Excess Sudden Cardiac Deaths after Short-Term Clarithromycin Administration in the CLARICOR Trial: Why Is This So, and Why Are Statins Protective?

@article{Winkel2011ExcessSC,
  title={Excess Sudden Cardiac Deaths after Short-Term Clarithromycin Administration in the CLARICOR Trial: Why Is This So, and Why Are Statins Protective?},
  author={Per Winkel and J{\o}rgen Hilden and J{\o}rgen Fischer Hansen and Per Rossen Hildebrandt and Jens Kastrup and Hans J{\o}rn Kolmos and Erik Kj{\o}ller and Christian M. Jespersen and Christian Gluud and Gorm Boje Jensen},
  journal={Cardiology},
  year={2011},
  volume={118},
  pages={63 - 67}
}
Objectives: To elucidate potential mechanisms for the clarithromycin-induced excess mortality observed in the CLARICOR trial during 2.6 year follow-up of patients with stable coronary artery disease. Methods: Cox analyses using out-of-hospital death as a proxy for sudden death compared to in-hospital (nonsudden) death. Result: In 100 of 189 (53%) cardiovascular (CV) deaths in which it was possible to examine the question, there was a strong association between place of death and the… 
View on PubMed
doi.org
36 Citations
Background Citations
5
Results Citations
1

Figures and Tables from this paper

36 Citations

Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10years in the CLARICOR randomised, blinded clinical trial.

Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease: A CLARICOR trial sub-study.

Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up—A CLARICOR Trial Sub-Study

Elevated PAPP-A levels are associated with increased long- term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.

Statistical analysis plan for data originating from the CLARICOR ( clarithromycin ofr patients with stable coronary heart disease )

Background: The purpose of the predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC) study is exploratory and hypothesis generating. We want to identify biochemical…

Prognostic value of 12 novel cardiological biomarkers in stable coronary artery disease. A 10-year follow-up of the placebo group of the Copenhagen CLARICOR trial

The addition of 10 novel biomarkers to the prediction model improved the correct prediction of all-cause death and the composite outcome by <1.5% during the 10-year prediction of cardiovascular events and mortality in patients with stable coronary heart disease.

Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study.

Osteoprotegerin independently predicts mortality in patients with stable coronary artery disease: The CLARICOR trial

Serum OPG has a long-lasting independent predictive power as to all-cause mortality and cardiovascular death in patients with stable CAD and remained an independent predictor of mortality even after adjustment for both clinical and conventional cardiovascular risk markers.

Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial

The data from the placebo patients are nevertheless useful to identify new prognostic biomarkers in patients with stable coronary artery disease, and data from both trial groups are useful to assess important potential skewness between randomised groups.

Antibiotics for secondary prevention of coronary heart disease.

Meta-analyses at maximum follow-up showed that antibiotics versus placebo or no intervention seemed to increase the risk of all-cause mortality, and the risks of systematic errors using Cochrane 'Rosk of bias' tool.

Macrolides use and the risk of sudden cardiac death

The increased risk of sudden cardiac death in patients with stable coronary heart disease who are not taking statins following clarithromycin treatment suggests that plaque formation and rupture may be a result of the sudden cardiacDeath risk induced by macrolide antibiotics.

References

SHOWING 1-10 OF 16 REFERENCES

Statin Treatment Prevents Increased Cardiovascular and All-Cause Mortality Associated With Clarithromycin in Patients With Stable Coronary Heart Disease

Concomitant statin treatment in stable patients with coronary heart disease abrogated the observed increased CV mortality associated with 2 weeks of clarithromycin and 6-year follow up confirmed these results.

Clarithromycin for 2 Weeks for Stable Coronary Heart Disease: 6-Year Follow-Up of the CLARICOR Randomized Trial and Updated Meta-Analysis of Antibiotics for Coronary Heart Disease

The 6-year mortality of clarithromycin- versus placebo-exposed patients and updated meta-analyses showed no significant effect of antibiotics on mortality, and the necessity to consider carefully the strength of the indication before administering antibiotics to patients with coronary heart disease is stressed.

Intervention with Clarithromycin in Patients with Stable Coronary Heart Disease

The design of a large-scale intervention study on the effects of a macrolide antibiotic on coronary events in patients with stable coronary heart disease (documented myocardial infarction and/or angina pectoris) to detect a reduction in coronary events of 20%.

Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial

It is found that short term clarithromycin in patients with stable coronary heart disease may cause significantly higher cardiovascular mortality and the long term safety of clarithroitcin in Patients with stable ischaemic heart disease should be examined.

High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease.

High serum YKL-40 is associated with MI, cardiovascular and all-cause mortality in patients with stable CAD and following multivariable adjustment for cardiovascular risk factors and selected medical treatments Y contributed significantly to prediction of all- cause mortality.

Rapid immunomodulation by rosuvastatin in patients with acute coronary syndrome.

Rosuvastatin exerts rapid immunomodulatory effects on the level of T-cell activation in patients with ACS and significantly reduced plasma concentrations of pro-inflammatory cytokines TNF-alpha and IFN-gamma at 72 h.

Arrhythmic and sudden death in chronic ischemic heart disease--a review of epidemiological data.

This paper is an update of a reveiw on the epidemiology of sudden and arrhythmic death and the term presumed arrhythmmic death is used in a modified version of the CAST criteria.

Antimicrobial-associated QT interval prolongation: pointes of interest.

  • R. OwensT. Nolin
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2006
It is important that clinicians be knowledgeable about drugs with QT liability, as well as the risk factors that increase the probability of TdP, and must rely upon multiple data sources to determine the risk versus the benefit for newly approved drugs.

Trends from 1987 to 2004 in sudden death due to coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

The term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future and a quantitative method for cumulative risk assessment of vulnerable patients needs to be developed.