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Ischemic heart disease

Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment

25 Apr, 17 | by flee

Current societal guidelines advise differing dosing strategies when it comes to statin usage. The European Society of Cardiology/European Atherosclerosis Society recommends targeting a low-density lipoprotein cholesterol (LDL-C) level less than 70 mg/dL or a 50% LDL-C reduction in very high risk patients while the American College of Cardiology/American Heart Association task force advises high intensity statins without a particular LDL-C target in similar populations. This study reports on the association between achieved LDL-C levels after a year on statin therapy and subsequent major adverse cardiac events (MACE) among 31,000 Israeli patients with previous ischemic heart disease aged 30 to 84 who were at least 80% adherent to their statin therapy.The primary outcome was a combination of myocardial infarction, unstable angina, stroke, percutaneous coronary intervention and coronary artery bypass grafting, or all-cause mortality over a mean 1.6 years of follow up, after adjusting for socioeconomic factors, comorbidities and medication usage. There was no difference in incidence of adverse outcomes between low (≤ 70.0 mg/dL), and moderate (70.1 – 100.0 mg/dL) LDL-C groups (hazard ratio [HR], 1.02; 95% CI, 0.97-1.07; P = .54) but a lower incidence in moderate comared to high (≥ 100.0 mg/dL) LDL-C groups (HR, 0.89; 95% CI, 0.84-0.94; P < .001). Sensitivity analyses for age cutoffs and propensity matching reached similar conclusions. In a nonlinear regression analysis, the authors found that lower LDL-C levels did correlate with reduced MACE rates, but only to a level of approximately 90 mg/dL.


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

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