|Year : 2003 | Volume
| Issue : 2 | Page : 2
|Date of Web Publication||22-Jun-2010|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Cardiovascular News. Heart Views 2003;4:2
Are Lipid-Lowering Drugs Also Antiarrhythmic Drugs?
Randomized trials of lipid-lowering drugs suggest reduction of sudden death (SD) in patients with atherosclerotic heart disease (ASHD). Because SD is usually secondary to VT/VF, this observation suggests that lipid-lowering therapy has antiarrhythmic effects. To evaluate the antiarrhythmic effects of lipid-lowering drug therapy, investigators in Canada and Germany analyzed ventricular tachyarrhythmia (VT/VF) recurrences recorded by an implantable cardioverter defibrillator (ICD) in patients with atherosclerotic heart disease in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.
The probability of VT/VF recurrence in patients with ASHD treated with an ICD in the AVID trial who did not receive lipid-lowering drug therapy (n = 279) was compared with that in patients who received early and consistent lipid-lowering therapy (n = 83). In addition, all-cause mortality and cardiac mortality of all patients in the AVID trial with ASHD who did not receive lipid-lowering therapy (n = 564) were compared with that of those who received early and consistent lipid-lowering therapy (n =149).
Multivariate analysis showed that lipid-lowering therapy was associated with a reduction in the relative hazard for VT/VF recurrence of 0.40 (95% confidence interval [CI] 0.15 to 0.58) (adjusted p = 0.003) in the ICD subgroup. Lipid-lowering therapy was also associated with a reduction in the relative hazard for all-cause mortality of 0.36 (95% CI 0.15 to 0.68) (adjusted p = 0.03) and a reduction in the relative hazard for cardiac mortality of 0.39 (95% CI 0.16 to 0.78) (adjusted p = 0.04) in the larger study population.
The study concluded that in patients with ASHD who have received an ICD, lipid-lowering therapy is associated with reduction in the probability of VT/VF recurrence, suggesting that part of the benefit of lipid-lowering therapy may be due to an antiarrhythmic effect.
J Am Coll Cardiol 2003;42:81- 87
Sustained Reduction of Aldosterone in response to the angiotensin receptor blocker Valsartan in Patients With Chronic Heart Failure: Results FromVal-HeFT
Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker (ARB) on plasma aldosterone levels in patients with NYHA class II through IV heart failure.
Val-HeFT evaluated the efficacy of a high dose of the ARB valsartan in patients with moderate to severe HF followed up for an average of 23 months. In this large trial, several plasma neurohormones including aldosterone were measured at baseline and during follow-up.
Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150 ± 160 pg/mL, mean ± SD; n = 2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137 ± 124 pg/mL, mean ± SD; n = 2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8 ±3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8 ± 3.0 pg/mL (SEM) (-17.4%) in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor b-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs.
Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.
Benefits and risks of Abciximab use in primary angioplasty for acute myocardial infarction: CADILLAC Tril
Trials of platelet glycoprotein IIb/IIIa inhibitors as adjuncts to primary percutaneous coronary intervention for acute myocardial infarction (MI)have shown improved early clinical and angiographic outcomes with treatment. However, variations in trial designs, modest sample sizes, and limited long-term follow-up have precluded these studies from being definitive.
As a prespecified secondary analysis of The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial, we compared early and late outcomes by abciximab assignment among 2,082 patients randomized in an open-label, 2x2 factorial-design trial of primary stenting versus angioplasty and abciximab treatment (n=1052) versus no abciximab treatment (n =1030). Baseline characteristics were balanced between groups. Abciximab treatment was associated with a significant reduction in the composite end point of death, MI, ischemia-driven target-vessel revascularization (TVR), or disabling stroke at 30 days (4.6% versus 7.0%; relative risk, 0.65; 95% CI, 0.46 to 0.93; P=0.01). Subacute thrombosis also was significantly reduced with abciximab treatment. At 12 months, however, rates of the composite end point did not differ significantly (18.4% for controls versus 16.9% for abciximab-treated patients; relative risk, 0.92; 95% CI, 0.76 to 1.10; P=0.29), reflecting a decrease in the relative difference in TVR rates (ie, no effect of abciximab on reducing restenosis).
In an angiographic substudy (n=656), myocardial salvage, restenosis, and infarct-artery reocclusion at 7 months were unaffected by abciximab treatment. There was no significant interaction between stenting and abciximab treatment.
Adjunctive abciximab treatment during primary percutaneous coronary intervention significantly enhanced 30-day event-free survival, predominantly by reducing ischemia-driven TVR. Abciximab treatment did not affect the composite end point at 1 year, reflecting a lack of effect on restenosis.
Randomized Comparison of Percutaneous Transluminal Coronary Angioplasty and Medical Therapy in Stable Survivors of Acute Myocardial Infarction With Single Vessel Disease
Percutaneous transluminal coronary angioplasty of the infarct-related artery in stable survivors of acute myocardial infarction is often performed, even in patients without any symptoms or residual ischemia. Despite the lack of randomized studies, it is widely believed that this intervention will improve the clinical outcome of these patients.
Three hundred patients with single vessel disease of the infarct vessel and no or minor angina pectoris in the subacute phase (1 to 6 weeks) after an acute myocardial infarction were randomized to angioplasty (n=149) or medical therapy (n=151). Primary end point was the survival free of reinfarction, (re)intervention, coronary artery bypass surgery, or readmission for severe angina pectoris at 1 year. The event-free survival at 1 year was 82% in the medical group and 90% in the angioplasty group (P=0.06). This difference was mainly driven by the difference in the need for (re)interventions (20 versus 8, P=0.03). At long-term follow-up (mean, 56 months), survival was 89% and 96% (P=0.02). Survival free of reinfarction, (re)intervention, or coronary artery bypass surgery was 66% and 80% in the medically and interventionally treated patients, respectively (P=0.05). The use of nitrates was significantly lower in the angioplasty group, both at 1 year (38% versus 67%, P=0.001) and at long-term follow-up (36% versus 55%, P=0.006).
The authors conclude that percutaneous revascularization of the infarct-related coronary artery in stable patients with single vessel disease improves clinical outcome at long-term follow-up and reduces the use of nitrates. However, it is recommended that their results should be reproduced in a larger sample size before percutaneous coronary intervention in low-risk patients after myocardial infarction can be recommended as routine treatment in clinical practice.
Bilateral versus unilateral internal mammary revascularization in patients with diabetes
Japanese investigators evaluated the benefit of bilateral internal mammary artery (BIMA) grafts in coronary bypass grafting (CABG) for patients with diabetes. Elective, isolated, primary, multiple CABG was performed using skeletonized internal mammary artery (IMA) grafts for multivessel disease in 1,131 patients, 467 (41.3%) of whom had type 2 diabetes mellitus.
between 277 patients with diabetes using single IMA (SIMA) grafts and 190 using BIMA grafts (median follow-up, 8.1 years). Hospital mortality was similar in both groups. Early patency rate of all grafts was significantly higher using BIMA than using SIMA (97.7% versus 93.8%, P=0.0012). Survival rates were not significantly different between SIMA and BIMA groups. Late cardiac mortality was significantly higher in patients with low ejection fraction (0.4 or lower) compared with preserved ejection fraction (higher than 0.4) (P=0.0001). In patients with preserved ejection fraction, 10-year survival rate was significantly higher using BIMA than using SIMA (87.8 ± 3.5% versus 75.2 ± 3.4%, P=0.04), and 10-year all death-free or repeat CABG or recurrent myocardial infarction-free rate was significantly higher using BIMA than using SIMA (86.6 ± 3.6% versus 69.0 ± 3.7%, P=0.0086). The hazard ratio for all death or repeated CABG or recurrent myocardial infarction in patients with preserved ejection fraction was markedly lower in the BIMA group (0.53; 95% CI, 0.31 to 0.9; P=0.019).
The study concludes that skeletonized BIMA grafts are beneficial in coronary revascularization for diabetic patients with preserved ejection fraction but have limited survival benefit for those with reduced ejection fraction attributable to high cardiac mortality.
Long-term results of the radial artery used for myocardial revascularization
There is no information available on the long-term results of radial artery (RA) grafts used as coronary artery bypass conduits.
A study in Italy reports the long-term (105 ± 9 months) angiographic results of a series of 90 consecutive patients in whom the RA was used as a coronary artery bypass conduit directly anastomosed to the ascending aorta. The long-term patency and perfect patency rates of the RA were 91.6% and 88%, respectively, versus 97.5% and 96.3% for internal thoracic artery grafts. The severity of stenosis of the target vessel clearly influenced long-term RA patency, whereas location of the target vessel and long-term use of calcium channel blockers did not influence angiographic results. Preserved endothelial function and absence of flow-limiting, fibrous, intimalhyperplasia were also documented.
The study concludes that ten years after surgery, RA grafts have excellent patency and perfect patency rates. Appropriate surgical technique and correct indication are the key factors for long-term RA patency.
Novel passive implantable atrial defibrillator using transcutaneous radiofrequency energy transmission successfully cardioverts atrial fibrillation
Conventional methods for cardioversion of atrial fibrillation (AF) to sinus rhythm have numerous difficulties. A novel method for cardioversion using the passive implantable atrial defibrillator (PIAD) was tested in acute animal models. This device does not have a battery or a capacitor to store energy and is activated by transferring RF energy across the skin from an external transmitter to the subcutaneously implanted defibrillator. On activation, a novel monophasic shock waveform with 5% tilt is delivered to the heart via 2 intracardiac defibrillation leads.
Cardioversion attempts with the device were assessed in 2 phases: a feasibility and efficacy study and randomized comparison against standard waveforms. Defibrillation leads were placed transvenously into the distal coronary sinus and the right atrial appendage. These were connected to the subcutaneously implanted PIAD. Sustained AF was induced by rapid atrial pacing. The transmitter coil was placed on the skin overlying the defibrillator, and defibrillation synchronized to the R wave was attempted. The method was found to be efficacious at very low voltage and energy, with 100% cardioversion success observed for 10-ms 100-V shocks (mean energy, 1.54±0.02 J). The PIAD waveform had a higher cardioversion success rate than a truncated, 70% tilt monophasic exponential pulse (100 V, 100% versus 78.0±7.57%; P=0.001). There were no postshock complications.
Considering these animal results, this method is promising for cardioverting AF in symptomatic patients.
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