Clinical question
Is coffee consumption safe after acute myocardial infarction?

Bottom line
Coffee consumption does not increase the risk of cardiovascular events following acute myocardial infarction (AMI).

Reference
Silletta MG, Marfisi R, Levantesi G, et al, for the GISSI-Prevenzione Investigators. Coffee consumption and risk of cardiovascular events after acute myocardial infarction. Circulation 2007;116(25):2944-2951.

Study design: Cohort (prospective)

Synopsis
The relation between coffee consumption and cardiovascular disease has been studied extensively, but results are still debated. In addition, little evidence is available on patients with established coronary heart disease. Prospectively ascertained information among 11,231 Italian patients (9584 males and 1647 females) with recent (< or = 3 months) myocardial infarction enrolled in the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico)-Prevenzione trial was used. Usual dietary habits were assessed at baseline and updated at 0.5 and 1.5 years. Coffee consumption was categorized as never/almost never, < 2 cups per day, 2 to 4 cups per day, and > 4 cups per day. Medication use and fasting glucose were assessed at 0.5, 1, 1.5, 2.5, and 3.5 years. Risk was evaluated with Cox proportional hazards with time-varying covariates. The main outcome measure was the cumulative incidence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke). A total of 1167 cardiovascular events occurred during 36,961 person-years of follow-up. After multivariable adjustment for potential confounders in the time-dependent analysis, the relative risk of cardiovascular events across categories of coffee consumption was 1.02 (95% CI 0.87 to 1.20) for < 2 cups per day, 0.91 (95% CI 0.75 to 1.09) for 2 to 4 cups per day, and 0.88 (95% CI 0.64 to 1.20) for > 4 cups per day compared with abstainers (P for trend=0.18). Ultimately, coffee consumption did not change the risk of coronary heart disease events, stroke, and sudden death.

Clinical question
Which is more effective for patients at high risk of cardiovascular disease: ramipril, telmisartan, or both?

Bottom line
The angiotensin-converting enzyme inhibitor (ACEI) ramipril and the angiotensin receptor blocker (ARB) telmisartan are equally effective for secondary cardiovascular prevention. The combination of both drugs is no more effective and causes more adverse effects at greater cost. ACEIs should remain the drug of choice for secondary prevention in high risk cardiovascular patients unless the drug is not tolerated because of angioedema or cough, in which case ARBs provide an effective alternative.

Reference
The ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-1559.

Study design: Randomized controlled trial (double-blinded)

Synopsis
In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. The author compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001).

Clinical question
Are cholesterol and blood pressure associated with an increase in vascular mortality?

Bottom line
Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures.
Reference
Prospective Studies Collaboration, Lewington S, Whitlock G, Clarke R, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007;370(9602):1829-1839.

Study design: Meta-analysis (other)

Synopsis
These intrepid authors pooled data on nearly 900,000 individual patients enrolled in 61 prospective cohort studies. In these studies, approximately 55,000 patients died. Only 150,000 of the patients had lipid levels available, of whom approximately 5000 died. The authors evaluated the relationship between cholesterol level, blood pressure, age, and gender on vascular mortality (ischemic heart disease, stroke, and “other”). To reduce undue influence of a few outliers, they excluded patients with astronomical cholesterol readings. They don’t report how many patients dropped out of the studies or the number of deaths from all causes. They do, however, report MANY relationships. If you want all the data, get the paper. On the whole, the authors found that the higher the cholesterol level, the greater the risk of vascular death. They also report a nearly linear risk of vascular mortality that increases as the patient gets older, independent of gender. Blood pressure has a similar relationship and blood pressure and cholesterol have additive effects. In contrast with randomized trials that show statins may decrease stroke risk, lipids were weakly and inconsistently associated with stroke deaths. This reinforces the theory that statins may have beneficial effects independent of their effects on lipids.

Clinical question
Are omega-3 free fatty acids useful in the prevention of relapse in Crohn disease?

Bottom line
Daily supplementation with omega-3 free fatty acids (FFAs) was not effective for the prevention of relapse in Crohn disease.

Reference
Feagan BG, Sandborn WJ, Mittmann U, et al. Omega-3 free fatty acids for the maintenance of remission in Crohn disease. The EPIC randomized controlled trials. JAMA 2008;299:1690-1697.

Study design: Randomized controlled trial (double-blinded)

Synopsis
Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. The authors determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease. Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn’s Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively. Patients with a Crohn’s Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted. Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease. For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease.

Clinical Question:
Are antibiotics or nasal steroids truly beneficial in the treatment of acute maxillary sinusitis?

Bottom Line:
Neither an antibiotic nor a topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting.

Reference:
Williamson IG, Rumsby K, Benge S, et al. Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis. A randomized controlled trial. JAMA 2007;298(21):2487-2496.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Acute sinusitis is a common clinical problem that usually results in a prescription for antibiotics but the role of antibiotics is debated. Anti-inflammatory drugs such as topical steroids may be beneficial but are underresearched. The authors determine the effectiveness of amoxicillin and topical budesonide in acute maxillary sinusitis. They did a double-blind, randomized, placebo-controlled factorial trial of 240 adults (aged > or =16 years) with acute nonrecurrent sinusitis (had > or =2 diagnostic criteria: purulent rhinorrhea with unilateral predominance, local pain with unilateral predominance, purulent rhinorrhea bilateral, presence of pus in the nasal cavity) at 58 family practices (74 family physicians) between November 2001 and November 2005. Patients were randomized to 1 of 4 treatment groups: antibiotic and nasal steroid; placebo antibiotic and nasal steroid; antibiotic and placebo nasal steroid; placebo antibiotic and placebo nasal steroid. A dose of 500 mg of amoxicillin 3 times per day for 7 days and 200 mug of budesonide in each nostril once per day for 10 days. Proportion clinically cured at day 10 using patient symptom diaries and the duration and severity of symptoms. The proportions of patients with symptoms lasting 10 or more days were 29 of 100 (29%) for amoxicillin vs 36 of 107 (33.6%) for no amoxicillin (adjusted odds ratio, 0.99; 95% confidence interval, 0.57-1.73). The proportions of patients with symptoms lasting 10 or more days were 32 of 102 (31.4%) for topical budesonide vs 33 of 105 (31.4%) for no budesonide (adjusted odds ratio, 0.93; 95% confidence interval, 0.54-1.62). Secondary analysis suggested that nasal steroids were significantly more effective in patients with less severe symptoms at baseline.

Clinical Question:
Can drug treatment improve passage of ureteral stones?

Bottom Line:
This meta-analysis of low-quality studies shows that ureteral stone passage can be enhanced by treating patients with an alpha-blocker such as tamsulosin (Flomax) or the calcium channel blocker nifedipine (Procardia). Better studies may refute these findings, but for now either approach is an option.

Reference:
Singh A, Alter HJ, Littlepage A. A systematic review of medical therapy to facilitate passage of ureteral calculi. Ann Emerg Med 2007;50(5):552-563.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
The researchers conducting this study combined the results of small studies evaluating the effectiveness of alpha-blockers, a calcium channel blocker, or both, to increase the passage of ureteral calculi. The meta-analysis was well done. Two authors independently searched several databases, including the Cochrane database, to find randomized studies. They also conducted a hand search of urologic journals and conference proceedings. Two authors also independently abstracted data. They identified 22 studies. Only 1 study was considered to be of good quality with a Jadad score of 3 (out of a possible 5), with all the rest scoring 1 or 2. All but 1 of the studies was unblinded, and the researchers did not report on whether allocation was concealed in the studies. There was mild heterogeneity found among the alpha-blocker studies, as well as evidence of publication bias. Alpha-blockers, primarily tamsulosin, were studied in 16 trials enrolling 1235 men. Nine trials evaluated the time to stone expulsion in patients with stones of 3 mm to 18 mm in size and located in the distal portion of the ureter, with a 2-day to 6-day average improvement in time to stone passage. The calcium channel blocker was studied in 9 trials of 686 patients with an average stone size of greater than 5 mm located in all aspects of the ureter. The average reduction in time to stone expulsion was not reported, though stone passage was more likely, on average, with treatment (relative risk = 1.50; 95% CI, 1.34-1.68) over the various periods of follow-up.

Clinical Question:
Can specific wording make a difference in addressing patients’ unmet concerns?

Bottom Line:
After eliciting a patient’s chief concern, asking “Is there something else you want to address in the visit today?” decreases the likelihood of them leaving with unmet concerns. Asking this variation of the more typical, “Is there anything else you want to address in the visit today?” did not increase the average visit duration. The authors did not study whether patient satisfaction was improved.

Reference:
Heritage J, Robinson JD, Elliott MN, Beckett M, Wilkes M. Reducing patients’ unmet concerns in primary care: the difference one word can make. J Gen Intern Med 2007;22(10):1429-1433.

Study Design:
Cross-sectional

Synopsis:
In primary, acute-care visits, patients frequently present with more than 1 concern. Various visit factors prevent additional concerns from being articulated and addressed. The investigators test an intervention to reduce patients’ unmet concerns. They did a cross-sectional comparison of 2 experimental questions, with videotaping of office visits and pre and postvisit surveys. Twenty outpatient offices of community-based physicians equally divided between Los Angeles County and a midsized town in Pennsylvania were included. A volunteer sample of 20 family physicians (participation rate = 80%) and 224 patients approached consecutively within physicians (participation rate = 73%; approximately 11 participating for each enrolled physician) seeking care for an acute condition. After seeing 4 nonintervention patients, physicians were randomly assigned to solicit additional concerns by asking 1 of the following 2 questions after patients presented their chief concern: “Is there anything else you want to address in the visit today?” (ANY condition) and “Is there something else you want to address in the visit today?” (SOME condition). Patients’ unmet concerns: concerns listed on previsit surveys but not addressed during visits, visit time, unanticipated concerns: concerns that were addressed during the visit but not listed on previsit surveys. Relative to nonintervention cases, the implemented SOME intervention eliminated 78% of unmet concerns (odds ratio (OR) = .154, p = .001). The ANY intervention could not be significantly distinguished from the control condition (p = .122). Neither intervention affected visit length, or patients’; expression of unanticipated concerns not listed in previsit surveys.

Clinical Question:
Do warm packs prevent perineal trauma when applied to the perineum during labor?

Bottom Line:
The application of perineal warm packs in late second stage does not reduce the likelihood of nulliparous women requiring perineal suturing but significantly reduces third- and fourth-degree lacerations, pain during the birth and on days 1 and 2, and urinary incontinence. This simple, inexpensive practice should be incorporated into second stage labor care.

Reference:
Dahlen HG, Homer CS, Cooke M, Upton AM, Nunn R, Brodrick B. Perineal outcomes and maternal comfort related to the application of perineal warm packs in the second stage of labor: A randomized controlled trial. Birth 2007;34(4):282-290.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
In this randomized controlled trial of 717 women the use of warm packs from late second-stage labor until crowning was compared with usual care that did not include warm packs. Although masking of women and their birth attendants was not possible, the outcome assessors were masked. Eligible women were nulliparous with singleton term pregnancy in cephalic presentation who anticipated a normal delivery and had not performed perineal massage. Warm packs consisted of perineal pads soaked in boiled tap water at a temperature of approximately 45 degrees centigrade. The trial was conducted in an ethnically diverse population in Australia, where 75% of women are immigrants from other countries. With a study size adequate to detect a 10% difference, there was no difference between groups for the principal outcome of need for perineal suture. However, the number of third- and fourth-degree lacerations was reduced in the wam pack group, (31/357 vs 15/360; number needed to treat [NNT] = 22; 95% CI, 12-109). Women receiving warm packs were less likely to report severe pain during birth than women who were not given warm packs (59% vs 82%, respectively). There were also modest, statistically significant reductions in mean perineal pain scores on days 1 and 2 postpartum using a 10-point visual analog scale, with less than 1-point mean differences. At 3 months postpartum women who had received warm packs were less likely to report urinary incontinence (36/276 vs 46/277; NNT = 28).

Clinical Question:
What is the risk for thrombocytopenia with unfractionated heparin versus low-molecular-weight heparin in patients treated for acute venous thromboembolism?

Bottom Line:
There was no difference in risk of thrombocytopenia between unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in patients with acute deep venous thrombosis (DVT) or pulmonary embolism (PE).

Reference:
Morris TA, Castrejon S, Devendra G, Gamst AC. No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous thrombosis with either low-molecular-weight heparin or unfractionated heparin: a metaanalysis. Chest 2007:132(4):1131-1139.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
A thorough search of English language literature was done to identify randomized controlled trials comparing the incidence of thrombocytopenia with UFH versus LMWH in patients with objectively diagnosed DVT or PE. Two independent reviewers evaluated studies for inclusion and quality. Studies were rated on the basis of 9 criteria; a score of 8 was needed to be considered high enough quality for inclusion. Thrombocytopenia was defined as platelet counts between 80,000 mm3 to 120,000 mm3 or a decrease in platelets by at least 50%. A secondary analysis included all definitions of thrombocytopenia specified in the respective articles. The diagnosis of heparin-induced thrombocytopenia (HIT) required an objective test, such as a heparin-induced serotonin release assay, heparin-induced platelet aggregation, or heparin-platelet factor 4 (PF4) enzyme-linked immunosorbent assay. Heparin-induced thrombocytopenia thrombosis (HITT) was defined as thrombocytopenia with new arterial or venous thrombosis.

Thirteen studies including 5275 patients were included for analysis of the primary outcome, 4 for the outcome of HIT, and 5 for HITT. The incidence of thrombocytopenia was 1.2% for enoxaparin-treated patients and 1.5% for those receiving UFH. Only a total of 5 patients had serologically confirmed HIT (2 receiving LMWH, 3 receiving UFH), and only 1 patient in the UFH group had HITT. These results may be limited by the lack of routine serologic testing for HIT among patients with thrombocytopenia.

Clinical Question:
In patients with acute coronary syndromes who are managed with percutaneous coronary intervention, is fondaparinux as safe and effective as enoxaparin?

Bottom Line:
For patients with acute coronary syndromes (ACS) who undergo percutaneous coronary intervention (PCI), fondaparinux is equally as effective as enoxaparin and results in less major bleeding.

Reference:
Mehta SR, Granger CB, Eikelboom JW, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention. J Amer Coll Cardiol 2007;50(18):1742-1751.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
This study was a preplanned analysis of patients from the OASIS-5 trial (Fifth Organization to Assess Strategies in Ischemic Syndromes), which evaluated the efficacy and safety of subcutaneous fondaparinux (2.5 mg daily) versus enoxaparin (1 mg/kg twice daily) in patients with unstable angina or non-ST-segment elevation myocardial infarction. Primary end points were rates of major bleeding and the composite of death, myocardial infarction, or stroke at days 9, 30, and 180. Results were analyzed by intention to treat. Patients were matched for baseline characteristics. PCI was done in 6238 patients of the 12,715 enrolled in the main trial who underwent cardiac catheterization during the period of study drug administration. Fondaparinux and enoxaparin were given for a mean of 2.4 days and 2.6 days, respectively, before PCI. More than 90% of patients received a thienopyridine, and approximately 40% were treated with glycoprotein (GP) IIb/IIIa inhibitors. At 30 days and 6 months, there was no difference in the rate of the composite primary end point or in the rates of the individual events. Major bleeding at day 9 was significantly lower among patients receiving fondaparinux [2.4% vs 5.1%; number needed to treat = 40; 95% CI, 25 - 86]. This difference persisted at 180 days. The reduction in bleeding with fondaparinux was seen both in patients who did and did not receive treatment with a GP IIb/IIIa inhibitor.