Imperial College London

ProfessorSimonThom

Faculty of MedicineNational Heart & Lung Institute

Emeritus Professor
 
 
 
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Contact

 

+44 (0)20 7594 1100s.thom

 
 
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Assistant

 

Mrs Yvonne Green +44 (0)20 7594 1100

 
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Location

 

330ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

411 results found

Howard J, Wood F, Finegold J, Nowbar A, Thompson DM, Arnold A, Rajkumar C, Connolly S, Cegla J, Stride C, Sever P, Northon C, Thom S, Shun-Shin M, Francis Det al., 2021, Side effect patterns in a crossover trial of statin, placebo and no treatment, Journal of the American College of Cardiology, ISSN: 0735-1097

BackgroundMost people who begin statins abandon them, most commonly because of side-effects. ObjectivesAssess daily symptom scores on statin, placebo and no treatment in participants who had abandoned statins.MethodsParticipants received 12 one-month medication bottles, 4 containing atorvastatin 20mg, 4 placebo and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the nocebo ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo. Results60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% confidence interval 4.7 to 11.3) in no-tablet months. It was higher in statin months (16.3, 13.0 to 19.6, p<0.001), but also in placebo months (15.4, 12.1 to 18.7, p<0.001), with no difference between the two (p=0.388). The corresponding nocebo ratio was 0.90.In the individual-patient daily data, neither symptom intensity on starting (odds ratio 1.02, 95% CI 0.98 to 1.06, p=0.28) nor extent of symptom relief on stopping (1.01, 95% CI 0.98 to 1.05, p=0.48) distinguished between statin and placebo.Stopping was no more frequent for statin than placebo (p=0.173), and subsequent symptom relief was similar between statin and placebo.6 months after the trial, 30/60 (50%) of participants were back taking statins. ConclusionsThe majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo.

Journal article

Huang Y, Gu B, Salles II, Taylor KA, Yu L, Ren J, Liu X, Emerson M, Longstaff C, Hughes AD, Thom SA, Xu XY, Chen Ret al., 2021, Fibrinogen-mimicking, multi-arm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy, Science Advances, Vol: 7, ISSN: 2375-2548

Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multi-arm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This novel system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines.

Journal article

Thompson D, Al-Lamee R, Foley M, Dehbi HM, Thom S, Davies JE, Francis DP, Patel P, Gupta P, ORBITA Investigatorset al., 2021, Achieving optimal adherence to medical therapy by telehealth: Findings from the ORBITA medication adherence sub-study, Pharmacology Research and Perspectives, Vol: 9, Pages: e00710-e00710, ISSN: 2052-1707

INTRODUCTION: The ORBITA trial of percutaneous coronary intervention (PCI) versus a placebo procedure for patients with stable angina was conducted across six sites in the United Kingdom via home monitoring and telephone consultations. Patients underwent detailed assessment of medication adherence which allowed us to measure the efficacy of the implementation of the optimization protocol and interpretation of the main trial endpoints. METHODS: Prescribing data were collected throughout the trial. Self-reported adherence was assessed, and urine samples collected at pre-randomization and at follow-up for direct assessment of adherence using high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS). RESULTS: Self-reported adherence was >96% for all drugs in both treatment groups at both stages. The percentage of samples in which drug was detected at pre-randomization and at follow-up in the PCI versus placebo groups respectively was: clopidogrel, 96% versus 90% and 98% versus 94%; atorvastatin, 95% versus 92% and 92% versus 91%; perindopril, 95% versus 97% and 85% versus 100%; bisoprolol, 98% versus 99% and 96% versus 97%; amlodipine, 99% versus 99% and 94% versus 96%; nicorandil, 98% versus 96% and 94% versus 92%; ivabradine, 100% versus 100% and 100% versus 100%; and ranolazine, 100% versus 100% and 100% versus 100%. CONCLUSIONS: Adherence levels were high throughout the study when quantified by self-reporting methods and similarly high proportions of drug were detected by urinary assay. The results indicate successful implementation of the optimization protocol delivered by telephone, an approach that could serve as a model for treatment of chronic conditions, particularly as consultations are increasingly conducted online.

Journal article

Howard JP, Wood F, Finegold J, Nowbar A, Thompson D, Arnold AD, Rajkumar C, Christopher SB, Connolly S, Cegla J, Sever PS, Norton C, Thom S, Shun-Shin M, Francis Det al., 2020, A Three-arm N-of-1 Trial With Statin, Placebo and Tablet Free Periods, to Verify Side Effects and Identify Their Cause: The SAMSON Trial, Scientific Sessions of American-Heart-Association / Resuscitation Science from the Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E480-E481, ISSN: 0009-7322

Conference paper

Howard JP, Wood F, Finegold J, Nowbar A, Thompson D, Arnold AD, Rajkumar C, Christopher SB, Connolly S, Cegla J, Sever PS, Norton C, Thom S, Shun-Shin M, Francis Det al., 2020, A Three-arm N-of-1 Trial With Statin, Placebo and Tablet Free Periods, to Verify Side Effects and Identify Their Cause: The SAMSON Trial, Scientific Sessions of American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E480-E481, ISSN: 0009-7322

Conference paper

Wood FA, Howard JP, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DPet al., 2020, N-of-1 trial of a statin, placebo, or No treatment to assess side effects., New England Journal of Medicine, Vol: 383, Pages: 2182-2184, ISSN: 0028-4793

Journal article

Stanton AV, James K, Brennan MM, O'Donovan F, Buskandar F, Shortall K, El-Sayed T, Kennedy J, Hayes H, Fahey AG, Pender N, Thom SAM, Moran N, Williams DJ, Dolan Eet al., 2020, Omega-3 index and blood pressure responses to eating foods naturally enriched with omega-3 polyunsaturated fatty acids: a randomized controlled trial., Sci Rep, Vol: 10

Diets low in seafood omega-3 polyunsaturated fatty acids (PUFAs) are very prevalent. Such diets have recently been ranked as the sixth most important dietary risk factor-1.5 million deaths and 33 million disability-adjusted life-years worldwide are attributable to this deficiency. Wild oily fish stocks are insufficient to feed the world's population, and levels of eicosapentaenoic acid and docosahexaenoic acid (DHA) in farmed fish have more than halved in the last 20 years. Here we report on a double-blinded, controlled trial, where 161 healthy normotensive adults were randomly allocated to eat at least three portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least three omega-3-PUFA enriched (or control) eggs/week, for 6 months. We show that regular consumption of omega-3-PUFA enriched chicken-meat and eggs significantly increased the primary outcome, the red cell omega-3 index (mean difference [98.75% confidence interval] from the group that ate both control foods, 1.7% [0.7, 2.6]). Numbers of subjects with a very high-risk omega-3 index (index < 4%) were more than halved amongst the group that ate both enriched foods. Furthermore, eating the enriched foods resulted in clinically relevant reductions in diastolic blood pressure (- 3.1 mmHg [- 5.8, - 0.3]). We conclude that chicken-meat and eggs, naturally enriched with algae-sourced omega-3-PUFAs, may serve as alternative dietary sources of these essential micronutrients. Unlike many lifestyle interventions, long-term population health benefits do not depend on willingness of individuals to make long-lasting difficult dietary changes, but on the availability of a range of commonly eaten, relatively inexpensive, omega-3-PUFA enriched foods.

Journal article

Chen R, Huang Y, Xu XY, Thom Set al., 2020, Red Blood Cell-Derived Vesicle

Patent

Al-lamee RK, Shun-Shin M, Howard J, Nowbar A, Rajkumar C, Thompson D, Sen S, Nijjer S, Petraco R, Davies J, Keeble T, Tang K, Malik I, Bual N, Cook C, Ahmad Y, Seligman H, Sharp A, Talwar S, Assomull R, Cole G, Keenan NG, Kanaganayagam GS, Sehmi JS, Wensel R, Harrell F, Mayet J, Thom S, Davies JE, Francis Det al., 2019, Dobutamine Stress Echocardiography Ischaemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echo-Stratified Analysis of ORBITA, Resuscitation Science Symposium (ReSS), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E985-E985, ISSN: 0009-7322

Conference paper

Al-Lamee R, Shun-Shin M, Howard J, Nowbar A, Rajkumar C, Thompson D, Sen S, Nijjer S, Petraco R, Davies J, Keeble T, Tang K, Malik I, Bual N, Cook C, Ahmad Y, Seligman H, Sharp A, Gerber R, Talwar S, Assomull R, Cole G, Keenan N, Kanaganayagam G, Sehmi J, Wensel R, Harrell Jr F, Mayet J, Thom S, Davies J, Francis Det al., 2019, Dobutamine stress echocardiography ischemia as a predictor of the placebo-controlled efficacy of percutaneous coronary intervention in stable coronary artery disease: the stress echo-stratified analysis of ORBITA, Circulation, Vol: 140, Pages: 1971-1980, ISSN: 0009-7322

BackgroundDobutamine stress echocardiography (DSE) is widely used to test for ischemia in patients with stable coronary artery disease (CAD). In this analysis we studied the ability of pre-randomization stress echo score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial. MethodsOne hundred and eighty-three patients underwent DSE before randomization. The stress echo score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of pre-randomization stress echo to predict the placebo-controlled effect of PCI on response variables was tested using regression modelling.ResultsAt pre-randomization, the stress echo score was 1.561.77 in the PCI arm (n=98) and 1.611.73 in the placebo arm (n=85). There was a detectable interaction between pre-randomization stress echo score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echo score (pinteraction=0.031). With our sample size we were unable to detect an interaction between stress echo score and any other patient-reported response variables: freedom from angina (pinteraction=0.116), physical limitation (pinteraction=0.461), quality of life (pinteraction=0.689), EQ-5D-5L quality of life score (pinteraction=0.789) or between stress echo score and physician-assessed Canadian Cardiovascular Society angina class (pinteraction=0.693), and treadmill exercise time (pinteraction=0.426). ConclusionsThe degree of ischemia assessed by DSE predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echo abnormality caused by a stenosis, the greater the reduction in symptoms from PCI.

Journal article

Gu B, Piebalgs A, Huang Y, Roi D, Lobotesis K, Longstaff C, Hughes AD, Chen R, Thom SA, Xu XYet al., 2019, Computational simulations of thrombolysis in acute stroke: Effect of clot size and location on recanalisation, Medical Engineering & Physics, Vol: 73, Pages: 9-17, ISSN: 1350-4533

Acute ischaemic stroke can be treated by intravenous thrombolysis whereby tissue plasminogen activator (tPA) is infused to dissolve clots that block blood supply to the brain. In this study, we aim to examine the influence of clot location and size on lysis pattern and recanalisation by using a recently developed computational modelling framework for thrombolysis under physiological flow conditions. An image-based patient-specific model is reconstructed which consists of the internal carotid bifurcation with the A1 segment of anterior cerebral arteries and M1 segment of middle cerebral arteries, and the M1 bifurcation containing the M2 segments. By varying the clot size and location, 7 scenarios are simulated mimicking thrombolysis of M1 and M2 occlusions. Our results show that initial breakthrough always occurs along the inner curvature of the occluded cerebral artery, due to prolonged tPA residence time in the recirculation zone. For a given occlusion site, lysis completion time appears to increase almost quadratically with the initial clot volume; whereas for a given clot volume, the simulated M2 occlusions take up to 30% longer for complete lysis compared to the corresponding M1 occlusions.

Journal article

Lung T, Jan S, de Silva HA, Guggilla R, Maulik PK, Naik N, Patel A, de Silva AP, Rajapakse S, Ranasinghe G, Prabhakaran D, Rodgers A, Salam A, Selak V, Stepien S, Thom S, Webster R, Lea-Laba T, Samarasekara K, Liyanage CK, Sopan V, Kumara W, Pathirana H, Perera L, Somasiri M, Wijesinghe A, Jayantha J, Liyanagamage S, de Silva M, Jayawardena C, Karunarathna D, Navinan MR, Shukri Z, Herath C, Seneviratne N, Isurangana A, Liyakath Z, Dasitha T, Rajakulenthiran G, Azam A, Jayawardena C, Jayawardena M, Sunderalingam V, Withana M, Annaraja A, Soza K, Dasanayake D, Soza K, de Silva D, Niyasdeen S, Chandradeva U, Fathima S, Jayawardana A, Chathurika R, de Mel M, Mendis T, Withanage S, Pieris K, de Mel M, Fernando G, Mettanda C, Withanage S, Pieris K, de Silva E, Wijerathna I, Thanushanthan J, Dharmawardena D, Gnanapragasam S, Weerawardena S, Suduwelikandage M, de Silva I, Wathsala S, Ekanayaka R, Dahanayaka A, Fernando V, Jayaweera L, Wijesinghe N, Dhakshinamurthy M, Arabhavi U, Sankarankutty H, Muddaseer M, Gudivada S, Moitra A, Tazeen A, Acharya K, Velappan P, Yoganathan A, Jose Vet al., 2019, Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial, LANCET GLOBAL HEALTH, Vol: 7, Pages: E1359-E1366, ISSN: 2214-109X

Journal article

Sluyter JD, Hughes AD, Camargo CA, Thom SAM, Parker KH, Hametner B, Wassertheurer S, Scragg Ret al., 2019, Identification of Distinct Arterial Waveform Clusters and a Longitudinal Evaluation of Their Clinical Usefulness, HYPERTENSION, Vol: 74, Pages: 921-928, ISSN: 0194-911X

Journal article

Elena Martinez-Perez M, Witt N, Parker KH, Hughes AD, Thom SAMet al., 2019, Automatic optic disc detection in colour fundus images by means of multispectral analysis and information content, PEERJ, Vol: 7, ISSN: 2167-8359

Journal article

Mohanan PP, Huffman MD, Baldridge AS, Devarajan R, Kondal D, Zhao L, Ali MY, Joseph J, Eapen K, Krishnan MN, Menon J, Thomas M, Lloyd-Jones DM, Harikrishnan S, Prabhakaran D, Vijayaraghavan G, Nambiar A, Zachariah G, Manjooran RJ, Sivasankaran S, Prabhakaran D, Lloyd-Jones DM, Reddy KS, Harikrishnan S, Bonow RO, Labarthe DR, Smith SC, Nallamothu B, Alexander T, Hemming K, Thom S, Sundaram KR, Cooper L, Huffman MD, Mohanan P, Devarajan R, Baldridge AS, Kondal D, Zhao L, Ali M, Arumugan P, Aneesh TC, Rajesh, Anoop, Natarajan, Raj S, Bahuleyan, Jinbert, Pramod, Varghese V, Nambiar, Bindu, Kathalankal, Susamma, Renga, Alphonsa, Ibrahimkutty, Joseph, Tony, Ullas, Ajmal, Siar, Pravya, Syam, Sajitha, Robby, Prasanna, Manikandan, Lekha, Somanathan, Abilash, Binu, Aneesh, Mathew, Andrews, Gopi A, Chacko, Libin, Abraham, Rony A, Ullas, Govindanunny, William LF, Raveendran, Athira, Vijayaraghavan, Kavitha, Saleem, Joshy, Kumar, Alpha, Venugopal, Vipin, Jayagopal, Devaki, Sasikumar, George M, Madhu, Abdullakutty, Mathew, Serrin, Joseph, Rajesh, Kumar S, Sandeep R, Haridas, Deepa, Viswanathan, Sivaprasad, Sreenivas, Gagan, Koshy, Raji, Jayaprakash, Brijesh, Mustafa, Anooja, Tahsin, Pradeesh, Ukken, Sudheer T, Punnoose, Kurian B, James KJ, Sreedharan, Mohan A, Sebastian, Robin, Nair, Aneesh, Manjooran, Jacob, Blessan, Nisha, Showjad, Dhamoadharan, Ramadas, Jobson, Suresh, Divy, Chacko, Saranya, Eapen, Sindhu, Shaji, Krishnan, Harikrishnan, Ajit, Suresh, Menon, Nisha, Mathew J, Thomas, Betto S, Muralidharan, Abraham M, Narayanan, Kumar, Manoj, Jayakumar, Thampy S, Abhilash, Santhosh, Manoj EB, Davies Det al., 2019, Microeconomic Costs, Insurance, and Catastrophic Health Spending Among Patients With Acute Myocardial Infarction in India Substudy of a Randomized Clinical Trial, JAMA NETWORK OPEN, Vol: 2, ISSN: 2574-3805

Journal article

Huang Y, Yu L, Ren J, Gu B, Longstaff C, Hughes AD, Thom SA, Xu XY, Chen Ret al., 2019, An activated-platelet-sensitive nanocarrier enables targeted delivery of tissue plasminogen activator for effective thrombolytic therapy, Journal of Controlled Release, Vol: 300, Pages: 1-12, ISSN: 0168-3659

It remains a major challenge to develop a selective and effective fibrinolytic system for thrombolysis with minimal undesirable side effects. Herein, we report a multifunctional liposomal system (164.6 ± 5.3 nm in diameter) which can address this challenge through targeted delivery and controlled release of tissue plasminogen activator (tPA) at the thrombus site. The tPA-loaded liposomes were PEGylated to improve their stability, and surface coated with a conformationally-constrained, cyclic arginine-glycine-aspartic acid (cRGD) to enable highly selective binding to activated platelets. The in vitro drug release profiles at 37 °C showed that over 90% of tPA was released through liposomal membrane destabilization involving membrane fusion upon incubation with activated platelets within 1 h, whereas passive release of the encapsulated tPA in pH 7.4 PBS buffer was 10% after 6 h. The release of tPA could be readily manipulated by changing the concentration of activated platelets. The presence of activated platelets enabled the tPA-loaded, cRGD-coated, PEGylated liposomes to induce efficient fibrin clot lysis in a fibrin-agar plate model and the encapsulated tPA retained 97.4 ± 1.7% of fibrinolytic activity as compared with that of native tPA. Furthermore, almost complete blood clot lysis was achieved in 75 min, showing considerably higher and quicker thrombolytic activity compared to the tPA-loaded liposomes without cRGD labelling. These results suggest that the nano-sized, activated-platelet-sensitive, multifunctional liposomes could facilitate selective delivery and effective release of tPA at the site of thrombus, thus achieving efficient clot dissolution whilst minimising undesirable side effects.

Journal article

Gu B, Piebalgs A, Huang Y, Longstaff C, Hughes A, Chen R, Thom S, Xu Xet al., 2019, Mathematical modelling of intravenous thrombolysis in acute ischaemic stroke: Effects of dose regimens on levels of fibrinolytic proteins and clot lysis time, Pharmaceutics, Vol: 11, ISSN: 1999-4923

Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future.

Journal article

Singh K, Devarajan R, Mohanan PP, Baldridge AS, Kondal D, Victorson DE, Karmali KN, Zhao L, Lloyd-Jones DM, Prabhakaran D, Goenka S, Huffman MD, ACS QUIK Investigatorset al., 2019, Implementation and acceptability of a heart attack quality improvement intervention in India: a mixed methods analysis of the ACS QUIK trial, Implementation Science, Vol: 14, ISSN: 1748-5908

BACKGROUND: The ACS QUIK trial showed that a multicomponent quality improvement toolkit intervention resulted in improvements in processes of care for patients with acute myocardial infarction in Kerala but did not improve clinical outcomes in the context of background improvements in care. We describe the development of the ACS QUIK intervention and evaluate its implementation, acceptability, and sustainability. METHODS: We performed a mixed methods process evaluation alongside a cluster randomized, stepped-wedge trial in Kerala, India. The ACS QUIK intervention aimed to reduce the rate of major adverse cardiovascular events at 30 days compared with usual care across 63 hospitals (n = 21,374 patients). The ACS QUIK toolkit intervention, consisting of audit and feedback report, admission and discharge checklists, patient education materials, and guidelines for the development of code and rapid response teams, was developed based on formative qualitative research in Kerala and from systematic reviews. After four or more months of the center's participation in the toolkit intervention phase of the trial, an online survey and physician interviews were administered. Physician interviews focused on evaluating the implementation and acceptability of the toolkit intervention. A framework analysis of transcripts incorporated context and intervening mechanisms. RESULTS: Among 63 participating hospitals, 22 physicians (35%) completed online surveys. Of these, 17 (77%) respondents reported that their hospital had a cardiovascular quality improvement team, 18 (82%) respondents reported having read an audit report, admission checklist, or discharge checklist, and 19 (86%) respondents reported using patient education materials. Among the 28 interviewees (44%), facilitators of toolkit intervention implementation were physicians' support and leadership, hospital administrators' support, ease-of-use of checklists and patient education materials, and availability

Journal article

Huffman MD, Mohanan PP, Devarajan R, Baldridge AS, Kondal D, Zhao L, Ali M, Spertus JA, Chan PS, Natesan S, Abdullakutty J, Krishnan MN, Abhilash TP, Renga S, Punnoose E, Unni G, Prabhakaran D, Lloyd-Jones DM, Vijayaraghavan G, Nambiar A, Zachariah G, Manjooran RJ, Sivasankaran S, Reddy KS, Harikrishnan S, Bonow RO, Labarthe DR, Smith SC, Nallamothu B, Alexander T, Hemming K, Thom S, Sundaram KR, Cooper L, Davies D, Arumugan P, Aneesh TC, Dr R, Anoop PT, Dr N, Raj S, Dr B, Mr J, Dr P, Varghese V, Dr N, Dr B, Dr K, Mrs S, Dr R, Ms A, Dr I, Dr J, Mr T, Dr U, Ajmal KA, Dr S, Pravya P, Dr S, Mrs S, Dr R, Mrs P, Dr M, Lekha MP, Dr S, Dr A, Dr B, Mr A, Dr M, Dr A, Gopi A, Dr C, Mr L, Dr A, Rony A, George M, Dr G, William LF, Dr R, Ms A, Dr V, Mrs K, Dr S, Mr J, Dr K, Ms A, Dr V, Mr V, Dr J, Devaki, Dr S, Dr M, Dr A, Ms S, Kumar S, Sandeep R, Dr H, Mrs D, Dr S, Dr S, Dr G, Dr K, Dr R, Dr J, Dr B, Dr M, Ms A, Dr T, Mr P, Dr U, Sudheer T, Dr P, Kurian B, Dr J, James KJ, Dr S, Mohan A, Dr S, Mr R, Dr N, Dr M, Mr J, Dr B, Mrs N, Dr S, Dr D, Dr R, Mr J, Dr S, Mrs D, Mrs S, Dr E, Mrs S, Dr S, Dr K, Dr H, Dr A, Dr M, Dr T, Sr B, Dr M, Dr N, Dr M, Dr J, Thampy S, Mr S, Manoj EBet al., 2019, Health-Related Quality of Life at 30 Days Among Indian Patients With Acute Myocardial Infarction Results From the ACS QUIK Trial, CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES, Vol: 12, ISSN: 1941-7705

Journal article

Selak V, Webster R, Stepien S, Bullen C, Patel A, Thom S, Arroll B, Bots ML, Brown A, Crengle S, Dorairaj P, Elley CR, Grobbee DE, Harwood M, Hillis GS, Laba T-L, Neal BC, Peiris D, Rafter N, Reid C, Stanton A, Tonkin A, Usherwood T, Wadham A, Rodgers Aet al., 2018, Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials, Heart, Vol: 105, Pages: 42-48, ISSN: 1355-6037

Objective The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy.Methods We conducted an individual participant data meta-analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy.Results Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0–1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively.Conclusions Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet

Journal article

Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Cabrera CP, Karaman I, Fu LN, Evangelou M, Witkowska K, Tzanis E, Hellwege JN, Giri A, Edwards DRV, Sun YV, Cho K, Gaziano JM, Wilson PWF, Tsao PS, Kovesdy CP, Esko T, Magi R, Milani L, Almgren P, Boutin T, Debette S, Ding J, Giulianini F, Holliday EG, Jackson AU, Li-Gao R, Lin W-Y, Luan J, Mangino M, Oldmeadow C, Prins BP, Qian Y, Sargurupremraj M, Shah N, Surendran P, Theriault S, Verweij N, Willems SM, Zhao J-H, Amouyel P, Connell J, de Mutsert R, Doney ASF, Farrall M, Menni C, Morris AD, Noordam R, Pare G, Poulter NR, Shields DC, Stanton A, Thom S, Abecasis G, Amin N, Arking DE, Ayers KL, Barbieri CM, Batini C, Bis JC, Blake T, Bochud M, Boehnke M, Boerwinkle E, Boomsma DI, Bottinger EP, Braund PS, Brumat M, Campbell A, Campbell H, Chakravarti A, Chambers JC, Chauhan G, Ciullo M, Cocca M, Collins F, Cordell HJ, Davies G, de Borst MH, de Geus EJ, Deary IJ, Deelen J, Del Greco FM, Demirkale CY, Dorr M, Ehret GB, Elosua R, Enroth S, Erzurumluoglu AM, Ferreira T, Franberg M, Franco OH, Gandin I, Gasparini P, Giedraitis V, Gieger C, Girotto G, Goel A, Gow AJ, Gudnason V, Guo X, Gyllensten U, Hamsten A, Harris TB, Harris SE, Hartman CA, Havulinna AS, Hicks AA, Hofer E, Hofman A, Hottenga J-J, Huffman JE, Hwang S-J, Ingelsson E, James A, Jansen R, Jarvelin M-R, Joehanes R, Johansson A, Johnson AD, Joshi PK, Jousilahti P, Jukema JW, Jula A, Kahonen M, Kathiresan S, Keavney BD, Khaw K-T, Knekt P, Knight J, Kolcic I, Kooner JS, Koskinen S, Kristiansson K, Kutalik Z, Laan M, Larson M, Launer LJ, Lehne B, Lehtimaki T, Liewald DCM, Lin L, Lind L, Lindgren CM, Liu Y, Loos RJF, Lopez LM, Lu Y, Lyytikainen L-P, Mahajan A, Mamasoula C, Marrugat J, Marten J, Milaneschi Y, Morgan A, Morris AP, Morrison AC, Munson PJ, Nalls MA, Nandakumar P, Nelson CP, Niiranen T, Nolte IM, Nutile T, Oldehinkel AJ, Oostra BA, O'Reilly PF, Org E, Padmanabhan S, Palmas W, Palotie A, Pattie A, Penninx BWJH, Perolet al., 2018, Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018), NATURE GENETICS, Vol: 50, Pages: 1755-1755, ISSN: 1061-4036

Journal article

Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Cabrera CP, Karaman I, Fu LN, Evangelou M, Witkowska K, Tzanis E, Hellwege JN, Giri A, Edwards DRV, Sun YV, Cho K, Gaziano JM, Wilson PWF, Tsao PS, Kovesdy CP, Esko T, Magi R, Milani L, Almgren P, Boutin T, Debette S, Ding J, Giulianini F, Holliday EG, Jackson AU, Li-Gao R, Lin W-Y, Luan J, Mangino M, Oldmeadow C, Prins BP, Qian Y, Sargurupremraj M, Shah N, Surendran P, Theriault S, Verweij N, Willems SM, Zhao J-H, Amouyel P, Connell J, de Mutsert R, Doney ASF, Farrall M, Menni C, Morris AD, Noordam R, Pare G, Poulter NR, Shields DC, Stanton A, Thom S, Abecasis G, Amin N, Arking DE, Ayers KL, Barbieri CM, Batini C, Bis JC, Blake T, Bochud M, Boehnke M, Boerwinkle E, Boomsma DI, Bottinger EP, Braund PS, Brumat M, Campbell A, Campbell H, Chakravarti A, Chambers JC, Chauhan G, Ciullo M, Cocca M, Collins F, Cordell HJ, Davies G, de Borst MH, de Geus EJ, Deary IJ, Deelen J, Del Greco FM, Demirkale CY, Dorr M, Ehret GB, Elosua R, Enroth S, Erzurumluoglu AM, Ferreira T, Franberg M, Franco OH, Gandin I, Gasparini P, Giedraitis V, Gieger C, Girotto G, Goel A, Gow AJ, Gudnason V, Guo X, Gyllensten U, Hamsten A, Harris TB, Harris SE, Hartman CA, Havulinna AS, Hicks AA, Hofer E, Hofman A, Hottenga J-J, Huffman JE, Hwang S-J, Ingelsson E, James A, Jansen R, Jarvelin M-R, Joehanes R, Johansson A, Johnson AD, Joshi PK, Jousilahti P, Jukema JW, Jula A, Kahonen M, Kathiresan S, Keavney BD, Khaw K-T, Knekt P, Knight J, Kolcic I, Kooner JS, Koskinen S, Kristiansson K, Kutalik Z, Laan M, Larson M, Launer LJ, Lehne B, Lehtimaki T, Liewald DCM, Lin L, Lind L, Lindgren CM, Liu Y, Loos RJF, Lopez LM, Lu Y, Lyytikainen L-P, Mahajan A, Mamasoula C, Marrugat J, Marten J, Milaneschi Y, Morgan A, Morris AP, Morrison AC, Munson PJ, Nalls MA, Nandakumar P, Nelson CP, Niiranen T, Nolte IM, Nutile T, Oldehinkel AJ, Oostra BA, O'Reilly PF, Org E, Padmanabhan S, Palmas W, Palotie A, Pattie A, Penninx BWJH, Perolet al., 2018, Publisher correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits, Nature Genetics, Vol: 50, Pages: 1755-1755, ISSN: 1061-4036

Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0205-x, published online 17 September 2018.

Journal article

Piebalgs A, Gu B, Roi D, Lobotesis K, Thom S, Xu Xet al., 2018, Computational simulations of thrombolytic therapy in acute ischaemic stroke, Scientific Reports, Vol: 8, Pages: 1-13, ISSN: 2045-2322

Ischaemic stroke can occur when an artery to the brain is blocked by a blood clot. The use of thrombolytic agents, such as tissue plasminogen activator (tPA), to dissolve the occluding clot is limited by the risk of intracerebral haemorrhage (ICH), a known side effect associated with tPA. We developed a computational thrombolysis model for a 3D patient-specific artery coupled with a compartmental model for temporal concentrations of tPA and lysis proteins during intravenous infusion of tPA, in order to evaluate the effects of tPA dose on the efficacy of thrombolytic therapy and the risk of ICH. The model was applied to a 3-mm-long fibrin clot with two different fibrin fibre radii in the middle cerebral artery (MCA) – a setting relevant to ischaemic stroke, and results for different tPA dose levels and fibrin fibre radii were compared. Our simulation results showed that clot lysis was accelerated at higher tPA doses at the expense of a substantial increase in the risk of ICH. It was also found that a fine clot with a smaller fibre radius dissolved much slowly than a coarse clot due to a slower tPA penetration into the clots.

Journal article

Poulter NR, Savopoulos C, Anjum A, Apostolopoulou M, Chapman N, Cross M, Falaschetti E, Fotiadis S, James RM, Kanellos I, Szigeti M, Thom S, Sever P, Thompson D, Hatzitolios AIet al., 2018, Randomized crossover trial of the impact of morning or evening dosing of antihypertensive agents on 24-hour ambulatory blood pressure: the HARMONY trial, Hypertension, Vol: 72, Pages: 870-873, ISSN: 0194-911X

Some data suggest that nocturnal dosing of antihypertensive agents may reduce cardiovascular outcomes more than daytime dosing. This trial was designed to evaluate whether ambulatory blood pressure monitoring levels differ by timing of drug dosing. Patients aged 18 to 80 years with reasonably controlled hypertension (≤150/≤90 mm Hg) on stable therapy of ≥1 antihypertensive agent were recruited from 2 centers in London and Thessaloniki. Patients were randomized to receive usual therapy either in the morning (6 am–11 am) or evening (6 pm–11 pm) for 12 weeks when participants crossed over to the alternative timing for a further 12 weeks. Clinic blood pressures and a 24-hour recording were taken at baseline, 12, and 24 weeks and routine blood tests were taken at baseline. The study had 80% power to detect 3 mm Hg difference in mean 24-hour systolic blood pressure (α=0.05) by time of dosing. A 2-level hierarchical regression model adjusted for center, period, and sequence was used. Of 103 recruited patients (mean age, 62; 44% female), 95 patients (92%) completed all three 24-hour recordings. Mean 24-hour systolic and diastolic blood pressures did not differ between daytime and evening dosing. Similarly, morning and evening dosing had no differential impact on mean daytime (7 am–10 pm) and nighttime (10 pm–7 am) blood pressure levels nor on clinic levels. Stratification by age (≤65/≥65 years) or sex did not affect results. In summary, among hypertensive patients with reasonably well-controlled blood pressure, the timing of antihypertensive drug administration (morning or evening) did not affect mean 24-hour or clinic blood pressure levels.

Journal article

Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Cabrera CP, Karaman I, Fu LN, Evangelou M, Witkowska K, Tzanis E, Hellwege JN, Giri A, Edwards DRV, Sun YV, Cho K, Gaziano JM, Wilson PWF, Tsao PS, Kovesdy CP, Esko T, Magi R, Milani L, Almgren P, Boutin T, Debette S, Ding J, Giulianini F, Holliday EG, Jackson AU, Li-Gao R, Lin W-Y, Luan J, Mangino M, Oldmeadow C, Prins BP, Qian Y, Sargurupremraj M, Shah N, Surendran P, Theriault S, Verweij N, Willems SM, Zhao J-H, Amouyel P, Connell J, de Mutsert R, Doney ASF, Farrall M, Menni C, Morris AD, Noordam R, Pare G, Poulter NR, Shields DC, Stanton A, Thom S, Abecasis G, Amin N, Arking DE, Ayers KL, Barbieri CM, Batini C, Bis JC, Blake T, Bochud M, Boehnke M, Boerwinkle E, Boomsma DI, Bottinger EP, Braund PS, Brumat M, Campbell A, Campbell H, Chakravarti A, Chambers JC, Chauhan G, Ciullo M, Cocca M, Collins F, Cordell HJ, Davies G, de Borst MH, de Geus EJ, Deary IJ, Deelen J, Del Greco FM, Demirkale CY, Dorr M, Ehret GB, Elosua R, Enroth S, Erzurumluoglu AM, Ferreira T, Franberg M, Franco OH, Gandin I, Gasparini P, Giedraitis V, Gieger C, Girotto G, Goel A, Gow AJ, Gudnason V, Guo X, Gyllensten U, Hamsten A, Harris TB, Harris SE, Hartman CA, Havulinna AS, Hicks AA, Hofer E, Hofman A, Hottenga J-J, Huffman JE, Hwang S-J, Ingelsson E, James A, Jansen R, Jarvelin M-R, Joehanes R, Johansson A, Johnson AD, Joshi PK, Jousilahti P, Jukema JW, Jula A, Kahonen M, Kathiresan S, Keavney BD, Khaw K-T, Knekt P, Knight J, Kolcic I, Kooner JS, Koskinen S, Kristiansson K, Kutalik Z, Laan M, Larson M, Launer LJ, Lehne B, Lehtimaki T, Liewald DCM, Lin L, Lind L, Lindgren CM, Liu Y, Loos RJF, Lopez LM, Lu Y, Lyytikainen L-P, Mahajan A, Mamasoula C, Marrugat J, Marten J, Milaneschi Y, Morgan A, Morris AP, Morrison AC, Munson PJ, Nalls MA, Nandakumar P, Nelson CP, Niiranen T, Nolte IM, Nutile T, Oldehinkel AJ, Oostra BA, O'Reilly PF, Org E, Padmanabhan S, Palmas W, Palotie A, Pattie A, Penninx BWJH, Perolet al., 2018, Genetic analysis of over one million people identifies 535 new loci associated with blood pressure traits, Nature Genetics, Vol: 50, Pages: 1412-1425, ISSN: 1061-4036

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

Journal article

Webster R, Salam A, De Silva HA, Selak V, Stepien S, Rajapakse S, Amarasekara S, Amarasena N, Billot L, de Silva AP, Fernando M, Guggilla R, Jan S, Jayawardena J, Maulik PK, Mendis S, Mendis S, Munasinghe J, Naik N, Prabhakaran D, Ranasinghe G, Thom S, Tisserra N, Senaratne V, Wijekoon S, Wijeyasingam S, Rodgers A, Patel Aet al., 2018, Fixed low-dose triple combination antihypertensive medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: a randomized clinical trial, JAMA: Journal of the American Medical Association, Vol: 320, Pages: 566-579, ISSN: 0098-7484

Journal article

Al-Lamee R, Howard JP, Shun-Shin MJ, Thompson D, Dehbi H-M, Sen S, Nijjer S, Petraco R, Davies J, Keeble T, Tang K, Malik IS, Cook C, Ahmad Y, Sharp ASP, Gerber R, Baker C, Kaprielian R, Talwar S, Assomull R, Cole G, Keenan NG, Kanaganayagam G, Sehmi J, Wensel R, Harrell FE, Mayet J, Thom SA, Davies JE, Francis DPet al., 2018, Fractional flow reserve and instantaneous wave-free ratio as predictors of the placebo-controlled response to percutaneous coronary intervention in stable single-vessel coronary artery disease: physiology-stratified analysis of ORBITA, Circulation, Vol: 138, Pages: 1780-1792, ISSN: 0009-7322

BACKGROUND : There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS : We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS : Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR (Pinteraction=0.318) or iFR (Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR (Pinteraction<0.00001) and

Journal article

Singh K, Crossan C, Laba T-L, Roy A, Hayes A, Salam A, Jan S, Lord J, Tandon N, Rodgers A, Patel A, Thom S, Prabhakaran Det al., 2018, Cost-effectiveness of a fixed dose combination (polypill) in secondary prevention of cardiovascular diseases in India: Within-trial cost-effectiveness analysis of the UMPIRE trial, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 262, Pages: 71-78, ISSN: 0167-5273

BackgroundThe Use of Multidrug Pill In Reducing cardiovascular Events (UMPIRE) trial, showed that access to a cardiovascular polypill (aspirin, statin and two blood pressure lowering drugs) significantly improved adherence, lowered systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDLc) in patients with or at high risk of cardiovascular disease (CVD). We aimed to analyze the within-trial cost-effectiveness of the polypill strategy versus usual care in India.MethodsRelative effectiveness and costs of polypill versus usual care groups in UMPIRE were estimated from the health sector perspective. Only direct medical costs were considered. The effectiveness of the polypill was reported as a percentage increase in adherence and mean reductions in SBP, and LDL-c, over the 15-month trial period. Healthcare resource utilization and costs were collected for each patient during the trial. Polypill price was constructed using a range of scenarios: $0.06–$0.94/day. The cost-effectiveness of the polypill was measured as the additional cost for 10% increase in adherence, and per unit reduction in SBP and LDL-c.ResultsOverall, the mean cost per patient was significantly lower with the polypill strategy (−$203 per person, (95% CI: −286, −119, p < 0.01). In scenario analyses that varied polypill price assumptions, incremental cost-effectiveness ratios for a polypill strategy ranged between cost-saving to $75 per 10% increase in adherence for polypill price of $0.94 per day.ConclusionsThe polypill strategy was cost-saving compared to usual care among patients with or at high risk of CVD in India.

Journal article

Williams B, MacDonald TM, Morant SV, Webb DJ, Sever P, McInnes GT, Ford I, Cruickshank JK, Caulfield MJ, Padmanabhan S, Mackenzie IS, Salsbury J, Brown MJet al., 2018, Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies, Lancet Diabetes and Endocrinology, Vol: 6, Pages: 464-475, ISSN: 2213-8595

BackgroundIn the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs. We did three substudies to assess the mechanisms underlying this superiority and the pathogenesis of resistant hypertension.MethodsPATHWAY-2 was a randomised, double-blind crossover trial done at 14 UK primary and secondary care sites in 314 patients with resistant hypertension. Patients were given 12 weeks of once daily treatment with each of placebo, spironolactone 25–50 mg, bisoprolol 5–10 mg, and doxazosin 4–8 mg and the change in home systolic blood pressure was assessed as the primary outcome. In our three substudies, we assessed plasma aldosterone, renin, and aldosterone-to-renin ratio (ARR) as predictors of home systolic blood pressure, and estimated prevalence of primary aldosteronism (substudy 1); assessed the effects of each drug in terms of thoracic fluid index, cardiac index, stroke index, and systemic vascular resistance at seven sites with haemodynamic monitoring facilities (substudy 2); and assessed the effect of amiloride 10–20 mg once daily on clinic systolic blood pressure during an optional 6–12 week open-label runout phase (substudy 3). The PATHWAY-2 trial is registered with EudraCT, number 2008–007149–30, and ClinicalTrials.gov, number NCT02369081.FindingsOf the 314 patients in PATHWAY-2, 269 participated in one or more of the three substudies: 126 in substudy 1, 226 in substudy 2, and 146 in substudy 3. Home systolic blood pressure reduction by spironolactone was predicted by ARR (r2=0·13, p<0·0001) and plasma renin (r2=0·11, p=0·00024). 42 patients had low renin concentrations (predefined as the lowest tertile of plasma renin), of which 31 had a plasma aldosterone concentration greater than the mean value for all 126 patients (250 pmol/L). Thus, 31 (25% [95% CI 17–33]) of 126 patients were deemed to have inap

Journal article

Crossan C, Dehbi H-M, Williams H, Poulter N, Rodgers A, Jan S, Thom S, Lord Jet al., 2018, A protocol for an economic evaluation of a polypill in patients with established or at high risk of cardiovascular disease in a UK NHS setting: RUPEE (NHS) study., BMJ Open, Vol: 8, ISSN: 2044-6055

INTRODUCTION: The 'Use of a Multi-drug Pill in Reducing cardiovascular Events' (UMPIRE) trial was a randomised controlled clinical trial evaluating the impact of a polypill strategy on adherence to indicated medication in a population with established cardiovascular disease (CVD) of or at high risk thereof. The aim of Researching the UMPIRE Processes for Economic Evaluation in the National Health Service (RUPEE NHS) is to estimate the potential health economic impact of a polypill strategy for CVD prevention within the NHS using UMPIRE trial and other relevant data. This paper describes the design of a modelled economic evaluation of the impact of increased adherence to the polypill versus usual care among the UK UMPIRE participants. METHODS AND ANALYSIS: As recommended by the International Society for Pharmacoeconomics and Outcomes Research and the Society for Medical Decision Making modelling guidelines, a review of published CVD models was undertaken to identify the most appropriate modelling approach and structure. The review was carried out in the electronic databases, MEDLINE and EMBASE. 40 CVD models were identified from 57 studies, the majority of economic models were health state transition cohort models and individual-level simulation models. The findings were discussed with clinical experts to confirm the approach and structure. An individual simulation approach was identified as the most suitable method to capture the heterogeneity in the population at CVD risk. RUPEE-NHS will use UMPIRE trial data on adherence to estimate the long-term cost-effectiveness of the polypill strategy. DISSEMINATION: The evaluation findings will be presented in open-access scientific and healthcare policy journals and at national and international conferences. We will also present findings to NHS policy makers and pharmaceutical companies.

Journal article

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