MORE CHALLENGES, MORE INSIGHTS Another Dip into ACC.17 BEFORE WE GO THIS MONTH, WE LEAVE YOU WITH A LOOK AT FIVE MORE TRIALS PRESENTED AT ACC.17. GEMINI-ACS 1: Generates Hypotheses Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor remains the antithrombotic mainstay for patients with an acute coronary syndrome (ACS), regardless of treatment strategy. In previous studies evaluating the addition of an oral anticoagulant (OAC) to antiplatelet therapy in ACS patients (WARIS II and ATLAS ACS-TIMI 51), superior efficacy was offset by a significantly greater risk of major bleeding. In addition, recent trials (WOEST and PIONEERAF- PCI) comparing dual versus triple antithrombotic treatment regimens in patients with atrial fibrillation (AFib) undergoing PCI now provide support for withholding aspirin, favoring the combination of a P2Y12 inhibitor and an OAC. Building on these findings, the phase II GEMINI-ACS-1 trial presented at ACC.17 was designed to evaluate the safety of adding aspirin (100 mg daily) versus low-dose rivaroxaban (2.5 mg twice daily) to those already on a P2Y12 inhibitor for an ACS (56 percent received ticagrelor and 44 percent clopidogrel, as selected by the investigator). The study of 3,037 patients was conducted at 371 sites in 21 countries (with 77 percent of patients enrolled in Europe) between April 2015 and October 2016. Initiation of the study regimen one to 10 days after the index event was associated with no significant difference in the primary endpoint of TIMI non–CABG clinically significant bleeding (5.3 percent for rivaroxaban vs. 4.9 percent for aspirin; p = 0.58). The median duration of treatment was 291 days. TIMI bleeding requiring medical attention was the most common type of bleeding that occurred in the study, at 4 percent in each group. No significant differences were observed for other key secondary bleeding endpoints. Rates of ischemic events were similar in both groups; however, the study was not powered to independently assess them. The results of the GEMINI-ACS-1 trial add to the growing body of evidence supporting the safety of dual antithrombotic therapy using a P2Y12 inhibitor and an OAC. “Absent another indication for an anticoagulant (i.e., Afib), it is still premature, however, to abandon the standard practice of DAPT in this population,” says Ty Gluckman, MD, FACC. This phase II study has generated hypotheses that would need to be tested in an adequately powered phase III study, he adds, although whether one will be conducted isn’t currently known. “One unanswered question is whether a dual antithrombotic regimen that included rivaroxaban would be cost effective, if a phase III study achieved similar results with comparable efficacy and safety,” says Gluckman. Another question is what patient population, beyond those with Afib in need of PCI, might benefit preferentially from a dual antithrombotic regimen that includes a P2Y12 inhibitor and an OAC. One unanswered question is whether a dual antithrombotic regimen that included rivaroxaban would be cost effective, if a phase III study achieved similar results with comparable efficacy and safety. Ty Gluckman, MD, FACC EINSTEIN CHOICE: Treatment of VTE Extended treatment with low-dose rivaroxaban provided nearly a three-fold greater reduction in recurrent venous thromboembolism (VTE) than aspirin with a similar rate of bleeding in patients who had completed six to 12 months of anticoagulation in the EINSTEIN CHOICE study. It is the first study to directly compare low-dose rivaroxaban and aspirin (100 mg) in this population in whom there is equipoise regarding the benefit of continued therapy. The international multicenter study enrolled 3,396 patients. After a median follow-up of 351 days, compared with aspirin (4.4 percent), there was a significant reduction in symptomatic fatal or non-fatal recurrent VTE, with rivaroxaban 10 mg and 20 mg (1. 2 percent and 1.5 percent, respectively; p < 0.001). There was no statistically significant difference in the rates of bleeding between the three treatment groups, which occurred in 0.4 percent of the rivaroxaban 10 mg group, 0.5 percent of the rivaroxaban 20 mg group and 0.3 percent of the aspirin group. There were no differences between groups for any of the secondary efficacy or safety endpoints. In patients who suffered a provoked VTE, the rate of a recurrent VTE was lower with both doses of rivaroxaban (0.9 percent and 1.4 percent for the 10 and 20 mg doses) versus aspirin (3.6 percent). The number needed to treat to prevent one VTE was 30 with the 10 mg dose of rivaroxaban and 33 with the 20 mg dose of rivaroxaban. “Combining the results from the EINSTEIN CHOICE and the AMPLIFY EXT studies, the data are convincing now that extending the duration of treatment with rivaroxaban or apixaban can reduce the risk of recurrent VTE without drastically increasing the risk of bleeding,” says Salim Virani, MD, FACC. Another important observation is that even lower doses of these medications are effective. “Furthermore, these benefits are seen in patients with both provoked and unprovoked VTE,” notes Virani. Combining the results from the EINSTEIN CHOICE and the AMPLIFY EXT studies, the data are convincing now that extending the duration of treatment with rivaroxaban or apixaban can reduce the risk of recurrent VTE without drastically increasing the risk of bleeding. Salim Virani, MD, FACC Screen to Prevent (S2P): Study For Sports Participation The single-center S2P study has shown that a protocol consisting of a questionnaire, resting electrocardiogram (ECG), and a screening MRI could be a cost-effective approach to prevent sudden cardiac death (SCD) in young athletes, according to results presented by Paolo E. Angelini, MD. In the U.S., a basic history and physical remains the predominant screening approach for student athletes, thus the “exact incidence of SCD in population-based studies is not available,” said Angelini. He stated that a list of high-risk cardiovascular conditions (hr-CVC) has not been well defined. In the S2P study, Angelini and colleagues employed their screening protocol in 5,255 youth ages 11-14 (average age 13 years; 32 percent white, 23 percent black and 19 percent Hispanic) between 2010 and 2017 at the Texas Heart Institute in Houston. They found that symptoms identified in the history and physical and on ECG did not correlate with any hr-CVC and alone were insufficient to identify structural hr-CVCs and their severity. On MRI screening, the most frequent abnormality was an ECG defect, found in 40 individuals, followed by anomalous origin of the right coronary artery in 23 individuals, and cardiomyopathy in 15 (12 of whom had dilated cardiomyopathy). The investigators also performed quantitative MRI in 1,159 of the participants to help establish parameters for left ventricular mass and left ventricular end-diastolic volume. The investigators state these data support the use of this protocol to derive prevalence data in the general population, rather than in the SCD population, that can then be used to screen youth for sports or other strenuous activities. “It is safe, accurate, comfortable and likely cost-effective” in high-risk populations to identify those at risk for SCD, Angelini said. The S2P study provides a first step in defining “high risk” by using prevalence data. Further research is needed to explore its potential to prevent SCD in young athletes. RESET-HCM: Exploratory Study of Exercise Training The appropriate amount of exercise for patients with hypertrophic cardiomyopathy (HCM) remains a persistent question. Some concerns are whether exercise could trigger ventricular arrhythmias or induce remodeling. Guideline recommendations continue to be based on expert consensus because of the lack of objective data. The RESET-HCM study has demonstrated that moderate-intensity aerobic training was safe and effective in patients with HCM, according to results presented by Sara Saberi, MD, MS, in a Featured Clinical Research presentation. The 57 patients randomized to the exercise training group had an increase in the primary endpoint of exercise capacity at 16 weeks compared with the 56 patients in the usual activity group – a mean increase of 1.35 ml/ kg/min versus 0.08 ml/kg/min from the mean peak VO2 at baseline of 22 ml/ kg/min (p = 0.02). The patients in the study were ages 18-80 years, with a mean age of 50, and 42 percent were women. Their history included obstructive HCM in 17 percent, implantable cardioverter-defibrillator (ICD) in 34 percent and sustained ventricular tachycardia or aborted sudden cardiac death in 4 percent. The study period was 2010 to 2015. In the exercise training group, patients were given a one-hour consultation with a certified exercise physiologist, a tailored exercise program (including cycling, walking, jogging, swimming or using an elliptical trainer) to perform at home and instruction to increase their duration of exercise. In the first week, they were to exercise 20 minutes three times a week at 60 percent of their heart-rate reserve (calculated by their baseline cardiopulmonary exercise test) and a perceived moderate intensity. For weeks two to four, they were to increase the duration by 5-10 minutes a week, for a maximum of 60 minutes, and exercise four to seven times a week at 70% of their heart-rate reserve and a perceived moderate intensity. This level of exercise was to be maintained through week 16. In the usual activity group, the patients were instructed to continue with their current exercise practice. By 16 weeks, more patients in the exercise training group were exercising regularly, compared with before the study and against the usual activity group (93 percent vs. 28 percent). No differences were found between the groups for cardiac remodeling or quality of life, based on self-reported questionnaires, other than improvement related to physical function. No major adverse events occurred, including death, aborted sudden cardiac death, appropriate ICD shocks or sustained ventricular tachycardia. Exercise training was not associated with an increase in any non-fatal arrhythmias. They study, however, was not designed to establish long-term safety, stated the investigators. Further research is required to determine the clinical importance of the improvements in the primary and secondary outcomes in this study, as well as establishing the safety of moderate or higher levels of activity and any potential impact on disease progression. The RESET-HCM study has demonstrated that moderate-intensity aerobic training was safe and effective in patients with HCM. CVD-REAL: SGLT-2 Inhibitors and Heart Failure Treatment with a sodium glucose cotransporter-2 inhibitor (SGLT-2i) was associated with a marked reduction in hospitalization for heart failure (HHF) in new users when compared with treatment with other glucose-lowering drugs (oGLD), according to research presented by Mikhail Kosiborod, MD, FACC, in a Featured Clinical Research presentation. In a large, real-world study across six countries, non-parsimonious propensity scores for SGLT-2i initiation were used to match groups in which a broad population of patients with type 2 diabetes received either SGLT-2i or oGLD treatment. The incidence of HHF was collected via primary care and hospital records in the U.K. and Germany, medical claims and electronic health records in the U.S., and national registries in Sweden, Norway and Denmark. Hazard ratios for HHF were estimated by country and database and pooled in a meta-analysis. The study included 364,828 patients, evenly divided between each treatment group, with a mean age of 57 years and 44 percent were women. At baseline, 3 percent had HF, 13 percent established cardiovascular disease, and 27 percent had micro vascular disease. For the primary endpoint of HHF, there was a reduction that favored the SGLT-2i in each country. In total, there were 961 HHF during the study period, and the incidence was lower with the SGLT-2i (hazard ratio [HR], 0.61; p < 0.001). The SGLT-2i was also associated with a lower incidence of the secondary endpoint of all-cause death in each country and the total number was 1,334 (HR, 0.49; p < 0.001) and the secondary endpoint of HHF or all-cause death (1,983 events; HR,0. 54; p < 0.001). In the analysis, there were no signs of significant heterogeneity across the countries, despite the geographic variations in the patient groups receiving SGLT-2i treatment, suggesting the cardiovascular benefits observed are likely class-related, according to the investigators. The results of their analyses align with the findings of the EMPA-REG OUTCOME study, and they think the benefits observed with the SGLT-2i treatment will translate into real-world clinical practice and also may extend to patients with type 2 diabetes at the lower end of the cardiovascular risk spectrum.
Published by American College of Cardiology. View All Articles.
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