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Precision Medicine to Reduce Bleeding with PCI   

5 May, 15 | by Alistair Lindsay

 

Periprocedural bleeding remains one of the most common adverse events after percutaneous coronary intervention (PCI) and is associated with increased mortality.  Although strategies to minimize PCI bleeding have been identified, these strategies are infrequently applied to patients at highest bleeding risk.  Using a pre-post study design, Spertus et al. evaluated the impact of assessing individual patient bleeding risk from validated models and providing this bleeding risk estimate in personalized informed consent documents for PCI.  The intent of the intervention was to increase the procedural team’s awareness of patients at low, moderate, and risk for PCI related bleeding and thereby influence the use of bleeding avoidance strategies (i.e. bivalirudin, radial access, and vascular closure devices) and reduce periprocedural bleeding events.  The study included 7408 pre-intervention PCI and 3529 post-intervention PCI from 9 hospitals in the United States. Following implementation of the intervention, use of bleeding avoidance strategies increased (odds ratio for use of bleeding avoidance strategies: 1.81, 95% confidence interval 1.44-2.27), especially among higher risk individuals (OR 2.03, 95% CI 1.58-2.61).  Furthermore, bleeding rates were lower following implementation of the intervention (1.0 v. 1.7%, OR 0.62, 95% CI 0.44 to 0.87 after adjustment for contemporary trends).  Following the intervention, significant variation remained both between and within hospitals with regards to use of bleeding avoidance strategies.

Conclusion: Providing clinicians with individual patient bleeding risks immediately prior to PCI was associated with increased and targeted use of bleeding avoidance strategies and lower risk-adjusted bleeding rates.  However, significant variability in the approach to bleeding avoidance persisted after implementation of this tool.

Summarized by Javier A. Valle and Steven M. Bradley

  •  Spertus JA, Decker C, Gialde E, et al. Precision medicine to improve use of bleeding avoidance strategies and reduce bleeding in patients undergoing percutaneous coronary intervention: prospective cohort study before and after implementation of personalized bleeding risks. BMJ. 2015 Mar 24;350:h1302.

 

 

Relationship Between Physical Activity and Mortality     

5 May, 15 | by Alistair Lindsay

 

The 2008 Physical Activity Guidelines for Americans recommended 150 to 300 minutes of moderate-intensity or 75 to 150 minutes of vigorous-intensity aerobic activity weekly for optimal health. However, these guidelines acknowledged uncertainty on the upper threshold of benefit or potential harms of high activity levels.  Using data from 6 pooled cohorts from the National Cancer Institute Cohort Consortium (baseline 1992-2003) with self-reports of leisure-time physical activity (LTPA), Arem and colleagues aimed to address this question. The total cohort consisted of 661,137 men and women with a median age of 62 years and a median follow-up of 14.2 years in which 116,686 deaths were accrued. When compared to subjects with no reported LTPA, individuals exercising less than the recommended minimum of 7.5metabolic-equivalent hours per week exhibited a 20% mortality benefit (HR 0.80 [95% CI 0.78-0.82]), individuals exercising 1 to 2 times the recommended minimum exhibited a 31% mortality benefit (HR 0.69 [95%CI 0.67-0.70]), and individuals exercising 2 to 3 times the minimum experienced a 37% mortality benefit (HR 0.63 [95%CI 0.62-0.65]). Researchers observed a ceiling of mortality benefit at the threshold of 3 to 5 times the minimum suggested LTPA (HR 0.61 [95%CI 0.59-0.62]). Additionally, there was no evidence of harm associated with exercise at a level of 10 times or more than the recommended minimum (HR 0.69 [95%CI 0.59-0.78]). Similar dose-response and threshold effects were seen for cardiovascular and cancer mortality.

Conclusion: Achieving the minimum levels of physical activity recommended in the 2008 Physical Activity Guidelines was associated with a mortality benefit.  Increasing health benefits were observed with increasing levels of physical activity up to 5 times the minimum recommended activity level and no harm was associated with higher levels of physical activity.  These findings support physical activity as cornerstone of optimal health and reduce concerns for potential harm associated with high levels of physical activity.

 

Summarized by Jehu S. Mathew and Steven M. Bradley

  •  Arem H, Moore SC, Patel A, Hartge P, Berrington de Gonzalez A, Visvanathan K, Campbell PT, Freedman M, Weiderpass E, Adami HO, Linet MS, Lee IM, Matthews CE. Leisure time physical activity and mortality: A detailed pooled analysis of the dose-response relationship. JAMA Internal Med. 2015 Apr 6.

 

Long-Term Outcomes of Transcatheter Aortic Valve Replacement 

5 May, 15 | by Alistair Lindsay

The Placement of Aortic Transcatheter Valves (PARTNER) trial demonstrated that transcatheter aortic valve replacement (TAVR) for high-risk patients with aortic stenosis resulted in similar outcomes at 1, 2 and 3 years compared with surgical aortic valve replacement (SAVR). The present study reports the 5-year outcomes of this trial. The study enrolled 699 patients who were randomized to SAVR or TAVR (via a transfemoral or transapical approach). Overall, mean age was 84.1 years, 94% were NYHA Class 3 or 4, and the mean Society of Thoracic Surgeons Predicted Risk of Mortality at 30 days was 11.8%. At 5 years, there were no significant differences in mortality between groups (67.8% in the TAVR group versus 62.4% in the SAVR group; hazard ratio 1.04, 95% CI 0.86–1.24; p=0.76). Additionally, there were no significant differences in cardiovascular mortality, stroke, or need for repeat hospital admission. Patients receiving TAVR experienced more major vascular complications (11.9% vs 4.7%; p=0.0002) and fewer major bleeding events (26.6% vs 34.4%; p=0.003). Development of moderate or severe aortic regurgitation was more common following TAVR (14% vs 1%; p<0·0001) and this was associated with higher mortality at 5 years (72.4% for moderate or severe aortic regurgitation compared with 56.6% for those with mild aortic regurgitation or less; p=0·003).

Conclusion: Outcomes from the original PARTNER study continue to demonstrate that TAVR is a suitable alternative to SAVR in high-risk patients with aortic stenosis. The overall mortality of greater than 60% at 5 years following both TAVR and SAVR in this population is striking. Although advances in TAVR technology, improved imaging and valve sizing, and operator experience may lead to better outcomes, the underlying risk of mortality related to comorbid illness remains important to discuss with patients considering either approach to the management of severe aortic stenosis.

Summarized by Jehu S. Mathew and Steven M. Bradley

  • Mack MJ, Leon MB, Smith CR, Miller DC, Moses JW, Tuzcu EM, Webb JG, Douglas PS, Anderson WN, Blackstone EH, Kodali SK, Makkar RR, Fontana GP, Kapadia S, Bavaria J, Hahn RT, Thourani VH, Babaliaros V, Pichard A, Herrmann HC, Brown DL, Williams M, Davidson MJ, Svensson LG, investigators Pt, Akin J. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (partner 1): A randomised controlled trial. Lancet. 2015 Mar 15. pii: S0140-6736(15)60308-7.

Clinical Outcomes at 1 Year Following Transcatheter Aortic Valve Replacement  

16 Apr, 15 | by Alistair Lindsay

To date, long-term outcome data following transcatheter aortic valve replacement (TAVR) has only been available from clinical trial data.  Evaluating long-term outcomes of TAVR in real-world use is important to ensure the anticipated benefits are observed in routine clinical practice.  Using data from the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve therapies registry merged with Centers for Medicare & Medicaid Services administrative claims data, this study evaluated 1-year outcomes of mortality, stroke, and rehospitalization among 12,182 patients who underwent TAVR between November 2011 and June 2013.  In this cohort, the 1-year mortality rate 23.7%, the stroke rate was 4.1%, the rate of heart failure was 14.3%, and 1.4% had aortic valve reintervention.  A total of 53.2% were readmitted to the hospital within 1-year.   In multivariate analysis, patient characteristics associated with increased mortality included advancing age (age >95 hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.24 to 2.09), male gender (HR 1.21; 95% CI 1.12 to 1.31), severe lung disease (HR 1.39; 95% CI 1.25 to 1.55), renal failure (dialysis HR 1.66; 95% CI 1.41 to 1.95) and Cr > 2mg/dL (HR 1.26; 95%CI 1.10 to 1.44), nontransfemoral access (HR 1.37; 95% CI 1.27 to 1.28), and STS Predicted Risk of Mortality (PROM) score greater than 15% compared with less than 8% (HR 1.82; 95% CI 1.60 to 2.06).  In addition, the authors found the median predicted mortality for this cohort was 7.1% which was lower than the median predicted mortality for patients in the clinical trials that established the efficacy of TAVR (~11% in these prior trials).

 

Conclusion: The 1-year outcomes of patients undergoing TAVR are similar to outcomes seen during prior clinical trials with a 1-year mortality of 23.7% and stroke 4.1%.  However, the lower predicted mortality in this observational cohort may reflect use of TAVR in a lower risk population than prior clinical trials.

 

Summarized by Lauren E. Thompson and Steven M. Bradley

 

  • Holmes DR Jr, Brennan JM, Rumsfeld JS, Dai D, O’Brien SM, Vemulapalli S, Edwards FH, Carroll J, Shahian D, Grover F, Tuzcu EM, Peterson ED, Brindis RG, Mack MJ; STS/ACC TVT Registry. JAMA. 2015;313(10):1019-1028. doi:10.1001/jama.2015.1474.

Second-generation stents fail to BEST CABG

16 Apr, 15 | by Alistair Lindsay

The technology of drug eluting stents for percutaneous coronary intervention (PCI) has improved over time with resultant improvements in patient outcomes.  Although prior studies have demonstrated the benefit of surgical coronary artery bypass grafting (CABG) over transcatheter PCI among patients with multivessel coronary artery disease (CAD), these studies did not incorporate newer generation drug-eluting stents.  The multicenter BEST trial randomized 880 patients with multivessel CAD to PCI with an everolimus-eluting stent or to CABG. The primary end point for this non-inferiority study was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years.  The results of the study non-significantly favored CABG at 2 years of follow-up with the primary end-point occurring in 7.9% of the CABG group and 11% of the PCI group.  This advantage achieved statistical significance in longer term follow-up (median 4.6 years, 10.6% vs. 15.3%, HR, 1.47; 95% CI, 1.01 to 2.13; P=0.04).  The majority of this benefit was driven by a higher rate of repeat revascularization among patients treated with PCI; there were no significant differences in the rates of death, overall myocardial infarction or stroke between CABG and PCI.

 

Conclusions: In this large randomized trial of patients with multi-vessel coronary disease, CABG continued to demonstrate lower rates of adverse events in comparison to patients treated with modern generation drug-eluting stents.  This difference in outcomes was driven by higher rates of repeat revascularization with PCI and not by differences in the rates of myocardial infarction, stroke or death.

 

Summarized by Hussain Contractor and Steven M. Bradley

 

  • Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, Kang SJ, Lee SW, Lee CW, Park SW, Choo SJ, Chung CH, Lee JW, Cohen DJ, Yeung AC, Hur SH, Seung KB, Ahn TH, Kwon HM, Lim DS, Rha SW, Jeong MH, Lee BK, Tresukosol D, Fu GS, Ong TK.  Trial of everolimus-eluting stents or bypass surgery for coronary disease.  N Engl J Med. 2015 Mar 26;372(13):1204-12.

Aspiration thrombectomy fails to demonstrate benefit in primary PCI  

16 Apr, 15 | by Alistair Lindsay

Although primary percutaneous coronary intervention (PPCI) restores epicardial coronary flow in the majority of patients with ST-segment myocardial infarction, this approach can lead to microvascular obstruction resulting from distal embolization of thrombus.  Manual thrombectomy (i.e. aspiration thrombectomy) prior to PPCI has been proposed as a method to reduce thrombus burden and resultant distal embolization with PPCI.  Although results from early studies of aspiration thrombectomy suggested improvements in patient outcomes, subsequent trials have failed to demonstrate a clinical benefit of aspiration thrombectomy prior to PPCI.  This large, multi-centre, international trial furthers the evidence that aspiration does not offer benefit in the routine care of patients undergoing PPCI.  This study randomized 10,732 patients with ST elevation myocardial infarction to routine manual thrombectomy prior to PCI or standard PCI alone.  The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days with a primary safety end-point of stroke within 30 days.  Crossover rates between groups were low and the primary analysis was by intention-to-treat.  Compared to standard PPCI, treatment with aspiration thrombectomy did not reduce rates of the primary outcome (6.9% vs. 7.0%, HR, 0.99; 95% CI, 0.85 to 1.15; P=0.86) or individual components of the primary outcome.  In a pre-specified sub-group analysis, there was no difference in patient outcomes as a function of initial thrombus burden. Furthermore, there was a significant increase in stroke in the thrombectomy group (0.7% vs. 0.3%, HR, 2.06; 95% CI, 1.13 to 3.75; P=0.02) within the first 30 days. 

Conclusions: In this large randomised controlled trial, routine aspiration thrombectomy did not improve patient outcomes for patients presenting with acute ST-elevation myocardial infarction.  Rates of stroke in patients undergoing thrombectomy were significantly elevated at 30 days.  Aspiration thrombectomy should no longer be a part of routine PCI care.

 

Summarized by Hussain Contractor and Steven M. Bradley

 

  • Jolly SS, Cairns JA, Yusuf S, Meeks B, Pogue J, Rokoss MJ, Kedev S, Thabane L, Stankovic G, Moreno R, Gershlick A, Chowdhary S, Lavi S, Niemelä K, Steg PG, Bernat I, Xu Y, Cantor WJ, Overgaard CB, Naber CK, Cheema AN, Welsh RC, Bertrand OF, Avezum A, Bhindi R, Pancholy S, Rao SV, Natarajan MK, Ten Berg JM, Shestakovska O, Gao P, Widimsky P and Džavík V.  Randomized Trial of Primary PCI with or without Routine Manual Thrombectomy.  N Engl J Med. 2015 Mar 16. [Epub ahead of print]

Risk of adverse events changes over time following hospitalization

1 Apr, 15 | by Alistair Lindsay

Readmissions and death after hospitalization are common.  However, there no data on how the risk for these adverse events changes over time following hospitalization.  In this study, the authors explored the absolute risk and changes in risk over time for readmission and mortality in the year following hospitalization for myocardial infarction (MI), pneumonia or heart failure (HF) among more than 3 million Medicare fee-for-service beneficiaries.  The risk of readmission was highest in the first few days following discharge for all three conditions (Figure 1).  The risk of readmission declined by 50% by day 13 after discharge following hospitalization for MI and day 38 after discharge following hospitalization for HF.  However, the risk of hospitalization remained elevated in the year following discharge for these three conditions relative to the general Medicare population (Figure 2).  The risk of mortality was highest on day 1 after hospitalization for all three conditions.

Conclusions: This study demonstrates the risk of readmission and death following hospitalization for MI, HF, and PNA is highest immediately following hospital discharge.  Although these risks decreased fairly rapidly following hospital discharge, these risks remain elevated relative to the general population for the entire year following hospitalization. This extended period of risk is not currently recognized in the majority of interventions to reduce readmissions and mortality.

Summarized by Javier A. Valle and Steven M. Bradley

  • Dharmarajan K, Hsieh AF, Kulkarni VT,  et al. Trajectories of risk after hospitalization for heart failure, acute myocardial infarction, or pneumonia: retrospective cohort study.  BMJ. 2015 Feb 5;350:h411

Figure 1: Figure 1                                                                                                                                     Figure 2:

Figure 2

Does Defibrillation Threshold Testing Confer Benefit to ICD Recipients?

1 Apr, 15 | by Alistair Lindsay

Defibrillation threshold (DFT) testing to confirm an implantable cardioverter-defibrillator (ICD) could effectively terminate ventricular fibrillation is widely accepted as part of routine practice without much evidence of efficacy. However, advances in ICD technology and evidence of initial shock efficacy have called into question the importance of DFT testing. While testing rarely results in immediate complications, ICD shocks can have adverse long-term consequences and DFT requires sedation that adds costs and complexity to the procedure. Healey and colleagues explored the efficacy and safety of ICD implantation with and without DFT testing in the single blind, multicenter, randomized non-inferiority Shockless IMPLant Evaluation (SIMPLE) trial. ICD candidates (including secondary prevention and cardiac resynchronization recipients) were randomized to each arm (1247 without DFT and 1253 receiving standard therapy). After a mean of 3.1 years of follow-up, there were no differences between groups in the primary combined outcome of failed appropriate shock or arrhythmic death (90 [7% per year] in the no-testing group and 104 [8% per year] in the standard group; HR 0.86, 95% CI 0.65–1.14; pnon-inferiority <0.0001) with consistent results for each respective individual endpoint as well as total mortality and time to first appropriate shock. Researchers also examined two 30-day composites of safety outcomes, which also failed to show differences between treatment arms.

Conclusion

While routine DFT testing following ICD implantation appears safe, this strategy did not result in improved patient outcomes when compared to device implantation without testing. SIMPLE provides evidence that DFT testing should be reconsidered as a routine aspect of clinical practice in ICD implantation.

Summarized by Jehu S. Mathew and Steven M. Bradley

  • Healey JS, Hohnloser SH, Glikson M, et al. Cardioverter defibrillator implantation without induction of ventricular fibrillation: A single-blind, non-inferiority, randomised controlled trial (simple). Lancet. 2015;385:785–91.

 

Risks of NSAID Use after Myocardial Infarction

1 Apr, 15 | by Alistair Lindsay

Nonsteroidal anti-inflammatory drugs (NSAID) are frequently used as over-the-counter and prescription medications.  Although prior studies have raised concern about the cardiovascular safety of these medications, detailed information on the risk of these medications in patients after myocardial infarction (MI) is lacking. In this study, retrospective Danish National Patient Registry data was evaluated for all patients >30 years old, admitted with first myocardial infarction (MI) between 2002-2011 and who survived to 30 days post-discharge.  All claimed medications were identified for anti-platelet agents and NSAIDS and evaluated as a time-varying covariate in the analysis to ensure outcomes were properly allocated when patients were or were not exposed.   Importantly, the only over-the-counter NSAID available in Denmark is ibuprofen at low doses, thus reducing potential misclassification resulting from lack of data capture on over-the-counter use of NSAIDS. The primary study outcome was bleeding events with a secondary cardiovascular composite outcome of cardiovascular death, nonfatal recurrent MI, ischemic stroke, transient ischemic attach, or systemic arterial emboli.   In the final cohort of 61,971 patients, 34% had filled an NSAID prescription during the period of observation.  In multivariate adjusted models there was increased risk of bleeding with NSAIDS (HR 2.02, 95% CI 1.81-2.26) and increased risk of cardiovascular events (HR 1.40, 95% CI 1.30-1.49).  Notably this relationship was independent of anti-platelet treatment, NSAID type, or length of use.

Conclusion:  Despite guideline recommendations to avoid NSAID use in patients with cardiovascular disease, about 1/3 of the cohort received an NSAID in this study.  NSAID use was associated with both increased risk of bleeding and cardiovascular events regardless of concomitant anti-thrombotic use.  Further education is necessary to reduce use of NSAIDs in this high-risk population.

Summarized by Lauren E. Thompson and Steven M. Bradley

  • Schjerning Olsen AM, Gislason GH, McGettigan P, et al. Association of NSAID Use With Risk of Bleeding and Cardiovascular Events in Patients Receiving Antithrombotic Therapy After Myocardial Infarction. JAMA. 2015;313:805-814.

Coronary sinus reduction for intractable angina

2 Mar, 15 | by Alistair Lindsay

An increasing number of patients have angina that is refractory to maximal medical therapy and unable to be addressed with revascularization procedures. Prior small studies have suggested the promise of generating a pressure gradient upstream of the myocardial venous drainage system to relieve angina.  This can be accomplished through the percutaneous implantation of a device that reduces the orifice for coronary sinus blood flow.  The Coronary Sinus Reducer for Treatment of Refractory Angina (COSIRA) trial randomized 104 patients with Canadian Cardiovascular Society (CCS) class III or IV angina, evidence of myocardial ischemia, and no remaining revascularization options to percutaneous implantation of a coronary sinus reducing device or a sham procedure in a double blind fashion.  At six months of follow-up, an improvement in at least 2 classes of CCS angina severity was noted with device implantation in 35% vs. 15% of sham controls (P=0.02).  An even higher proportion experienced improvements of at least 1 CCS class (71% vs. 42, P=0.003) and quality of life indices also favored the device group (P=0.03).  There were no differences in rates of adverse events between the two groups.

Conclusions

This small study demonstrates the potential for a device implanted in the coronary sinus to improve angina and quality of life among patients with refractory angina.  Larger trials are now needed to fully inform the potential risks and benefits of this novel invasive approach to improve angina symptom burden.

Summarized by Hussain Contractor and Steven M. Bradley

  • Verheye S, Jolicœur EM, Behan MW, Pettersson T, Sainsbury P, Hill J, Vrolix M, Agostoni P, Engstrom T, Labinaz M, de Silva R, Schwartz M, Meyten N, Uren NG, Doucet S, Tanguay JF, Lindsay S, Henry TD, White CJ, Edelman ER, Banai S. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med. 2015 Feb 5;372(6):519-27.

 

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