Month: November 2011

A Prospective, Randomized Trial of Transapical Transcatheter Aortic Valve Implantation (TAVI) vs. Surgical Aortic Valve Replacement (AVR) in Operable Elderly Patients With Aortic Stenosis (The STACCATO trial). This study was sponsored by the Danish Heart Foundation and was presented this year (2011).

This trial sought to compare outcomes after trans-apical trans-catheter Aortic Valve Implantation (TAVI) as compared with surgical aortic valve replacement (AVR) in elderly patients with severe aortic stenosis who were otherwise not at an elevated risk for undergoing surgical AVR.                                                                                                                                                                            The investigators planned to enroll 200 patients, but the Data Safety and Monitoring Board terminated the trial early after enrollment of 70 patients. Of these 70 patients, 34 underwent transapical TAVI and 36 underwent surgical AVR. Baseline characteristics were fairly similar between the two arms.  About one half of the patients (52%) were significantly symptomatic (New York Heart Association [NYHA] class III/IV). The mean aortic valve area was 0.7 cm².
The primary endpoint of all-cause mortality, stroke, or renal failure requiring dialysis was significantly higher  in the transapical TAVI arm as compared with the surgical AVR arm (14.7% vs. 2.8%).                                                                                                                                                                                                                                                                                                                                                                There was a higher incidence of death (8.8% vs. 0%) and stroke (5.9% vs. 2.8%).   Other significant events at 3 months were also higher in the transapical TAVI arm (23.5% vs. 5.6%).          Both aortic valve area and peak aortic valve gradient were significantly improved in both arms at follow-up, with no difference between the two arms.
The incidence of paravalvular aortic regurgitation was significantly higher in the transapical TAVI arm (moderate/severe: 13% vs. 0%; minimal: 43% vs. 6%; p < 0.001).   The incidence of permanent pacemaker implantation was 5.8% vs. 2.7%, p = 0.52, and mean hospital stay was 8.8 vs. 7.6 days, p = 0.32.

The results of this small trial indicate that transapical TAVI is not superior to surgical AVR in elderly patients with severe aortic stenosis who are otherwise candidates for surgical AVR; outcomes including mortality and strokes were all elevated in the transapical arm at 30 days and at 3 months.
These results suggest that transapical TAVI (in its current stage of development) use should be restricted to patients who are at high risk for surgical AVR.

Reference: A Prospective, Randomized Trial of Transapical Transcatheter Aortic Valve Implantation vs. Surgical Aortic Valve Replacement in Operable Elderly Patients With Aortic Stenosis: Presented by Dr. Leif Thuesen at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2011), San Francisco, CA, November 10, 2011.

The US FDA has issued a safety communication and updated the prescribing information for the cholesterol-lowering agent fenofibric acid (Trilipix, Abbott), stating that the drug may not lower the risk of major cardiovascular events. This is based on data from the ACCORD Lipid trial, in which the combination of fenofibrate plus simvastatin was compared with simvastatin alone in patients with type 2 diabetes mellitus.

Fenofibrate was approved in 2008 to be used with a statin to reduce triglycerides and increase HDL cholesterol in diabetic patients with mixed dyslipidemia and coronary disease or at risk of coronary disease who are already on optimal statin therapy to achieve their LDL-cholesterol goal.

Over nearly five years of follow-up in ACCORD trial, the composite of fatal cardiovascular events, nonfatal myocardial infarction (MI), and nonfatal stroke was around 11% in both patients randomized to simvastatin plus fenofibrate and patients randomized to simvastatin plus placebo. However, there was a strong trend toward fewer cardiac events in patients with high triglycerides and low HDL cholesterol treated with fenofibrate. In the current safety communication, the FDA refers to this result as “hypothesis raising” and needing confirmation by another trial.

The FDA has reviewed this trial as part of its ongoing investigation of the safety and efficacy of fenofibric acid. The agency notes that its review found that there was no significant difference in the risk of experiencing a major adverse cardiac event between the fenofibrate/simvastatin group and the simvastatin-alone group in the trial. In addition, a subgroup analysis showed that relative to treatment in men, there was an increase in the risk for major adverse cardiac events in women receiving the combination therapy vs simvastatin alone. But it adds that the clinical significance of this subgroup finding is unclear.

Based on these results and other clinical trials of similar drugs, the FDA says it has requested Abbott to conduct a clinical trial to evaluate the cardiovascular effects of fenofibric acid in patients at high risk for cardiovascular disease who are already taking statins.

These results from the trial have been added to the product label and to the patient medication guide. The agency says: “Healthcare professionals should consider the benefits and risks of Trilipix when deciding to prescribe the drug.”

Source: heart.org

According to a new study by Hermida, R.C. et al (from University of Vigo, Spain), published on October 24, 2011 in the Journal of the American Society of Nephrology,  among patients with chronic kidney disease (CKD) and hypertension, taking at least one antihypertensive medication at bedtime significantly improves blood-pressure (BP) control, with an associated decrease in risk for cardiovascular events.

The study included 661 patients with CKD who were randomly assigned either to take all prescribed hypertension medications on awakening or to take at least one of them at bedtime. Ambulatory BP at 48 hours was measured at least once a year and/or at three months after any adjustment in treatment.

The composite measure of cardiovascular events used included death, MI, angina pectoris, revascularization, heart failure, arterial occlusion of lower extremities, occlusion of the retinal artery, and stroke.

Patients were followed for a median of 5.4 years; during that time, patients who took at least one BP-lowering medication at bedtime had approximately one-third the CVD risk as those who took all medications on awakening .

A similar significant reduction in risk with bedtime dosing was noted when the composite CVD outcome included only cardiovascular death, MI, and stroke.

Patients taking their medications at bedtime also had a significantly lower mean BP while sleeping, and a greater proportion of these patients had ambulatory BP control.

The researchers estimate that for each 5-mm-Hg decrease in mean sleep-time systolic BP, there was a 14% reduction in the risk for cardiovascular events during follow-up.

According the authors of this study: Treatment at bedtime is the most cost-effective and simplest strategy of successfully achieving the therapeutic goals of adequate asleep BP reduction and preserving or reestablishing the normal 24-hour BP-dipping pattern.

Reference:      Hermida RC, Ayala DE, Mojón A, Fernández JR. Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol 2011; DOI:10.1681/ASN.2011040361.