Meta-analysisEffects of HDL-modifiers on cardiovascular outcomes: A meta-analysis of randomized trials
Section snippets
Background
Cardiovascular disease still represents the leading cause of mortality in developed countries. In fact, despite the great achievements in treating acute myocardial infarction [1], [2], [3], [4], the results are still unsatisfactory in some high-risk subsets of patients [5], [6], [7]. Dyslipidemia has been addressed as one of the most prominent risk factors for Coronary Artery Disease (CAD) and the reduction of low-density lipoprotein cholesterol (LDL-C) still remains the primary objective of
Eligibility and search strategy
The literature was scanned by formal searches of electronic databases (MEDLINE, Cochrane and EMBASE) for clinical studies and furthermore the scientific session abstracts, searched on the American College of Cardiology (www.acc.org), American Heart Association (www.aha.org), and European Society Congress (www.escardio.org) websites, for oral presentations and/or expert slide presentations from January 1970 to March 2013. In addition, manual search of unpublished data of registered clinical
Eligible studies
Among 9297 potentially relevant publications, a total of 18 randomized clinical trials were finally included, 12 trials comparing niacin to optimal medical therapy and 6 trials with CETP inhibitors (Fig. 1) [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45]. A total of 69,515 patients were included, 34,042 (48.9%) receiving a HDL-modifier, either niacin or CETP inhibitor, and 35,473 (51%) optimal medical therapy plus eventual placebo
Primary endpoint
Follow-up length ranged from 3 to 95 months. In particular, the duration of follow-up was shorter than 1 year in 3 trials [37], [41], [42], between 1 and 3 years in 11 trials [28], [30], [32], [33], [34], [35], [36], [38], [40], [43], [44], and longer than 3 years in 4 trials [29], [31], [39], [45]. Data on cardiovascular mortality were available in 69,515 patients (100%). Cardiovascular death was observed in a total of 2002 patients (2.9%). As shown in Fig. 2, HDL-modifiers did not
Discussion
Present meta-analysis represents the first attempt to define a role of HDL-rising therapies, both with niacin or CETP-inhibitors, in the prevention of cardiovascular events, after the publication of large randomized trials with these drugs. Our main finding is that these pharmacological strategies do not provide significant benefits in cardiovascular mortality. However, a reduction in myocardial infarction and coronary revascularization was observed with niacin. No relationship was observed
Limitations
Some limitations should be addressed in present study. In particular, a major one relates to the synthesis of data from heterogeneous trials. In fact, although the study populations might seem relatively similar with regard to their high cardiovascular risk, a significant heterogeneity was found for secondary endpoints (mainly coronary revascularization). However, no heterogeneity was observed for primary endpoint. In fact, sensitivity analysis showed stability of the results of the primary
Conclusions
The present meta-analysis has shown that both niacin and CETP inhibitors do not provide significant benefits in cardiovascular mortality and are associated with higher risk of new onset diabetes (niacin) or hypertension (CETP). Significant, but modest benefits in myocardial infarction and coronary revascularization were observed with niacin, independently from the extent of HDL raising, at the expense of higher risk of new-onset diabetes. Therefore, based on current available trials,
Funding
None.
Conflict of interest
None.
Authorship contribution
MV; AS; HS; GDL; provided to data collection, GDL to project management; GDL and HS to production and scientific revision of the manuscript.
Prof. Giuseppe De Luca is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data analysis.
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