Statins research unfinished saga: desirability versus feasibilityReport as inadecuate




Statins research unfinished saga: desirability versus feasibility - Download this document for free, or read online. Document in PDF available to download.

Cardiovascular Diabetology

, 4:8

First Online: 07 June 2005Received: 03 June 2005Accepted: 07 June 2005

Abstract

Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action the so-called -class effect-. However, statins differ in multiple characteristics, including liver and renal metabolism, half-life, effects on several serum lipid components, bioavailability and potency. Some are fungal derivatives, and others are synthetic compounds. The percentage absorption of an oral dose, amount of protein binding, degree of renal excretion, hydrophilicity, and potency on a weight basis is variable. These differences may be even greater in diabetic patients, who may present diabetes-induced abnormalities in P450 isoforms and altered hepatic metabolic pathways. Thus, it is obvious that head-to-head comparisons between different statins are preferable than trial-to-trial comparisons. Such assessments are of utmost importance, especially in cases in which specific populations with a distinct lipid profile and altered metabolic pathways, like diabetics, are studied. It should be specially pinpointed that patients with metabolic syndrome and diabetes constitute also a special population regarding their atherogenic dyslipidemia, which is usually associated with low HDL-cholesterol, hypertriglyceridemia and predominance of small dense LDL-cholesterol. Therefore, these patients may benefit from fibrates or combined statin-fibrate treatment. This policy is not accomplished since in the real world things are more complex. Trials would require very large sample sizes and long-term follow-up to detect significant differences in myocardial infarction or death between two different statins. Moreover, the fact that new compounds are under several phases of research and development represents an additional drawback for performing the trials. Ideally, head-to-head trials regarding clinically important outcomes should be conducted for all drugs. Nonetheless, the desirability of performing such trials, which epitomize modern evidence-based medicine, is frequently superseded by the feasibility dictated by pragmatic and economic circumstances. In the latter case, in absence of solid systematic documentation of comparable health benefits and long-term safety, both researchers and practicing physicians should allude to the weight of scientific endorsement behind the arguments and seek for the possible strengths and weaknesses intrinsic to each specific study. In any case, conclusions based on surrogate endpoints cannot completely substitute head-to-head comparisons regarding patients- outcome.

Keywordscoronary artery disease diabetes hyperlipidemia statins trials List of abbreviations usedALLIANCEAggressive Lipid-Lowering Initiation Abates New Cardiac Events

ASAPAtorvastatin versus Simvastatin on Atherosclerosis Progression

CADcoronary artery disease

EXCELExpanded Clinical Evaluation of Lovastatin

HDLhigh-density lipoproteins

LDLlow-density lipoprotein

MImyocardial infarction

PROVE-ITPravastatin or Atorvastatin Evaluation and Infection Therapy

REVERSALReversal of Atherosclerosis with Aggressive Lipid Lowering

RLP-Cremnant-like particles cholesterol

VLDLvery low-density lipoproteins

WOSCOPSWest of Scotland Coronary Prevention Study

4SScandinavian Simvastatin Survival Study

Download fulltext PDF



Author: Enrique Z Fisman - Yehuda Adler - Alexander Tenenbaum

Source: https://link.springer.com/article/10.1186/1475-2840-4-8







Related documents