|Year : 2002 | Volume
| Issue : 1 | Page : 1
|Date of Web Publication||22-Jun-2010|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Cardiovascular News. Heart Views 2002;3:1
Combination therapy with oral sildenafil and inhaled iloporost effective for severe pulmonary hypertension
The investigators evaluated the safety and effectiveness of sildenafil (Viagra), alone and in combination with inhaled iloprost, for treatment of pulmonary hypertension. 30 patients with severe pulmonary arterial hypertension (n = 16), chronic thromboembolic pulmonary hypertension (n = 13), or pulmonary hypertension due to aplasia of the left pulmonary artery (n = 1), all classified as New York Heart Association class III or IV were then randomized to receive 12.5 mg of oral sildenafil, 50 mg of sildenafil, 12.5 mg of sildenafil plus inhaled iloprost, or 50 mg of sildenafil plus inhaled iloprost.
The study showed in rank order of pulmonary vasodilatory potency (maximum reduction of pulmonary vascular resistance and increase in cardiac index), 50 mg of sildenafil plus iloprost was most effective, followed by 12.5 mg of sildenafil plus iloprost. Iloprost alone and 50 mg of sildenafil were almost equally effective but were less potent than the combination regimens. In patients who received 50 mg of sildenafil plus iloprost, the maximum change in pulmonary vasodilatory potency was -44.2% (95% CI, -49.5% to -38.8%). compared with -14.1% (CI, -19.1% to -9.2%) in response to nitric oxide.
Although limited by the small sample and lack of long-term data, the study concluded that oral sildenafil is a potent pulmonary vasodilator that acts synergistically with inhaled iloprost to cause strong pulmonary vasodilatation in both severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Furthermore, this combination therapy may become a novel approach for the treatment of pulmonary hypertension.
Bosentan beneficial in pulmonary arterial hypertension
Bostenthan is an orally administered dual endothelin-receptor antagonist that was shown in a preliminary study to improve exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary arterial hypertension. Ribin et al investigated the effect of bosentan on exercise capacity in a large number of patients and compared two doses.
In a double-blind, placebo-controlled study, 213 patients with pulmonary arterial hypertension (primary or associated with connective-tissue disease) were randomly assigned to receive placebo or 62.5 mg of bosentan twice daily for 4 weeks followed by either of two doses of bosentan (125 or 250 mg twice daily) for a minimum of 12 weeks. The primary end point of the study was the degree of change in exercise capacity. Secondary end points included the change in the Borg dyspnea index, the change in the World Health Organization (WHO) functional class, and the time to clinical worsening. At week 16, patients treated with bosentan had an improved six-minute walking distance; the mean difference between the placebo group and the combined bosentan groups was 44 m (95 percent confidence interval, 21 to 67; P<0.001). Bosentan also improved the Borg dyspnea index and WHO functional class and increased the time to clinical worsening.
The study comcluded that bosentan is beneficial in patients with pulmonary arterial hypertension and is well tolerated at a dose of 125 mg twice daily. Endothelin-receptor antagonism with oral bosentan is an effective approach to therapy for pulmonary arterial hypertension.
Blood Levels of Long-Chain n-3 Fatty Acids and the Risk of Sudden Death
Experimental data suggest that long-chain n-3 polyunsaturated fatty acids found in fish have antiarrhythmic properties, and a randomized trial suggested that dietary supplements of n-3 fatty acids may reduce the risk of sudden death among survivors of myocardial infarction. Whether long-chain n-3 fatty acids are also associated with the risk of sudden death in those without a history of cardiovascular disease is unknown.
Albert and colleagues conducted a prospective, nested case-control analysis among apparently healthy men who were followed for up to 17 years in the Physicians' Health Study. The fatty-acid composition of previously collected blood was analyzed by gas-liquid chromatography for 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls matched with them for age and smoking status.
The study found that baseline blood levels of long-chain n-3 fatty acids were inversely related to the risk of sudden death both before adjustment for potential confounders (P for trend = 0.004) and after such adjustment (P for trend = 0.007). As compared with men whose blood levels of long-chain n-3 fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men with levels in the third quartile (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence interval, 0.05 to 0.71).
The study concludes that n-3 fatty acids found in fish are strongly associated with a reduced risk of sudden death among men without evidence of prior cardiovascular disease.
Paclitaxel Derivate-Eluting Polymer Stent System Implantation for In-Stent Restenosis: Clinical and Angiographic Outcome
It has been shown that antiproliferative drugs such as paclitaxel lower the amount of intimal hyperplasia after stent implantation in de-novo lesions. Whether they are also beneficial in in-stent restenosis is unknown. 15 consecutive patients with elective indication to percutaneous coronary intervention for in-stent restenosis were treated with the QuaDS-QP2 stent implantation. At 6 months, 3 patients had target lesion revascularization (20%). Two patients had restenosis (13.3%); one experienced restenosis in a gap between 2 drug-eluting stents, and the other had stent occlusion leading to NQWMI. At 12 months, 1 patient suffered from NQWMI, and 8 of 13 patients (61.5%) had angiographic restenosis (late loss=1.36±0.94 mm with a loss index=0.62±0.44).
The study concluded that this first experience with QuaDS-QP2 stent implantation for in-stent restenosis revealed minimal intimal hyperplasia at the 6-month follow-up. However, the antiproliferative effect was not maintained at the 12-month follow-up, resulting in delayed occurrence of angiographic restenosis.
Dairy consumption, obesity, and the insulin resistance syndrome in young adults. The CARDIA study.
Using the prospective, multicenter Coronary Artery Risk Development In Young Adults (CARDIA) study, investigators examined the 10-year cumulative incidence of insulin resistance syndrome (IRS) relative to dairy consumption as estimated by diet history interviews.
A total of 3157 black and white adults between the ages of 18 and 30 at baseline were included in the study and followed for an average of 10 years. Pereira and colleagues report that milk and milk drinks were the most commonly consumed dairy products, followed by butter, cream, and cheeses. Generally, whites were more likely to consume more dairy products than blacks, and women consumed more dairy than men. When dairy consumption was used to stratify study participants, the authors found that overweight people who ate 35 or more servings of dairy products per week were 72% less likely to develop IRS than people who ate less than 10 servings of dairy products per week. Of note, the inverse association between dairy intake and IRS was observed in overweight, but not leaner, participants. Fiber and protein intake were also associated with IRS, although neither confounded the association between dairy and IRS. The authors also noted inverse associations between dairy consumption and development of obesity, abnormal glucose homeostasis, elevated blood pressure, and dyslipidemia in overweight young adults, regardless of race.
The study demonstrated that young, overweight adults who consume high amounts of dairy products have a reduced risk of developing insulin resistance syndrome (IRS), a precursor to type 2 diabetes and cardiovascular disease (CVD) . Pereira et al point out that just as rates of diabetes and CVD have escalated over the past 3 decades, dairy consumption has declined, particularly in young people who now turn to sugary soft drinks rather than a glass of milk. While factors such as smoking and low physical activity are known to promote insulin resistance, the impact of diet is poorly understood.
Role of prostacylin in the cardiovascular response to thromboxane A2.
Recently Mukherjee D et al analyzed the risk cardiovascular events associated with selective COX-2 inhibitors , by reviewing data from the two major trials VIGOR and CLASS and demonstrated significantly higher risk of myocardial infarction when compared to placebo.
The study of Cheng et al, in mice could help shed light on why COX-2 inhibitors might increase the risk of thrombotic events . COX-1, the form of cyclooxygenase found in platelets, makes TxA2, which causes blood vessels to constrict and platelets aggregate - an early step in clot formation. COX-2, by contrast, is expressed in blood vessels and is a major source of PGI2, which dilates blood vessels and prevents the activation of platelets.
The investigators inflicted injury on the carotid artery with a catheter in animals bred to lack receptors for PGI2. They showed that both the vascular response and the corresponding activation of platelets were both markedly exaggerated. Similarly, mice that over expressed receptors for TxA2 also produced these exaggerated effects. The effect was diminished when researchers either deleted the TxA2 receptor or blocked the receptor using an experimental drug. When the researchers deleted both the TxA2 receptor and the PGI2 receptor, it cancelled out the effect of inactivating the PGI2 receptor alone.
Compiled by: Dr. Jassim Al Suwaidi
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