Effect of PCI on Long-Term Survival

From The Journal of Family Practice

Effect of PCI on Long-Term SurvivalOutcomes in patients with stable ischemic HD

December 1, 2015

There was no difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone after extended 15-year follow-up in patients with stable ischemic heart disease, according to extended survival information for 1,211 patients. Median duration of follow-up for all patients was 6.2 years; the median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years.

Researchers found:

• 561 deaths occurred; 180 during the follow-up period in the original trial and 381 during the extended follow-up period.

• There were 284 deaths (25%) in the PCI group and 277 (24%) in the medical therapy group (aHR, 1.03).

Citation: Sedlis SP, Hartigan PM, Teo KK, et al. Effect of PCI on long-term survival in patients with stable ischemic heart disease. N Engl J Med.2015;373:1937-1946. doi: 10.1056/NEJMoa1505532.

Commentary: The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial compared a strategy of optimal medical therapy for advanced coronary artery disease versus optimal medical therapy plus percutaneous coronary intervention (PCI) and found no difference in outcome between these 2  groups. This was a landmark trial and has influenced guidelines and changed the practice of interventional cardiology. The current study follows patients from the original COURAGE cohort for up to 15 years and continues to show no survival advantage in either group. In addition, no high-risk subgroup of patients has been identified that showed a survival benefit from PCI compared with optimal medical therapy alone in the original study or in the extended cohort. This study adds further evidence that PCI can be used for treatment of angina that does not respond to medical treatment but will not offer a survival advantage over optimal medical therapy. —Matthew Sorrentino, MD

Pain Medications for Acute Low Back Pain

  • Opioids and muscle relaxants are often prescribed alongside nonsteroidal anti-inflammatory drugs (NSAIDs) for patients with acute low back pain, although these additional medications are associated with an increased risk of adverse events.
  • In patients with nontraumatic, nonradicular, acute low back pain, there were no significant differences among groups in pain or functional outcomes at 1 week or 3 months comparing the addtion of cyclobenzaprine or oxycodone/acetaminophen or placebo to naproxen.
  • Naproxen alone was also associated with reduced risk of adverse events compared to either naproxen combination therapy.

The American College of Physician and the American Pain Society recommend acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line medications for patients with low back pain (Ann Intern Med 2007 Oct 2;147(7):478).  However, opioids, NSAIDS, and muscle relaxants alone or in combination are commonly prescribed to patients with low back pain presenting to the emergency department (Spine (Phila Pa 1976) 2010 Nov 15;35(24):E1406).  Some evidence suggests that muscle relaxants and opioid medication may improve pain in patients with acute low back pain, but these medications are also associated with an increased risk of adverse events and, with opioids in particular, there is the potential for abuse and addiction (Ann Intern Med 2007 Oct 2;147(7):478, Cochrane Database Syst Rev 2003;(2):CD004252).  A recent randomized trial compared the addition of one of three regimens (cyclobenzaprine 5 mg or oxycodone 5 mg/acetaminophen 325 mg or placebo) to naproxen 500 mg twice daily in 323 adults 21-64 years old (mean age 39 years) presenting to the emergency department with nontraumatic, nonradicular, acute musculoskeletal low back pain.  Patients were instructed to take 1 tablet of the randomized medication every 8 hours as needed, but they were instructed to take a second tablet if sufficient relief was not achieved within 30 minutes.  All patients also received a 10 minute educational intervention discussing additional therapies to help alleviate pain.

Low back pain was assessed at baseline and during follow-up with the Roland-Morris Disability Questionnaire (RMDQ).  RMDQ scores range from 0-24 with higher scores indicating increasing impairment, and all patients had a baseline RMDQ score ≥ 5 at emergency department discharge (mean score 18.7).  The minimum clinically important difference in RMDQ scores at follow-up was defined as a 5 point improvement on the RMDQ. Comparing the addition of cyclobenzaprine or oxycodone/acetaminophen or placebo to naproxen, there were no significant differences in mean RMDQ score improvement at 1-week follow-up (10.1 points vs. 11.1 points vs. 9.8 points, respectively).  There were also no significant differences at 1-week follow-up in mean RMDQ scores, worst low back pain, frequency of low back pain episodes, use of low back pain medication, the desire for the same medication for subsequent low back pain episodes, and time to return to usual activities.  There were no significant differences among the groups in mean RMDQ score, worst pain, pain frequency, use of mediation, or opioid use at 3 months. Cyclobenzaprine and oxycodone/acetaminophen were each associated with significant increases in the rate of adverse events (sedation and gastrointestinal symptoms) compared to placebo, however.  Adverse events were reported in 33% of patients randomized to cyclobenzaprine (p < 0.05 vs. placebo, NNH 7), 40% of patients randomized to oxycodone plus acetaminophen (p < 0.05 vs. placebo, NNH 5), and 21% of patients randomized to placebo.

While opioids and muscle relaxants are commonly prescribed to patients presenting with acute low back pain, based on this trial naproxen alone is as effective as combination therapy in relieving pain. These results also suggest that the addition of these medications to naproxen may place the patient at an increased risk of harm.  Furthermore, approximately 25% of patients in each group still experienced moderate-to-severe low back pain at the 3-month follow-up, indicating that the initial choice of pain medication may not impact the development of chronic low back pain.

For more information, see the Acute low back pain topic in DynaMed Plus.  DynaMed users click here.

What to do about the “weekend effect”

https://apis.google.com/_/scs/apps-static/_/js/k=oz.gapi.en_US.yVQP03EdYog.O/m=auth/exm=plusone/rt=j/sv=1/d=1/ed=1/am=AQ/rs=AGLTcCNJHTRTh8JJEhBJv0DdIP_GrcSLtw/t=zcms/cb=gapi.loaded_1What to do about the “weekend effect”

BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h4840 (Published 10 September 2015) Cite this as: BMJ 2015;351:h4840

Fiona Godlee, editor in chief, The BMJ

Does being admitted to hospital at the weekend increase your risk of dying in the next 30 days compared with admission during the week? If so, is your death avoidable, and would a fully operational seven day service prevent it? A new Analysis article by Nick Freemantle and colleagues sheds some light on these questions but leaves many more to be answered (doi:10.1136/bmj.h4596).

The findings confirm these authors’ previous work published in 2012 (doi:10.1258/jrsm.2012.120009). They find that patients admitted on Saturdays and Sundays have an increased relative risk of death of 10% and 15%, respectively. They also find a smaller increased risk of death for patients admitted on Mondays and Fridays, extending the “weekend effect” to those days. They conclude that around 11 000 more patients die each year within 30 days if they are admitted between Friday and Monday than if they’re admitted on other days of the week. When adjustments are made for the fact that patients admitted at weekends are sicker, the increased risk of death within 30 days is less but still present and, in the authors’ words, not ignorable.

What these figures actually mean is now hotly debated. The secretary of state for health seized on them before they were published to support his call for more senior consultants to work at weekends. This leap, from a statistical excess of deaths in patients admitted at weekends to a solution focused on more senior medical staff working at weekends, is just one way in which these data are being abused and the public misled.

The weekend effect is real, concludes Helen Crump in her review of the evidence (doi:10.1136/bmj.h4473). Paul Aylin confirms this in his Editorial but explains that we are left with a range of possible explanations (doi:10.1136/bmj.h4652). These need to be scrutinised before assumptions and suggestions harden into policy. The evidence is conflicting but seems to point more to the importance of a fully functioning service than to simply needing more senior medical cover. One study found no weekend effect on intensive care units, which have more consistent staffing levels. Another found that the weekend effect was not reduced if stroke specialists did ward rounds seven days a week but was affected by the level of nurse staffing. This link between nurse staffing and overall hospital mortality has been reproduced, says Aylin, in a recent very large European study.

Whether the right answer is more senior medical cover or an overall improvement in staffing levels at weekends, the cost is likely to be substantial, as Martin McKee points out, possibly exceeding the cost per quality adjusted life year threshold set by NICE (doi:10.1136/bmj.h4723).

Clearly something needs to be done to reduce the risk of death in patients admitted to hospital at weekends. But using these data to beat up on senior doctors, most of whom already work at weekends, is neither constructive nor evidence based. We need a dispassionate look at the existing evidence, a focused effort to improve the evidence base, and a collaborative debate about the best response.

Cite this as: BMJ 2015;351:h4840

Dual anti-platelet therapy for secondary prevention of CV events in patients with prior MI

REFERENCE Udell JA, Bonaca MP, Collet JP, et al. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J. 2015 Aug 31. pii: ehv443. (Review) PMID: 26324537

AIMS: Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations, with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascular mortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with aspirin alone in high-risk patients with a history of prior myocardial infarction (MI).
METHODS AND RESULTS: A total of 33 435 patients were followed over a mean 31 months among one trial of patients with prior MI (63.3% of total) and five trials with a subgroup of patients that presented with, or had a history of, a prior MI (36.7% of total). Extended DAPT decreased the risk of major adverse cardiovascular events compared with aspirin alone (6.4 vs. 7.5%; risk ratio, RR 0.78, 95% confidence intervals, CI, 0.67-0.90; P = 0.001) and reduced cardiovascular death (2.3 vs. 2.6%; RR 0.85, 95% CI 0.74-0.98; P = 0.03), with no increase in non-cardiovascular death (RR 1.03, 95% CI 0.86-1.23; P = 0.76). The resultant effect on all-cause mortality was an RR of 0.92 (95% CI 0.83-1.03; P = 0.13). Extended DAPT also reduced MI (RR 0.70, 95% CI 0.55-0.88; P = 0.003), stroke (RR 0.81, 95% CI 0.68-0.97; P = 0.02), and stent thrombosis (RR 0.50, 95% CI 0.28-0.89; P = 0.02). There was an increased risk of major bleeding (1.85 vs. 1.09%; RR 1.73, 95% CI 1.19-2.50; P = 0.004) but not fatal bleeding (0.14 vs. 0.17%; RR 0.91, 95% CI 0.53-1.58; P = 0.75).
CONCLUSION: Compared with aspirin alone, DAPT beyond 1 year among stabilized high-risk patients with prior MI decreases ischaemic events, including significant reductions in the individual endpoints of cardiovascular death, recurrent MI, and stroke. Dual antiplatelet therapy beyond 1 year increases major bleeding, but not fatal bleeding or non-cardiovascular death.

Courtesy of Evidence Updates from British Medical Journal

Nonsteroidal anti-inflammatory drugs and non-opioids for acute renal colic.

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Afshar K1, Jafari S, Marks AJ, Eftekhari A, MacNeily AECochrane Database Syst Rev. 2015 Jun 29;6:CD006027. doi: 10.1002/14651858.CD006027.pub2.



Renal colic is acute pain caused by urinary stones. The prevalence of urinary stones is between 10% and 15% in the United States, making renal colic one of the common reasons for urgent urological care. The pain is usually severe and the first step in the management is adequate analgesia. Many different classes of medications have been used in this regard including non-steroidal anti-inflammatory drugs and narcotics.


The aim of this review was to assess benefits and harms of different NSAIDs and non-opioids in the treatment of adult patients with acute renal colic and if possible to determine which medication (or class of medications) are more appropriate for this purpose. Clinically relevant outcomes such as efficacy of pain relief, time to pain relief, recurrence of pain, need for rescue medication and side effects were explored.


We searched the Cochrane Renal Group’s Specialised Register (to 27 November 2014) through contact with the Trials’ Search Co-ordinator using search terms relevant to this review.


Only randomised or quasi randomised studies were included. Other inclusion criteria included adult patients with a clinical diagnosis of renal colic due to urolithiasis, at least one treatment arm included a non-narcotic analgesic compared to placebo or another non-narcotic drug, and reporting of pain outcome or medication adverse effect. Patient-rated pain by a validated tool, time to relief, need for rescue medication and pain recurrence constituted the outcomes of interest. Any adverse effects (minor or major) reported in the studies were included.


Abstracts were reviewed by at least two authors independently. Papers meeting the inclusion criteria were fully reviewed and relevant data were recorded in a standardized Cochrane Renal Group data collection form. For dichotomous outcomes relative risks and 95% confidence intervals were calculated. For continuous outcomes the weighted mean difference was estimated. Both fixed and random models were used for meta-analysis. We assessed the analgesic effects using four different outcome variables: patient-reported pain relief using a visual analogue scale (VAS); proportion of patients with at least 50% reduction in pain; need for rescue medication; and pain recurrence. Heterogeneity was assessed using the I² test.


A total of 50 studies (5734 participants) were included in this review and 37 studies (4483 participants) contributed to our meta-analyses. Selection bias was low in 34% of the studies or unclear in 66%; performance bias was low in 74%, high in 14% and unclear in 12%; attrition bias was low in 82% and high in 18%; selective reporting bias low in 92% of the studies; and other biases (industry funding) was high in 4%, unclear in 18% and low in 78%.Patient-reported pain (VAS) results varied widely with high heterogeneity observed. For those comparisons which could be pooled we observed the following: NSAIDs significantly reduced pain compared to antispasmodics (5 studies, 303 participants: MD -12.97, 95% CI -21.80 to – 4.14; I² = 74%) and combination therapy of NSAIDs plus antispasmodics was significantly more effective in pain control than NSAID alone (2 studies, 310 participants: MD -1.99, 95% CI -2.58 to -1.40; I² = 0%).NSAIDs were significantly more effective than placebo in reducing pain by 50% within the first hour (3 studies, 197 participants: RR 2.28, 95% CI 1.47 to 3.51; I² = 15%). Indomethacin was found to be less effective than other NSAIDs (4 studies, 412 participants: RR 1.27, 95% CI 1.01 to 1.60; I² = 55%). NSAIDs were significantly more effective than hyoscine in pain reduction (5 comparisons, 196 participants: RR 2.44, 95% CI 1.61 to 3.70; I² = 28%). The combination of NSAIDs and antispasmodics was not superior to NSAIDs only (9 comparisons, 906 participants: RR 1.00, 95% CI 0.89 to 1.13; I² = 59%). The results were mixed when NSAIDs were compared to other non-opioid medications.When the need for rescue medication was evaluated, Patients receiving NSAIDs were significantly less likely to require rescue medicine than those receiving placebo (4 comparisons, 180 participants: RR 0.35, 95% CI 0.20 to 0.60; I² = 24%) and NSAIDs were more effective than antispasmodics (4 studies, 299 participants: RR 0.34, 95% CI 0.14 to 0.84; I² = 65%). Combination of NSAIDs and antispasmodics was not superior to NSAIDs (7 comparisons, 589 participants: RR 0.99, 95% CI 0.62 to 1.57; I² = 10%). Indomethacin was less effective than other NSAIDs (4 studies, 517 participants: RR 1.36, 95% CI 0.96 to 1.94; I² = 14%) except for lysine acetyl salicylate (RR 0.15, 95% CI 0.04 to 0.65).Pain recurrence was reported by only three studies which could not be pooled: a higher proportion of patients treated with 75 mg diclofenac (IM) showed pain recurrence in the first 24 hours of follow-up compared to those treated with 40 mg piroxicam (IM) (60 participants: RR 0.05, 95% CI 0.00 to 0.81); no significant difference in pain recurrence at 72 hours was observed between piroxicam plus phloroglucinol and piroxicam plus placebo groups (253 participants: RR 2.52, 95% CI 0.15 to12.75); and there was no significant difference in pain recurrence within 72 hours of discharge between IM piroxicam and IV paracetamol (82 participants: RR 1.00, 95% CI 0.65 to 1.54).Side effects were presented inconsistently, but no major events were reported.


Although due to variability in studies (inclusion criteria, outcome variables and interventions) and the evidence is not of highest quality, we still believe that NSAIDs are an effective treatment for renal colic when compared to placebo or antispasmodics. The addition of antispasmodics to NSAIDS does not result in better pain control. Data on other types of non-opioid, non-NSAID medication was scarce.Major adverse effects are not reported in the literature for the use of NSAIDs for treatment of renal colic.

Treating neuropathic pain with amitriptyline


Moore RA, Derry S, Aldington D, et al. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Jul 6;7:CD008242. (Review) PMID: 26146793

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of amitriptyline for fibromyalgia are now dealt with in a separate review.Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.

OBJECTIVES: To assess the analgesic efficacy of amitriptyline for relief of chronic neuropathic pain, and the adverse events associated with its use in clinical trials. SEARCH

METHODS: We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with two clinical trial registries, and the reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own hand searched database for older studies.
SELECTION CRITERIA: We included randomised, double-blind studies of at least four weeks` duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain conditions.
DATA COLLECTION AND ANALYSIS: We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks` duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.

MAIN RESULTS: We included 15 studies from the earlier review and two new studies (17 studies, 1342 participants) in seven neuropathic pain conditions. Eight cross-over studies with 302 participants had a median of 36 participants, and nine parallel group studies with 1040 participants had a median of 84 participants. Study quality was modest, though most studies were at high risk of bias due to small size.There was no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition. Only third-tier evidence was available. For only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo (very low quality evidence).More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The risk ratio (RR) was 1.5 (95% confidence interval (CI) 1.3 to 1.8) and the number needed to treat for an additional harmful outcome was 5.2 (3.6 to 9.1) (low quality evidence). Serious adverse events were rare. Adverse event and all-cause withdrawals were not different, but were rarely reported (very low quality evidence).

AUTHORS’ CONCLUSIONS: Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many people with neuropathic pain. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain, but only a minority of people will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all.

Medical marijuana: Show me the data


Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73. doi: 10.1001/jama.2015.6358. (Review) PMID: 26103030

IMPORTANCE: Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.

OBJECTIVE: To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.

DATA SOURCES: Twenty-eight databases from inception to April 2015.

STUDY SELECTION: Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome.

DATA EXTRACTION AND SYNTHESIS: Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. MAIN OUTCOMES AND

MEASURES: Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.

RESULTS: A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.

CONCLUSIONS AND RELEVANCE: There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.