HMG-CoA reductase inhibitors or as they are commonly known as statins have been postulated to produce significant reductions in major vascular events irrespective of age, but their efficacy and benefit among patients older than 75 years have not been well documented. In a recent meta-analysis published in The Lancet, by The Cholesterol Treatment Trialists’ Collaboration (CTT collaboration), the influence of advancing age and statin therapy on major vascular episodes in 28 statin trials was analyzed. The collaboration found that statins do reduce the risk of vascular events in older people but have no effect, irrespective of age, on non-vascular mortality and cancer incidence. In the past, 14 meta-analyses have been done each with inconsistent evidence about the use of statins among older people (generally >65 years). This gap in evidence concerning the perception of risk-benefit for the use of statins as the primary prevention in people older than 75 years may be one of the reasons explaining why statin therapy is often discontinued in older patients. Unlike these studies, the present meta-analysis conducted by the CTT collaboration analyzed individual participant data from randomized controlled trials of 186, 854 participants who were older than 75 years with a median follow-up of 4·9 years.
“No drug is completely harmless. When statins are used in people with low cardiovascular risk, the risks and benefits need to be weighed against each other. Statins have been associated with a slight increase in the incidence of muscle pain, diabetes, and hemorrhagic stroke, but their benefits in the prevention of major vascular events are shown to be much greater.”-Bernard M. Y. Cheng Ph.D.
The researchers noted that the analysis showed a 21% reduction in cardiovascular events per 1 mmol/L reduction in LDL cholesterol overall. This was significant in all age groups, including those above 75 years of age. For major coronary events, the overall reduction is 24% per 1 mmol/L reduction in LDL, but this was seen to decreases slightly with age. The investigators also noted that statin therapy did not have optimal results and should not be recommended among patients who have heart failure or those who are on renal dialysis. Similar risk reductions for major vascular events and cardiovascular mortality were seen in all age groups when participants with a history of heart failure or renal dialysis were excluded.
“There are limitations in this meta-analysis. The included clinical trials concentrated on efficacy endpoints—adverse events, especially if non-serious, were not as fully recorded and analyzed, which limited the ability of this meta-analysis to develop insights into the risks of side-effects for older people with statins. Last, not all relevant trials could be included in the meta-analysis if they were not part of the collaboration, and the trials included, if done many years ago, might not reflect contemporary management. More research in older people is needed to enrich the evidence on the risks and benefits of statins.”-Karen S. L. Lam M.D.
In an accompanying editorial titled “Never too old for statin treatment?” by Bernard M. Y. Cheng Ph.D. and Karen S. L. Lam M.D. from the University of Hong Kong, Bernard M. Y. Cheng debated the benefits and adverse effects of statins and questioned why the adverse effects of statins were at times, undermined. He remarked, “No drug is completely harmless. When statins are used in people with low cardiovascular risk, the risks and benefits need to be weighed against each other. Statins have been associated with a slight increase in the incidence of muscle pain, diabetes, and hemorrhagic stroke, but their benefits in the prevention of major vascular events are shown to be much greater.” The authors also compared and scrutinized the various trials included in the meta-analysis. They believed, “The included clinical trials concentrated on efficacy endpoints—adverse events, and especially if they were non-serious, the adverse effects were not as fully recorded and analyzed, which limited the ability of this meta-analysis to develop insights into the risks of side-effects for older people with statins. Lastly, not all relevant trials could be included in this meta-analysis if they were not a part of the collaboration, and the trials included, if done many years ago, may have not reflected contemporary management. More research in older people was needed to enrich the evidence on the risks and benefits of statins.” In all, further trials will be required to enable health care professionals to provide patients with accurate information and enable them to make informed choices. This meta-analysis mirrors the results of standard trials and shows that irrespective of age, statin therapy does produce significant reductions in major vascular events.
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