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Howard J, Wood F, Finegold J, et al., 2021, Side effect patterns in a crossover trial of statin, placebo and no treatment, Journal of the American College of Cardiology, Vol: 78, Pages: 1210-1222, 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.
Rahimi K, Bidel Z, Nazarzadeh M, et 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
Gencer B, Mach F, Murphy SA, 2021, Efficacy of Evolocumab on Cardiovascular Outcomes in Patients With Recent Myocardial Infarction: A Prespecified Secondary Analysis From the FOURIER Trial (vol 5, pg 952, 2020), JAMA CARDIOLOGY, Vol: 6, Pages: 980-980, ISSN: 2380-6583
Sever P, Gouni-Berthold I, Keech A, et al., 2021, LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial., European Journal of Preventive Cardiology, Vol: 28, Pages: 805-812, ISSN: 2047-4873
AIMS: Some trials have reported diminished efficacy for statins in the elderly, and in women compared with men. We examined the efficacy and safety of evolocumab by patient age and sex in the FOURIER trial, the first major cardiovascular outcome trial of a PCSK9 inhibitor. METHODS AND RESULTS: FOURIER was a randomised, double blind trial, comparing evolocumab with placebo in 27,564 patients with atherosclerotic cardiovascular disease receiving statin therapy (median follow-up 2.2 years). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina or coronary revascularisation. Cox proportional hazards models were used to assess the efficacy of evolocumab versus placebo stratified by quartiles of patient age and by sex. There were small variations in the cardiovascular event rate across the age range (for the primary endpoint, Kaplan-Meier at 3 years 15.6%, >69 years, vs. 15.1%, ≤56 years, P = 0.45); however, the relative efficacy of evolocumab was consistent regardless of patient age (for the primary endpoint (Q1 hazard ratio, 95% confidence interval) 0.83, 0.72-0.96, Q2 0.88, 0.76-1.01, Q3 0.82, 0.71-0.95, Q4 0.86, 0.74-1.00; Pinteraction = 0.91), and the key secondary endpoint (cardiovascular death, myocardial infarction, stroke) (Q1 0.74 (0.61-0.89), Q2 0.83 (0.69-1.00), Q3 0.78 (0.65-0.94), Q4 0.82 (0.69-0.98)); Pinteraction = 0.81). Women had a lower primary endpoint rate than men (Kaplan-Meier at 3 years 12.5 vs. 15.3%, respectively, P < 0.001). Relative risk reductions in the primary endpoint and key secondary endpoint were similar in women (0.81 (0.69-0.95) and 0.74 (0.61-0.90), respectively) compared with men (0.86 (0.80-0.94) and 0.81 (0.73-0.90), respectively), Pinteraction = 0.48 and 0.44, respectively. Adverse events were more common in women and with increasing age but, with the exception of injection site reactions, ther
Sever P, Gouni-Berthold I, Keech A, et al., 2021, LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial., Eur J Prev Cardiol, Vol: 28, Pages: 805-812
AIMS: Some trials have reported diminished efficacy for statins in the elderly, and in women compared with men. We examined the efficacy and safety of evolocumab by patient age and sex in the FOURIER trial, the first major cardiovascular outcome trial of a PCSK9 inhibitor. METHODS AND RESULTS: FOURIER was a randomised, double blind trial, comparing evolocumab with placebo in 27,564 patients with atherosclerotic cardiovascular disease receiving statin therapy (median follow-up 2.2 years). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina or coronary revascularisation. Cox proportional hazards models were used to assess the efficacy of evolocumab versus placebo stratified by quartiles of patient age and by sex. There were small variations in the cardiovascular event rate across the age range (for the primary endpoint, Kaplan-Meier at 3 years 15.6%, >69 years, vs. 15.1%, ≤56 years, P = 0.45); however, the relative efficacy of evolocumab was consistent regardless of patient age (for the primary endpoint (Q1 hazard ratio, 95% confidence interval) 0.83, 0.72-0.96, Q2 0.88, 0.76-1.01, Q3 0.82, 0.71-0.95, Q4 0.86, 0.74-1.00; Pinteraction = 0.91), and the key secondary endpoint (cardiovascular death, myocardial infarction, stroke) (Q1 0.74 (0.61-0.89), Q2 0.83 (0.69-1.00), Q3 0.78 (0.65-0.94), Q4 0.82 (0.69-0.98)); Pinteraction = 0.81). Women had a lower primary endpoint rate than men (Kaplan-Meier at 3 years 12.5 vs. 15.3%, respectively, P < 0.001). Relative risk reductions in the primary endpoint and key secondary endpoint were similar in women (0.81 (0.69-0.95) and 0.74 (0.61-0.90), respectively) compared with men (0.86 (0.80-0.94) and 0.81 (0.73-0.90), respectively), Pinteraction = 0.48 and 0.44, respectively. Adverse events were more common in women and with increasing age but, with the exception of injection site reactions, ther
Marston NA, Oyama K, Jarolim P, et al., 2021, Combining High-Sensitivity Troponin With the American Heart Association/American College of Cardiology Cholesterol Guidelines to Guide Evolocumab Therapy, CIRCULATION, Vol: 144, Pages: 249-251, ISSN: 0009-7322
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- Citations: 5
Sever P, Pocock S, 2021, 'Lowering systolic blood pressure to 120 mmHg or <i>The</i> <i>Lancet'</i>s true grit': Response, EUROPEAN HEART JOURNAL, Vol: 42, Pages: 2055-2056, ISSN: 0195-668X
Ramakrishnan A, Shah A, Thom S, et al., 2021, 182 Tissue doppler E’ velocity and E/e’ predict 19-year cardiovascular mortality in hypertension, British Cardiovascular Society Virtual Annual Conference, ‘Cardiology and the Environment’, Publisher: BMJ Publishing Group, Pages: A140-A142, ISSN: 1355-6037
Background We have previously shown that tissue Doppler assessments of left ventricular (LV) diastolic function predict cardiac events in a hypertensive population over a period of 4 years. These out-performed traditional echocardiographic measures in a well-treated hypertensive population.Purpose We aimed to test whether tissue Doppler assessment of LV diastolic function would predict cardiovascular (CV) mortality in the Hypertension Associated Cardiovascular Disease sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).Methods ASCOT was a multicentre randomised trial with a 2x2 factorial design. Inclusion criteria for the study included hypertension and three other CV risk factors, including male sex and age over 55. Protocols, including for echocardiography, have been detailed previously.This study comprised the 519 patients recruited to the St Mary’s Hospital site of the ASCOT study, who were followed for a median of 19 years with mortality flagged by the Office for National Statistics. We have used all reported deaths on or before 31st January 2019. CV deaths include deaths due to coronary heart disease (CHD), stroke and other CV causes. Echocardiography was performed one year after blood pressure control. mean tissue Doppler E’ was calculated as the average of septal, lateral and inferior wall measurements over three cycles. The ratio of the transmitral Doppler E wave velocity and the composite mean of E’ was used to calculate E/E’ ratio. Statistical analysis was performed using Python including multivariable Cox proportional hazards regression. A two-sided P-value <0.05 was considered statistically significant.Results After a median of 19 years (±5 years), 317 patients survived (mean age at baseline 60y, 38 female) and 202 did not (mean age 68y, 30 female). Twenty-three deaths were due to CHD, 11 were due to stroke, 27 were due to other CV causes, and 76 were due to cancer. Baseline characteristics were not signi
Messerli FH, Brguljan J, Rexhaj E, et al., 2021, Lowering systolic blood pressure to 120 mmHg or The Lancet's true grit, EUROPEAN HEART JOURNAL, Vol: 42, Pages: 2052-2059, ISSN: 0195-668X
Messerli FH, Brguljan J, Rexhaj E, et al., 2021, Lowering systolic blood pressure to 120 mmHg or <i>The</i> <i>Lancet</i>'s true grit: Epilogue, EUROPEAN HEART JOURNAL, Vol: 42, Pages: 2059-2059, ISSN: 0195-668X
Sever P, 2021, William Stanley Peart, MB BS (London) 1943, FRCP 1974, FRS 1969, KBE 1985, clinician, scientist and teacher (Born 31 Mar 1922, Died 14 Mar 2019), JOURNAL OF HUMAN HYPERTENSION, Vol: 35, Pages: 487-489, ISSN: 0950-9240
Chen J, Spracklen CN, Marenne G, et al., 2021, The trans-ancestral genomic architecture of glycemic traits, Nature Genetics, Vol: 53, Pages: 840-860, ISSN: 1061-4036
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Fagundes A, Morrow D, Oyama K, et al., 2021, BIOMARKER PREDICTION OF MAJOR CORONARY EVENTS AND COMPLEX REVASCULARIZATION PROCEDURES IN PATIENTS WITH STABLE ATHEROSCLEROSIS, 70th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 2-2, ISSN: 0735-1097
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
Copland E, Canoy D, Nazarzadeh M, et 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
Gupta A, Godec T, Mackay J, et al., 2021, INFLUENCE OF AGE, SEX AND AN OCCURRENCE OF CARDIOVASCULAR EVENT ON SEASONAL VARIATIONS IN BLOOD PRESSURES IN HYPERTENSIVE PATIENTS: INSIGHTS FROM THE ASCOT COHORT, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E145-E146, ISSN: 0263-6352
Harvey G, Godec T, Kapil V, et al., 2021, COMPARING THE DISCRIMINATIVE ABILITY OF DIFFERENT ELECTROGRAPHIC CRITERIA FOR LEFT VENTRICULAR HYPERTROPHY IN PREDICTING CARDIOVASCULAR EVENTS IN HYPERTENSIVE PATIENTS, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E165-E166, ISSN: 0263-6352
Gupta A, Whiteley W, Godec T, et al., 2021, LONG TERM BENEFITS OF BLOOD PRESSURE TREATMENT ON THE INCIDENCE OF ATRIAL FIBRILLATION, HEART FAILURE AND CARDIOVASCULAR MORBIDITY AND MORTALITY: 20-YEARS FOLLOW-UP OF ASCOT-LEGACY, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E8-E8, ISSN: 0263-6352
Gupta A, Rostamian S, Mackay J, et al., 2021, THE DEVELOPMENT OF RESISTANT HYPERTENSION INDEPENDENT OF THE PRECEDING PERIOD OF THE BLOOD PRESSURE CONTROL IS ASSOCIATED WITH THE INCREASED RISK OF CARDIOVASCULAR EVENTS AND DEATH, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E358-E358, ISSN: 0263-6352
Gupta A, Whiteley W, Godec T, et al., 2021, THE RELATIONSHIP BETWEEN BP-CONTROL, BP-VARIABILITY AND ANTIHYPERTENSIVE TREATMENT WITH THE LONG-TERM RISK OF CARDIOVASCULAR EVENT: LESSONS FROM THE ASCOT-LEGACY 20 YEAR FOLLOW-UP, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E148-E148, ISSN: 0263-6352
Warren H, Traylor M, Garofalidou T, et al., 2021, HYPERTENSIVE PATIENTS WITH GREATER GENETIC RISK RESPOND LESS EFFECTIVELY TO TREATMENT AND ARE MORE LIKELY TO BE TREATMENT RESISTANT, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E359-E359, ISSN: 0263-6352
Surendran P, Feofanova EV, Lahrouchi N, et al., 2021, Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals, Nature Genetics, Vol: 53, Pages: 1-2, ISSN: 1061-4036
Marston NA, Patel PN, Kamanu FK, et al., 2021, Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients With Cardiometabolic Disease, CIRCULATION, Vol: 143, Pages: 470-478, ISSN: 0009-7322
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- Citations: 22
Deedwania P, Murphy SA, Scheen A, et al., 2021, Efficacy and Safety of PCSK9 Inhibition With Evolocumab in Reducing Cardiovascular Events in Patients With Metabolic Syndrome Receiving Statin Therapy Secondary Analysis From the FOURIER Randomized Clinical Trial, JAMA CARDIOLOGY, Vol: 6, Pages: 139-147, ISSN: 2380-6583
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- Citations: 31
Sever P, 2021, Severe orthostatic hypotension and weight loss associated with cancer therapy., Br J Cardiol, Vol: 28
Two cases of orthostatic hypotension associated with weight loss following cancer treatment are described. Conventional treatments for orthostatic hypotension proved ineffective. A hypothesis of association with skeletal muscle wasting is discussed.
Howard JP, Wood F, Finegold J, et 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
Howard JP, Wood F, Finegold J, et 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
Surendran P, Gao H, Zhang W, et al., 2020, Discovery of rare variants associated with blood pressure regulation trhough meta-analaysis of 1.3 million individuals, Nature Genetics, Vol: 52, Pages: 1314-1332, ISSN: 1061-4036
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency, MAF > 0.05). In a meta-analysis of up to >1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (MAF≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated SNVs within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (e.g.GATA5, PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
Wood FA, Howard JP, Finegold JA, et 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
Gencer B, Marston NA, Im K, et al., 2020, Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials, LANCET, Vol: 396, Pages: 1637-1643, ISSN: 0140-6736
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- Citations: 109
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