ESC 2019 guidelines on chronic coronary syndromes: could calcium scoring improve detection of coronary artery disease in patients with low risk score. Findings from a retrospective cohort of patients in a district general hospital.

BACKGROUND: The European Society of Cardiology (ESC) published an updated stable chest pain guideline in 2019, recommending the use of an updated pre-test probability (PTP) risk score (RS) to assess the likelihood of coronary artery disease (CAD). We sought to compare the 2019 and 2013 PTPRS in a contemporary cohort of patients. METHODS: 612 patients who were investigated with computed tomography coronary angiography (CTCA) for stable chest pain were included in a retrospective analysis. RESULTS: There were 255 patients with 2019 PTPRS 15-50% with a 9% yield of severe CAD on CTCA, compared with 402 patients and a 4% yield using the 2013 PTPRS (p = 0.01). 355 patients had a 2019 PTPRS of <15%, with 3% found to have severe CAD, compared with 67 patients and none with severe CAD using the 2013 PTPRS (p = 0.14). 336 of patients with 2019 PTPRS of <15% had a calcium score as part of the CTCA. 223 of these had a zero calcium score and only one had severe CAD. In comparison, 113 patients had a positive calcium score, and 10 (9%) had severe CAD (p < 0.001). DISCUSSION: The ESC 2019 PTPRS classifies more patients as at lower risk of CAD and hence reduces the risk overestimation associated with the 2013 PTPRS. However, in patients with a 2019 PTPRS of <15%, who would not be investigated, the use of the calcium score detected the majority of patients with significant CAD, who may benefit from secondary prevention and an associated mortality benefit as per the SCOT-Heart trial.

Effect of a common X-linked angiotensin II type 2-receptor gene polymorphism (-1332 G/A) on the occurrence of premature myocardial infarction and stenotic atherosclerosis requiring revascularization.

OBJECTIVES: To assess the association of the angiotensin II type 2 (AT2) receptor (-1332 G/A) gene polymorphism with premature coronary artery disease (CAD) and investigate for a further role in both myocardial infarction and predominantly stenotic atherosclerosis requiring revascularisation. METHODS AND RESULTS: We investigated 885 families, which consisted of at least one sibling affected with premature CAD and at least one unaffected sibling. Genotyping of subjects was performed using a restriction enzyme digestion of an initial 310 bp PCR fragment that included the AT2 (-1332 G/A) locus. The mean age of the 1143 individuals affected by premature CAD at the time of event was 50.6+/-9.1 years. The genetic data were analyzed for these families using the X-linked sibling transmission disequilibrium test (XS-TDT). We observed significant evidence for an association for the AT2 (-1332 G) locus and premature CAD (p-exact value=0.028). This was driven by a highly significant result in men (p-exact value=0.005). We performed further analyses to investigate for an association with myocardial infarction (Group 1) and stenotic atherosclerosis that was of sufficient severity as to require revascularization (Group 2). We found an increase in the frequency of the G/GG genotype in both Groups 1 and 2, being most marked in Group 2 (XS-TDT, p-exact value=0.0134); logistic regression (p=0.033, OR 1.38; 95% CI of 1.212-1.507). CONCLUSION: We have observed evidence of association between the X-linked AT2 (-1332 G/A) polymorphism and premature CAD with further evidence of a statistically significant association with stenotic atherosclerosis requiring revascularization.

Perindopril.

Perindopril is a third-generation ACE inhibitor that is characterised as a small, lipophilic molecule with a therapeutically active carboxyl side group. These and other features combine to make this a unique member of a very well-established class of drugs that have proven efficacy in a wide range of cardiovascular diseases. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) demonstrated benefit in the secondary prevention of patients with stroke, whereas the Perindopril and Remodelling in Elderly with Acute Myocardial Infarction (PREAMI) trial supports extended routine use after myocardial infarction. The most recent evidence from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) show that perindopril is able to improve the prognosis of patients with a relatively low global cardiovascular risk, denoted either by the presence of stable coronary artery disease or of essential hypertension in conjunction with at least three other risk factors. The fact that major relative risk reductions have been reported for these two studies is matched by the significance of the findings to modern clinical practice. Both studies were conducted in the context of advance concomitant care that is typically better in clinical trials than in routine practice. In particular, the benefits observed were seen to be of a similar magnitude, and also independent of those resulting from statin therapy. Of particular interest is the likely complimentary action of these treatment strategies with regard to the stabilisation of atheromatous plaques. Perindopril is a well-established drug, the full value of which is only now becoming fully apparent.

Cost-effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decision-analytical modelling.

OBJECTIVES: To identify and prioritise key areas of clinical uncertainty regarding the medical management of non-ST elevation acute coronary syndrome (ACS) in current UK practice. DATA SOURCES: Electronic databases. Consultations with clinical advisors. Postal survey of cardiologists. REVIEW METHODS: Potential areas of important uncertainty were identified and 'decision problems' prioritised. A systematic literature review was carried out using standard methods. The constructed decision model consisted of a short-term phase that applied the results of the systematic review and a long-term phase that included relevant information from a UK observational study to extrapolate estimated costs and effects. Sensitivity analyses were undertaken to examine the dependence of the results on baseline parameters, using alternative data sources. Expected value of information analysis was undertaken to estimate the expected value of perfect information associated with the decision problem. This provided an upper bound on the monetary value associated with additional research in the area. RESULTS: Seven current areas of clinical uncertainty (decision problems) in the drug treatment of unstable angina patients were identified. The agents concerned were clopidogrel, low molecular weight heparin, hirudin and intravenous glycoprotein antagonists (GPAs). Twelve published clinical guidelines for unstable angina or non-ST elevation ACS were identified, but few contained recommendations about the specified decision problems. The postal survey of clinicians showed that the greatest disagreement existed for the use of small molecule GPAs, and the greatest uncertainty existed for decisions relating to the use of abciximab (a large molecule GPA). Overall, decision problems concerning the GPA class of drugs were considered to be the highest priority for further study. Selected papers describing the clinical efficacy of treatment were divided into three groups, each representing an alternative strategy. The strategy involving the use of GPAs as part of the initial medical management of all non-ST elevation ACS was the optimal choice, with an incremental cost-effectiveness ratio (ICER) of 5738 pounds per quality-adjusted life-year (QALY) compared with no use of GPAs. Stochastic analysis showed that if the health service is willing to pay 10,000 pounds per additional QALY, the probability of this strategy being cost-effective was around 82%, increasing to 95% at a threshold of 50,000 pounds per QALY. A sensitivity analysis including an additional strategy of using GPAs as part of initial medical management only in patients at particular high risk (as defined by age, ST depression or diabetes) showed that this additional strategy was yet more cost-effective, with an ICER of 3996 pounds per QALY compared with no treatment with GPA. Value of information analysis suggested that there was considerable merit in additional research to reduce the level of uncertainty in the optimal decision. At a threshold of 10,000 pounds per QALY, the maximum potential value of such research in the base case was calculated as 12.7 million pounds per annum for the UK as a whole. Taking account of the greater uncertainty in the sensitivity analyses including clopidogrel, this figure was increased to approximately 50 million pounds. CONCLUSIONS: This study suggests the use of GPAs in all non-ST elevation ACS patients as part of their initial medical management. Sensitivity analysis showed that virtually all of the benefit could be realised by treating only high-risk patients. Further clarification of the optimum role of GPAs in the UK NHS depends on the availability of further high-quality observational and trial data. Value of information analysis derived from the model suggests that a relatively large investment in such research may be worthwhile. Further research should focus on the identification of the characteristics of patients who benefit most from GPAs as part of medical management, the comparison of GPAs with clopidogrel as an adjunct to standard care, follow-up cohort studies of the costs and outcomes of high-risk non-ST elevation ACS over several years, and exploring how clinicians' decisions combine a normative evidence-based decision model with their own personal behavioural perspective.