Clinical Question:
Is multidetector computed tomography safe and accurate for evaluating coronary disease in patients with dilated cardiomyopathy?

Bottom Line:
Multidetector computed tomography is feasible, safe, and accurate for identification of idiopathic versus ischemic DCM, and may represent an alternative to coronary angiography.

Reference:
Andreini D, Pontone G, Pepi M, et al. Diagnostic accuracy of multidetector computed tomography coronary angiography in patients with dilated cardiomyopathy. J Am Coll Cardiol 2007;49:2044-2050.

Study Design:
Diagnostic test evaluation

Synopsis:
These investigators assessed the safety, feasibility, and diagnostic accuracy of multidetector computed tomography (MDCT) in dilated cardiomyopathy (DCM) of unknown etiology. Multidetector computed tomography is an appropriate noninvasive tool for coronary artery disease (CAD) detection, particularly in patients with low probability of the disease, such as patients with DCM of unknown origin. They studied 61 unknown origin DCM patients (ejection fraction: 33.9 +/- 8.6%, group 1) and 139 patients with normal cardiac function with indications for coronary angiography (group 2, control population). All underwent coronary MDCT and angiography. Multidetector computed tomography images were acquired by light speed 16-slice computed tomography. The degree of stenosis was estimated in 15 coronary artery segments according to the American Heart Association model. In group 1, no MDCT-related complications were found, while 10 complications were associated with conventional angiography (p = 0.001). Overall feasibility of coronary artery visualization was 97.2% (863 of 888 segments). The most frequent cause of artifacts was interference from a hypertrophic cardiac venous system (10 artifacts, 40%). In group 2, overall feasibility was 96.1% (p = NS vs. group 1). In group 1, all cases with normal (44 cases) or pathological (17 cases) coronary arteries by conventional coronary angiography were correctly detected by MDCT, with, in 1 case, disparity of stenosis severity. In group 1, sensitivity, specificity, and positive and negative predictive values of MDCT for the identification of >50% stenosis were 99%, 96.2%, 81.2%, and 99.8%, respectively. In group 2, sensitivity and negative predictive values were lower than in group 1 (86.1% vs. 99% and 96.4% vs. 99.8%, respectively); specificity (96.4%) and positive predictive value (86.1%) were not significantly different versus group 1.

Clinical Question:
What is the optimal dose of aspirin for secondary prevention of stroke or myocardial infarction?

Bottom Line:
In this systematic review of 11 studies including more than 41,000 data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding.

Reference:
Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: A systematic review. JAMA 2007;297:2018-2024.

Study Design:
Systematic review

Synopsis:
More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose. The investigators reviewed the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety. A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included. Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production, dosages as high as 1300 mg/d are approved for use. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%). The available evidence, predominantly from secondary-prevention observational studies, supports that dosages greater than 75 to 81 mg/d do not enhance efficacy, whereas larger dosages are associated with an increased incidence of bleeding events, primarily related to gastrointestinal tract toxicity.

Clinical Question:
What are the effects of tolvaptan in patients hospitalized with heart failure?

Bottom Line:
Tolvaptan initiated for acute treatment of patients hospitalized with heart failure had no effect on long-term mortality or heart failure-related morbidity. Tolvaptan improved symptoms of heart failure in the short-term but did not reduce long-term mortality or heart failure-related morbidity in patients hospitalized for decompensated heart failure.

Reference:
Konstam MA, Gheorghiade M, Burnett JC, et al, for the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators. Effects of oral tolvaptan in patients hospitalized for worsening heart failure. The EVEREST outcome trial. JAMA 2007;297:1319-1331. Gheorghiade M, Konstam MA, Burnett JC, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure. The EVEREST clinical status trials. JAMA 2007;297:1332-1343.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Tolvaptan, a vasopressin V2 receptor blocker, shows promise for management of heart failure. The authors investigated the effects of tolvaptan initiated in patients hospitalized with heart failure. The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study. The outcome trial comprised 4133 patients within 2 short-term clinical status studies, who were hospitalized with heart failure, randomized at 359 North American, South American, and European sites between October 7, 2003, and February 3, 2006, and followed up during long-term treatment. Within 48 hours of admission, patients were randomly assigned to receive oral tolvaptan, 30 mg once per day (n = 2072), or placebo (n = 2061) for a minimum of 60 days, in addition to standard therapy. Dual primary end points were all-cause mortality (superiority and noninferiority) and cardiovascular death or hospitalization for heart failure (superiority only). Secondary end points included changes in dyspnea, body weight, and edema. During a median follow-up of 9.9 months, 537 patients (25.9%) in the tolvaptan group and 543 (26.3%) in the placebo group died (hazard ratio, 0.98; 95% confidence interval [CI], 0.87-1.11; P = .68). The upper confidence limit for the mortality difference was within the prespecified noninferiority margin of 1.25 (P<.001). The composite of cardiovascular death or hospitalization for heart failure occurred in 871 tolvaptan group patients (42.0%) and 829 placebo group patients (40.2%; hazard ratio, 1.04; 95% CI, 0.95-1.14; P = .55). Secondary end points of cardiovascular mortality, cardiovascular death or hospitalization, and worsening heart failure were also not different. Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea, day 1 body weight, and day 7 edema. In patients with hyponatremia, serum sodium levels significantly increased. The Kansas City Cardiomyopathy Questionnaire overall summary score was not improved at outpatient week 1, but body weight and serum sodium effects persisted long after discharge. Tolvaptan caused increased thirst and dry mouth, but frequencies of major adverse events were similar in the 2 groups.

Clinical Question:
Does vasodilator therapy improve long-term outcomes in patients with aortic insufficiency?

Bottom Line:
Treatment with an angiotensin-converting enzyme inhibitor, hydralazine, or nifedipine (Procardia) does not consistently improve hemodynamic parameters in patients with aortic insufficiency (AI). With the exception of one small study showing a benefit with nifedipine, treatment does not slow the progression of AI as measured by rates of atrial valve replacement.

Reference:
Mahajerin A, Gurm HS, Tsai TT, Chan PS, Nallamothu BK. Vasodilator therapy in patients with aortic insufficiency: A systematic review. Am Heart J 2007;153:454-461.

Study Design:
Systematic review

Synopsis:
The use of vasodilators to improve long-term outcomes in asymptomatic patients with chronic aortic insufficiency (AI) is controversial. The authors reviewed MEDLINE, PREMEDLINE, Current Contents, and Cochrane databases to identify relevant clinical trials on asymptomatic patients with chronic AI of at least moderate severity. We included those studies that involved long-term vasodilator therapy (including hydralazine, calcium-channel blockers, and angiotensin-converting enzyme inhibitors) and assessed either hemodynamic and structural parameters or clinical outcomes. Data on patient demographics, study protocols, and outcomes were abstracted. Ten studies with 544 asymptomatic patients with chronic AI were identified. Treatment duration with vasodilators ranged from 12 weeks to 7 years. Of these, 8 studies compared vasodilators with placebo or no therapy, with 5 demonstrating improvements in at least 1 hemodynamic or structural parameter with vasodilators and 3 showing little or no apparent benefit. The remaining 2 studies directly compared outcomes between 2 different vasodilators. Both of these studies demonstrated greater improvements in hemodynamic and structural parameters with angiotensin-converting enzyme inhibitors compared with hydralazine and nifedipine. Clinical outcomes were primarily reported in only 2 of the 10 studies. Although one study suggested that the use of vasodilators slowed the rate of progression to surgery for aortic valve replacement, another showed no difference.

Clinical Question:
How safe and effective is ranolazine in the treatment of acute coronary syndromes?

Bottom Line:
Ranolazine (Ranexa) is no more effective than placebo in reducing adverse events in the treatment of acute coronary syndromes (ACS).

Reference:
Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes. The MERLIN-TIMI 36 randomized trial. JAMA 2007;297:1775-1783.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS). This authors try to determine the efficacy and safety of ranolazine during long-term treatment of patients with non-ST-elevation ACS. They did a randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia. The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91).

Clinical Question:
Do percutaneous coronary interventions improve outcomes when added to optimal medical
therapy in patients with stable coronary disease?

Bottom Line:
Optimal medical therapy (treatment with a statin, an antiplatelet agent, an anti-anginal
medication, and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker)
is as effective as percutaneous coronary interventions (PCIs) followed by optimal medical
therapy for patients with chronic stable coronary artery disease (CAD).

Reference:
Boden WE, O’Rourke RA, Teo KK, et al, for the COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-1516.

Study Design:
Randomized controlled trial (single-blinded)

Synopsis:
In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events. A randomized trial was done involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6). There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).

Clinical Question:
Is an algorithm using multi-slice coronary computed tomography a safe and effective diagnostic approach for patients with acute chest pain?

Bottom Line:
Multi-slice coronary computed tomography (MSCT) effectively diagnoses or excludes coronary disease as the cause of acute chest pain in the majority of patients, reducing time to final diagnosis.

Reference:
Goldstein JA, Gallagher MJ, O’Neill WW, et al. A randomized controlled trial of multi-slice coronary computed tomography for evaluation of acute chest pain. J Amer Coll Cardiol 2007;49:863-871.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
The authors ompared the safety, diagnostic efficacy, and efficiency of multi-slice computed tomography (MSCT) with standard diagnostic evaluation of low-risk acute chest pain patients. Over 1 million patients have emergency center evaluations for acute chest pain annually, at an estimated diagnostic cost of over $10 billion. Multi-slice computed tomography has a high negative predictive value for exclusion of coronary artery stenoses. So what they did, they randomized patients to MSCT (n = 99) versus SOC (n = 98) protocols. The MSCT patients with minimal disease were discharged; those with stenosis >70% underwent catheterization, whereas cases with intermediate lesions or non-diagnostic scans underwent stress testing. Outcomes included: safety (freedom from major adverse events over 6 months), diagnostic efficacy (clinically correct and definitive diagnosis), as well as time and cost of care. Both approaches were completely (100%) safe. The MSCT alone immediately excluded or identified coronary disease as the source of chest pain in 75% of patients, including 67 with normal coronary arteries and 8 with severe disease referred for invasive evaluation. The remaining 25% of patients required stress testing, owing to intermediate severity lesions or non-diagnostic scans. During the index visit, MSCT evaluation reduced diagnostic time compared with SOC (3.4 h vs. 15.0 h, p < 0.001) and lowered costs (1,586 dollars vs. 1,872 dollars, p < 0.001). Importantly, MSCT patients required fewer repeat evaluations for recurrent chest pain (MSCT, 2 of 99 (2.0%) patients vs. SOC, 7 of 99 (7%) patients; p = 0.10).

Clinical Question:
Is the addition of aspirin to warfarin safe and more effective than warfarin alone?

Bottom Line:
Except for patients with mechanical heart valves, the addition of aspirin to therapeutic warfarin doses does not decrease the risk of death or of thromboembolism and does not increase the risk of a major bleed.

Reference:
Dentali F, Douketis JD, Lim W, Crowther M. Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease. A meta-analysis of randomized trials. Arch Intern Med 2007;167:117-124.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
For patients receiving oral anticoagulant (OAC) therapy, deciding whether to add aspirin to their treatment is a common clinical scenario with no clear guidelines to aid practice. The authors performed a systematic review and meta-analysis of randomized controlled trials comparing these 2 treatment strategies (combined aspirin-OAC therapy vs OAC therapy alone) to assess the therapeutic benefits and risks. They looked on randomized controlled trials published up to June 2005 in MEDLINE, EMBASE, and Cochrane Library databases. In addition they selected only randomized controlled trials with at least 3 months of follow-up that compared aspirin-OAC therapy with OAC therapy alone, in which OAC was administered to achieve the same target international normalized ratio or was given at the same fixed dose in both treatment arms. Two reviewers independently extracted data on study characteristics and outcomes. Pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated for study outcomes in patients receiving aspirin-OAC therapy and OAC therapy alone. Ten studies were included, totaling 4180 patients. The risk for arterial thromboembolism was lower in patients receiving combined aspirin-OAC therapy compared with OAC therapy alone (OR, 0.66; 95% CI, 0.52-0.84). However, these benefits were limited to patients with a mechanical heart valve (OR, 0.27; 95% CI, 0.15-0.49). There was no difference in the risk for arterial thromboembolism with these treatments in patients with atrial fibrillation (OR, 0.99; 95% CI, 0.47-2.07) or coronary artery disease (OR, 0.69; 95% CI, 0.35-1.36). There was no difference in all-cause mortality with either treatment (OR, 0.98; 95% CI, 0.77-1.25). The risk for major bleeding was higher in patients receiving aspirin-OAC therapy compared with OAC therapy alone (OR, 1.43; 95% CI, 1.00-2.02).

Clinical Question:
Is low-dose aspirin effective in preventing serious vascular events in patients with peripheral arterial disease?

Bottom Line:
Low-dose aspirin prevents major vascular events in patients with peripheral arterial disease with a number needed to treat (NNT) of 14 for 2 years. The study was too small to assess whether there is a risk reduction in critical leg ischemia events. Many of these patients have an indication for aspirin based on the presence of established coronary artery disease or diabetes.

Reference:
Critical Leg Ischaemia Prevention Study (CLIPS) Group; Catalano M, Born G, Peto R. Prevention of serious vascular events by aspirin amongst patient with peripheral arterial disease: randomized, double-blind trial. Journal of Internal Medicine 2007;261:276-284.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The authors assessed the prophylactic efficacy of aspirin and a high-dose antioxidant vitamin combination in patients with peripheral arterial disease (PAD) in terms of reduction of the risk of a first vascular event (myocardial infarction, stroke, vascular death) and critical limb ischaemia. Randomized, placebo-controlled, double-blind clinical trial with 2 x 2 factorial design. Thirty-seven European angiology/vascular medicine units. A total of 366 outpatients with stage I-II PAD documented by angiography or ultrasound, with ankle/brachial index <0.85 or toe index <0.6; 210 patients completed the follow-up. Four treatment groups: (i) oral aspirin (100 mg daily), (ii) oral antioxidant vitamins (600 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily), (iii) both or (iv) neither, given for 2 years. Major vascular events (cardiovascular death, myocardial infarction or stroke) and critical leg ischaemia. Seven of 185 patients allocated aspirin and 20 of 181 allocated placebo suffered a major vascular event (risk reduction 64%, P = 0.022); five and eight patients, respectively, suffered critical leg ischaemia (total 12 vs. 28, P = 0.014). There was no evidence that antioxidant vitamins were beneficial (16/185 vs. 11/181 vascular events). Neither treatment was associated with any significant increase in adverse events. Inclusion of this trial in a meta-analysis of other randomized trials of anti-platelet therapy in PAD makes the overall results highly significant (P < 0.001) and suggests that low-dose aspirin reduces the incidence of vascular events by 26%.

Clinical Question:
Is treatment with a glitazone after angioplasty effective in decreasing the need for revascularization?

Bottom Line:
The use of a thiazolidinedione (glitazone) following percutaneous coronary intervention (PCI) will decrease the need for revascularization over the following 6 months. The effect occurs in patients with and without diabetes and is likely due to an effect other than on blood glucose control. The studies in this meta-analysis were small, and further research is necessary before putting these results into practice.

Reference:
Riche DM, Valderrama R, Henyan NN. Thiazolidinediones and risk of repeat target vessel revascularization following percutaneous coronary intervention. Diabetes Care 2007;30:384-88.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
Thiazolidinediones (TZDs) (rosiglitazone and pioglitazone) are a class of antidiabetes agents that have a high affinity for peroxisome proliferator-activated receptor-gamma. TZDs initiate a multitude of physiologic processes that may elicit benefits as systemic agents for the prevention of restenosis requiring revascularization following percutaneous coronary intervention (PCI). Numerous trials have evaluated the impact of TZDs on repeat target vessel revascularization (TVR) in patients following PCI; however, several limitations (small sample size, inconclusive results, and risk factor stratification) complicate definitive conclusions. A meta-analysis was performed to evaluate the impact of TZDs on repeat TVR following PCI. Included trials met the following criteria: 1) prospective, randomized controlled trials evaluating available TZDs versus standards of care; 2) well-described protocol; 3) minimum of 6 months of follow-up; and 4) data provided on repeat TVR. Data are presented as relative risks (RRs) with 95% CIs. Seven clinical trials (n = 608) met the inclusion criteria. Upon meta-analysis, the risk of repeat TVR was significantly reduced in patients who received TZD therapy compared with standards of care (RR 0.35 [95% CI 0.22-0.57]). In studies using rosiglitazone (0.45 [0.25-0.83]) and pioglitazone (0.24 [0.11-0.51]), risk of repeat TVR was significantly reduced. Risk of repeat TVR was also significantly reduced among patients with (0.34 [0.19-0.63]) and without (0.37 [0.18-0.77]) diabetes.