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Year : 2007  |  Volume : 8  |  Issue : 2  |  Page : 32-33 Table of Contents     

Cardiovascular News

Date of Web Publication17-Jun-2010

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How to cite this article:
. Cardiovascular News. Heart Views 2007;8:32-3

How to cite this URL:
. Cardiovascular News. Heart Views [serial online] 2007 [cited 2023 Jun 7];8:32-3. Available from: https://www.heartviews.org/text.asp?2007/8/2/32/64199

Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of randomized trials

Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence is mixed regarding the influence of medications of this class on cardiovascular outcomes. Investigators sought to systematically evaluate the effect of pioglitazone on ischemic cardiovascular events. A database containing individual patient-level time-to-event data collected during pioglitazone clinical trials was transferred from the drug's manufacturer for independent analysis. Trials were included if they were randomized, double-blinded, and controlled with placebo or active comparator.

The primary outcome was a composite of death, myocardial infarction, or stroke. Secondary outcome measures included the incidence of serious heart failure. A fixed-effects approach was used to combine the estimates across the duration strata and statistical heterogeneity across all the trials was tested with the I2 statistic. A total of 19 trials enrolling 16,390 patients were analyzed. Study drug treatment duration ranged from 4 months to 3.5 years. Death, myocardial infarction, or stroke occurred in 375 of 8554 patients (4.4%) receiving pioglitazone and 450 of 7836 patients (5.7%) receiving control therapy (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.72-0.94;P = .005).

Progressive separation of time-to-event curves became apparent after approximately 1 year of therapy. Individual components of the primary end point were all reduced by a similar magnitude with pioglitazone treatment, with HRs ranging from 0.80 to 0.92. Serious heart failure was reported in 200 (2.3%) of the pioglitazone-treated patients and 139 (1.8%) of the control patients (HR, 1.41; 95% CI, 1.14-1.76; P = .002). The magnitude and direction of the favorable effect of pioglitazone on ischemic events and unfavorable effect on heart failure was homogeneous across trials of different durations, for different comparators, and for patients with or without established vascular disease. There was no evidence of heterogeneity across the trials for either end point (I2 = 0%; P = .87 for the composite end point and I2 = 0%; P = .97 for heart failure).

Pioglitazone is associated with a significantly lower risk of death, myocardial infarction, or stroke among a diverse population of patients with diabetes. Serious heart failure is increased by pioglitazone, although without an associated increase in mortality.

Statin treatment in children with familial hypercholesterolemia: The younger, the better

In a previous randomized placebo-controlled trial, investigators demonstrated that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. The investigators continued to follow up these children to explore the relation between the age of statin initiation and carotid IMT after follow-up on statin treatment. They also examined safety aspects of statin therapy during this long-term follow-up.

All 214 children who initially participated in the previous placebo-controlled study were eligible for the follow-up study. After completion of the placebo-controlled study, all children continued treatment with pravastatin 20 or 40 mg, depending on their age. Blood samples were taken on a regular basis for lipids and safety parameters, and a carotid IMT measurement was performed after an average treatment period of 4.5 years. Follow-up data for 186 children were available for the statistical analyses. Multivariate analyses revealed that age at statin initiation was an independent predictor for carotid IMT after follow-up with adjustment for carotid IMT at initiation of statin treatment, sex, and duration of treatment. Early initiation of statin treatment was associated with a subsequently smaller IMT. Furthermore, no serious laboratory adverse events were reported during follow-up, and statin treatment had no untoward effects on sexual maturation.

These data indicate that early initiation of statin treatment delays the progression of carotid IMT in adolescents and young adults. The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might be beneficial in the prevention of atherosclerosis in adolescence.

Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease

Exposure to air pollution from traffic is associated with adverse cardiovascular events. The mechanisms for this association are unknown. Investigators conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial, vascular, and fibrinolytic function.

In a double-blind, randomized, crossover study, 20 men with prior myocardial infarction were exposed, in two separate sessions, to dilute diesel exhaust (300 mug per cubic meter) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility. During the exposure, myocardial ischemia was quantified by ST-segment analysis using continuous 12-lead electrocardiography. Six hours after exposure, vasomotor and fibrinolytic function were assessed by means of intraarterial agonist infusions.

During both exposure sessions, the heart rate increased with exercise (P < 0.001); the increase was similar during exposure to diesel exhaust and exposure to filtered air (P = 0.67). Exercise-induced ST-segment depression was present in all patients, but there was a greater increase in the ischemic burden during exposure to diesel exhaust (-22 ΁ 4 vs -8 ΁ 6 millivolt seconds, P<0.001). Exposure to diesel exhaust did not aggravate preexisting vasomotor dysfunction, but it did reduce the acute release of endothelial tissue plasminogen activator (P=0.009; 35% decrease in the area under the curve).

Brief exposure to dilute diesel exhaust promotes myocardial ischemia and inhibits endogenous fibrinolytic capacity in men with stable coronary heart disease. The study findings point to ischemic and thrombotic mechanisms that may explain in part the observation that exposure to combustion-derived air pollution is associated with adverse cardiovascular events.

Prevalence of rheumatic heart disease detected by echocardiographic screening

Epidemiologic studies of the prevalence of rheumatic heart disease have used clinical screening with echocardiographic confirmation of suspected cases. Investigators hypothesized that echocardiographic screening of all surveyed children would show a significantly higher prevalence of rheumatic heart disease.

Randomly selected schoolchildren from 6 through 17 years of age in Cambodia and Mozambique were screened for rheumatic heart disease according to standard clinical and echocardiographic criteria. Clinical examination detected rheumatic heart disease that was confirmed by echocardiography in 8 of 3677 children in Cambodia and 5 of 2170 children in Mozambique; the corresponding prevalence rates and 95% confidence intervals (CIs) were 2.2 cases per 1000 (95% CI, 0.7 to 3.7) for Cambodia and 2.3 cases per 1000 (95% CI, 0.3 to 4.3) for Mozambique. In contrast, echocardiographic screening detected 79 cases of rheumatic heart disease in Cambodia and 66 cases in Mozambique, corresponding to prevalence rates of 21.5 cases per 1000 (95% CI, 16.8 to 26.2) and 30.4 cases per 1000 (95% CI, 23.2 to 37.6), respectively. The mitral valve was involved in the great majority of cases (87.3% in Cambodia and 98.4% in Mozambique).

Systematic screening with echocardiography, as compared with clinical screening, reveals a much higher prevalence of rheumatic heart disease (approximately 10 times as great). Since rheumatic heart disease frequently has devastating clinical consequences and secondary prevention may be effective after accurate identification of early cases, these results have important public health implications.


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