Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).
Background-Hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young, is characterized by cardiac hypertrophy, myocyte disarray, and interstitial fibrosis. We propose that hypertrophy and fibrosis are secondary to the activation of trophic and mitotic factors and, thus, potentially reversible. We determined whether the blockade of angiotensin II, a known cardiotrophic factor, could reverse or attenuate interstitial fibrosis in a transgenic mouse model of human HCM. Methods and Results-We randomized 24 adult cardiac troponin T (cTnT-Q 92 ) mice, which exhibit myocyte disarray and interstitial fibrosis, to treatment with losartan or placebo and included 12 nontransgenic mice as controls. The mean dose of losartan and the mean duration of therapy were 14.2Ϯ5.3 mg · kg -1 · d -1 and 42Ϯ9.6 days, respectively. Mean age, number of males and females, and heart/body weight ratio were similar in the groups. Collagen volume fraction and extent of myocyte disarray were increased in the cTnT-Q 92 mice (placebo group) compared with nontransgenic mice (9.9Ϯ6.8% versus 4.5Ϯ2.2%, Pϭ0.01, and 27.6Ϯ10.6% versus 3.9Ϯ2.3%, PϽ0.001, respectively). Treatment with losartan reduced collagen volume fraction by 49% to 4.9Ϯ2.9%. The expression of collagen 1␣ (I) and transforming growth factor-1, a mediator of angiotensin II profibrotic effect, were also reduced by 50%. Losartan had no effect on myocyte disarray. Conclusions-Treatment with losartan reversed interstitial fibrosis and the expression of collagen 1␣ (I) and transforming growth factor-1 in the hearts of cTnT-Q 92 mice. These findings suggest that losartan has the potential to reverse or attenuate interstitial fibrosis, a major predictor of sudden cardiac death, in human patients with HCM. Key Words: cardiomyopathy Ⅲ fibrosis Ⅲ collagen Ⅲ death, sudden H ypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death (SCD) in the young, 1 is caused by mutations in sarcomeric proteins. 2 It is clinically diagnosed by unexplained cardiac hypertrophy and pathologically by myocyte hypertrophy, disarray, and interstitial fibrosis. 3 Hypertrophy and fibrosis are the major determinants of mortality, morbidity, and SCD 4,5 in HCM and in all acquired forms of cardiac diseases.The genetic basis of HCM has been elucidated, and research efforts are being directed to decipher its molecular pathogenesis and to determine the reversibility of the phenotypes. We previously proposed that interstitial fibrosis, like cardiac hypertrophy, occurs "secondary" to the activation of trophic and mitotic factors in the heart 6 and, thus, is potentially reversible by blocking cardiotrophic factors such as angiotensin II (Ang II). However, despite the well-established role of Ang II blockers in the attenuation of cardiac hypertrophy and fibrosis in acquired cardiac diseases, they are not conventionally used in the treatment of patients with HCM, a genetic paradigm of cardiac hypertrophy and fibrosis. We determined the effects of blocking Ang II on the int...
Background-The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results-We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6-or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; Pϭ0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72-49.96; Pϭ0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60 -2.47; Pϭ0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42-7.03; Pϭ0.005) among diabetic patients. Conclusions-Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607. (Circulation. 2012;125:505-513.)
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