference by procedure (13% vs. 12%). A total of 382 deaths occurred over a mean follow-up of 2.3 years. Diabetic patients had a poorer prognosis following both surgery (adjusted hazards ratio (HR) 1.43, 95% confidence interval (CI) 1.08, 1.89) and percutaneous intervention (adjusted HR 2.58, 95% CI 1.43, 4.63). Among non-diabetic patients, no significant differences in mortality were detected between the two procedures. Among diabetic patients, no significant difference was detected in those with two-vessel disease. In those with impaired left ventricular function and triple-vessel disease, angioplasty was associated with a significantly higher risk of death (adjusted HR 3.58, 95% CI 1.40, 9.19). CONCLUSIONS: This is the first study to demonstrate statistically significant results that support the BARI trial findings. Our study demonstrated a significant difference for triple-vessel disease but not two-vessel disease. The former may be due to incomplete revascularization using percutaneous intervention. Our results require corroboration from randomized trials.

Outcomes following coronary artery bypass grafting and percutaneous transluminal coronary angioplasty in the stent era: a prospective study of all 9890 consecutive patients operated on in Scotland over a two year period.

OBJECTIVE: To determine current outcomes of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG). DESIGN: The Scottish coronary revascularisation register provided prospectively collected data on case mix and in-hospital complications for all revascularisation procedures between April 1997 and March 1999 (4775 PTCA; 5115 CABG). Linkage to routine hospital discharge and death data provided follow up information on survival and repeat revascularisation. RESULTS: Stents were used in 51% of PTCA procedures. CABG patients were older, had more severe coronary disease, and had greater comorbidity. PTCA was more likely to be undertaken as an urgent or emergency procedure. Perioperative death and urgent surgery followed 0.3% and 0.6% of PTCA procedures, respectively. Case fatality rates were higher following CABG, with 6.7% dead within two years compared with 3.4% following PTCA. PTCA was more often followed by readmission for ischaemic heart disease, repeat angiography, or revascularisation: 22.8% of patients had repeat revascularisation within two years, compared with 1.8% following CABG. CONCLUSIONS: The severity of coronary heart disease was greater than in previously published registry studies and randomised trials. Despite this, overall survival figures were comparable and repeat revascularisation rates lower, particularly following PTCA. Perioperative death and urgent surgery following PTCA were also lower. These favourable outcomes may be attributable, in part, to increased use of bail out and elective stenting.