Potential use of PCSK9 inhibitors as a secondary preventative measure for cardiovascular disease following acute coronary syndrome: a UK real-world study.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a major development in the prevention of cardiovascular disease (CVD) and is one of the most significant discoveries since the development of statin therapy. Administration of two human monoclonal antibodies to PCSK9 (alirocumab and evolocumab) can significantly reduce low-density lipoprotein cholesterol (LDL-c) concentrations, thus improving lipid management. Accordingly, guidelines on the specific indications for alirocumab and evolocumab usage have been released. This multicentre study aimed to estimate the proportion of patients treated for an acute myocardial infarction (MI) who could be considered for PCSK9 inhibitors under the current National Institute for Health and Care Excellence (NICE) lipid targets criteria. METHODS: The records of 596 patients in two large hospitals in Liverpool, UK were analysed. Information was collected on lipid profiles during and after admission, lipid-lowering therapy and previous CVD. RESULTS: At least 2.2% of patients were eligible for PCSK9 inhibitors post-MI under the current NICE guidance. Additionally, 29% of patients failed to achieve LDL-c concentrations <2.0 mmol/L despite maximum statin therapy and failed to meet eligibility for PCSK9 inhibitors as per the NICE criteria. This cohort represents a group of patients 'in limbo', in which statin therapy alone is not sufficient to reduce LDL-c. CONCLUSIONS: PCSK9 inhibitors are expensive and so their use must be highly selective. At present, in a real-world setting with ezetimibe underprescribing, ~2% of patients are eligible and a further 30% are deprived of benefit and improved outcomes by lack of optimisation and/or potential use of PCSK9 inhibitors.

A direct comparison of decision rules for early discharge of suspected acute coronary syndromes in the era of high sensitivity troponin.

BACKGROUND: We tested the hypothesis that a single high sensitivity troponin at limits of detection (LOD HSTnT) (<5 ng/l) combined with a presentation non-ischaemic electrocardiogram is superior to low-risk Global Registry of Acute Coronary Events (GRACE) (<75), Thrombolysis in Myocardial Infarction (TIMI) (≤1) and History, ECG, Age, Risk factors and Troponin (HEART) score (≤3) as an aid to early, safe discharge for suspected acute coronary syndrome. METHODS: In a prospective cohort study, risk scores were computed in consecutive patients with suspected acute coronary syndrome presenting to the Emergency Room of a large English hospital. Adjudication of myocardial infarction, as per third universal definition, involved a two-physician, blinded, independent review of all biomarker positive chest pain re-presentations to any national hospital. The primary and secondary outcome was a composite of type 1 myocardial infarction, unplanned coronary revascularisation and all cause death (MACE) at six weeks and one year. RESULTS: Of 3054 consecutive presentations with chest pain 1642 had suspected acute coronary syndrome (52% male, median age 59 years, 14% diabetic, 20% previous myocardial infarction). Median time from chest pain to presentation was 9.7 h. Re-presentations occurred in eight hospitals with 100% follow-up achieved. Two hundred and eleven (12.9%) and 279 (17%) were adjudicated to suffer MACE at six weeks and one year respectively. Only HEART ≤3 (negative predictive value MACE 99.4%, sensitivity 97.6%, %discharge 53.4) and LOD HSTnT strategy (negative predictive value MACE 99.8%, sensitivity 99.5%, %discharge 36.9) achieved pre-specified negative predictive value of >99% for MACE at six weeks. For type 1 myocardial infarction alone the negative predictive values at six weeks and one year were identical, for both HEART ≤3 and LOD HSTnT at 99.8% and 99.5% respectively. CONCLUSION: HEART ≤3 or LOD HSTnT strategy rules out short and medium term myocardial infarction with ≥99.5% certainty, and short-term MACE with >99% certainty, allowing for early discharge of 53.4% and 36.9% respectively of suspected acute coronary syndrome. Adoption of either strategy has the potential to greatly reduce Emergency Room pressures and minimise follow-up investigations. Very early presenters (<3 h), due to limited numbers, are excluded from these conclusions.