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Gordon T McInnes

Publications and source records attributed to Gordon T McInnes.

At least 19 recordsLinked to original sources
PubMed2006

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy.

In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy. Baseline characteristics were similar in the valsartan (N=3263) and amlodipine (N=3817) groups. Time on monotherapy was 3.2 years (78% of treatment exposure time). The average in-trial blood pressure was similar in both groups. Event rates in the monotherapy group were 16% to 39% lower than in the main VALUE trial. In the first analysis, we censored patients when they discontinued monotherapy ("censored"); in the second, we counted events regardless of subsequent therapy (intention-to-treat principle). We also assessed the impact of duration of monotherapy on outcomes. No difference was found in primary composite cardiac end points, strokes, myocardial infarctions, and all-cause deaths with both analyses. Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses (hazard ratios: 0.63, P=0.004 and 0.78, P=0.045, respectively). Longer duration of monotherapy amplified between-group differences in heart failure. New-onset diabetes was lower in the valsartan group with both analyses (odds ratios: 0.78, P=0.012 and 0.82, P=0.034). Thus, despite lower absolute event rates in monotherapy patients, the relative risks of heart failure and new-onset diabetes favored valsartan. Moreover, these findings support the feasibility of comparative prospective trials in lower-risk hypertensive patients.

Aged↗
PubMed2006

Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients: the VALUE trial.

CONTEXT: Type 2 diabetes is emerging as a major health problem, which tends to cluster with hypertension in individuals at high risk of cardiovascular disease. OBJECTIVE: To test for the first time the hypothesis that treatment of hypertensive patients at high cardiovascular risk with the angiotensin-receptor blocker (ARB) valsartan prevents new-onset type 2 diabetes compared with the metabolically neutral calcium-channel antagonist (CCA) amlodipine. DESIGN: Pre-specified analysis in the VALUE trial. Follow-up averaged 4.2 years. The risk of developing new diabetes was calculated as an odds ratio (OR) with 95% confidence intervals (CI) for different definitions of diabetes. PATIENTS: A sample of 9995 high-risk, non-diabetic hypertensive patients. INTERVENTIONS: Valsartan or amlodipine with or without add-on medication [hydrochlorothiazide (HCTZ) and other add-ons, excluding other ARBs, angiotensin-converting enzyme (ACE) inhibitors, CCAs]. MAIN OUTCOME MEASURE: New diabetes defined as an adverse event, new blood-glucose-lowering drugs and/or fasting glucose > 7.0 mmol/l. RESULTS: New diabetes was reported in 580 (11.5%) patients on valsartan and in 718 (14.5%) patients on amlodipine (OR 0.77, 95% CI 0.69-0.87, P < 0.0001). Using stricter criteria (without adverse event reports) new diabetes was detected in 495 (9.8%) patients on valsartan and in 586 (11.8%) on amlodipine (OR 0.82, 95% CI 0.72-0.93, P = 0.0015). CONCLUSION: Compared with amlodipine, valsartan reduces the risk of developing diabetes mellitus in high-risk hypertensive patients.

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PubMed2006

Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial.

BACKGROUND: In the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial the primary outcome (cardiac morbidity and mortality) did not differ between valsartan and amlodipine-based treatment groups, although systolic blood pressure (SBP) and diastolic blood pressure reductions were significantly more pronounced with amlodipine. Stroke incidence was non-significantly, and myocardial infarction was significantly lower in the amlodipine-based regimen, whereas cardiac failure was non-significantly lower on valsartan. OBJECTIVES: The study protocol specified additional analyses of the primary endpoint according to: sex; age; race; geographical region; smoking status; type 2 diabetes; total cholesterol; left ventricular hypertrophy; proteinuria; serum creatinine; a history of coronary heart disease; a history of stroke or transient ischemic attack; and a history of peripheral artery disease. Additional subgroups were isolated systolic hypertension and classes of antihypertensive agents used immediately before randomization. METHODS: The 15,245 hypertensive patients participating in VALUE were divided into subgroups according to baseline characteristics. Treatment by subgroup interaction analyses were carried out by a Cox proportional hazard model. Within each subgroup, treatment effects were assessed by hazard ratios and 95% confidence intervals. RESULTS: For cardiac mortality and morbidity, the only significant subgroup by treatment interaction was of sex (P = 0.016), with the hazard ratio indicating a relative excess of cardiac events with valsartan treatment in women but not in men, but SBP differences in favour of amlodipine were distinctly greater in women. No other subgroup showed a significant difference in the composite cardiac outcome between valsartan and amlodipine-based treatments. For secondary endpoints, a sex-related significant interaction was found for heart failure (P < 0.0001), with men but not women having a lower incidence of heart failure with valsartan. CONCLUSION: As in the whole VALUE cohort, in no subgroup of patients were there differences in the incidence of the composite cardiac endpoint with valsartan and amlodipine-based treatments, despite a greater blood pressure decrease in the amlodipine group. The only exception was sex, in which the amlodipine-based regimen was more effective than valsartan in women, but not in men, whereas the valsartan regimen was more effective in preventing cardiac failure in men than in women.

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PubMed2006

Influence of a single dose of 20 mg tadalafil, a phosphodiesterase 5 inhibitor, on ambulatory blood pressure in subjects with hypertension.

AIMS: To test the non-inferiority of a single dose of tadalafil 20 mg compared with placebo with respect to 26-h mean ambulatory systolic and diastolic blood pressure in treated and untreated hypertensive subjects. METHODS: A multicentre, randomized, double-blind, placebo-controlled crossover study in 114 subjects with hypertension (36 subjects on no therapy with daytime mean ambulatory blood pressure >/= 140/85 mmHg; 38 subjects on two to four classes of antihypertensive agents with daytime mean ambulatory blood pressure >/=140/85 mmHg and 40 subjects on two to four classes of antihypertensive agents with ambulatory blood pressure < 140/85 mmHg). RESULTS: Overall tadalafil reduced mean ambulatory blood pressure monitor systolic and diastolic blood pressure by 4.8 mmHg [95% confidence interval (Cl) 3.7, 5.9; P < 0.01] and 2.9 mmHg (95% CI 1.9, 3.6; P < 0.01), respectively, compared with placebo. In hypertensive subjects with uncontrolled blood pressure on two to four classes of antihypertensive agents (n = 36) tadalafil reduced mean ABPM systolic and diastolic blood pressure by 7.5 mmHg (95% CI 5.4, 9.6; P < 0.01) and 4.3 mmHg (95% CI 6.1, 8.9; P < 0.01) compared with placebo. CONCLUSIONS: In patients with uncontrolled hypertension on multiple agents the addition of tadalafil 20 mg lowered mean 26-h blood pressure.

Antihypertensive Agents↗
PubMed2005

Lowering blood pressure for cardiovascular risk reduction.

The association between blood pressure and cardiovascular risk is continuous, with no known lower threshold; epidemiologically, the lower the blood pressure, the better. In reality, the relationship must be J- or U-shaped, as a blood pressure of zero is associated with 100% mortality. However, the level of blood pressure control below which risk increases is well below that achieved in clinical practice, and reducing blood pressure is a cornerstone of strategies to reduce cardiovascular risk. Even relatively small reductions in blood pressure (systolic blood pressure 10-12 mmHg, diastolic blood pressure 5-6 mmHg) substantially reduce cardiovascular risk. Optimal cardiovascular protection is achievable through early and aggressive blood pressure control, but precisely which agents confer the greatest benefits for cardiovascular protection remains widely debated. Angiotensin II receptor blockers (ARBs) appear to be unique in providing additional protection beyond blood pressure control, whereas similar claims for other agents do not withstand close scrutiny. Nearly all patients with hypertension require several antihypertensive treatments to reach their target blood pressure, and it is important to choose treatments that are well tolerated and have complementary modes of action. For this reason, ARBs such as telmisartan emerge as logical choices for combination therapy, particularly when combined with a diuretic, as they fulfil all the essential requirements for combination therapy and are effective in a wide range of different types of patient. Regrettably, a rigorous approach to blood pressure control using multiple agents is still rare in general practice, partly because of a lack of understanding and partly because of 'professional non-compliance'. Prescribing habits must change, and soon, if we are to avoid an upsurge in cardiovascular complications.

Antihypertensive Agents↗
PubMed2005

Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial--lipid-lowering arm (ASCOT-LLA).

OBJECTIVE: This study aims to establish the benefits of lowering cholesterol in diabetic patients with well-controlled hypertension and average/below-average cholesterol concentrations, but without established coronary disease. RESEARCH DESIGN AND METHODS: In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA), 10,305 hypertensive patients with no history of coronary heart disease (CHD) but at least three cardiovascular risk factors were randomly assigned to receive 10 mg atorvastatin or placebo. Effects on total cardiovascular outcomes in 2,532 patients who had type 2 diabetes at randomization were compared. RESULTS: During a median follow-up of 3.3 years, concentrations of total and LDL cholesterol among diabetic participants included in ASCOT-LLA were approximately 1 mmol/l lower in those allocated atorvastatin compared with placebo. There were 116 (9.2%) major cardiovascular events or procedures in the atorvastatin group and 151 (11.9%) events in the placebo group (hazard ratio 0.77, 95% CI 0.61-0.98; P = 0.036). For the individual components of this composite end point, the number of events occurring in the diabetes subgroup was small. Therefore, although fewer coronary events (0.84, 0.55-1.29; P = 0.14) and strokes (0.67, 0.41-1.09; P = 0.66) were observed among the patients allocated atorvastatin, these reductions were not statistically significant. CONCLUSIONS: Atorvastatin significantly reduced the risk of major cardiovascular events and procedures among diabetic patients with well-controlled hypertension and without a history of CHD or markedly elevated cholesterol concentrations. The proportional reduction in risk was similar to that among participants who did not have diagnosed diabetes. Allocation to atorvastatin prevented approximately 9 diabetic participants from suffering a first major cardiovascular event or procedure for every 1,000 treated for 1 year.

Adult↗
PubMed2004

Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial.

BACKGROUND: The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test the hypothesis that for the same blood-pressure control, valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk. METHODS: 15?245 patients, aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a randomised, double-blind, parallel-group comparison of therapy based on valsartan or amlodipine. Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint, defined as a composite of cardiac mortality and morbidity. Patients from 31 countries were followed up for a mean of 4.2 years. FINDINGS: Blood pressure was reduced by both treatments, but the effects of the amlodipine-based regimen were more pronounced, especially in the early period (blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month; 1.5/1.3 mm Hg after 1 year; p<0.001 between groups). The primary composite endpoint occurred in 810 patients in the valsartan group (10.6%, 25.5 per 1000 patient-years) and 789 in the amlodipine group (10.4%, 24.7 per 1000 patient-years; hazard ratio 1.04, 95% CI 0.94-1.15, p=0.49). INTERPRETATION: The main outcome of cardiac disease did not differ between the treatment groups. Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes. The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk.

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PubMed2004

Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial.

The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test whether, for the same achieved blood pressures, regimens based on valsartan or amlodipine would have differing effects on cardiovascular endpoints in high risk hypertension. But inequalities in blood pressure, favouring amlodipine, throughout the multiyear trial precluded comparison of outcomes. A technique of serial median matching, applied at 6 months when treatment adjustments intended to achieve control of blood pressure were complete, created 5006 valsartan-amlodipine patient pairs matched exactly for systolic blood pressure, age, sex, and the presence or absence of previous coronary disease, stroke, or diabetes. Subsequent combined cardiac events, myocardial infarction, stroke, and mortality were almost identical in the two cohorts, but admission to hospital for heart failure was significantly lower with valsartan. Reaching blood pressure control (systolic <140 mm Hg) by 6 months, independent of drug type, was associated with significant benefits for subsequent major outcomes; the blood pressure response after just 1 month of treatment predicted events and survival.

Amlodipine↗
PubMed2004

How important is optimal blood pressure control?

BACKGROUND: Evidence for the cardiovascular benefits of antihypertensive treatment is among the strongest in medicine. Randomized, prospective, unconfounded studies in thousands of people have shown that even small reductions in blood pressure for short periods substantially improve cardiovascular outcomes. Recent evidence has emphasized the importance of optimal blood pressure control, particularly in patients with high cardiovascular risk, such as those with type 2 diabetes mellitus. OBJECTIVE: This article discusses optimal target blood pressure goals, reviews the effects of antihypertensive treatment in high-risk patients, presents current guidelines for blood pressure control, discusses the failure worldwide to achieve such control, and suggests approaches to improved treatment. CONCLUSIONS: In high-risk patients, small improvements in blood pressure control are associated with large reductions in cardiovascular risk. National and international guidelines for the management of hypertension therefore now recommend rigorous blood pressure targets. Despite extensive clinical evidence, the delivery of care for hypertension remains unsatisfactory. Hypertension is underdiagnosed and undertreated, and recommended target blood pressures are rarely achieved. Physicians appear reluctant to make changes to treatment, which would lead to more effective use of antihypertensive drugs. Overwhelming evidence supports the benefit of optimal blood pressure control in patients with hypertension. Several studies have shown that such control can be achieved, but most likely requires combination treatment. Combination treatment is likely to be successful only if drugs are well tolerated and patients are compliant. The angiotensin II receptor antagonists (sartans) have the therapeutic advantage of efficacy, excellent tolerability, and a good record of compliance. Blood pressure control can be more easily accomplished by using sartans early in treatment and by recognizing the benefits of even small reductions in blood pressure.

Angiotensin II↗
PubMed2004

Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.

BACKGROUND: The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed dyslipidaemic. METHODS: Of 19 342 hypertensive patients (aged 40-79 years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, 10,305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being non-fatal myocardial infarction and fatal CHD. Data were analysed by intention to treat. FINDINGS: Treatment was stopped after a median follow-up of 3.3 years. By that time, 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group (hazard ratio 0.64 [95% CI 0.50-0.83], p = 0.0005). This benefit emerged in the first year of follow-up. There was no significant heterogeneity among prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121 placebo, 0.73 [0.56-0.96], p = 0.024), total cardiovascular events (389 vs 486, 0.79 [0.69-0.90], p = 0.0005), and total coronary events (178 vs 247, 0.71 [0.59-0.86], p = 0.0005) were also significantly lowered. There were 185 deaths in the atorvastatin group and 212 in the placebo group (0.87 [0.71-1.06], p = 0.16). Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months, and by 1.1 mmol/L after 3 years of follow-up. INTERPRETATION: The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time. These findings may have implications for future lipid-lowering guidelines.

Adult↗
PubMed2004

The role of olmesartan medoxomil in the management of hypertension.

Intensive blood pressure control is a desirable and obtainable goal in patients with hypertension, according to the most recent treatment guidelines from Europe and the US. Achieving target blood pressure depends on the efficacy of antihypertensive treatment and patient compliance. Olmesartan medoxomil, a non-peptidergic angiotensin AT1 receptor antagonist, has been shown to be effective and well tolerated. Continuation of initial treatment is higher with AT1 receptor antagonists than for any other class of antihypertensive drugs. Olmesartan medoxomil may also have end-organ protective effects that provide additional clinical benefit. Optimal blood pressure control may be achieved faster if initial treatment contains the most efficacious and well tolerated antihypertensive drug or drugs. The ongoing European study, known as OLMEBEST (Efficacy and safety of OLMEsartan: reduction of Blood pressure in the treatment of patients suffering from mild to moderate ESsenTial hypertension), will provide important information on the use of olmesartan medoxomil as an initial treatment for hypertension.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2003

Effect of area-based deprivation on the severity, subtype, and outcome of ischemic stroke.

BACKGROUND AND PURPOSE: Markers of low socioeconomic status (deprivation) are associated with stroke and its causes. In the United Kingdom, area-based deprivation measures are available routinely through links with postal codes. We hypothesized that deprivation is associated with ischemic stroke risk factors, severity, subtype, and outcome. METHODS: We studied 2026 patients, each with at least 2 years of outcome follow-up by record linkage after first admission with ischemic stroke to an acute stroke unit. Baseline factors recorded routinely were age, sex, medical history, blood pressure, and stroke severity and subtype. Deprivation was assessed by the Womersley score (WS) and Murray score (MS). RESULTS: Higher WS and MS were associated with stroke at younger age (eg, WS linear regression coefficient (r)=-0.26; 95% confidence interval [CI], -0.51 to -0.01 per additional point), smoking (odds ratio [OR], 1.12; 95% CI, 1.08 to 1.17), and claudication (OR, 1.09; 95% CI, 1.01 to 1.17); WS was associated with higher systolic blood pressure (r=0.13; 95% CI, 0.02 to 0.24); and MS was associated with severe stroke. Deprivation was not associated with case fatality in univariate analysis or after correction for all baseline factors. Deprivation was associated with readmission to hospital as a result of any vascular event in univariate analysis (hazard ratio [HR], 1.05; 95% CI, 1.02 to 1.09) and after correction for all baseline factors (HR, 1.06; 95% CI, 1.02 to 1.10). CONCLUSIONS: Tackling health inequalities in stroke should focus on stroke primary prevention by tackling deprivation, including promoting changes in lifestyle.

Aged↗
PubMed2003

Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.

BACKGROUND: The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed dyslipidaemic. METHODS: Of 19342 hypertensive patients (aged 40-79 years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, 10305 with non-fasting total cholesterol concentrations 6.5 mmol/L or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being non-fatal myocardial infarction and fatal CHD. Data were analysed by intention to treat. FINDINGS: Treatment was stopped after a median follow-up of 3.3 years. By that time, 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group (hazard ratio 0.64 [95% CI 0.50-0.83], p=0.0005). This benefit emerged in the first year of follow-up. There was no significant heterogeneity among prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121 placebo, 0.73 [0.56-0.96], p=0.024), total cardiovascular events (389 vs 486, 0.79 [0.69-0.90], p=0.0005), and total coronary events (178 vs 247, 0.71 [0.59-0.86], p=0.0005) were also significantly lowered. There were 185 deaths in the atorvastatin group and 212 in the placebo group (0.87 [0.71-1.06], p=0.16). Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months, and by 1.1 mmol/L after 3 years of follow-up. INTERPRETATION: The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time. These findings may have implications for future lipid-lowering guidelines.

Adult↗