You don't need to be signed in to read BMJ Blogs, but you can register here to receive updates about other BMJ products and services via our site.

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.

 

HDL and Cardiovascular Risk: Rethinking the Relationship

17 Feb, 15 | by Alistair Lindsay

Although lower HDL levels are associated with increased cardiovascular risk, therapies to raise HDL levels have failed to reduce cardiovascular events.  In this sub-study of the longitudinal Dallas Heart Study, the authors turn their attention from absolute levels of HDL to reverse cholesterol transport in the shape of HDL efflux capacity.  This efflux capacity is a measure of HDL particles’ ability to accept cholesterol from macrophages.  Using a novel fluorescent cellular assay, HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity were measured in 2924 adults with no history of cardiovascular disease.  The primary end-point was a cardiovascular event, which included a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes over a median of 9.4 years of follow-up.  In this study, cholesterol efflux capacity was inversely associated with future cardiovascular events.  The addition of HDL efflux to a risk-model that included biochemical and traditional risk factors resulted in improved cardiovascular risk discrimination.

Conclusions

Cholesterol efflux capacity appears to be a novel biomarker associated with incident cardiovascular risk.  Furthermore, this study suggests a refined understanding of HDL metabolism and cardiovascular risk may inform drug targets to improve patient outcomes.

Summarized by Hussain Contractor and Steven M. Bradley

Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland IJ, Yuhanna IS, Rader DR, de Lemos JA, Shaul PW. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014 Dec 18;371(25):2383-93.

Surgical Repair of Moderate Mitral Regurgitation at the Time of CABG Lacks Clear Benefit

17 Feb, 15 | by Alistair Lindsay

Ischemic mitral regurgitation (MR) is common and associated with poor outcomes among patients undergoing bypass surgery.  However, it remains unknown whether repair of ischemic MR concurrent to CABG leads to better patient outcomes.  To address this important clinical question, this multi-center study randomly assigned 301 patients with moderate ischemic MR to CABG alone or CABG plus mitral valve repair.  The primary end-point was the echocardiographic parameter of left ventricular end-systolic volume index (LVESVI) at 1-year, which is a measure of left ventricular remodeling and is a known predictor of poor outcomes. Secondary end-points included major adverse cardiac or cerebrovascular events and functional assessments using the Minnesota heart failure questionnaire.  At 1-year post-operation, there were no statistically significant differences in LVESVI or mean change in LVESI from baseline, quality of life indices, or mortality outcomes.  The addition of MV repair to CABG did result in a higher rate of serious neurological events that included stroke, transient ischemic attack, and metabolic encephalopathy (3.1% vs 9.6%, P=0.03). Concurrent MV repair was also associated with lower levels of moderate to severe MR at 1 year (11.2% vs. 31.0%, P<0.001).

Conclusions

Among patients undergoing CABG, the addition of surgical repair for moderate ischemic regurgitation did not improve LVESI, quality of life, or mortality outcomes.  Although rates of moderate and severe MR at 1-year were reduced with surgical repair, this potential benefit appears offset by increased short term risk of adverse neurologic events.

Summarized by Hussain Contractor and Steven M. Bradley

  • Smith PK, Puskas JD, Ascheim DD, Voisine P, Gelijns AC, Moskowitz AJ, Hung JW, Parides MK, Ailawadi G, Perrault LP, Acker MA, Argenziano M, Thourani V, Gammie JS, Miller MA, Pagé P, Overbey JR, Bagiella E, Dagenais F, Blackstone EH, Kron IL, Goldstein DJ, Rose EA, Moquete EG, Jeffries N, Gardner TJ, O’Gara PT, Alexander JH and Michler RE. Surgical treatment of moderate ischemic mitral regurgitation. N Engl J Med. 2014 Dec 4;371(23):2178-88.

The DENERHTN Randomized Controlled Trial: Renal Denervation for Resistant Hypertension Revisited

17 Feb, 15 | by Alistair Lindsay

Despite large reductions in blood pressure seen in early studies of renal denervation, the SYMPLICITY HTN-3 randomized trial failed to show a reduction in systolic blood pressure with renal denervation when compared to medical therapy alone. As a result, interest in renal denervation as a treatment for resistant hypertension has waned.  In the DENERHTN trial, Azizi and colleagues assessed the incremental benefit of adding renal denervation to standardized stepped-care antihypertensive treatment (SSAHT) for patients with resistant hypertension in an open-label, randomized-controlled trial with blinded endpoint evaluation. After four weeks of a standardized anti-hypertensive regimen to confirm resistant hypertension, patients were randomized to renal denervation in addition to SSAHT versus SSAHT alone. The primary endpoint was the mean change in daytime systolic blood pressure after six months as assessed by ambulatory monitoring. Of the 106 patients randomized (53 in each group), 101 had endpoints available for final analysis (48 in the intervention group and 53 in the control group). At six months, patients receiving renal denervation had a significant difference in mean change in daytime ambulatory systolic blood pressure when compared to the control group with a baseline-adjusted difference of −5.9 mm Hg (−11.3 to −0.5; p=0.03). These differences were obtained with a similar number of anti-hypertensives and drug-adherence in both groups as well as an acceptable safety profile for the intervention (three minor adverse events with renal denervation and a comparable decrease in estimated glomerular filtration rate in both groups).

Conclusions

When added to a stepped antihypertensive treatment strategy, renal denervation led to a greater decrease in ambulatory blood pressure for patients with resistant hypertension than medications alone. These findings may reinvigorate interest in renal denervation and point to the need for additional trials to fully inform the role of this procedure in hypertension care.

 

Summarized by Jehu S. Mathew and Steven M. Bradley


  • Azizi M, Sapoval M, Gosse P, Monge M, Bobrie G, Delsart P, Midulla M, Mounier-Vehier C, Courand PY, Lantelme P, Denolle T, Dourmap-Collas C, Trillaud H, Pereira H, Plouin PF, Chatellier G, the Renal Denervation for Hypertension i. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (denerhtn): A multicentre, open-label, randomised controlled trial. Lancet. 2015 Jan 23. pii: S0140-6736(14)61942-5. [Epub ahead of print]

Coronary Artery Disease Screening Using CT Angiography Lacks Benefit

1 Feb, 15 | by Alistair Lindsay

Although prior studies of screening for coronary artery disease (CAD) in high-risk patients have failed to demonstrate benefit, screening with cardiac coronary computed tomography (CCTA) may hold promise by providing more detail on the extent of coronary atherosclerosis.  This trial randomized 900 patients with a 3 to 5 years history of type 1 or 2 diabetes mellitus, but without known CAD, to screening with cardiac CCTA versus usual care.  Patients randomized to CCTA received management recommendations based on scan results that included aggressive risk factor modification for findings of CAD.  The primary outcome was a composite of all-cause mortality, nonfatal myocardial infarction, or unstable angina requiring hospitalization.  There were no significant differences between the CCTA screening and usual care groups on any of the outcomes in both intention-to-treat and as-treated analysis. Notably there were lower than expected rates of events (~2%) in both the treatment and control groups.

Conclusion:  Screening with CCTA did not result in a decrease in mortality or non-fatal MI among diabetic patients without CAD symptoms.  Although a larger trial may be needed because the low event rate reduced the power of this study, routine screening with CCTA is not recommended currently.

Summarized by Lauren E. Thompson and Steven M. Bradley

  • Muhlestein JB, Lappé DL, Lima JA, Rosen BD, May HT, Knight S, Bluemke DA, Towner SR, Le V, Bair TL, Vavere AL, Anderson JL. Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial. JAMA. 2014;312(21):2234-2243. doi:10.1001/jama.2014.15825.

The SAFETY Clinical Trial: Intensive Outpatient Follow-up to Improve Outcomes after Hospitalization for Atrial Fibrillation

1 Feb, 15 | by Alistair Lindsay

The prevalence of atrial fibrillation (AF) is increasing with a concurrent rise in the number of hospitalizations for AF. The standard versus atrial fibrillation-specific management strategy (SAFETY) trial sought to test a nurse-led intervention following hospital discharge for chronic, non-valvular AF on patient outcomes of unplanned admission or all-cause death. Participants in the intervention arm received Holter monitoring and a home visit from a cardiac nurse within one to two weeks after discharge to tailor management of AF and comorbid disorders. After a median of 905 days of follow-up, 127 (76%) patients receiving the SAFETY intervention reached the primary endpoint compared to 137 (82%) patients receiving standard management (hazard ratio 0.97, 95% CI 0.76–1.23; p=0.85). When assessed as the proportion of the actual compared to the maximum possible number of days alive and not hospitalized, the SAFETY arm had a median of 900 (IQR 767–1025) of 937 maximum event-free days versus 860 (IQR 752–1047) of 937 maximum event-free days for the standard treatment group (effect size 0.22, 95% CI 0.21–0.23; p=0.04). There were no differences between groups in hospitalizations for AF, cardioversions, falls, bleeding events, acute coronary syndrome, or cerebrovascular events.

Conclusions

A nurse-led, home-based, multidisciplinary intervention among chronic AF patients following hospitalization improved the number of days alive and out of the hospital but not event-free survival or AF-specific secondary outcomes. However, the intensive nature of the intervention studied in the present trial may not be extensible to general practice.

Summarized by Jehu S. Mathew and Steven M. Bradley

  • Stewart S, Ball J, Horowitz JD, Marwick TH, Mahadevan G, Wong C, Abhayaratna WP, Chan YK, Esterman A, Thompson DR, Scuffham PA, Carrington MJ. Standard versus atrial fibrillation-specific management strategy (SAFETY) to reduce recurrent admission and prolong survival: pragmatic, multicentre, randomised controlled trial. Lancet. 2014 Nov 17. pii: S0140-6736(14)61992-9.

Why is Atherosclerotic Cardiovascular Disease Risk Overestimated by the ACC/AHA Pooled Cohort Equation?

1 Feb, 15 | by Alistair Lindsay

The 2013 ACC/AHA Cholesterol Guidelines expand the recommendations for statin use to populations previously felt to be at lower risk. Central to risk-estimation in these guidelines is a new equation for determination of atherosclerotic cardiovascular disease (ASCVD) risk. However, this risk model has been criticized overestimating ASCVD risk in validation studies of the model.  Using the Women’s Health Study, Cook et al. sought to determine the reasons for risk-overestimation by the ACC/AHA model. Among 27,542 women, 632 experienced an ASCVD event, defined as any myocardial infarction, any stroke, or death from a cardiovascular cause. The average 10-year predicted risk was 3.6% in comparison to an observed risk of 2.2%. When stratified by risk, the ratio between predicted to actual rates was greater for lower risk groups (less than 7.5% risk; ratio 1.90 or higher) than higher risk groups (greater than or equal to 7.5% risk; ratio over 1.4). Statin use and revascularization rates increased over the period of the cohort study, particularly among patients at highest ASCVD risk. Sequentially controlling for statin use, revascularization procedures, and confounding by indication did not attenuate the overestimation of risk by the model.  Failure to capture events was unlikely to explain these differences given the given the excellent follow-up (97.2%) in the Women’s Health Study.

Conclusion

Changing trends in statin use, revascularization, and underascertainment of events failed to explain the overestimation of ASCVD risk by the ACC/AHA risk prediction model.  Further efforts are needed to recalibrate the model using contemporary data to ensure optimal guidance in ASCVD risk reduction recommendations.

Summarized by Jehu S. Mathew and Steven M. Bradley

  •  Cook NR, Ridker PM. Further Insight Into the Cardiovascular Risk Calculator: The Roles of Statins, Revascularizations, and Underascertainment in the Women’s Health Study. JAMA Intern Med. 2014 Dec 1;174(12):1964-71.

 

Left atrial appendage closure in atrial fibrillation – is a comparison against warfarin still meaningful?  

20 Dec, 14 | by Alistair Lindsay

The majority of patients with nonvalvular atrial fibrillation (AF) have an indication for anti-coagulation to reduce the risk of stroke. As the left atrial appendage (LAA) is thought to the be the predominant source of thromboembolic events in the setting of AF, LAA closure may provide an alternative to anti-coagulation for stroke risk reduction without the associated bleeding concerns of anti-coagulation. This multi-center, randomized, unblinded trial compared LAA closure to warfarin in patients with AF and at least one other stroke risk factor (i.e. CHADS2 scores ≥ 1).   Patients were followed for four years and the primary outcome was a composite of stroke, systemic embolism, and cardiovascular/unexplained death. In the intention to treat analysis for efficacy the LAA closure groups had 2.3 events per 100 patient-years compared to 3.8 events per 100 patient-years in the warfarin group (relative risk 0.60 favoring device; 95% credible interval, 0.41-1.05). The most frequent adverse event with the device was serious pericardial effusion and survival curves demonstrated an earlier risk of adverse events in the device group.

 Conclusion: These long term results comparing a LAA closure device with warfarin suggest a potential role for LAA closure in AF stroke prevention. However, in an era of rapid uptake of newer oral anticoagulants with better safety profiles and similar stroke reduction efficacy as warfarin, it remains unclear if LAA has a role in contemporary care.

Summarized by Lauren E. Thompson and Steven M. Bradley

Percutaneous Left Atrial Appendage Closure vs Warfarin for Atrial Fibrillation A Randomized Clinical Trial. Reddy VY, Sievert H, Halperin J, Doshi SK, Buchbinder M, Neuzil P, Huber K, Whisenant B, Kar S, Swarup V, Gordon N, Holmes D; for the PROTECT AF Steering Committee and Investigators. JAMA. 2014;312(19):1988-1998. doi:10.1001/jama.2014.15192.

The spectrum of coronary artery disease and risk of myocardial infarction  

20 Dec, 14 | by Alistair Lindsay

Clinicians often dichotomize coronary artery disease (CAD) on the basis of obstruction to blood flow given the implications of this threshold on considerations for revascularization. As a result, nonobstructive CAD is often characterized as less significant, although this may oversimplify the risks associated with nonobstructive disease. In this retrospective cohort of patients who underwent elective coronary angiography in the Veterans Affairs health care system, the authors evaluated the relationship between gradations of CAD burden and 1-year outcomes of non-fatal myocardial infarction (MI) and mortality. CAD burden was defined by both thresholds for no CAD, nonobstructive CAD, and obstructive CAD as well as the number of vessels involved (1-vessel, 2-vessel, or 3-vessel/left main). Among 37,674 patients who underwent elective angiography, 22.3% had non-obstructive CAD and 55.4% had obstructive CAD. Compared with patients with no CAD, risk adjusted 1-year MI rates progressively increased with greater CAD burden [1-vessel nonobstructive (HR 2.0; 95%CI, 0.8-5.1); 2-vessel nonobstructive (HR 4.6; 95%CI, 2.0-10.5); 3-vessel nonobstructive (HR 4.5; 95% CI, 1.6-12.5), 1-vessel obstructive (HR 9.0; 95% CI, 4.2-19); 2-vessel obstructive (HR 16.5; 95% CI, 8.1-33.7); 3-vessel/left main obstructive (HR 19.5; 95% CI, 9.9-38.2)]. Risk adjusted 1-year mortality was also significantly higher among patients with 3-vessel nonobstructive CAD and any level of obstructive CAD.

 Conclusion: This study highlights that CAD is not a dichotomous disease that is either present or absent, but is a spectrum of progressive disease with corresponding risk. Greater attention to the spectrum of CAD risk may result in better patient outcomes.

Summarized by Lauren E. Thompson

Nonobstructive Coronary Artery Disease and Risk of Myocardial Infarction. Maddox TM, Stanislawski MA, Grunwald GK, Bradley SM, Ho PM, Tsai TT, Patel MR, Sandhu A, Valle J, Magid DJ, Leon B, Bhatt DL, Fihn SD, Rumsfeld JS. JAMA. 2014;312(17):1754-1763. doi:10.1001/jama.2014.14681.

Latest from Heart

Latest from Heart

Cardiology Masterclasses

Cardiology Masterclasses