Adherence to antihypertensive medication and association with patient and practice factors.
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Adult↗
Biomedical subjects
T M MacDonald
Publications and source records attributed to T M MacDonald.
Impact on cardiovascular events of increasing high density lipoprotein cholesterol with and without lipid lowering drugs.
OBJECTIVE: To estimate the impact on cardiovascular events of changes in high density lipoprotein (HDL) adjusted for changes in total cholesterol. DESIGN: Cohort study based on a record linkage database. SETTING: Community study in Tayside, Scotland, UK. PATIENTS: 18,815 patients were identified for the study between 1989 and 2001. MAIN OUTCOME MEASURES: Cardiovascular events. RESULTS: 5510 patients taking lipid lowering treatment who had not been hospitalised previously for cardiovascular disease had 314 cardiovascular events recorded (9407 person years of follow up). Patients whose HDL rose by > 20% were less likely to have an event (23.5/1000 person years, 95% confidence interval (CI) 17.3 to 29.6) compared with patients whose HDL did not rise (42.6/1000 person years, 95% CI 35.5 to 49.7, adjusted relative risk 0.60, 95% CI 0.44 to 0.83). HDL change and cardiovascular outcome were not significantly associated among patients who had been hospitalised previously for cardiovascular disease or among patients who were not taking lipid lowering drugs. CONCLUSION: In this study a rise in HDL independently predicted reduced cardiovascular risk in patients taking lipid lowering treatment who had not been hospitalised previously for cardiovascular disease.
Cardiovascular Diseases↗
Does an automated thyroid register improve the clinical management of hypothyroid patients? An observational study.
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Female↗
Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data.
OBJECTIVE: To look for evidence of a relation between antibiotic resistance and prescribing by general practitioners by analysis of prescribing at both practice and individual patient level. DESIGN: Repeated cross-sectional study in 1995 and 1996. SETTING: 28 general practices in the Ninewells Hospital laboratory catchment area, Tayside, Scotland. SUBJECTS REVIEWED: 8833 patients registered with the 28 practices who submitted urine samples for analysis. MAIN OUTCOME MEASURES: Resistance to trimethoprim in bacteria isolated from urine samples at practice and individual level simultaneously in a multilevel model. RESULTS: Practices showed considerable variation in both the prevalence of trimethoprim resistance (26-50% of bacteria isolated) and trimethoprim prescribing (67-357 prescriptions per 100 practice patients). Although variation in prescribing showed no association with resistance at the practice level after adjustment for other factors (P = 0.101), in the multilevel model resistance to trimethoprim was significantly associated with age, sex, and individual-level exposure to trimethoprim (P < 0.001) or to other antibiotics (P = 0.002). The association with trimethoprim resistance was strongest for people recently exposed to trimethoprim, and there was no association for people with trimethoprim exposure more than six months before the date of the urine sample. DISCUSSION: Analysis of practice level data obscured important associations between antibiotic prescribing and resistance. The results support efforts to reduce unnecessary prescribing of antibiotics in the community and show the added value of individual patient data for research on the outcomes of prescribing.
Adolescent↗
Application of a propensity score to adjust for channelling bias with NSAIDs.
PURPOSE: To compare the relative risks of upper GI haemorrhage (UGIH) in users of Newer versus Older, non-specific NSAIDs when adjusted for channelling bias by regression on individual covariates, a propensity score and both. METHODS: Cohort study of patients prescribed NSAIDs between June 1987 and January 2000. Exposure to Newer and Older non-specific NSAIDs was identified, and risk factors evaluated for each patient. Results of multiple covariate analyses and the propensity scoring technique to assess potential channelling bias in comparisons between Newer and Older non-specific NSAIDs were compared. RESULTS: This study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to Older non-specific NSAIDs. Patients receiving Newer NSAIDs were older, more likely to have a history of GI symptoms, and at higher risk for GI complications. Adjusting for these risk factors reduced the relative risks of UGIH on meloxicam and coxibs versus Older non-specific NSAIDs to 0.84 (95%CI 0.60, 1.17) and 0.36 (0.14, 0.97) respectively. CONCLUSIONS: Channelling towards high GI risk patients occurred in the prescribing of Newer NSAIDs. Propensity scores highlighted the markedly different risk profiles of users of Newer and Older non-specific NSAID. Correcting for channelling bias, coxib exposure, but not meloxicam exposure, was associated with less UGIH than Older non-specific NSAID exposure. In the present study, corrections made by regression on a propensity score and on individual covariates were similar.
Adult↗
Cardiovascular prophylaxis with aspirin: costs of supply and management of upper gastrointestinal and renal toxicity.
AIMS: To determine the cost to the NHS of prescribed low-dose aspirin. METHODS: This was a population based observational cohort study. Patients from Tayside Scotland (17 244 new users of dispensed aspirin each with 10 matched comparators) were included. A pragmatic analysis totalled costs from the start to end of the study and compared these with a matched cohort of aspirin nonusers to estimate excess costs. Fastidious analyses were done of subjects with no prior history of upper gastrointestinal (UGI) or renal disease where the cost that occurred during aspirin exposure, the 30 days following aspirin exposure and subsequent nonexposure was calculated adjusting for risk factors in each period. RESULTS: Subjects took aspirin for only 1.18 of the 2.53 years follow-up (47% compliance). Aspirin use cost an additional 49.86 UK pounds per year (pragmatic analysis) made up of 1.96 UK pounds for aspirin tablets (4%), 5.49 UK pounds for dispensing costs (11%), 24.60 UK pounds for UGI complications (49%) and 17.81 UK pounds for renal complications (36%). The costs for managing complications were substantially lower in the fastidious analysis (2.66 UK pounds for UGI complications and 2.92 UK pounds for renal complications). Assuming that the antiplatelet trial meta-analysis is an accurate assessment of the benefits of aspirin, the costs of preventing one vascular event lay between 62 500 UK pounds (primary prevention, pragmatic analysis) and 867 UK pounds (secondary prevention, fastidious analysis). These costs may be underestimates due to the low compliance observed. CONCLUSIONS: Compliance with aspirin was poor. Serious adverse events were uncommon but despite this aspirin cost the NHS between 6 and 25 times the cost of aspirin tablets due to dispensing costs and the cost of managing adverse effects.
Acute Kidney Injury↗
The thyroid epidemiology, audit, and research study: thyroid dysfunction in the general population.
The objective of this study was to define the level of treated thyroid dysfunction in a complete and representative population base in an area of sufficient dietary iodine intake. We used record-linkage technology to retrospectively identify subjects treated for hyperthyroidism or hypothyroidism in the general population of Tayside, Scotland from 1 January 1993 to 30 April 1997. Thyroid status was ascertained by record linkage of patient-level datasets containing details of treatments for hyperthyroidism and hypothyroidism. We identified 620 incident cases of hyperthyroidism, an incidence rate of 0.77/1000 x yr [95% confidence interval (CI), 0.70-0.84] in females and 0.14/1000 x yr (95% CI, 0.12-0.18) in males. There were 3,486 incident cases of diagnosed primary hypothyroidism, an incidence rate of 4.98/1000 x yr (95% CI, 4.81-5.17) in females and 0.88/1000 x yr (95% CI, 0.80-0.96) in males. For both hyperthyroidism and hypothyroidism, the incidence increased with age, and females were affected two to eight times more than males across the age range. The midyear point prevalence of all-cause hypothyroidism rose from 2.2% in 1993 to 3.0% in 1996. The level of thyroid dysfunction in Tayside, Scotland is higher than previously reported, and it increased from 1993 to 1996.
Age Distribution↗
Effect of ibuprofen on cardioprotective effect of aspirin.
Treatment with ibuprofen might limit the cardioprotective effects of aspirin. We aimed to assess whether patients with known cardiovascular disease who take low-dose aspirin and ibuprofen have increased risk of cardiovascular mortality. We studied 7107 patients who were discharged after first admission for cardiovascular disease between April, 1989, and April, 1997, and who were prescribed low-dose aspirin (<325 mg/day) and survived for at least 1 month. Compared with those who used aspirin alone, patients taking aspirin plus ibuprofen had an increased risk of all-cause mortality (adjusted hazard ratio 1.93, 95% CI 1.30-2.87, p=0.0011) and cardiovascular mortality (1.73, 1.05-2.84, p=0.0305). Our finding lends support to the hypothesis that ibuprofen may interact with the cardioprotective effects of aspirin, at least in patients with established cardiovascular disease.
Adult↗
Does a prolonged QT peak identify left ventricular hypertrophy in hypertension?
BACKGROUND: Left ventricular hypertrophy is a powerful predictor of death. Hypertensive subjects with left ventricular hypertrophy can have increased QT (end) dispersion, which is associated with cardiac death. Despite its prognostic value, QT (end) dispersion is not widely used. QTp (i.e. start of QRS to peak of T wave) is easier to measure. Therefore, we tested the hypothesis that long QT peak was associated with left ventricular hypertrophy and assessed its cost-effectiveness at diagnosing left ventricular hypertrophy. METHODS: ECGs and echocardiograms were recorded in 47 hypertensive patients. The onset of the QRS complex and peak of T wave of lead I of each subject's ECGs were digitised by one observer blind to results of the echocardiogram. Receiver-operator characteristics curves were plotted to determine the sensitivity and specificity of different cut-off values of QT peak at predicting left ventricular hypertrophy (defined as left ventricular mass index> or =134 g/m2 in male, > or =110 g/m2 in female). RESULTS: The heart-rate corrected QT peak of lead I correlated with left ventricular mass index (r=0.45, P=0.002). If all patients with a prolonged QT peak (> or =300 ms) had an echocardiogram, then no cases of left ventricular hypertrophy would be missed (100% sensitive). This novel ECG criterion not only had better positive and negative predictive values than the Sokolow-Lyon voltage criteria, but also resulted in more cost-effective resource use (< pound 370 vs. pound 1750/case of left ventricular hypertrophy detected). CONCLUSION: If the results of this small pilot study are confirmed in larger studies, then measuring QT peak of lead I may become a cost-effective way of identifying hypertensives who are likely to have echocardiographic left ventricular hypertrophy.
Adult↗
Why not prescribe the best drugs for hypertension now?
As Westernised societies have become more affluent, the attitudes of the population have become more risk-aware. People are now intolerant of small risks as well as the physical or mental discomforts from drug side effects. Safety and tolerability are now major forces driving the development of new medicines for the treatment of chronic illnesses and the prevention of increasingly rare events. For example, over the past decades, lower and lower treatment thresholds have been recommended in hypertension. Public perception of risk strongly influences the acceptability of lifetime treatment, especially for mild hypertension. This era has also witnessed great advances in the development of antihypertensive drugs that combine efficacy with unsurpassed tolerability. However, the philosophy of Scottish teachers of Materia medica still appears to be followed-'never be the first or the last to prescribe a new drug'. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists are as safe and as efficacious as other antihypertensive medications and better tolerated. Large trials (HOT, HOPE, UKPDS and PROGRESS) point to the need for rigorous control of blood pressure particularly in high-risk individuals. Antihypertensive drugs that act on the renin-angiotensin system will probably impact significantly on achieving optimal blood pressure levels. Should it not now be accepted that high-risk patients should have ACE inhibitors and angiotensin II receptor antagonists prescribed as first-line agents? We review the evidence for the use of ACE inhibitors and angiotensin II receptor antagonists as antihypertensive agents.
Angiotensin Receptor Antagonists↗
Channelling of patients taking NSAIDs or cyclooxygenase-2-specific inhibitors and its effect on interpretation of outcomes.
When new drugs with improved safety or efficacy are introduced, they may be preferentially prescribed to specific populations of patients. Safety and efficacy may be underestimated if such channelling effects are not recognized. Meloxicam and cyclooxygenase (COX)-2-specific inhibitors were developed as safer alternatives to non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of osteoarthritis and rheumatoid arthritis. Studies of the use of meloxicam and COX-2-specific inhibitors demonstrate that both of these drugs are being prescribed to patients at increased risk of gastrointestinal adverse drug events. In the case of COX-2-specific inhibitors, this channelling appears to represent a prescribing pattern consistent with current recommendations. Subsequent analysis of the data, after adjusting for channelling bias, showed that the risk of gastrointestinal toxicity for meloxicam was similar to that for other NSAIDs, while COX-2-specific inhibitors reduced the risk of developing gastrointestinal adverse drug events by approximately 60%. These studies serve as examples of observed channelling bias and highlight the need for adjusting for channelling in order to provide a valid assessment of relevant outcomes for drugs likely to be preferentially prescribed to specific populations.
Aged↗
Channelling bias and the incidence of gastrointestinal haemorrhage in users of meloxicam, coxibs, and older, non-specific non-steroidal anti-inflammatory drugs.
BACKGROUND: Although clinical trial results suggest that meloxicam has less gastrointestinal toxicity than most other non-steroidal anti-inflammatory drugs (NSAIDs), in practice it has been associated with a large number of yellow card reports of gastrointestinal complications. AIMS: To estimate whether meloxicam and the coxibs, rofecoxib and celecoxib, have been channelled towards high risk patients, and to estimate the risk of hospitalisation for gastrointestinal haemorrhage associated with the use of these drugs, allowing for the effects of channelling. PATIENTS: Using the UK General Practice Research Database, this study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to older non-specific NSAIDs. METHODS: Cohort study of patients who received a prescription for an NSAID between June 1987 and January 2001. Exposure to newer NSAIDs (meloxicam, rofecoxib, celecoxib) and to older non-specific NSAIDs was identified. Channelling was assessed on factors including: demographic variables; diagnosis of arthritis; history of NSAID use or gastrointestinal events, including gastrointestinal haemorrhage; and use of ulcer healing drugs. RESULTS: Most risk factors for gastrointestinal haemorrhage were more prevalent among patients prescribed the newer NSAIDs. Adjusting for these risk factors reduced the relative risks of gastrointestinal haemorrhage on meloxicam and coxibs versus older non-specific NSAIDs to 0.84 (95% confidence interval 0.60, 1.17) and 0.36 (0.14, 0.97), respectively. CONCLUSIONS: Channelling towards high risk gastrointestinal patients occurred in the prescribing of newer NSAIDs. After attempting to correct for channelling bias, coxib exposure, but not meloxicam exposure, was associated with a significantly lower risk of gastrointestinal haemorrhage than older non-specific NSAID exposure.
Anti-Inflammatory Agents, Non-Steroidal↗
Is aldosterone the missing link in refractory hypertension?: aldosterone-to-renin ratio as a marker of inappropriate aldosterone activity.
Use of the random aldosterone-to-renin ratio (ARR) as a reliable marker of inappropriate aldosterone activity has led to primary aldosteronism (PA) being increasingly diagnosed in hypertensive patients. At least 10% of hypertensives have been found to have PA, the majority of whom presumably have bilateral adrenal hyperplasia or idiopathic hyperaldosteronism as an aetiology for PA. Whilst these patients clearly have excess aldosterone activity, they have in common many features that are found in hypertensive patients in general, amongst which include heightened angiotensin II adrenal sensitivity. Whether these individuals belong within the spectrum of 'essential hypertension' is being debated, but is probably irrelevant clinically since they appear to respond favourably to spironolactone treatment. In addition, there is recent evidence suggesting that these patients overexpress a key enzyme involved in aldosterone production, the aldosterone synthase, the activity of which appears to relate to its genotypic variation.
Aldosterone↗
Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction.
The vascular endothelium maintains a relatively vasodilated state via the release of nitric oxide (NO), a process that could be disrupted by hyperhomocysteinaemia. Since endothelial dysfunction is associated with increased systemic vascular resistance that is the hallmark of sustained arterial hypertension, we hypothesised that in patients with both hypertension and coeliac disease with hyperhomocysteinaemia (via malabsorption of essential cofactors), treatment of the latter disease could improve blood pressure (BP) control. A single patient with proven sustained hypertension and newly-diagnosed coeliac disease had baseline and post-treatment BP and endothelial function assessed by ambulatory BP monitoring (ABPM) and brachial artery forearm occlusion plethysmography respectively. This 49 year-old woman had uncomplicated sustained hypertension proven on repeated ABPM carried out 6 weeks apart (daytime mean 151/92 mm Hg and 155/95 mm Hg), and sub-clinical coeliac disease (gluten-sensitive enteropathy). Initial assessments revealed raised homocysteine levels with low normal vitamin B(12) level. It was likely that she had impaired absorption of essential cofactors for normal homocysteine metabolism. She adhered to a gluten-free diet and was give oral iron, folate and B(6) supplementations as well as B(12) injections for 3 months. Her BP had improved by 6 months and normalised by 15 months (daytime ABPM mean 128/80 mm Hg). There was parallel restoration of normal endothelial function with normalisation of her homocysteine levels. These observations suggest that sub-clinical coeliac disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of aetiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.
Blood Pressure↗
Adherence to prescribed oral hypoglycaemic medication in a population of patients with Type 2 diabetes: a retrospective cohort study.
AIMS: To evaluate the patterns and predictors of adherence in all patients with Type 2 diabetes in the community receiving treatment with a single oral hypoglycaemic drug. In particular, to test the hypothesis that one tablet per day is associated with better adherence than more than one. METHODS: The study design was a retrospective cohort study set in the Tayside region of Scotland (population approx. 400 000). Participants were residents of Tayside from 1 January 1993 until 31 December 1995 with at least 12 months of prescriptions of oral hypoglycaemic drugs (OHDs). The main outcome measures were adherence indices for sulphonylureas and metformin separately, adjusting for prescribing while hospitalized. RESULTS: Of the total 2920 subjects identified, adequate adherence (> or = 90%) was found in 31% of those prescribed sulphonylureas alone (n = 1329, median adherence = 300 days per year), and in 34% of those prescribed metformin alone (n = 528, median = 302 days per year). There were significant linear trends of poorer adherence with each increase in the daily number of tablets taken (p = 0.001) and increase in co-medication (p = 0.0001) for sulphonylureas alone after adjustment for other factors. CONCLUSIONS: In the community only one in three with Type 2 diabetes had adequate adherence to OHDs. One tablet per day administration was associated with greater adherence than multiple tablets. Poor adherence is a major obstacle to the benefit of complex drug regimens in the treatment of Type 2 diabetes.
Administration, Oral↗
Prognosis following first acute myocardial infarction in Type 2 diabetes: a comparative population study.
AIMS: To estimate the incidence of death and macrovascular complications after a first myocardial infarction for patients with Type 2 diabetes. RESEARCH DESIGN: In a retrospective, incidence cohort study in the Tayside Region of Scotland we studied all patients hospitalized with a diagnosis of first acute myocardial infarction from 1 April 1993 to 31 December 1994. The primary endpoint was time to death. Secondary endpoints were 2-year incidence of hospital admission for angina, myocardial infarction, stroke, heart failure, coronary angiography, coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA). RESULTS: The 147 patients with Type 2 diabetes had significantly worse survival with an increase in relative hazard of 67% compared with non-diabetic patients. After adjustment for age, sex, smoking status, prior heart failure, prior angina, delay to hospitalization, site of infarction, drug therapy with aspirin, beta-blockers, streptokinase and hyperlipidaemia and treated hypertension, Type 2 diabetes was still associated with a 40% higher death rate compared with people without diabetes (P < 0.05) There was no significant difference in death rates in those aged over 70 years, but an indication of a trend in younger individuals with a four-fold increase in death rate in those with diabetes aged < 60 years, compared with a rate ratio of 2.6 in those with diabetes aged 61-70 years. CONCLUSIONS: Among hospitalized patients with first acute myocardial infarction, Type 2 diabetes mellitus is consistently associated with increased mortality and increased hospital admission for heart failure. The estimated 4-year survival rate is only 50%. Our results indicate that younger subjects with Type 2 diabetes and acute myocardial infarction are a high-risk group deserving of special study, and support the argument for aggressive targeting of coronary risk factors among patients with Type 2 diabetes.
Aged↗
Is exercise blood pressure a marker of vascular endothelial function?
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Blood Pressure↗
Epidemiology and economic burden of viral hepatitis: an observational population based study.
OBJECTIVE: To describe the epidemiology and estimate the health resource use of patients with viral hepatitis in Tayside, Scotland, using record linkage techniques. DESIGN: A retrospective observational study. SETTING: Liver disease database, Tayside, Scotland. PATIENTS: All subjects resident in Tayside in the study period 1989-1999 and registered on the Epidemiology of Liver Disease in Tayside (ELDIT) database. MAIN OUTCOME MEASURES: Incidence and prevalence of known viral hepatitis in Tayside, survival of subjects diagnosed with viral hepatitis, and the health resource use with respect to hospital admissions compared with the general population. RESULTS: There were 4992 patients identified with viral hepatitis in the study period 1989-1999; 86 were IgM positive anti-hepatitis A, 187 patients were hepatitis B surface antigen (HBsAg) positive, and 469 were anti-hepatitis C (HCV) positive. HCV and HBsAg seropositive patients were more likely to be hospitalised and stay in hospital longer, less likely to survive after six years, and used more drugs of potential abuse than the general population. There was an increase in cost per admission and per patient as a consequence of liver disease. CONCLUSIONS: A record linkage population based study of viral hepatitis allows outcomes to be identified and costed. Those at risk of viral hepatitis infection in the Tayside population should be informed about the future implication to their health and costs to society. The health service should investigate the cost effectiveness of vaccination and opportunity costs to the health service of viral hepatitis taking into consideration the increasing incidence and prevalence of disease.
Adult↗