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Pre-operative aspirin does not influence CABG outcomes.

28 Apr, 16 | by flee

Aspirin is a common therapy for risk reduction among patients with coronary artery disease.  However, among patients undergoing coronary artery bypass surgery, the benefits of aspirin on the risk of myocardial infarction and stroke may be outweighed by perioperative bleeding risk.   To address this question, the ATACAS trial randomized 2100 patients to either receive 100 mg aspirin daily or matching placebo for 4 days immediately prior to the operation with all patients resuming aspirin within 24 hours of their bypass surgery. The primary outcome was a composite of death and thrombotic episodes (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days.  Overall rates of post-operative myocardial infarction were 14.8%, which is higher than typical for studies of post-bypass outcomes and may reflect use of troponin surveillance for the identification of this outcome.  There were no significant differences in the primary endpoint or individual components of the primary end-point between aspirin treatment and placebo groups.

Conclusions: In this large trial of perioperative aspirin therapy, there was no difference in clinical outcomes from administration or discontinuation of aspirin in the pre-operative period.  Although these findings suggest either strategy is safe, the trail appears to have limited outcomes assessment to the post-operative period.  As a result, this trial may underestimate the impact of aspirin therapy as it relates to events in the immediate preoperative period.  Additional analyses of event rates in this preoperative period may further inform optimal perioperative use of aspirin therapy.

Summarized by Hussain Contractor and Steven M. Bradley

Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, Wallace S; ATACAS Investigators of the ANZCA Clinical Trials Network. Stopping vs. Continuing Aspirin before Coronary Artery Surgery. N Engl J Med. 2016 Feb 25;374(8):728-37.

Mailing Nicotine Patches Improves Smoking Abstinence

29 Mar, 16 | by flee

Although clinical trials of nicotine replacement therapy (NRT) have consistently demonstrated higher rates of smoking cessation, the effectiveness of NRT may be lower in real-world settings, especially in the absence of behavioral support.  Accordingly, there is a need for randomized clinical trials to evaluate the effectiveness of NRT alone.  Cunningham et al conducted a randomized trial on adult smokers across Canada testing the impact of mailing nicotine patches to smokers without behavioral support on quit rates.  A total of 500 adults smoking more than 10 cigarettes daily were randomized to the experimental arm (mailed a 5-week supply of nicotine patches) or control arm (no nicotine patches mailed).  The primary outcome was self-reported abstinence from smoking at 6 months.  Self-reported nicotine abstinence rates were higher in the experimental arm (OR 2.65, 95% CI 1.44-4.89, p=0.002).  Of those who claimed abstinence, biochemical validation via saliva analysis for cotinine was available in 50.9%.  Biochemically validated abstinence at 6 months was found in 14 patients (2.8%) of 500 in the experimental cohort compared to 5 (1.0%) of 499 in the control group (OR 2.85, 95% CI 1.02-7.96, p=0.046).

 

Conclusion:  This work suggests access to nicotine patches alone, without concurrent behavioral support, promotes tobacco cessation.  However, low rates of biochemically validated smoking cessation limits the significance of the study findings.

 

Summarized by Amneet Sandhu and Steven M. Bradley

 

Cunningham JA, Kushnir V, Selby P, Tyndale RF, Zawertailo L and Leatherdale ST.  Effect of Mailing Nicotine Patches on Tobacco Cessation Among Adult Smokers: A Randomized Clinical Trial.  JAMA Intern Med. 2016: 176(2): 184-190.


 

Statin does not protect against acute kidney injury following cardiac surgery

29 Mar, 16 | by flee

Although statins affect mechanisms that lead to postoperative acute kidney injury (AKI), observational studies have failed to demonstrate a consistent effect of statin therapy on the risk of AKI after cardiac surgery. The Statin AKI Cardiac Surgery randomized control trial sought to determine if high-dose, short-term atorvastatin reduced the risk of AKI following cardiac surgery.  This double-blind, placebo-controlled, single center trial, evaluated high-dose perioperative atorvastatin on AKI in 615 patients undergoing elective coronary artery bypass surgery, valvular heart surgery, or ascending aortic surgery.  The intervention arm received atorvastation 80mg the day prior to surgery, 40mg day of surgery, and 40mg daily for the duration of hospitalization. Patients were randomized with stratification for prior statin use, presence of chronic kidney disease (GFR < 60 ml/min/1.73m2), and history or diabetes. The primary outcome of AKI was defined as an increase of 0.3mg/dL in serum creatinine or initiation of renal replacement therapy within 48 hours of surgery.  The study was terminated after a second interim analysis for concern of increased risk of AKI among statin naïve patients and for futility among patients who were previously on a statin.

 

 

Conclusion: High-dose statin therapy does not reduce the risk of AKI following cardiac surgery.

 

Summarized by Lauren E. Thompson and Steven M. Bradley

 

Billings FT 4th, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ. High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

JAMA. 2016;315(9):877-888.

Genetic similarities in cardiomyopathies

29 Feb, 16 | by flee

The incidence of peripartum cardiomyopathy is 1 in 4000 pregnant women in Western Europe, but is as high as 1 in 100 in Haiti and Nigeria.  Although peripartum cardiomyopathy can resolve, it can also be devastating as evidenced by a 5 to 10% mortality rate and the condition accounting for 4% of all U.S. women receiving heart transplantation.  Although risk factors such as pre-eclampsia, twin pregnancies, and advanced maternal age have been identified, little is known about the pathophysiology of peripartum cardiomyopathy and an individual’s susceptibility to this condition.  In comparison, the genetic underpinnings of what was previously considered idiopathic dilated cardiomyopathy are increasingly understood.  Given phenotypic similarities between peripartum cardiomyopathy and dilated cardiomyopathy, the authors sought to evaluate the contribution of genetic variants previously described in dilated cardiomyopathy among women with peripartum cardiomyopathy.  In this study, 172 women with peripartum cardiomyopathy underwent genetic sequencing of 43 genes associated with dilated cardiomyopathy.  The prevalence of variants was compared both with a population of patients with dilated cardiomyopathy and healthy controls.  A total of 26 distinct truncating variants were identified in eight genes among the women with peripartum cardiomyopathy.  The prevalence of these variants in women with peripartum cardiomyopathy (15%) were similar to that of patients with dilated cardiomyopathy (17%, P=0.81) and more common than a healthy population (4.7%, P = 1.3×10−7). Two-thirds of these variants were in the gene TTN which encodes for the very large structural cardiac sarcomeric protein titin.  Seven of these TTN variants had been previously described in patients with dilated cardiomyopathy.  Furthermore, TTN truncating variants in women with peripartum cardiomyopathy were correlated with a lower ejection fraction at 1-year follow-up (P = 0.005).

Conclusions

In this study of a well-characterized cohort of women with peripartum cardiomyopathy, genetic variants of the structural protein titin, which have previously been described in dilated cardiomyopathy, were implicated in development of the peripartum cardiomyopathy.  Further characterization of the pathophysiology and genetics of this condition will afford better risk prediction and may eventually lead to more targeted therapeutics.

Summarized by Hussain Contractor and Steven M. Bradley

Ware JS, Li J, Mazaika E, Yasso CM, DeSouza T, Cappola TP, Tsai EJ, Hilfiker-Kleiner D, Kamiya CA, Mazzarotto F, Cook SA, Halder I, Prasad SK, Pisarcik J, Hanley-Yanez K, Alharethi R, Damp J, Hsich E, Elkayam U, Sheppard R, Kealey A, Alexis J, Ramani G, Safirstein J, Boehmer J, Pauly DF, Wittstein IS, Thohan V, Zucker MJ, Liu P, Gorcsan J 3rd, McNamara DM, Seidman CE, Seidman JG and Arany Z. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies. N Engl J Med. 2016 Jan 6. [Epub ahead of print]

TAVR adoption and outcomes in German national practice

29 Feb, 16 | by flee

The advent of transcatheter aortic valve replacement (TAVR) has afforded an alternative to surgical aortic valve replacement (SAVR) for high-risk or non-operative candidates for aortic valve surgery.  However, the adoption of TAVR may not be limited to the patient population for who the procedure has studied and outcomes in routine clinical practice may not reflect those of prior randomized trials. In this retrospective study including data on all TAVR and SAVR procedures in Germany from 2007 to 2013, the authors examine the use of these procedures in clinical practice and associated patient outcomes.  A total of 32,581 TAVI and 55,992 SAVR (without concomitant revascularization) were performed during this period.  Use of TAVR increased from 144 procedures in 2007 to 9147 in 2013, while the number of SAVRs decreased from 8622 to 7048 over the same period.  Compared with patients receiving SAVR, patients receiving TAVR were older (81.0±6.1. years vs 70.2±10.0 years) and higher risk as assessed by logistic EuroScore (22.4% vs 6.3%).  Over the period of study, in-hospital mortality following TAVR decreased from 13.2% to 5.4%.  Concurrently, in-hospital mortality following SAVR declined from 3.8% to 2.2%.  Importantly, the risk-score for patients undergoing TAVR increased over time, suggesting improvements in mortality were not a result of increasing use of TAVR in a lower risk population.  Complications of permanent pacemaker implantation were higher following TAVR (17.7% vs. 4.0%, P<0.001) as were rates of stroke (2.5% vs. 1.8%, P<0.001), and acute kidney injury (5.5% vs. 3.0%, P<0.001) while bleeding events were less frequent following TAVR (8.2% vs. 14.0%,  P<0.001).

Conclusions

In a nationwide evaluation of TAVR and SAVR performed in Germany between 2007 and 2013, there was a large increase in the use of TAVR that did not appear related to expanded use in lower risk patients.  Furthermore, outcomes of both TAVR and SAVR improved during this period.  These findings are consistent with a learning curve in the use of TAVR and highlight the importance of continued evaluation of the use and outcomes of this procedure in routine practice to ensure optimal patient care.

Summarized by Hussain Contractor and Steven M. Bradley

Reinöhl J, Kaier K, Reinecke H, Schmoor C, Frankenstein L, Vach W, Cribier A, Beyersdorf F, Bode C and Zehender M. Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice. N Engl J Med. 2015 Dec 17;373(25):2438-47.

Effect of caloric restriction on heart failure with preserved ejection fraction

2 Feb, 16 | by flee

Therapies that improve outcomes are lacking for heart failure with preserved ejection fraction (HFpEF). The impact of exercise and diet interventions on HFpEF patients has not been studied.  In this single center study of 100 patients,  the effect of caloric restriction (~400 kcal/day) and or aerobic exercise training (3x a week hour long supervised sessions) on co-primary outcomes of exercise capacity (measured by peak oxygen consumption) and quality of life (QOL) (measured by the Minnesota Living with Heart Failure Questionnaire) were evaluated using a 2×2 factorial design,.  Additional exploratory outcomes included: exercise time, 6-minute walk distance, ventilator anaerobic threshold, ventilation/carbon dioxide output slope, other QOL measures (Kansas City Cardiomyopathy Questionnaire, 36-item Short-Form Health Survey), and left ventricular mass and volume. Patient included were obese (BMI >30) with HFpEF (EF ≥ 50%) without segmental wall motion abnormalities, significant valvular or ischemic disease, or pulmonary disease.  The majority of patients in this trial were female, NYHA class II or III, hypertensive, and on diuretic therapy.Both diet and exercise interventions significantly increased exercise capacity (peak VO2, diet 1.3ml/kg body mass/min, 95% CI 0.8-1.8, P <0.001 and exercise, 1.2ml/kg body mass/min, 95% CI, 0.7-1.7, p <0.001) and had an additive effect with improvement in peak VO2 of 2.5ml/kg/min.  There was no difference in QOL by MLHF with either diet or exercise (exercise, -1 unit, 95% -8-5, p 0.7; diet -6 unit, -12-1, p 0.08).

 

Conclusion: Although the 20-week diet and exercise interventions improved peak VO2 amongh patients with HFpEF, the lack of improvement in QOL scores raise questions about the clinical significance of these findings.  While diet and exercise may not significantly impact HRpEF symptoms, optimizing diet and exercise remains central to cardiovascular health.

 

Summarized by Lauren E. Thompson and Steven M. Bradley

 

Kitzman DW, et al. Effect of Caloric Restriction or Aerobic Exercise Training
on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction
A Randomized Clinical Trial. JAMA. 2016 Jan 5;315(1):36-46

COURAGE at 15 years

2 Feb, 16 | by flee

Although PCI improves morbidity and mortality in the context of an acute coronary syndrome, the benefit of PCI in the setting of stable ischemic heart disease appears limited to symptom relief.  This was best demonstrated by the COURAGE trial that randomized 2287 patients with stable angina to either intensive medical therapy alone or medical therapy with PCI.  The study found symptom reduction was greater in the first 6 to 24 months following PCI, but PCI did not impact cardiovascular events or all cause survival.  A prior follow-up study of COURAGE patients suggested mortality at 5 years may have been trending toward benefit with PCI.  In the current study, 15 years of survival data was gathered on 1211 patients (53% of the original cohort) with nearly all of these patients coming from the U.S. Veterans Affairs system.  In this cohort, a total of 561 deaths had occurred in follow-up with 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (HR, 1.03; 95% CI, 0.83 to 1.21; P=0.76); demonstrating no long-term survival advantage with PCI for stable ischemic heart disease. Data on cause of death and any additional therapies such as PCI or CABG outside of the initial 5yr trial period were unavailable.

 

Conclusions: In 15-year follow-up of approximately half of the original COURAGE trial cohort, there was no difference in mortality between those randomized to PCI and medical therapy.  Ongoing studies will inform whether PCI can improve outcomes beyond symptom burden when targeted to patients with significant demonstrable ischemia.

 

Summarized by Hussain Contractor and Steven M. Bradley

 

Sedlis SP, Hartigan PM, Teo KK, Maron DJ, Spertus JA, Mancini GB, Kostuk W, Chaitman BR, Berman D, Lorin JD, Dada M, Weintraub WS and Boden WE. Effect of PCI on Long-Term Survival in Patients with Stable Ischemic Heart Disease. N Engl J Med. 2015 Nov 12;373(20):1937-46.

Ranolazine ineffective as antianginal following incomplete revascularization

2 Feb, 16 | by flee

Ranolazine is a novel anti-anginal medication that operates via late sodium channel blockade, reducing intracellular calcium during ischemia.  Prior studies suggest ranolazine is effective in reducing the symptoms of angina among patients with ischemic heart disease.  Although revascularization is often used to address symptoms, incomplete revascularization with residual ischemic symptoms is common.  In the current study, the investigators evaluated ranolazine versus placebo in post-PCI patients with incomplete revascularization on the rates of ischemia-driven revascularization or hospitalization.  The investigators enrolled 2651 patients into this trial, randomizing to ranolazine or placebo within 14 days of the index percutaneous intervention.  Patients were included if they had a history of angina and underwent PCI, but were incompletely revascularized (>50% stenosis in at least one lesion in an epicardial vessel greater than 2.0mm in diameter).  The investigators measured time to ischemia-driven revascularization or hospitalization from randomization, as well as endpoints of time to sudden cardiac death, cardiovascular death or myocardial infarction.  After a median follow-up of 643 days, there was no significant difference between placebo and ranolazine for the primary endpoint (hazard ratio 0.95, 95% confidence interval 0.82 – 1.10), or for rates of ischemia-driven or hospitalization.  Results were similar across subgroups, including patients with acute coronary syndromes and those without.  There were higher rates of discontinuation of ranolazine than placebo because of adverse events (14 vs. 11%, p=0.04).

 

Conclusions: Ranolazine was no more effective than placebo in the prevention of ischemia driven revascularization or hospitalization among patients with chronic angina undergoing incomplete revascularization.  These findings raise questions about the relative efficacy of ranolazine to meaningfully improve symptoms among patients with ischemic heart disease.

 

Summarized by Javier A. Valle and Steven M. Bradley

 

Ranolazine in patients with incomplete revascularization after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomized, double-blind placebo-controlled trial.  Weisz et al. Lancet 2016; 387: 136-145

Repair versus replacement for ischemic mitral regurgitation

8 Jan, 16 | by flee

Whether repair or replacement is the preferred approach to surgical correction of ischemic mitral regurgitation is debated.  The Cardiothoracic Surgical Trials Network previously reported 1-year results of a randomized study of these two approached and found no differences echocardiographic or clinical outcomes. This paper reports the 2-year echocardiographic and clinical outcome results from this randomized trial of 251 patients with severe ischemic mitral regurgitation.  At 2 years follow-up, there were no significant differences in mortality (19% after repair versus 23% after replacement; P=0.39). Compared with replacement, the rate of recurrence of moderate or severe mitral regurgitation was significantly higher following repair (58.8% versus 3.8%; P<0.001).  Although the rate of major adverse cardiovascular events did not differ between the groups (42.1% in the repair group versus 42.4% in the replacement group), there were more serious heart failure events following repair (24.0 per 100 patient-years vs. 15.2 per 100 patient-years, P=0.05) and no significant difference in the rate of bleeding events between the two groups (3.5% in the repair group versus 5.3% in the replacement group; P=0.41).

Conclusions

In this study of mitral valve replacement versus repair for ischemic mitral regurgitation, no differences were observed in left ventricular remodeling or mortality at two years of follow-up.  However, there are significant differences in durability with much higher rates of severe mitral regurgitation following repair. The issue of durability as it relates to clinical outcomes will be important to monitor in continued follow-up of this study population.

Summarized by Hussain Contractor and Steven M. Bradley

Goldstein D, Moskowitz AJ, Gelijns AC, Ailawadi G, Parides MK, Perrault LP, Hung JW, Voisine P, Dagenais F, Gillinov AM, Thourani V, Argenziano M, Gammie JS, Mack M, Demers P, Atluri P, Rose EA, O’Sullivan K, Williams DL, Bagiella E, Michler RE, Weisel RD, Miller MA, Geller NL, Taddei-Peters WC, Smith PK, Moquete E, Overbey JR, Kron IL, O’Gara PT, and Acker MA. Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation. N Engl J Med. 2015 Nov 9. [Epub ahead of print]

SPRINT to lower blood pressure targets

8 Jan, 16 | by flee

Epidemiologic studies have demonstrated increasing cardiovascular risk at a systolic blood pressure above 115 mmHg.  However, blood pressure treatment targets are less clear with clinical trials limited to evidence of benefit below 150mmHg. The Systolic Blood Pressure Intervention Trial (SPRINT) sought to determine outcomes following treatment to a target of less than 120mmHg (intensive treatment) compared with a target of less than 140mmHg (standard treatment).   The study randomized 9361 non-diabetic patients with systolic hypertension (>130mmHg) and at least one other cardiac risk factor.  The primary outcome was a composite of major adverse cardiovascular events or cardiovascular death. The choice of pharmacological agents was not mandated, but the use of a thiazide based regimen was encouraged.  At 1-year, the mean systolic blood pressures were 121.4mmHg in the intensive treatment group and 136.2mmHg in the standard treatment group. The mean number of blood pressure medications required in the intensive treatment group was 2.8 compared with 1.8 in the standard treatment group.  The trial was stopped early in response to a strong signal of benefit with treatment to less than 120mmHg for the primary outcome (1.65% per year vs. 2.19% per year; hazard ratio 0.75; 95% confidence interval, 0.64 to 0.89; P<0.001).  This benefit was observed at a median follow-up of 3.26 years.  In addition, all-cause mortality was lower in the intensive treatment group (hazard ratio, 0.73; 95% confidence interval 0.60 to 0.90; P = 0.003).   Rates of hypotension, syncope, electrolyte disturbance, and acute renal failure were higher in the intensive treatment group.

Conclusions

In this large randomized study of non-diabetic patients with systolic hypertension, treating blood pressure to a target of 120mmHg led to significant cardiovascular and mortality benefits.  Translating these results into real-world practice without the intensive monitoring associated with a clinical trial is likely to be challenging, but holds the potential to significantly improve health outcomes in the general population.

Summarized by Hussain Contractor and Steven M. Bradley

Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16.

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