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Peter Sleight

Publications and source records attributed to Peter Sleight.

At least 19 recordsLinked to original sources
PubMed2006

Home telemonitoring of vital signs and cardiorespiratory signals in heart failure patients: system architecture and feasibility of the HHH model.

BACKGROUND: The Home or Hospital in Heart Failure Study (HHH) is a European Community funded trial (QLGA-CT-2001-02424) which compares usual care of heart failure (HF) with three home-based interventions in a multicenter, multicountry (Italy, Poland and UK), randomized controlled clinical trial. Home telemonitoring (HT) of clinical parameters represents a potential alternative (or addition) to traditional home care models. Nocturnal respiratory disorders (periodic breathing, sleep apnea) are very common in HF, and are associated with increased morbidity and mortality. We developed an integrated HT system for monitoring of both vital signs and respiration. All measurements were patient-managed. This paper describes the architecture of this system, and assesses its feasibility. METHODS AND RESULTS: 461 clinically stable patients were randomized first to usual vs home-monitored care; the latter were further randomized to 3 strategies. Over a 12-month follow-up 2 of these 3 groups (195 patients, age: 60+/-11 years, NYHA class II-III: 97%, LVEF 28+/-7%) underwent self-administered home monitoring of vital signs (weekly--12 parameters using an interactive voice response system) and respiration (monthly--24-hour recording). Data were transmitted over conventional telephone lines; 81% of actually practicable vital signs measurements were completed by the patients (range: 75% (PL)-93% (UK)), as well as 92% of practicable respiratory recordings (range: 85% (PL)-99% (UK)). 87% of nighttime recordings were eligible for the study (good quality signals for > or = 2.5 h). CONCLUSIONS: This study, the largest so far, demonstrates that self-managed home telemonitoring of both vital signs and respiration is feasible in HF patients, with surprisingly high compliance. We found an excellent rate of acceptable nocturnal respiratory recordings, which are those with the greatest clinical relevance.

Aged↗
PubMed2006

Progress and problems for randomized clinical trials: from streptomycin to the era of megatrials.

Randomized clinical trials (RCTs) are the definitive contributors to evidence-based medicine. RCTs assessing serious outcomes in cardiovascular disease have grown, with 'megatrials' becoming more common with the realization that wrong conclusions resulted from random error in inadequately sized trials. Simple design and a heterogeneous patient population were early features, but multinational trials have increased in scientific, logistical, bureaucratic, regulatory, and legal complexity. These studies now exceed the financial means of academia or medical charities. Governments have left the bill with the pharmaceutical industry, encouraging a symbiosis with academics, who contribute medical and scientific expertise, and access to patients. Industry provides pharmacological, pharmaceutical, technical and regulatory know-how, good clinical practice expertise, and legal assistance during the trial. Study supervision is then in the hands of an independent steering committee and associated subcommittees, until appropriate dissemination of results. Prospectively defined interaction with the sponsor facilitates unbiased design and conduct, but arrangements need careful implementation to avoid conflicts of interest. The patient is protected by a strong data safety monitoring board that is wholly independent. Megatrials are under threat from over-regulation, increasing costs, and difficulties in execution. These issues merit urgent public and political education and debate.

Computer Security↗
PubMed2006

Benefits, challenges, and registerability of the polypill.

Guidelines for the management of cardiovascular disease (CVD) stress the importance of treating global risk, rather than individual risk, factors. Patients at high cardiovascular (CV) risk, for example, benefit from a combination of aspirin, antihypertensive agents, lipid-lowering drugs, and possibly folic acid. As the number of medications that a patient requires increases, adherence and compliance to therapy are likely to decrease. The use of affordable, multiple-target, fixed-combination 'polypills', which concomitantly reduce multiple risk factors without increasing the pill burden or the risk of adverse effects, has the potential to improve CV risk factor management, thereby reducing the incidence of CVD. This review discusses the benefits of the polypill and the challenges and requirements for its success and registerability. Discussions with regulatory bodies are required in order to obtain some 'balance' between an overcautious registration approach and the potentially large public health benefits that are likely to arise from the use of polypills.

Adrenergic beta-Antagonists↗
PubMed2006

Predictors of adverse outcome among patients with hypertension and coronary artery disease.

OBJECTIVES: We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD). BACKGROUND: Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies. METHODS: We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling. RESULTS: Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk. CONCLUSIONS: In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Frequency-dependent baroreflex control of blood pressure and heart rate during physical exercise.

BACKGROUND: It is widely recognised that during exercise vagal heart rate control is markedly impaired but blood pressure control may or may not be retained. We hypothesised that this uncertainty arose from the differing responses of the vagus (fast) and sympathetic (slow) arms of the autonomic effectors, and to differing sympatho-vagal balance at different exercise intensities. METHODS AND RESULTS: We studied 12 normals at rest, during moderate (50% maximal heart rate) and submaximal (80% maximal heart rate) exercise. The carotid baroreceptors were stimulated by sinusoidal neck suction at the frequency of the spontaneous high- (during moderate exercise) and low-frequency (during submaximal) fluctuations in heart period and blood pressure. The increases in these oscillations induced by neck suction were measured by autoregressive spectral analysis. At rest neck stimulation increased variability at low frequency (RR: from 6.99+/-0.24 to 8.87+/-0.18 ln-ms2; systolic pressure: from 3.05+/-1.7 to 4.09+/-0.17 ln-mm Hg2) and high frequency (RR: from 4.67+/-0.25 to 6.79+/-0.31 ln-ms2; systolic pressure: from 1.93+/-0.2 to 2.67+/-0.125 ln-mm Hg2) (all p<0.001). During submaximal exercise RR variability decreased but systolic pressure variability rose (p<0.01 vs rest); during submaximal exercise low-frequency neck stimulation increased the low-frequency fluctuations in blood pressure (2.35+/-0.51 to 4.25+/-0.38 ln-mm Hg2, p<0.05) and RR. Conversely, neck suction at high frequency was ineffective on systolic pressure, and had only minor effects on RR interval during moderate exercise. CONCLUSION: During exercise baroreflex control is active on blood pressure, but the efferent response on blood pressure and heart rate is only detected during low frequency stimulation, indicating a frequency-dependent effect.

Adult↗
PubMed2005

Prior blunt chest trauma may be a cause of single vessel coronary disease; hypothesis and review.

Prompted by a case where a patient (with no risk factors, and single vessel disease) developed angina pectoris after previous blunt chest trauma, we searched Medline for blunt chest trauma and myocardial ischaemia. We found 77 cases describing AMI after blunt chest trauma, but only one reporting angina pectoris. We focused on the age and sex distribution, type of trauma, the angiography findings and the time interval between the trauma and the angiography. The age distribution was atypical, compared to AMI in general; 82% of the patients with AMI after blunt chest trauma were less than 45 years old, and only 2.5% more than 60 years old. The most common trauma was a road traffic accident, and the LAD was the vessel most often affected. Angiography revealed 12 cases with completely normal vessels, which might be due to spasm or recanalisation; 31 cases showed occlusion but no atherosclerosis, which strongly suggested a causal relation between the trauma and subsequent occlusion. AMI should therefore be considered in patients suffering from chest pain after blunt chest trauma. Because traumatic AMI might often be the result of an intimal tear or dissection, thrombolytic therapy might worsen the situation and acute PCI must be considered preferable. It seems likely that lesser damage could lead to longer-term stenosis we suspect that this sequence is grossly under-reported. This could have medico-legal implications.

Accidents, Traffic↗
PubMed2005

Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.

CONTEXT: Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration. OBJECTIVE: To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled international trial (the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993, and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years. INTERVENTION: Daily dose of natural source vitamin E (400 IU) or matching placebo. MAIN OUTCOME MEASURES: Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations. RESULTS: Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients (11.6%) in the vitamin E group vs 586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.84-1.06; P = .30); for cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95% CI, 0.71-1.09; P = .24); and for major cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively (RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.13; 95% CI, 1.01-1.26; P = .03) and hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure. CONCLUSION: In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.

Aged↗
PubMed2005

Global differences in blood pressure control and clinical outcomes in the INternational VErapamil SR-Trandolapril STudy (INVEST).

BACKGROUND: The INternational VErapamil SR-Trandolapril Study (INVEST), a prospective, randomized, antihypertensive trial, found that two different medication regimens produced similar blood pressure (BP) control with equivalent cardiovascular (CV) outcomes (death from any cause, nonfatal myocardial infarction [MI], or nonfatal stroke). HYPOTHESIS: The study was undertaken to investigate whether differences exist by global regions in demographics, treatment, and outcomes in the INVEST trial. METHODS: Data were analyzed for 22,576 patients with stable coronary artery disease (CAD) enrolled in INVEST. We investigated differences in patient characteristics, treatment approaches, BP control, and clinical outcomes by creating three global regions based on geographical location: Northern Americas (NA), Caribbean (CA), and Eurasia (EA). RESULTS: We observed significant regional differences in patient characteristics, treatment patterns, BP control, and CV outcomes. At baseline, patients from NA were older and had greater body mass index, higher rates of diabetes, peripheral vascular disease, and coronary revascularization, but lower rates of MI or left ventricular hypertrophy than patients in CA and EA. At 24 months, there were regional differences in both study and nonstudy antihypertensive drug use. Despite having higher mean baseline BP, patients from CA and EA achieved lower mean systolic BP throughout study follow-up. Furthermore, patients from both CA and EA had lower rates of all-cause mortality, fatal or nonfatal MI, fatal or nonfatal stroke, and newly diagnosed diabetes than patients from NA. CONCLUSIONS: In INVEST, regional differences in medication utilization, BP control, and CV outcomes were identified. These disparities warrant further investigation to define appropriate care for patients with hypertension and stable CAD from an international public health perspective.

Aged↗
PubMed2005

Results of the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial by geographical region.

OBJECTIVE: To examine regional differences in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial. DESIGN: Double-blind, randomized, international clinical trial. SETTING: Six hundred and sixty-one clinical centers in 15 countries. PATIENTS: Hypertensive volunteers (n = 16,602) with > or =1 additional cardiovascular risk factor, grouped into four regions: USA (n = 8144), Canada (n = 3405), Western Europe (Spain, UK, Italy, Sweden, Germany; n = 2048) or 'other' (Bulgaria, Israel, Mexico, Czech Republic, Hungary, Poland, Slovakia, Brazil; n = 2879); subgroupings included country and state/province within the USA and Canada. INTERVENTIONS: Randomized to COER-verapamil or the investigator's choice of either atenolol or hydrochlorothiazide, titrated and additional drugs added as required. MAIN OUTCOME MEASURES: Baseline characteristics; blood pressure control, medication adherence and lost-to-follow-up at 2 years; and composite primary endpoint (stroke, myocardial infarction, cardiovascular death) by regional groupings. RESULTS: Regional differences were found at baseline for age, gender, blood pressure, percentage receiving antihypertensive drug therapy, initial choice of atenolol or hydrochlorothiazide, and risk factor profile. Blood pressure control rates increased markedly during follow-up in all regions, but varied significantly by region. Blood pressure control, medication adherence and lost-to-follow-up rates were poorest in the USA. After adjustment for baseline differences, the primary-event rate for each region was significantly lower than for the USA. Although baseline factors, blood pressure control and event rates varied by region, treatment differences did not. CONCLUSION: Despite differences in baseline and follow-up measures across geographical regions, the absence of treatment differences by region suggests that the overall findings of CONVINCE are robust.

Aged↗
PubMed2005

Impact of cigarette smoking in high-risk patients participating in a clinical trial. A substudy from the Heart Outcomes Prevention Evaluation (HOPE) trial.

BACKGROUND: In recent large cardiovascular trials done in stable patients, 14-31% of the participants were smokers; the consequences of smoking in these trials using medications known to reduce cardiovascular events, have not been assessed. DESIGN: We evaluated the cardiovascular outcomes according to smoking status of men and women participating in the Heart Outcomes Prevention Evaluation trial. METHODS: The occurrence of cardiovascular events was documented among participants who did not change their smoking status during the trial. There were 2728 'never smokers', 5241 'former smokers' and 936 'current smokers', and all had stable cardiovascular disease or diabetes with at least one other risk factor. None had previous congestive heart failure or known left ventricular ejection fraction < 0.40. RESULTS: During the 4.5-year follow-up, there were 641 cardiovascular deaths, 978 myocardial infarctions, 358 strokes and 1021 deaths. In comparison to 'never smokers', smokers had relative risks adjusted for confounding variables including medications known to reduce cardiovascular mortality and morbidity, for cardiovascular death of 1.65 [95% confidence interval (CI), 1.28-2.14], for myocardial infarction of 1.26 (95% CI, 1.01-1.58), for stroke of 1.42 (95% CI, 1.00-2.04), and for total mortality of 1.99 (95% CI, 1.63-2.44). The rates of these events among 'former smokers' were not different from those of 'never smokers'. CONCLUSIONS: Smoking increased the risk of mortality and morbidity among high-risk patients despite the use of medications known to reduce cardiovascular events. Smoking cessation programs should be reinforced even for patients participating in clinical trials.

Aged↗
PubMed2004

Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions.

BACKGROUND: Lower blood cholesterol concentrations have consistently been found to be strongly associated with lower risks of coronary disease but not with lower risks of stroke. Despite this observation, previous randomised trials had indicated that cholesterol-lowering statin therapy reduces the risk of stroke, but large-scale prospective confirmation has been needed. METHODS: 3280 adults with cerebrovascular disease, and an additional 17256 with other occlusive arterial disease or diabetes, were randomly allocated 40 mg simvastatin daily or matching placebo. Subgroup analyses were prespecified of first "major vascular event" (ie, non-fatal myocardial infarction or coronary death, stroke of any type, or any revascularisation procedure) in prior disease subcategories. Subsidiary outcomes included any stroke, and stroke sub-type. Comparisons are of all simvastatin-allocated versus all placebo-allocated participants (ie, "intention-to-treat"), which yielded an average difference in LDL cholesterol of 1.0 mmol/L (39 mg/dL) during the 5-year treatment period. FINDINGS: Overall, there was a highly significant 25% (95% CI 15-34) proportional reduction in the first event rate for stroke (444 [4.3%] simvastatin vs 585 [5.7%] placebo; p<0.0001), reflecting a definite 28% (19-37) reduction in presumed ischaemic strokes (p<0.0001) and no apparent difference in strokes attributed to haemorrhage (51 [0.5%] vs 53 [0.5%]; rate ratio 0.95 [0.65-1.40]; p=0.8). In addition, simvastatin reduced the numbers having transient cerebral ischaemic attacks alone (2.0% vs 2.4%; p=0.02) or requiring carotid endarterectomy or angioplasty (0.4% vs 0.8%; p=0.0003). The reduction in stroke was not significant during the first year, but was already significant (p=0.0004) by the end of the second year. Among patients with pre-existing cerebrovascular disease there was no apparent reduction in the stroke rate, but there was a highly significant 20% (8-29) reduction in the rate of any major vascular event (406 [24.7%] vs 488 [29.8%]; p=0.001). The proportional reductions in stroke were about one-quarter in each of the other subcategories of participant studied, including: those with coronary disease or diabetes; those aged under or over 70 years at entry; and those presenting with different levels of blood pressure or lipids (even when the pretreatment LDL cholesterol was below 3.0 mmol/L [116 mg/dL]). INTERPRETATION: Much larger numbers of people in the present study suffered a stroke than in any previous cholesterol-lowering trial. The results demonstrate that statin therapy rapidly reduces the incidence not only of coronary events but also of ischaemic strokes, with no apparent effect on cerebral haemorrhage, even among individuals who do not have high cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rate of ischaemic strokes by about one-quarter and so, after making allowance for non-compliance in the trial, actual use of this regimen would probably reduce the stroke rate by about a third. HPS also provides definitive evidence that statin therapy is beneficial for people with pre-existing cerebrovascular disease, even if they do not already have manifest coronary disease.

Adult↗
PubMed2004

Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, myocardial infarction, stroke, heart failure, need for revascularization, nephropathy, and diabetes and its complications. Although angiotensin-II receptor blockers (ARBs) have been less extensively evaluated, theoretically they may have "protective" effects similar to those of ACE inhibitors, but with better tolerability. Currently, there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk populations with controlled hypertension. OBJECTIVES: Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone, and if telmisartan is at least as effective as ramipril. The Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors. The primary outcome for both trials is the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. METHOD: High-risk patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel, randomized, double-blind clinical trials. PROGRESS: Recruitment from 730 centers in 40 countries for ONTARGET (n = 25,620) was completed in July 2003. For TRANSCEND, 5776 patients (out of a projected total of 6000) have been recruited (by May 10, 2004). Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation (HOPE) trial, the basis of the design of the current study, confirming that patients are at high-risk.

Aged↗
PubMed2003

Current options in the management of coronary artery disease.

World Health Organization projections suggest that, for the foreseeable future, coronary artery disease (CAD) will remain the largest element of global disease burden, reflecting the aging of the population. Recent American College of Cardiology/American Heart Association guidelines estimate that 16.6 million Americans currently have stable angina. Chronic stable angina is associated with significant morbidity and mortality, thus highlighting the need for accurate and early detection and treatment. Clinical examination is the single most important step in evaluating risk. Age, sex, pain type, coexisting diabetes mellitus, hypertension, or known vascular disease are powerful predictors of prognosis and, except for special patient groups, are more reliable than ambulatory electrocardiographic recording, exercise testing, or electron-beam computed tomography. Cost-effective methods for screening the general population for "silent" risk factors predisposing them to atherosclerotic disease in later life are nevertheless required. Aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and lipid-lowering agents are currently the backbone of pharmacologic therapy, supplemented by lifestyle changes aimed at promoting exercise, weight reduction, and increased fruit and vegetable intake. However, side effects of chronic drug treatment, especially for those taking multidrug regimens, may affect quality of life and are the principal reason for poor compliance. Coronary bypass surgery and angioplasty are frequently used interventional procedures for CAD, although they can be invasive and costly, and they often need to be repeated. Current options for the management of CAD have their limitations, thus confirming the appropriateness of continuing the search for improved therapies to reverse the disease process and reduce the global burden.

Angina Pectoris↗