The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.     

Reductions in the risks of recurrent stroke in patients with and without diabetes: the PROGRESS Trial

BACKGROUND: Analyses of the risks of stroke were conducted for subjects with and without diabetes, participating in a randomized, double-blind, placebo-controlled trial of a perindopril-based blood pressure lowering regimen in 6105 people with prior stroke or transient ischaemic attack (TIA), followed for a median of 3.9 years. FINDINGS: Seven hundred and sixty-one patients had diabetes at baseline. Diabetes increased the risk of recurrent stroke by 35% (95% CI 10-65%) principally through an effect on ischaemic stroke (1.53, 95% CI 1.23-1.90). Active treatment reduced blood pressure by 9.5/4.6 mmHg in patients with diabetes and by 8.9/3.9 mmHg in patients without diabetes. The proportional risk reductions achieved for stroke in patients with diabetes, 38% (95% CI 8-58%), and patients without diabetes, 28% (95% CI 16-39%), were not significantly different (p homogeneity = 0.5). The absolute reduction in the risk of recurrent stroke in the patients with diabetes was equivalent to one stroke avoided among every 16 (95% CI 9-111) patients treated for 5 years. CONCLUSIONS: Diabetes is an important risk factor for stroke in patients with established cerebrovascular disease. Treatment with the ACE inhibitor perindopril with discretionary use of the diuretic indapamide produced reductions in the risk of recurrent stroke in patients with diabetes that were at least as great as those achieved in patients without diabetes.     

Blood Pressure Lowering for the Prevention of Cognitive Decline in Patients with Cerebrovascular Disease

Cerebrovascular disease and high blood pressure both appear to increase the risk of vascular dementia. PROGRESS aims to investigate whether blood pressure lowering with an angiotensin converting enzyme inhibitor-based regimen will reduce the risk of cognitive impairment in patients with a history of stroke or transient ischaemic attack. A total of at least 6000 patients will be randomised to receive perindopril (± indapamide) or matching placebo(s), with treatment and follow-up scheduled to continue for at least 4 years. Substudies will investigate the effects of treatment on cognitive decline in subgroups defined by apo-E genotype and on white matter lesions assessed by magnetic resonance imaging. Final results from the study should be available in 2001.     

Long-term efficacy of a new, fixed, very-low-dose angiotensin-converting enzyme-inhibitor/diuretic combination as first-line therapy in elderly hypertensive patients

OBJECTIVE: To determine the long-term efficacy and safety of a fixed, very-low-dose tablet combining one-half the standard dose of perindopril with one-quarter the standard dose of indapamide as first-line treatment in elderly patients. DESIGN: Double-blind, randomized, placebo-controlled study in an outpatient setting. PATIENTS AND INTERVENTIONS: Following a single-blind, placebo run-in period of 4 weeks, patients [65-85 years, with mild-to-moderate essential hypertension or isolated systolic hypertension (ISH)] were randomized to receive one tablet of perindopril 2 mg/indapamide 0.625 mg (Per/ Ind) (n=193) or placebo (n=190), daily for 12 weeks. After this first 12-week period, all patients on Per/Ind (n=138) and patients responding to placebo (n=61) were maintained on their previous regimen for a further 48 weeks. Patients in the placebo group whose blood pressure was not normalized, were switched to Per/Ind (n=60). MAIN OUTCOME MEASURE: The primary endpoint was the proportion of patients with blood pressure that normalized between weeks 0 and 60. RESULTS: After 1 year of treatment (intention-to-treat) supine systolic and diastolic blood pressure decreased by 23.0 +/- 15.3 mmHg and 13.3 +/- 94 mmHg with Per/Ind (n=253: 193 from randomized Per/Ind group and 60 from the placebo group switched at week 12). The mean decreases in systolic blood pressure were similar in essential hypertension and ISH (systolic blood pressure 23.2 versus 22.7 mmHg, respectively). Per/Ind treatment (n=253) achieved an initial normalization of blood pressure in 96.2% [95% confidence interval (CI) 93.6-98.9%; Kaplan-Meier estimate] of Per/Ind-treated patients; 79.8% (95% CI 74.1-85.5%) of these maintained a normalized blood pressure throughout the 1 -year follow-up. The incidence of adverse events was similarly low in the placebo and active therapy groups. Efficacy and safety results for the over 75 years subgroup were similar to those for the younger elderly subjects CONCLUSIONS: The fixed, very low-dose combination of perindopril 2 mg/indapamide 0.625 mg results in sustained blood pressure control when used as first line treatment of elderly hypertensive patients over 1-year, and is well-tolerated.     

Perindopril-based blood pressure lowering in individuals with cerebrovascular disease: consistency of benefits by age, sex and region

OBJECTIVE: To assess the consistency of the benefits of blood pressure lowering on secondary stroke risk by age, sex and geographic region of recruitment. DESIGN: Randomized, placebo-controlled trial. Participants were randomized to the angiotensin-converting enzyme (ACE) inhibitor perindopril (plus the diuretic indapamide if not indicated or contraindicated) or to placebo(s) over a mean follow-up of 3.9 years. Main analyses used Cox proportional hazards models on an intention-to-treat basis. Subgroup results were standardized for the proportion (42%) taking single-drug therapy. SETTING: A total of 172 centres in Asia, Australia, New Zealand and Europe. PARTICIPANTS: Patients (n = 6105) with a history of stroke or transient ischaemic attack, of whom 50% were aged over 65 years at baseline, 30% were women and 39% were from Asia. MAIN OUTCOME MEASURES: Stroke, coronary heart disease and major vascular events. RESULTS: Overall, treatment reduced stroke by 28% [95% confidence interval (CI) 17-38%] and major vascular events by 26% (16-44%), with separately significant reductions across subgroups defined by age (< or > or = 65 years), sex and region (Asia or not). Treatment was safe and well tolerated, and the absolute benefits were large; 5 years' treatment would be expected to avert at least one major vascular event among every 20 patients in all age, sex and region subgroups. There was some evidence of particularly large benefits among younger participants and those from Asia. CONCLUSIONS: Blood pressure lowering reduces secondary stroke risk, with large absolute benefits across groups defined by age, sex and geographic region.     

A pilot study of banxia houpu tang, a traditional Chinese medicine, for reducing pneumonia risk in older adults with dementia

OBJECTIVES: To evaluate whether the traditional Chinese herbal medicine Banxia Houpu Tang (BHT, formula magnolia et pinelliae) prevents aspiration pneumonia and pneumonia-related mortality in elderly people.
DESIGN: A prospective, observer-blinded, randomized, controlled trial.
SETTING: Two long-term care hospitals for handicapped elderly patients in Japan from March 2005 to February 2006.
PARTICIPANTS: One hundred four elderly patients (31 men and 73 women; mean age±standard deviation 83.5±7.8) with dementia and cerebrovascular disease, Alzheimer's disease, or Parkinson's disease.
INTERVENTION: Ninety-five participants (mean age 84.0, M:F=28:67) were randomly assigned to the BHT treatment group (n=47) or the control group (n=48) and took BHT or placebo for 12 months.
MEASUREMENTS: The occurrence of pneumonia, mortality due to pneumonia, and the daily amount of self-feeding.
RESULTS: Complete data were available for analysis on 92 of the 95 subjects randomized. Four patients in the BHT group developed pneumonia, and one of them died as a result. Fourteen patients in the control group developed pneumonia, and six of them died as a result. There was a significant difference between the two groups in pneumonia onset ( P =.008), and a tendency toward significance in pneumonia-related mortality ( P =.05). The relative risk of pneumonia in the BHT group compared with the control group was 0.51 (95% confidence interval (CI)=0.27–0.84, P =.008) and that of death from pneumonia was 0.41 (95% CI=0.10–1.03, P =.06) according to the Cox proportional hazards model. No adverse events were observed from treatment with BHT. The BHT group was able to maintain self-feeding better than the control group ( P =.006).
CONCLUSION: Treatment with BHT reduced the risk of pneumonia and pneumonia-related mortality in elderly patients with dementia.     

Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome: results of the randomized Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) Study

BACKGROUND: Angiotensin-converting enzyme inhibitors reduce mortality and remodeling after myocardial infarction in patients with left ventricular dysfunction. METHODS: Perindopril and Remodeling in Elderly With Acute Myocardial Infarction (PREAMI), a double-blind, randomized, parallel-group, multicenter, placebo-controlled study, determined whether similar benefits occur in elderly postinfarction patients with preserved left ventricular function. A total of 1252 patients 65 years or older with a left ventricular ejection fraction of 40% or higher and recent acute myocardial infarction were randomized to receive perindopril erbumine or placebo (8 mg/d) for 12 months. The combined primary end point was death, hospitalization for heart failure, or left ventricular remodeling. Secondary end points included cardiovascular death, hospitalization for reinfarction or angina, and revascularization. RESULTS: The primary end point occurred in 181 patients (35%) taking perindopril and 290 patients (57%) taking placebo, with a significant absolute risk reduction of 0.22 (95% confidence interval, 0.16 to 0.28; P<.001). A total of 126 patients (28%) and 226 patients (51%) in the perindopril and placebo groups, respectively, experienced remodeling. The mean increase in left ventricle end-diastolic volume was 0.7 mL with perindopril compared with 4.0 mL with placebo (P<.001). In the perindopril group, 40 deaths (6%) and 22 hospitalizations (4%) for heart failure occurred, whereas 37 deaths (6%) and 30 hospitalizations (5%) occurred in the placebo group. Treatment did not affect death, whereas the hospitalization rate for heart failure was slightly reduced (absolute risk reduction, 0.01; 95% confidence interval, -0.01 to 0.02). No treatment effect on other secondary end points was detected. CONCLUSION: We found that 1-year treatment with 8 mg/d of perindopril reduces progressive left ventricular remodeling that can occur even in the presence of small infarct size, but it was not associated with better clinical outcomes.     

Performance-based physical function and future dementia in older people

BACKGROUND: The association of physical function with progression to dementia has not been well investigated. We aimed to determine whether physical function is associated with incident dementia and Alzheimer disease (AD). METHODS: We performed a prospective cohort study of 2288 persons 65 years and older without dementia. Patients were enrolled from 1994 to 1996 and followed up through October 2003. Main outcome measures included incident dementia and AD. RESULTS: During follow-up 319 participants developed dementia (221 had AD). The age-specific incidence rate of dementia was 53.1 per 1000 person-years for participants who scored lower on a performance-based physical function test at baseline (< or = 10 points) compared with 17.4 per 1000 person-years for those who scored higher (> 10 points). A 1-point lower performance-based physical function score was associated with an increased risk of dementia (hazard ratio, 1.08; 95% confidence interval, 1.03-1.13; P < .001), an increased risk of AD (hazard ratio, 1.06; 95% confidence interval, 1.01-1.12; P = .01), and an increased rate of decline in the Cognitive Ability Screening Instrument scores (0.11 point per year; 95% confidence interval, 0.08-0.14; P < .001) after adjusting for age, sex, years of education, baseline cognitive function, APOE epsilon4 allele, family history of AD, depression, coronary heart disease, and cerebrovascular disease. CONCLUSIONS: Lower levels of physical performance were associated with an increased risk of dementia and AD. The study suggests that poor physical function may precede the onset of dementia and AD and higher levels of physical function may be associated with a delayed onset.     

Cross-sectional and longitudinal association between antihypertensive medications and cognitive impairment in an elderly population

BACKGROUND: The effect of antihypertensive medications on cognitive function has not been well studied. The authors' objectives were to investigate the cross-sectional and longitudinal association between the use of antihypertensive medications and cognitive function and to compare different antihypertensive medication classes with regard to this association in an elderly population. METHODS: The medical records of a convenience sample of patients (n = 993 cross-sectional and 350 longitudinal; mean age, 76.8 +/- 0.3 years; 74% women; 87% White) followed at a geriatric practice were reviewed. Data abstracted included demographics, medical history (Alzheimer's disease [AD] or vascular dementia [VaD]), use of antihypertensive medications, and results of cognitive assessments (the Mini-Mental Status Examination [MMSE] and the Clock Draw Test [CDT]). RESULTS: In the cross-sectional analysis, antihypertensive use was not associated with MMSE (p >.05), CDT (p >.05), or dementia diagnosis (odds ratio for AD, 0.8; 95% confidence interval [CI], 0.6 to 1.2; odds ratio for VaD, 1.6; 95% CI, 0.6 to 4.0). In the longitudinal analysis, antihypertensive use was associated with a lower rate of cognitive decline on the MMSE (-0.8 +/- 2 points in users vs -5.8 +/- 2.5 points in nonusers; p =.007) and on the CDT (-0.3 +/- 0.8 points in users vs -2.2 +/- 0.8 points in nonusers; p =.002), and with a lower risk for the development of cognitive impairment (odds ratio, 0.56; 95% CI, 0.38 to 0.83; p =.004). The trend was similar in patients with baseline AD (p =.02). Patients taking diuretics (p =.007), angiotensin-converting enzyme inhibitors (p =.016), and beta-blockers (p =.014) had a lower rate of cognitive decline, and patients taking angiotensin receptor blockers (p =.016) had improved cognitive scores. CONCLUSIONS: Antihypertensive use, particularly diuretics, angiotensin-converting enzymes inhibitors, beta-blockers, and angiotensin receptor blockers, may be associated with a lower rate of cognitive decline in older adults, including those with AD. Until a randomized clinical trial confirms our results, findings of this observational study should be interpreted with caution.     

The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment

BACKGROUND: Previous evidence suggests that treatment with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) has a positive impact on dementia. We decided to investigate the association between the use of statins and the prevalence of dementia and statins' impact on the progression of cognitive impairment. METHODS: This is a case-control and a retrospective cohort study of a community-based ambulatory primary care geriatric practice. We included a convenience sample of all patients (N = 655, mean age 78.7 +/- 0.3 years, 85% Caucasian, 74% women) with hypercholesterolemia or dementia, or using statins. We compared those using statins with those who do not with respect to the clinical diagnosis of dementia and its subtypes and the progression of cognitive impairment. RESULTS: At the initial visit, 35% had dementia, and 17% were using statins. After covariate adjustments, patients on statins were less likely to have dementia (odds ratio [OR] for dementia based on composite definition = 0.23; 95% confidence interval [CI] [0.1-0.56], p =.001, OR Alzheimer's disease = 0.37; 95% CI [0.19-0.74], p =.005, OR vascular dementia = 0.25; 95% CI [0.08-0.85], p =.027). At follow-up, patients on statins showed an improvement on their Mini-Mental Status Examination score by 0.7 +/- 0.4 compared to a decline by 0.5 +/- 0.3 in controls, p =.025 (OR for no change or improvement on statins = 2.81; 95% CI [1.02-8.43], p =.045) and scored higher on the Clock Drawing Test (difference of 1.5 +/- 0.1, p =.036). CONCLUSIONS: The use of statins is associated with a lower prevalence of dementia and has a positive impact on the progression of cognitive impairment.     

Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the Perindopril Protection against Recurrent Stroke Study (PROGRESS) CT Substudy in Japan.

Controversy persists as to whether reducing the blood pressure of patients with a history of stroke leads to an increased risk of silent brain infarct (SBI) and dementia. A total of 667 patients were randomized to receive the angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg daily), with or without the diuretic indapamide (2 mg daily) or matching placebo(s). Brain CT scanning was performed annually over the mean follow-up period of 3.9 years. Active treatment reduced the blood pressure (systolic/diastolic) by 5.2/2.6 mmHg over the follow-up period. A total of 119 new SBI were detected and 92% of them were lacunar type small infarcts. The frequency of reaching the primary end-point (recurrent symptomatic stroke or new SBI) was similar in the placebo group (26.5%) and in the active treatment group (25.9%). There was no significant difference in brain atrophy indices between two groups. In the subgroup with a history of large artery infarction, 7 out of 55 patients from the placebo group developed new SBI, while none of the 40 patients from the active treatment group did so (p = 0.020). The baseline diastolic blood pressure was significantly associated with the risk of new SBI (p = 0.004), but the stroke subtype was not. In conclusion, blood pressure-lowering with a perindopril-based regimen did not increase the risk of SBI and brain atrophy in patients with a history of stroke. The baseline diastolic blood pressure was an independent predictor of new SBI, but the index stroke subtype did not influence the risk of SBI.     

Exercise: a potential contributing factor to the relationship between folate and dementia

OBJECTIVES: To investigate whether exercise confounds the relationship between folate and cerebrovascular events, all-cause dementia, and Alzheimer's disease. DESIGN: Prospective cohort study. SETTING: Multiple centers in Canada. PARTICIPANTS: In the Canadian Study of Health and Aging, 466 people reported exercise levels, had folate measurements, and were not demented at baseline. After 5 years, 194 had adverse cerebrovascular events, and 65 had dementia (Alzheimer's disease in 47). MEASUREMENTS: Associations between folate and cerebrovascular outcomes were examined using logistic regression in the presence and absence of exercise and other confounders. RESULTS: Folate was associated with greater risk of Alzheimer's disease (odds ratio (OR)=2.12, 95% confidence interval (CI)=1.01-4.54) and cerebrovascular outcomes (OR=2.05, 95% CI=1.11-3.78) in adjusted analyses before the inclusion of exercise and neared significance with all-cause dementia (OR=1.80, 95% CI=0.94-3.45). After the inclusion of exercise, the association between folate and dementia and Alzheimer's disease was 29% and 25% lower, respectively, and neither association was any longer significant (Alzheimer's disease: OR=1.91, 95% CI=0.89-4.11; all-cause dementia: OR=1.62, 95% CI=0.84-3.15). Exercise was a significant confounder in the relationship between folate and Alzheimer's disease (P=.03) and dementia (P=.003) but not cerebrovascular outcomes (P=.64). Unlike folate, exercise was significantly associated with Alzheimer's disease (OR=0.43, 95% CI=0.19-0.98) and dementia (OR=0.35, 95% CI=0.17-0.72) in adjusted analyses. CONCLUSION: Exercise seems to account for much of the relationship between folate and incident dementia and Alzheimer's disease.     

Response to activated protein C in subjects with and without dementia. The Dutch Vascular Factors in Dementia Study.

We performed a cross-sectional case-control study among 295 subjects with dementia and 406 control subjects drawn from participants of the Rotterdam Study, a population-based cohort study among subjects aged 55 years or over, and from participants of the Rotterdam Stroke Databank, a hospital-based stroke registry, to evaluate the association of the factor V Leiden mutation and activated protein C (APC) response with dementia and its subtypes. The risk of dementia was 2.11-fold increased among carriers of factor V Leiden mutation relative to subjects lacking factor V Leiden mutation (95% confidence interval, CI, 0.93-4.77). The increased risks of vascular dementia and of Alzheimer's disease were 4.28 (95% CI 1.26-14.5) and 2.15 (95% CI 0.82-5.63), respectively. No association was found for APC response. We showed a nonsignificant twofold increased risk of dementia among subjects with factor V Leiden. The association appeared to be stronger for vascular dementia.     

White matter lesions on brain magnetic resonance imaging scan and 5-year cognitive decline: the Honolulu-Asia aging study

OBJECTIVES: To study white matter lesions (WMLs) and 5‐year cognitive decline in elderly Japanese‐American men. DESIGN: Longitudinal cohort study. SETTING: Population‐based study in Honolulu, Hawaii. PARTICIPANTS: Japanese‐American men aged 74 to 95 from the Honolulu‐Asia Aging Study (HAAS) who were free of prevalent dementia, underwent a protocol brain MRI scan at the fifth HAAS examination (1994–1996), and returned for cognitive testing 5 years later (N=267). MEASUREMENTS: WMLs were dichotomized as present (grade 3–9, 38.2%) or absent (grade 1–2, 61.8%). Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI), and 5‐year cognitive decline was defined as a drop in CASI score of 12 points or more (1 standard deviation). RESULTS: Men with WMLs on MRI at baseline were significantly more likely to experience cognitive decline at 5 years than those without (22.4% vs 34.4%, P=.03). Using multiple logistic regression, adjusting for age, education, apolipoprotein (Apo)E4 allele, large or small infarcts on MRI, baseline CASI score, and hypertension, those with WMLs were significantly more likely to develop 5‐year cognitive decline (odds ratio=2.00, 95% confidence interval=1.10–3.65, P=.02). This association was stronger in men who were cognitively intact and free of the ApoE4 genotype and clinical stroke at baseline. CONCLUSION: Presence of WMLs on MRI was significantly associated with higher odds of 5‐year cognitive decline in older Japanese‐American men. Presence of WMLs may help identify people at risk for developing dementia, who may benefit from early intervention.     

Physical exercise and the prevention of disability in activities of daily living in older persons with osteoarthritis

BACKGROUND: The prevention of disability in activities of daily living (ADL) may prolong older persons' autonomy (older persons are defined in this study as those aged > or =60 years). However, proved preventive strategies for ADL disability are lacking. A sedentary lifestyle is an important cause of disability. This study examines whether an exercise program can prevent ADL disability. METHODS: A 2-center, randomized, single-blind, controlled trial was conducted in which participants were assigned to an aerobic exercise program, a resistance exercise program, or an attention control group. Of the 439 community-dwelling persons aged 60 years or older with knee osteoarthritis originally recruited, the 250 participants initially free of ADL disability were used for this study. Incident ADL disability, defined as developing difficulty in transferring from a bed to a chair, eating, dressing, using the toilet, or bathing, was assessed quarterly during 18 months of follow-up. RESULTS: The cumulative incidence of ADL disability was lower in the exercise groups (37.1%) than in the attention control group (52.5%) (P =.02). After adjustment for demographics and baseline physical function, the relative risk of incident ADL disability for assignment to exercise was 0.57 (95% confidence interval, 0.38-0.85; P =.006). Both exercise programs prevented ADL disability; the relative risks were 0.60 (95% confidence interval, 0.38-0.97; P =.04) for resistance exercise and 0.53 (95% confidence interval, 0.33-0.85; P =.009) for aerobic exercise. The lowest ADL disability risks were found for participants with the highest compliance to exercise. CONCLUSIONS: Aerobic and resistance exercise may reduce the incidence of ADL disability in older persons with knee osteoarthritis. Exercise may be an effective strategy for preventing ADL disability and, consequently, may prolong older persons' autonomy.     

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents

Background Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.Methods Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug(clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events(a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.Results A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo.Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis(0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P 0.001) and major adverse cardiovascular and cerebrovascular events(4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85];P 0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo(2.1% vs. 4.1%; hazard ratio, 0.47; P 0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group(hazard ratio, 1.36 [95% CI, 1.00 to 1.85];P = 0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment(2.5% vs. 1.6%, P = 0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.Conclusions Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding.(Funded by a consortium of eight device and drug manufacturers and others; DAPT Clinical Trials.gov number, NCT00977938.)(From: N Engl J Med 2014; 371:2155-2166 December 4, 2014DOI: 10.1056 / NEJMoa1409312)     

Vascular Care in Patients with Alzheimer's Disease with Cerebrovascular Lesions—A Randomized Clinical Trial

OBJECTIVES: To investigate whether vascular care slows dementia progression in patients with Alzheimer's disease with cerebrovascular lesions on neuroimaging.
DESIGN: Multicenter randomized controlled clinical trial with 2-year follow-up.
SETTING: Neurological and geriatric outpatient clinics in 10 Dutch hospitals: three academic, five teaching, and two midsize community hospitals.
PARTICIPANTS: One hundred thirty community-dwelling patients with mild dementia fulfilling clinical criteria for Alzheimer's disease with cerebrovascular lesions on neuroimaging.
INTERVENTION: Patients randomized to vascular care were treated according to strict guidelines for hypercholesterolemia and hypertension. Acetylsalicylic acid, folic acid, and pyridoxine were prescribed. During visits every 3 months special attention was paid to smoking cessation, losing weight, and stimulating physical exercise.
MEASUREMENTS: Primary outcome was disability, measured according to the Interview for Deterioration in Daily activities in Dementia (IDDD). Secondary outcomes were changes on the Mini-Mental State Examination (MMSE), the Revised Memory and Behavioural Problems Checklist (RMBPC), a composite measure of "poor outcome" (death, institutionalization, or severe clinical decline), and costs.
RESULTS: Patients in the vascular and standard care condition declined equally on the IDDD (13.7 vs 11.0 points; difference 2.7, 95% confidence interval =−3.1–8.6). There was no treatment effect on the MMSE or RMBPC. There were no differences in institutionalization rate, "poor outcome" (41.4% vs 35.4%, P =.50), or costs. In the intervention group, there were three intracerebral hemorrhages and one gastrointestinal hemorrhage, versus none in the control group.
CONCLUSION: Multicomponent vascular care, combining pharmacological and nonpharmacological interventions, does not slow decline in patients with Alzheimer's disease with cerebrovascular lesions.     

Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.     

Comparison of medical treatment with percutaneous closure of patent foramen ovale in patients with cryptogenic stroke

OBJECTIVES: The purpose of this study was to compare the efficacy of medical treatment with percutaneous closure of patent foramen ovale (PFO). BACKGROUND: Patients with cryptogenic stroke and PFO are at risk for recurrent cerebrovascular events. METHODS: We compared the risk of recurrence in 308 patients with cryptogenic stroke and PFO, who were treated either medically (158 patients) or underwent percutaneous PFO closure (150 patients) between 1994 and 2000. RESULTS: Patients undergoing percutaneous PFO closure had a larger right-to-left shunt (p < 0.001; 95% confidence interval [CI] 1.38 to 3.07) and were more likely to have suffered more than one cerebrovascular event (p = 0.03; 95% CI 1.04 to 2.71). At four years of follow-up, percutaneous PFO closure resulted in a non-significant trend toward risk reduction of death, stroke, or transient ischemic attack (TIA) combined (8.5% vs. 24.3%; p = 0.05; 95% CI 0.23 to 1.01), and of recurrent stroke or TIA (7.8% vs. 22.2%; p = 0.08; 95% CI 0.23 to 1.11) compared with medical treatment. Patients with more than one cerebrovascular event at baseline and those with complete occlusion of PFO were at lower risk for recurrent stroke or TIA after percutaneous PFO closure compared with medically treated patients (7.3% vs. 33.2%; p = 0.01; 95% CI 0.08 to 0.81, and 6.5% vs. 22.2%; p = 0.04; 95% CI 0.14 to 0.99, respectively). CONCLUSIONS: Percutaneous PFO closure appears at least as effective as medical treatment for prevention of recurrent cerebrovascular events in cryptogenic stroke patients with PFO. It might be more effective than medical treatment in patients with complete closure and more than one cerebrovascular event.     

Association of Alzheimer's disease onset with ginkgo biloba and other symptomatic cognitive treatments in a population of women aged 75 years and older from the EPIDOS study

BACKGROUND: Peripheral C4A treatment (cerebral and peripheral vasotherapeutics) and especially Ginkgo biloba extracts are prescribed for a number of symptoms, particularly memory impairment, in elderly patients. It is postulated that because of its pharmacological actions, this treatment could prevent the decline of cognitive function, but no studies have been published to date to test its efficacy in prevention of Alzheimer's disease. The potential association between use of C4A treatments, in particular EGb 761 (standardized Ginkgo biloba extracts), and dementia of the Alzheimer type was investigated. METHODS: A case-control study was nested in a cohort of 1462 community-dwelling elderly women aged over 75 years. Sixty-nine women with Alzheimer-type dementia were compared with 345 paired women whose cognitive function remained normal. This study involved women whose cognitive function was evaluated at baseline by use of Pfeiffer's test and whose medication history was taken. The onset of cognitive impairment was investigated over a 7-year follow-up period. In order to study the factors associated with the onset of dementia, the data concerning women with a score of > or = 8 on Pfeiffer's test at inclusion, indicating normal cognitive function, were analyzed. RESULTS: A multivariate analysis including potential confounding factors showed that fewer women who developed Alzheimer's dementia had been prescribed C4A treatment (including EGb 761) for at least 2 years (odds ratio = 0.31, 95% confidence interval = 0.12-0.82, p =.018). Figures for EGb 761 alone were similar but did not reach statistical significance (odds ratio = 0.38, 95% confidence interval = 0.08-1.76, p =.22). CONCLUSION: These results suggest that C4A treatment may reduce the risk of developing Alzheimer's dementia in elderly women. The potential preventive effect of C4A treatments, including EGb 761, requires further examination. To establish a causal relationship, these findings have to be confirmed with prospective studies.