indapamide--perindopril-drug-combination and Stroke

The burden of vascular diseases remains substantial in patients with type 2 diabetes, requiring identification of further risk markers. We tested the absence of dorsalis pedis and posterior tibial pulses as predictors of major macrovascular and microvascular events, death, and cognitive decline in this population.. Data were derived from 11,120 patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study. Absent peripheral pulses at baseline were defined as absence of at least one dorsalis pedis or posterior tibial pulse.. Absent compared with present peripheral pulses (n = 2,218) were associated with increased 5-year risks for major macrovascular events (hazard ratio 1.47 [95% CI 1.28-1.69], P < 0.0001), myocardial infarction (1.45 [1.13-1.87], P = 0.003), stroke (1.57 [1.23-2.00], P = 0.0003), cardiovascular death (1.61 [1.33-1.95], P < 0.0001), heart failure (1.49 [1.21-1.84], P = 0.0002), all-cause mortality (1.48 [1.29-1.71], P < 0.0001), major microvascular events (1.17 [1.00-1.36], P = 0.04), nephropathy (1.24 [1.00-1.54], P = 0.04), end-stage renal disease or renal death (2.04 [1.12-3.70], P = 0.02), and peripheral neuropathy (1.13 [1.05-1.21], P = 0.0008) after multiple adjustment. Participants with absent dorsalis pedis or posterior tibial pulses had comparable hazard ratios. Risks increased proportionally with the number of absent peripheral pulses, with the highest risks observed in patients with three or four absent pulses. Every additional absent pulse increases the risk of all outcomes.. Absent dorsalis pedis and/or posterior tibial pulses are independent predictors of major vascular outcomes in patients with type 2 diabetes. These simple clinical indicators should be used to improve risk stratification and treatment of these patients.

Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diagnostic Techniques, Cardiovascular; Disease Progression; Drug Combinations; Female; Gliclazide; Humans; Hypoglycemic Agents; Indapamide; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Perindopril; Pulse; Risk Factors; Stroke

Moderate alcohol consumption has been associated with a reduced risk of mortality and coronary artery disease. The relationship between cardiovascular health and alcohol use in type 2 diabetes is less clear. The current study assesses the effects of alcohol use among participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial.. The effects of alcohol use were explored using Cox regression models, adjusted for potential confounders. The study end points were cardiovascular events (cardiovascular death, myocardial infarction, and stroke), microvascular complications (new or worsening nephropathy or retinopathy), and all-cause mortality.. During a median of 5 years of follow-up, 1,031 (9%) patients died, 1,147 (10%) experienced a cardiovascular event, and 1,136 (10%) experienced a microvascular complication. Compared with patients who reported no alcohol consumption, those who reported moderate consumption had fewer cardiovascular events (adjusted hazard ratio [aHR] 0.83; 95% CI 0.72-0.95; P = 0.008), less microvascular complications (aHR 0.85; 95% CI 0.73-0.99; P = 0.03), and lower all-cause mortality (aHR 0.87; 96% CI 0.75-1.00; P = 0.05). The benefits were particularly evident in participants who drank predominantly wine (cardiovascular events aHR 0.78, 95% CI 0.63-0.95, P = 0.01; all-cause mortality aHR 0.77, 95% CI 0.62-0.95, P = 0.02). Compared with patients who reported no alcohol consumption, those who reported heavy consumption had dose-dependent higher risks of cardiovascular events and all-cause mortality.. In patients with type 2 diabetes, moderate alcohol use, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality.

Topics: Aged; Alcohol Drinking; Antihypertensive Agents; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Drug Combinations; Female; Gliclazide; Humans; Hypertension; Hypoglycemic Agents; Indapamide; Male; Myocardial Infarction; Perindopril; Retrospective Studies; Risk Reduction Behavior; Stroke

The results of the Hypertension in the Very Elderly Trial showed positive benefits from blood pressure-lowering treatment in those aged 80 and over.. An analysis by the pre-specified subgroups [age, sex, history of cardiovascular disease (CVD) and initial SBP] was performed. The Hypertension in the Very Elderly Trial was a randomized, double-blind, placebo-controlled trial of 3845 participants aged 80 and over with SBPs of 160-199 mmHg and diastolic pressures below 110 mmHg recruited from Europe, China, Australasia and Tunisia. Active treatment was indapamide sustained-release 1.5 mg with the addition of perindopril 2-4 mg as required to reach a target blood pressure of less than 150/80 mmHg.. For total mortality, benefits were consistent: men [hazard ratio 0.82, 95% confidence interval (CI) 0.62-1.11], women (hazard ratio 0.77, 95% CI 0.66-0.99), those aged 80-84.9 (hazard ratio 0.76, 95% CI 0.60-0.96), those aged 85 and over (hazard ratio 0.87, 95% CI 0.64-1.20), those with a history of CVD (hazard ratio 0.76, 95% CI 0.48-1.20) and those without (hazard ratio 0.81, 95% CI 0.65-0.99), and similarly across a range of baseline SBPs. The point estimates for cardiovascular mortality, strokes, heart failure and cardiovascular events were all in favour of benefit. In the per-protocol analysis, strokes were reduced by 34% (P = 0.026), total mortality by 28% (P = 0.001), cardiovascular event by 37% (P < 0.001) and heart failure by 72% (P < 0.001).. In hypertensive patients aged 80 or more, treatment based on indapamide (sustained-release) 1.5 mg showed consistent benefits across pre-specified subgroups including those without established CVD (the majority), supporting the need for treatment even at this advanced age. There were too few aged 90 or over to determine benefit from treatment at extreme age.

Topics: Age Factors; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Indapamide; Male; Perindopril; Risk Assessment; Stroke

In everyday medical practice, physicians often need to manage patients whose blood pressure is not well controlled. Those with a history of cerebrovascular disease are a high-risk group in need of rapid blood pressure control.. The PICASSO study was a real-life, observational trial involving 9257 inadequately treated hypertensive patients who were switched from previous therapy to the fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg (PI) for 3 months. A subanalysis of data of 1117 hypertensive patients who met the clinical criteria of previous stroke or transient ischemic attack was performed. Twenty-four hour ambulatory blood pressure measurements (ABPMs) were also done in a small group of patients (n:38).. At baseline, mean systolic/diastolic blood pressure (SBP/DBP) was 161.5 ± 15.2/93.1 ± 9.9 mmHg. After 1 month with the fixed dose of PI, average office SBP/DBP decreased to 140.0 ± 11.9/83.5 ± 7.7 mmHg. After 3 months, SBP/DBP had dropped to 132.9 ± 9.8/80.0 ± 6.2 mmHg, by 28.6 ± 15.5/13.1 ± 10.0 mmHg (p < 0.001). Blood pressure control rate (< 140/90 mmHg) was 67.3% after 3 months. When data were stratified by baseline blood pressure, decreases in SBP/DBP were statistically significant in patients with all grades (1-3) of hypertension. In patients previously treated with an angiotensin-converting enzyme inhibitor ± hydrochlorothiazide (n = 677), blood pressure decreased by 29.8 ± 15.5/13.3 ± 10.2 mmHg (p < 0.001). Decreases in 24-h ABPM values were also significant (n = 38). Treatment was well tolerated; only a few adverse events were recorded.. This study suggests that fixed combination perindopril 10 mg/indapamide 2.5 mg is an effective and well-tolerated treatment for patients with a history of stroke or transient ischemic attack.. EGIS Pharmaceuticals Plc.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Female; Humans; Hungary; Hypertension; Indapamide; Ischemic Attack, Transient; Male; Middle Aged; Perindopril; Stroke; Treatment Outcome

to assess adherence of patients to antihypertensive therapy with fixed perindopril and indapamide combination (FPIC) as well as to elucidate causes of changes of therapy after 6 months.. In 6 months after termination of the FORSAGE observational program we interviewed over telephone 148 of 1299 patients who achieved target blood pressure (BP) values.. Adherence to treatment was high - 67.5% of patients continued to take the drug. In 87.9% of patients BP was kept on target level (<140 and 90 mm Hg), in 12.1% BP was above this level. Most patients were satisfied by results of treatment. Infrequent hypertensive crises persisted in 6.1% of patients; 3% of patients sought emergency service. Among 48 patients who stopped taking FPIC 22 (45.8%) made this decision themselves, 11 - on physicians advice. Main causes of cancellation of treatment were high cost of the drug, its absence in the list of concessional mediciations, physicians statement "course treatment completed, condition improved". Among those who stopped treatment 10 patients could not report values of their BP; in 28 (58.3%) BP was at and in 10 (20.8%) above target level; crises were registered in 8.3% of patients, 4.2% of patients called ambulances, 1 patient suffered stroke. Of 48 patients who stopped treatment with FLIC 19 consented to self report assessment health status; 84% of reported scores were above 5, but no score was equal to 9 or 10.

Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Drug Therapy, Combination; Humans; Hypertension; Indapamide; Medication Adherence; Perindopril; Stroke

To measure the placebo-controlled effects of combination therapy on hypotension, treatment discontinuation, and major renal outcomes, according to baseline blood pressure.. We conducted an analysis of the action in diabetes and vascular disease: preterax and diamicron-MR controlled evaluation ADVANCE and perindopril protection against recurrent stroke study PROGRESS trials, including 14 684 participants allocated combination therapy or placebo. The mean age was 65 years, 61% were men, and 64% were receiving background blood pressure lowering (BPL) therapy. Participants were stratified into five subgroups by baseline SBP less than 120, 120-129, 130-139, 140-159, and at least 160 mmHg. Discontinuation of study treatment during the active run-in phase and postrandomization follow-up was assessed for hypotension/dizziness and other causes. Major renal outcomes (sustained doubling in creatinine or renal death) were also assessed.. Discontinuation during the 4-6-week active run-in phase due to hypotension/dizziness ranged from 3.6% in those with SBP less than 120 mmHg to 1.3% in those with SBP at least 160 mmHg. Median follow-up in the randomized phase was 5.6 years, and discontinuation for hypotension was higher with combination therapy compared with placebo in the less than 120 mmHg group (4.7 vs. 1.2%). However, for each subgroup with baseline SBP 120-129, 130-139, and 140-159 mmHg, the absolute excess of discontinuation due to hypotension with combination therapy was 0.7%. Total discontinuations were only increased in the less than 120 mmHg group (18.4 vs. 12.5%) and the 120-129-mmHg subgroup (17.6 vs. 14.2%). There were no clear differences across the SBP subgroups for the combined renal outcome (overall, 0.8 vs. 0.6%).. Compared with those with baseline SBP 140-159 mmHg, side effects of dual combination BPL are essentially the same for people with SBP 130-139 mmHg and only modestly increased among patients with SBP 120-129 mmHg. During long-term therapy, side effects sufficient to stop treatment that are treatment related (i.e. occur in excess of rates seen with placebo) occur at less than 0.5%/year in patients with baseline SBP 120-139 mmHg. These results have important implications in assessing the likely balance of benefits and side effects of BPL with combination therapy among those with SBP 120-139 mmHg.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Hypertension; Hypotension; Indapamide; Male; Medication Adherence; Middle Aged; Multicenter Studies as Topic; Perindopril; Placebos; Proportional Hazards Models; Randomized Controlled Trials as Topic; Stroke

The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial.. Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 ('normal', n = 8,689), 24-27 ('mild dysfunction', n = 2,231) and <24 ('severe dysfunction', n = 212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis.. Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11-1.46 and 1.42, 95% CI 1.01-1.99; both p < 0.05), cardiovascular death (1.41, 95% CI 1.16-1.71 and 1.56, 95% CI 0.99-2.46; both p

Topics: Aged; Antihypertensive Agents; Cognition; Cognition Disorders; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Combinations; Drug Therapy, Combination; Educational Status; Female; Gliclazide; Humans; Hypoglycemia; Hypoglycemic Agents; Indapamide; Male; Mental Status Schedule; Myocardial Infarction; Perindopril; Risk Factors; Stroke