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

Naqash Sethi

BACKGROUND Antibiotics were believed to be able to reduce the risk of new harmful events in patients with coronary heart disease. In contrast, conflicting results have suggested that antibiotics might increase the risk of cardiovascular events and mortality. No previous systematic review using Cochrane methodology has been conducted on this topic.
OBJECTIVES
We assessed the benefits and harms of antibiotics versus placebo or no intervention for the secondary prevention of coronary heart disease in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, SCI‐EXPANDED, and BIOSIS in December 2019 in order to identify relevant trials.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data. Our primary outcomes were all‐cause mortality and quality of life. We also assessed four secondary outcomes. We extracted data at maximum and 24±6 months follow‐up. We assessed the risks of systematic errors using Cochrane ‘Risk of bias’ tool. The certainty of the body of evidence was assessed by GRADE.
MAIN RESULTS
We included 38 trials randomising a total of 26,638 participants (mean age 61.6 years). Trials assessing the effects of macrolides (28 trials; 22,059 participants) contributed with the vast majority of the data.
Meta‐analyses at maximum follow‐up showed that antibiotics seemed to increase the risk of all‐cause mortality (RR 1.06; 95% CI 0.99 to 1.13; P = 0.07; I2 = 0%; 25,774 participants; high certainty of evidence), stroke (RR 1.14; 95% CI 1.00 to 1.29; P = 0.04; I2 = 0%; 14,774 participants; high certainty of evidence), and probably also cardiovascular mortality (RR 1.11; 95% CI 0.98 to 1.25; P = 0.11; I2= 0%; 4674 participants; moderate certainty of evidence).
Meta‐analyses at 24±6 months follow‐up showed that antibiotics increased the risk of all‐cause mortality (RR 1.25; 95% CI 1.06 to 1.48; P = 0.007; I2 = 0%; 9517 participants; high certainty of evidence), cardiovascular mortality (RR 1.50; 95% CI 1.17 to 1.91; P = 0.001; I2 = 0%; 9044 participants; high certainty of evidence), and probably also sudden cardiac death (RR 1.77; 95% CI 1.28 to 2.44; P = 0.0005; I2 = 0%; 4520 participants; moderate certainty of evidence).
AUTHORS’ CONCLUSIONS
Our present review indicates that macrolides for secondary prevention of coronary heart disease seem harmful. Current evidence does, therefore, not support the clinical use of macrolides for the secondary prevention of coronary heart disease.

 

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