Imperial College London

Emeritus ProfessorKimFox

Faculty of MedicineNational Heart & Lung Institute

Emeritus Professor
 
 
 
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Contact

 

+44 (0)20 7594 7966kim.fox

 
 
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Assistant

 

Ms Deborah Curcher +44 (0)20 7594 7966

 
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Location

 

Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
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559 results found

Bouabdallaoui N, Messas N, Greenlaw N, Ferrari R, Ford I, Fox KM, Tendera M, P Naidoo D, Hassager C, Gabriel Steg P, Tardif J-C, CLARIFY Investigatorset al., 2021, Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease., Eur J Prev Cardiol, Vol: 28, Pages: 1460-1466

AIMS: Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the 'smoker's paradox' suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease. METHODS: The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers. RESULTS: Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p < 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p < 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p < 0.05). CONCLUSION: In contrast to the 'smoker's paradox', current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564).

Journal article

Curzen N, Nicholas Z, Stuart B, Wilding S, Hill K, Shambrook J, Eminton Z, Ball D, Barrett C, Johnson L, Nuttall J, Fox K, Connolly D, O'Kane P, Hobson A, Chauhan A, Uren N, McCann G, Berry C, Carter J, Roobottom C, Mamas M R R, Ford I, Hlatky MAet al., 2021, Fractional flow reserve derived from computed tomography coronary angiography in the assessment of stable chest pain. The FORECAST Randomised Trial, European Heart Journal, Vol: 42, Pages: 3844-3852, ISSN: 0195-668X

Aims: Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care.Methods and results: Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months. Secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized groups were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFRCT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from −£112 (−8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01).Conclusion: A strategy of CTCA with selective FFRCT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography.

Journal article

Rahimi K, Bidel Z, Nazarzadeh M, Copland E, Canoy D, Wamil M, Majert J, McManus RJ, Chalmers J, Davis BR, Pepine CJ, Teo KKet al., 2021, Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis, The Lancet, Vol: 398, Pages: 1053-1064, ISSN: 0140-6736

BackgroundThe effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline.MethodsWe did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission.FindingsWe included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and

Journal article

Mesnier J, Ducrocq G, Danchin N, Ferrari R, Ford I, Tardiff J-C, Tendera M, Fox K, Steg PGet al., 2021, International observational analysis of evolution and outcomes of chronic stable angina: The Multinational Observational CLARIFY Study, Circulation, Vol: 144, Pages: 512-523, ISSN: 0009-7322

BACKGROUND: Although angina is common in patients with stable coronary artery disease (CAD), limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization. METHODS: Using data from 32 691 patients with stable CAD from the prospective observational CLARIFY registry, anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis.RESULTS: Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0–4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.12−1.55 for persistence of angina; adjusted HR 1.37, 95% CI 1.11−1.70 for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted HR 0.97, 95% CI 0.82−1.15).CONCLUSIONS: Angina affects almost one-quarter of patients with stable CAD but resolves spontaneously in most patients.

Journal article

Darmon A, Ducrocq G, Elbez Y, Popovic B, Sorbets E, Ferrari R, Ford I, Tardif J-C, Tendera M, Fox KM, Steg PGet al., 2021, Prevalence, Incidence and Prognostic Implications of Left Bundle Branch Block in Patients with Chronic Coronary Syndromes (From the CLARIFY Registry), AMERICAN JOURNAL OF CARDIOLOGY, Vol: 150, Pages: 40-46, ISSN: 0002-9149

Journal article

Ford I, Robertson M, Greenlaw N, Bauters C, Lemesle G, Sorbets E, Ferrari R, Tardif J-C, Tendera M, Fox K, Steg PGet al., 2021, Simple risk models to predict cardiovascular death in patients with stable coronary artery disease, EUROPEAN HEART JOURNAL-QUALITY OF CARE AND CLINICAL OUTCOMES, Vol: 7, Pages: 287-294, ISSN: 2058-5225

Journal article

Leiter LA, Bhatt DL, McGuire DK, Teoh H, Fox K, Simon T, Mehta SR, Lev EI, Kiss RG, Dalby AJ, Bueno H, Ridderstrale W, Himmelmann A, Prats J, Liu Y, Lee JJ, Amerena J, Kosiborod MN, Steg PGet al., 2021, Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 77, Pages: 2366-2377, ISSN: 0735-1097

Journal article

Rahimi K, 2021, Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis, The Lancet, Vol: 397, Pages: 1625-1636, ISSN: 0140-6736

BackgroundThe effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure.MethodsWe did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat.FindingsData for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm

Journal article

Copland E, Canoy D, Nazarzadeh M, Bidel Z, Ramakrishnan R, Woodward M, Chalmers J, Teo KK, Pepine CJ, Davis BR, Kjeldsen S, Sundstrom J, Rahimi Ket al., 2021, Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis, The Lancet Oncology, Vol: 22, Pages: 558-570, ISSN: 1213-9432

BackgroundSome studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials.MethodsWe searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), β blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283).Findings33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4·2 years (IQR 3·0–5·0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0·99 [95% CI 0·95–1·04] for ACEIs; 0·96 [0·92&nda

Journal article

Leiter L, Bhatt DL, McGuire DK, Teoh H, Fox K, Simon T, Mehta SR, Lev EI, Kiss RG, Dalby AJ, Bueno H, Ridderstrale W, Himmelmann A, Prats J, Liu Y, Lee JL, Amerena J, Kosiborod MN, Steg PGet al., 2021, Relationship between diabetes-related factors and the effects of ticagrelor plus aspirin in THEMIS and THEMIS-PCI, JACC - Journal of the American College of Cardiology, ISSN: 0735-1097

BACKGROUND THEMIS (N=19,220) and its pre-specified THEMIS-Percutaneous Coronary Intervention (THEMIS-PCI, N=11,154) sub-analysis showed in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA1c 7.1%) and stable coronary artery disease without prior myocardial infarction [MI] or stroke, that ticagrelor plus aspirin (relative to placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, or intracranial bleeding) if they had a previous PCI.OBJECTIVES In these post hoc analyses, we examined whether the primary efficacy outcome (cardiovascular death, MI, stroke; 3-point MACE), primary safety outcome (TIMI-defined major bleeding) and net clinical benefit varied with diabetes-related factors.METHODS Outcomes were analyzed across baseline diabetes duration, HbA1c, and antihyperglycemic medications.RESULTS In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years; 11.1% for >20 years) and HbA1c (6.4% for ≤6.0%; 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR] 0.90; P=0.04) were generally consistent across subgroups. Major bleeding event rate (overall 1.6%) did not vary by diabetes duration or HbA1c and was increased similarly by ticagrelor across all subgroups (HR=2.32; P<0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA1c, and antihyperglycemic medications CONCLUSION Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.

Journal article

Davies A, Fox K, Galassi AR, Banai S, Yla-Herttuala S, Luescher TFet al., 2021, Management of refractory angina: an update, EUROPEAN HEART JOURNAL, Vol: 42, Pages: 269-280C, ISSN: 0195-668X

Journal article

Mak K-H, Vidal-Petiot E, Young R, Sorbets E, Greenlaw N, Ford I, Tendera M, Ferrari R, Tardiff J-C, Udell JA, Escobedo J, Fox K, Steg PGet al., 2021, Prevalence of diabetic and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities, European Journal of Preventive Cardiology, ISSN: 2047-4873

Background: In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods: CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia and Africa in 2009-2010, and followed-up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia, or prior revascularisation procedure. Results: Among 32,694patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to approximately 60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome(cardiovascular death, myocardial infarction or stroke)with an adjusted hazard ratio of1.28(95% CI 1.18-1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion: In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.

Journal article

Lüscher TF, Fox K, Hamm C, Carter RE, Taddei S, Simoons M, Crea Fet al., 2020, Scientific integrity: what a journal can and cannot do., European Heart Journal, Vol: 41, Pages: 4552-4555, ISSN: 0195-668X

Journal article

Gautier A, Ducrocq G, Ebez Y, Fox KM, Ferrari R, Ford I, Tardiff J-C, Feldman LJ, Steg Pet al., 2020, Cardiovascular risk of chronic coronary syndrome patients according to vascular phenotype, diabetes and smoking, European Journal of Preventive Cardiology, ISSN: 2047-4873

Journal article

Pavasini R, Camici PG, Crea F, Danchin N, Fox K, Manolis AJ, Marzilli M, Rosano GMC, Lopez-Sendon JL, Pinto F, Balla C, Ferrari Ret al., 2020, Anti-anginal drugs: Systematic review and clinical implications (vol 283, pg 55, 2019), INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 321, Pages: 23-23, ISSN: 0167-5273

Journal article

Darmon A, Ducrocq G, Jasilek A, Feldman L, Sorbets E, Ferrari R, Ford I, Tardif J-C, Tendera M, Fox KM, Steg PG, Darmon A, Ducrocq G, Jasliek A, Feldman LJ, Sorbets E, Ferrari R, Ford I, Tardif JC, Tendera M, Fox KM, Steg PGet al., 2020, Use of risk scores to identify lower and higher risk subsets among COMPASS-eligible patients with chronic coronary syndromes. Insights from the CLARIFY registry, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: WILEY, Pages: 58-65, ISSN: 0160-9289

Conference paper

Darmon A, Ducrocq G, Jasilek A, Feldman L, Sorbets E, Ferrari R, Ford I, Tardiff J-C, Tendera M, Fox K, Steg PGet al., 2020, Use of risk scores to identify lower and higher risk subsets among COMPASS-eligible patients with chronic coronary syndromes. Insights from the CLARIFY Registry, Clinical Cardiology (Hoboken): an indexed and peer-reviewed journal for advances in the treatment of cardiovascular disease, ISSN: 0160-9289

Background:The COMPASS trial showed a reduction of ischemic events with low‐dose rivaroxaban and aspirin in chronic coronary syndromes (CCS) compared with aspirin alone, at the expense of increased bleeding.Hypothesis:The CHA2DS2VaSc Score, REACH Recurrent Ischemic (RIS), and REACH Bleeding Risk Score (BRS) could identify patients with a favorable trade‐off between ischemic and bleeding events, among COMPASS‐eligible patients.Methods:We identified the COMPASS‐eligible population within the CLARIFY registry (>30.000 patients with CCS). High‐bleeding risk patients (REACH BRS > 10) were excluded, as in the COMPASS trial. Patients were categorized as low (0–1) or high (≥ 2) CHA2DS2VaSc; low (0–12) or intermediate (13–19) REACH RIS, and low (0–6) or intermediate (7–10) REACH BRS. Ischemic outcome was the composite of cardiovascular death, myocardial infarction or stroke. Bleeding was defined as serious bleeding (haemorrhagic stroke, hospitalization for bleeding, transfusion).Results:The COMPASS‐eligible population comprised 5.142 patients with ischemic and bleeding outcome of 2.3 (2.1–2.5) and 0.5 (0.4–0.6) per 100 patient‐years, respectively. Patients with intermediate REACH RIS (n = 1934 [37.6%]) had the higher ischemic risk (3.0 [2.6–3.4]) with similar bleeding risk (0.5 [0.4–0.7]) as the overall population. Patients with low CHA2DS2VaSc (n = 229 [4.4%]) had a very low ischemic risk (0.6 [0.3–1.3]) with similar bleeding risk (0.5 [0.2–1.1]).Conclusions:Intermediate REACH RIS identified potential optimal candidates for adjunction of low‐dose rivaroxaban while patients with low CHA2DS2VaSc score .appears unlikely to benefit from the COMPASS regimen. None of the three risk scores predicted the occurrence of serious bleeding.

Journal article

Gautier A, Ducrocq G, Elbez Y, Ferrari R, Ford I, Fox KM, Tardif JC, Tendera M, Steg Get al., 2020, CCS patients with polyvascular disease are a high risk but heterogenous subset of patients: insights from the CLARIFY registry, Publisher: OXFORD UNIV PRESS, Pages: 1365-1365, ISSN: 0195-668X

Conference paper

Biscaglia S, Campo G, Fox K, Tardif JC, Tendera M, Greenlaw N, Ford I, Stanley B, Ferraris R, Steg PGet al., 2020, Prognosis in patients with prior myocardial infarction and PEGASUS-TIMI 54 criteria in the CLARIFY registry, Publisher: OXFORD UNIV PRESS, Pages: 1431-1431, ISSN: 0195-668X

Conference paper

Steg P, Bhatt DL, James SK, Darlington O, Hoskin L, Simons T, Fox K, Leiter LA, Mehta S, Harrington RA, Himmelmann A, Ridderstrale W, Andersson M, Mellstrom C, Mcewan Pet al., 2020, Cost-effectiveness of ticagrelor in patients with type 2 diabetes and coronary artery disease with a history of PCI: an economic evaluation of THEMIS-PCI using a Swedish healthcare perpective, Publisher: OXFORD UNIV PRESS, Pages: 3538-3538, ISSN: 0195-668X

Conference paper

Ferrari R, Ford I, Fox K, Challeton JP, Correges A, Tendera M, Widimsky P, Danchin Net al., 2020, The efficacy and safety of trimetazidine in patients having been treated by percutaneous coronary intervention (ATPCI): Results of a randomised double-blind placebo-controlled trial, The Lancet, Vol: 396, Pages: 830-838, ISSN: 0140-6736

BackgroundAngina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable patients has not been shown to improve survival compared with optimal medical therapy. Trimetazidine is an antianginal agent that improves energy metabolism of the ischaemic myocardium and might improve outcomes and symptoms of patients who recently had a PCI. In this study, we aimed to assess the long-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients who had a recent successful PCI.MethodsWe did a randomised, double-blind, placebo-controlled, event-driven trial of trimetazidine added to standard background therapy in patients who had undergone successful PCI at 365 centres in 27 countries across Europe, South America, Asia, and north Africa. Eligible patients were aged 21–85 years and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST segment elevation myocardial infarction less than 30 days before randomisation. Patients were randomly assigned by an interactive web response system to oral trimetazidine 35 mg modified-release twice daily or matching placebo. Participants, study investigators, and all study staff were masked to treatment allocation. The primary efficacy endpoint was a composite of cardiac death; hospital admission for a cardiac event; recurrence or persistence of angina requiring an addition, switch, or increase of the dose of at least one antianginal drug; or recurrence or persistence of angina requiring a coronary angiography. Efficacy analyses were done according to the intention-to-treat principle. Safety was assessed in all patients who had at least one dose of study drug. This study is registered with the EU Clinical Trials Register (EudraCT 2010-022134-89).FindingsFrom Sept 17, 2014, to June 15, 2016, 6007 patients were enrolled and randomly assigned to receiv

Journal article

Ferrari R, Ford I, Fox K, Challeton JP, Correges A, Tendera M, Widimský P, Danchin N, ATPCI investigatorset al., 2020, Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial., Lancet, Vol: 396, Pages: 830-838

BACKGROUND: Angina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable patients has not been shown to improve survival compared with optimal medical therapy. Trimetazidine is an antianginal agent that improves energy metabolism of the ischaemic myocardium and might improve outcomes and symptoms of patients who recently had a PCI. In this study, we aimed to assess the long-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients who had a recent successful PCI. METHODS: We did a randomised, double-blind, placebo-controlled, event-driven trial of trimetazidine added to standard background therapy in patients who had undergone successful PCI at 365 centres in 27 countries across Europe, South America, Asia, and north Africa. Eligible patients were aged 21-85 years and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST segment elevation myocardial infarction less than 30 days before randomisation. Patients were randomly assigned by an interactive web response system to oral trimetazidine 35 mg modified-release twice daily or matching placebo. Participants, study investigators, and all study staff were masked to treatment allocation. The primary efficacy endpoint was a composite of cardiac death; hospital admission for a cardiac event; recurrence or persistence of angina requiring an addition, switch, or increase of the dose of at least one antianginal drug; or recurrence or persistence of angina requiring a coronary angiography. Efficacy analyses were done according to the intention-to-treat principle. Safety was assessed in all patients who had at least one dose of study drug. This study is registered with the EU Clinical Trials Register (EudraCT 2010-022134-89). FINDINGS: From Sept 17, 2014, to June 15, 2016, 6007 patients were enrolled and randomly assigned to rece

Journal article

Parma Z, Jasilek A, Greenlaw N, Ferrari R, Ford I, Tardiff J-C, Fox K, Tendera Met al., 2020, Incident heart failure in outpatients with chronic coronary syndrome: results from the international prospective CLARIFY registry, European Journal of Heart Failure, Vol: 22, Pages: 804-812, ISSN: 1388-9842

AimThe contemporary incidence of heart failure (HF) in patients with chronic coronary syndrome is unclear. We aimed to study the incidence and predictors of cardiovascular (CV) death, HF hospitalization or new‐onset HF not requiring hospitalization, in patients included in the CLARIFY registry.Methods and resultsCLARIFY is a contemporary, international registry of ambulatory patients with chronic coronary artery disease, conducted in 45 countries. At baseline, data on demographics, ethnicity, CV risk factors, medical history, cardiac parameters and medication were collected. Patients were followed up yearly up to 5 years. In this analysis, 26 769 patients with no HF history were included. At 5‐year follow‐up, 4393 patients (16.4%) reached the primary endpoint comprising CV death, HF hospitalization, or new‐onset HF. Only 16.7% of them (n = 732) required hospitalization for HF. All‐cause death occurred in 6.6% of patients (61.4% were CV). Age over 70 years, left ventricular ejection fraction <50%, Canadian Cardiovascular Society class ≥2 angina, atrial fibrillation or paced rhythm on the ECG, body mass index <20 kg/m2, and a history of stroke, were the most robust predictors of the primary outcome. Age <50 years, Asian ethnicity, and percutaneous revascularization were negative predictors of the outcome.ConclusionA sizeable proportion of patients with chronic coronary syndrome develop HF, which only infrequently requires hospitalization. Early identification of patients with HF may lead to early treatment, and help to further decrease mortality and morbidity. This concept needs confirmation in future studies.

Journal article

Bouabdallaoui N, Messas N, Greenlaw N, Ferrari R, Ford I, Fox KM, Tendera M, Naidoo DP, Hassager C, Steg PG, Tardif J-Cet al., 2020, Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease, EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY, Vol: 28, Pages: 1460-1466, ISSN: 2047-4873

Journal article

Biscaglia S, Campo G, Sorbets E, Ford I, Fox K, Greenlaw N, Parkhomenko O, Tardif J-C, Tavazzi L, Tendera M, Wetherall K, Ferrari R, Steg Get al., 2020, Relationship between physical activity and long-term outcomes in patients with stable coronary artery disease, European Journal of Preventive Cardiology, Vol: 27, Pages: 426-436, ISSN: 2047-4873

AIMS To ascertain the relationship between level of physical activity and outcomes and to discriminate the determinants of physical activity performance or avoidance.METHODS CLARIFY is an international prospective registry of 32370 consecutive outpatients with stable coronary artery disease who were followed for up to 5 years. Patients were grouped according to the level and frequency of physical activity: i) sedentary (n=5223; 16.1%); ii) only light physical activity most weeks (light; n=16634; 51.4%); iii) vigorous physical activity once or twice per week (vigorous ≤2×; n=5427; 16.8%); iv) vigorous physical activity three or more times per week (vigorous >2×; n=5086; 15.7%). The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke.RESULTS Patients performing vigorous physical activity ≤2× had the lowest risk of the primary outcome (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.93; P = .0031) taking the light group as reference. Engaging in more frequent exercise did not result in further outcome benefit. All-cause death, cardiovascular death, and stroke occurred less frequently in patients performing vigorous physical activity ≤2×. However, the rate of myocardial infarction was comparable between the four physical activity groups. Female sex, peripheral artery disease, diabetes, previous myocardial infarction or stroke, pulmonary disease, and body mass index all emerged as independent predictors of lower physical activity.CONCLUSION Vigorous physical activity once or twice per week was associated with superior cardiac outcomes compared to patients performing no or a low level of physical activity in outpatients with stable coronary artery disease.

Journal article

Vidal-Petiot E, Greenlaw N, Kalra PR, Garcia-Moll X, Tardif J-C, Ford I, Zamorano J, Ferrari R, Tendera M, Fox KM, Steg PGet al., 2020, Chronic Kidney Disease Has a Graded Association with Death and Cardiovascular Outcomes in Stable Coronary Artery Disease: An Analysis of 21,911 Patients from the CLARIFY Registry, JOURNAL OF CLINICAL MEDICINE, Vol: 9

Journal article

Mahmoudi M, Nicholas Z, Nuttall J, Bresser M, Maishman T, Berry C, Hlatky MA, Douglas P, Rajani R, Fox K, Curzen Net al., 2019, Fractional flow reserve derived from computed tomography coronary angiography in the assessment and management of stable chest pain: Rationale and design of the FORECAST trial, Cardiovascular Revascularization Medicine, ISSN: 1553-8389

BackgroundFractional flow reserve measurement based on computed tomography (FFRCT) is a novel, well validated, non-invasive method for determining the presence and extent of coronary artery disease (CAD) combined with a physiological assessment of vessel-specific ischemia in patients with chest pain. Previous studies indicate that FFRCT reduces the uptake of invasive angiography that shows no significant CAD, without compromising patient safety. The clinical effectiveness and economic impact of using FFRCT instead of other tests in the initial evaluation of patients with stable chest pain has not been tested in a randomized trial.MethodsThe FORECAST trial will randomise 1400 patients with stable chest pain to receive either FFRCT or routine clinical assessment as directed by the National Institute for Health and Care Excellence (NICE) CG95 guideline for Chest Pain of Recent Onset. The primary endpoint will be resource utilisation over the subsequent nine months, including non-invasive cardiac investigations, invasive coronary angiography, coronary revascularization, hospitalization for cardiac events, and the use of cardiac medications. Key pre-specified secondary endpoints will be major adverse cardiac events, angina severity, quality of life, patient satisfaction, time to definitive management plan, time to completion of initial evaluation, number of hospital attendances, and working days lost in patients who are in employment.ConclusionThe FORECAST randomized trial will assess the clinical and economic outcomes of using FFRCT as the primary test to evaluate patients presenting with stable chest pain.

Journal article

Vazir A, Westaby S, Fox K, 2019, Response to the commentary from Bisbal et al., titled 'Adipose graft transposition procedure: towards a novel strategy for myocardial scar and fibrosis reduction', EUROPEAN HEART JOURNAL, Vol: 40, Pages: 3573-3573, ISSN: 0195-668X

Journal article

Fox K, 2019, Angina due to obstructive coronary artery disease with type 2 diabetes., Eur Heart J Suppl, Vol: 21, Pages: G26-G27, ISSN: 1520-765X

Journal article

Fox K, 2019, Angina due to hypertension and dyslipidaemia., European Heart Journal Supplements, Vol: 21, Pages: G10-G10, ISSN: 1520-765X

Journal article

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