Randomized controlled trials cardiovascular disease

Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty acids in coronary heart disease a meta-analysis of randomized controlled trials. Am. J. Med. 2002 112 298-304. Psota TL, Gebauer SK, Kris-Eflierton P, Dietary omega-3 fatty acid intake and cardiovascular risk. Am. J. Cardiol. 2006 98(suppl) 3i-18i. 

The respiratory and cardiovascular adverse effects of topical therapy with timolol or betaxolol have been studied in a randomized, controlled trial in 40 elderly patients with glaucoma (83). Five of the 20 allocated to timolol discontinued treatment for respiratory reasons, compared with three of the 20 patients allocated to betaxolol There were no significant differences in mean values of spirometry, pulse, or blood pressure between the groups. This study confirms that beta-blockers administered as eye-drops can reach the systemic circulation and that serious adverse respiratory events can occur in elderly people, even if they are screened before treatment for cardiac and respiratory disease. These events can occur using either the selective betaxolol agent or the non-selective timolol. 

ADAPT Research Group. Cardiovascular and Cerebrovascular Events in the Randomized, Controlled Alzheimer s Disease Anti-Inflammatory Prevention Trial (ADAPT). WWW Plosclinicaltrials org 2007 e33 001-010. 

Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer — The Women s Health Study a randomized controlled trial. JAMA. 2005 294(l) 56-65. 

Macready AL, George TW, Chong MF, et al. Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease—FLAVURS a randomized controlled trial. Am J Clin Nutr. 2014 99(3) 479—489. 

B vitamin intake or vitamin blood concentrations have also been related to various cancers. The cancer types that have been best investigated with respeet to folic acid are colon cancer and colorectal cancer. Convincing evidence from observational studies led to the initiation of randomized controlled trials with folic acid in colorectal adenomas. However, similar to cardiovascular disease, there seems to be a discrepancy between the observational epidemiological studies that reported in the majority an inverse association of folate and cancer risk, and the effect of folic acid supplementation in the randomized controlled trials, which reported no effect of folic add on recurrence of colorectal adenoma risk. 

Heinz, J., Kropf, S., Domrose, U., Westphal, S., Borucki, K., Luley, C., Neumann, K.H., and Dierkes, J., 2010. B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease results of a randomized controlled trial. Circulation. 121 1432-1438. 

Experiments in animals have found that proliferation of vascular smooth muscle cells can be inhibited by calcitriol administration (Mitsuhashi et al. 1991). An over-active renin-angiotensin system (RAS) can impair renal function and deteriorate cardiovascular health (Li 2012), and down-regulation of RAS activity is one of the key mechanisms proposed for calcitriol (Li et al. 2002). Evidence to support this mechanism has been primarily obtained from animal experiments for example, treatment with calcitriol has been shown to down-regulate RAS and to improve cardiac function in la-hydroxylase knockout mice (Zhou et al. 2008), and in salt-sensitive rats with cardiac hypertrophy (Bae et al. 2011, Choi et al. 2011). However, a recent randomized controlled trial in patients with chronic kidney disease did not find improvements in left ventricular mass index or diastolic function by treatment with paricalcitol (active vitamin D analogue) (Thadhani et al. 2012). 

Cardiovascular The effects of calcium supplementation on vascular disease have been studied in a large, randomized, controlled trial in healthy postmenopausal women over 5 years [18 ]. There was a substantial increase in rates of vascular events, particularly myocardial infarction, in women who were randomized to calcium. These effects were more marked in those who were highly compliant with treatment. Calcium supplementation also appears to accelerate vascular disease in patients with renal impairment, including those not yet requiring hemodialysis. 

Cardiovascular In a systematic review of deaths in 12 randomized controlled trials of fish oil as dietary supplements in 32 779 patients there was no beneficial effect in three studies ( = 1148) of implantable cardiac defibrillators (OR = 0.90 95% Cl = 0.55, 1.46) or in six studies (n = 31 111) of sudden cardiac death (OR = 0.81 0.52,1.25). In 11 studies (n = 32 439 and n = 32 519) there was a reduction in deaths from cardiac causes (OR = 0.80 0.69,0.92) but no effect on dysrhythmias or all-cause mortahty [21 ]. However, it was later pointed out that there is some evidence that fish oils may be dysrhyth-mogenic in some subgroups of patients with heart disease 22f. These include an increased risk of ventricular tachycardia in patients with implantable cardiovertor defibrillators whose primary dysrhythmia was ventricular tachycardia [23 ], and an increased risk of cardiac death in patients with angina [24 ]. 

In three other meta-analyses that combined the results of randomized controlled trials for prevention or treatment of cardiovascular disease [82-84], no significant effect of daily vitamin E dietary supplementation up to 800IU/day (727mg/day of synthetic a-tocopherol) on cardiovascular deaths was found up to 6.3 years (400IU/day). 

Data on the effect of calcium antagonists on cardiovascular disease risks in patients with hypertension are available from one moderate-to-large scale randomized, placebo-controlled trial. In the Systolic Hypertension in Europe (Syst-Eur) trial, nitrendipine-based therapy produced an approximate 10/5 mmHg reduction in SBP-DBP in patients with systolic hypertension and a 42% reduction in the risk of stroke. Similar results were observed in two large, nonrandomized, placebo-controlled trials (with alternate treatment assignment), i.e. the Shanghai Trial of Nifedipine in the Elderly and the Systolic Hypertension in China (Syst-China) trial. 

In 534 individuals aged 30 years, whose mothers had participated in a double-blind, randomized, placebo-controlled trial of antenatal betamethasone (two intramuscular doses 24 hours apart) for the prevention of neonatal respiratory distress syndrome, there were no differences between those exposed to betamethasone and placebo in body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, or history of cardiovascular disease (397). After the oral glucose tolerance test, those who had been exposed to betamethasone had higher plasma insulin concentrations at 30 minutes (61 versus 52 mIU/1) and lower glucose concentrations at 120 minutes (4.8 versus 5.1 mmol/1) than did those exposed to placebo. Antenatal exposure to betamethasone might result in insulin resistance in adult offspring, but has no effect on cardiovascular risk factors at 30 years of age. 

Sildenafil was the first oral treatment for ED and is the most extensively evaluated (35). Overall success rates in patients with cardiovascular disease of 80% or greater have been recorded with no evidence of tolerance, Patients with diabetes with or without additional risk factors, with their more complex, and extensive pathophysiology, have an average success rate of 60%. In randomized trials to date, open-label or outpatient monitoring studies the use of sildenafil is not associated with any excess risk of myocardial infarction, stroke, or mortality (38-40), In patients with stable angina pectoris there is no evidence of an ischemic effect due to coronary steal, and in one large, double-blind, placebo-controlled, exercise study sildenafil 100 mg increased exercise time and diminished ischemia (41), A study of the hemodynamic effects in men with severe CAD identified no adverse cardiovascular effects and a potentially beneficial effect on coronary blood flow reserve (42), Studies in patients with and without diabetes have demonstrated improved endothelial function acutely and after long-term oral dose administration, which may have implications beyond... 

Jenkins, D.J. et al., Soluble fiber intake at a dose approved by the US Food and Drug Administration for a claim of health benefits serum lipid risk factors for cardiovascular disease assessed in a randomized controlled crossover trial, Am. J. Clin. Nutr., 75, 834, 2002. 

The Alzheimer s Disease Anti-inflammatory Prevention Trial (ADAPT) was another well designed quality chnical study that point toward increase risk of cardiovascular disease associated with the long term use of naproxen compared to placebo group. [153] ADAPT was a randomized, parallel, placebo-control-led, multicenter trial intended to study the efficacy of a naproxen (220 mg po twice a day) and celecoxib (200 mg po twice a day) vs. placebo. A total of 2, 625 dementia-free patients over age of 70 years were enrolled.. These data showed an apparent increase in cardiovascular and cerebrovascular events among... 

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