Statins reduce the risk of death from any cause
Statins reduce risk of death from any cause by 14%, risk of heart disease by 25%, risk of heart disease events by 27%, and stroke by 22% (n=56,934)
Eighteen randomised control trials (56,934 participants) were included. All-cause mortality was reduced by statins (odds ratio 0.86); as was combined fatal and non-fatal cardiovascular disease (risk ratio 0.75), combined fatal and non-fatal coronary heart disease events (risk ratio 0.73) and combined fatal and non-fatal stroke (risk ratio 0.78). Reduction of revascularisation rates (risk ratio 0.62) was also seen. There was no evidence of any serious harm caused by statin prescription. Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event. Authors’ conclusions: Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of cardiovascular disease treated with statins.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481400/
Related: CoQ10 may improve longevity and heart health in seniors
Statins reduce risk of death from any cause by 9% in women and 10% in men (n=174,149)
We performed meta-analyses on data from 22 trials of statin therapy versus control and five trials of more-intensive versus less-intensive statin therapy. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1.1 mmol/L (42.54 mg/dL) in statin vs control trials and roughly 0.5 mmol/L (19.34 mg/dL) for more-intensive vs less-intensive therapy). The proportional reductions per 1.0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio 0.84) and men (rate ratio 0.78) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk. These net benefits translated into all-cause mortality reductions with statin therapy for both women (rate ratio 0.91) and men (rate ratio 0.90). Interpretation: In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events.
https://pubmed.ncbi.nlm.nih.gov/25579834/
Benefits of statins increase over time and by level of cholesterol reduction; reduce the risk of heart disease events by 60% after several years given a typical LDL reduction of 70 mg/dL (meta-analysis)
Results: Reductions in LDL cholesterol (in the 164 trials) were 2.8 mmol/l (108 mg/dL) (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (101 mg/dL)(55%) with atorvastatin 80 mg/day, 1.8 mmol/l (70 mg/dL)(40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day, simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment concentrations of 4.8 mmol/l (185 mg/dL). Pravastatin and fluvastatin achieved smaller reductions. In the 58 trials, for an LDL cholesterol reduction of 1.0 mmol/l the risk of ischemic heart disease events was reduced by 11% in the first year of treatment, 24% in the second year, 33% in years three to five, and by 36% thereafter. Ischemic heart disease events were reduced by 20%, 31%, and 51% in trials grouped by LDL cholesterol reduction (means 0.5 mmol/l, 1.0 mmol/l, and 1.6 mmol/l) after results from first two years of treatment were excluded. After several years a reduction of 1.8 mmol/l would reduce ischemic heart disease events by an estimated 61%. Results from the same 58 trials, corroborated by results from the nine cohort studies, show that lowering LDL cholesterol decreases all stroke by 10% for a 1 mmol/l reduction and 17% for a 1.8 mmol/l reduction. Conclusions: Statins can lower LDL cholesterol concentration by an average of 1.8 mmol/l which reduces the risk of ischemic heart disease events by about 60% and stroke by 17%.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC162260/
Statins reduce risk of death from heart disease by 31% and death from any cause by 16%; atorvastatin and fluvastatin most effective (meta-analysis)
The systematic review showed that levels of blood lipids decreased during statin treatment. Network meta-analysis showed that statins were significantly more effective than the control in reducing the risk of coronary heart disease mortality (odds ratio 0.69) and all-cause mortality (odds ratio 0.84). In terms of reducing the risk of coronary heart disease morality, fluvastatin (77.3%), atorvastatin (72.3%) and lovastatin (68.4%) had higher cumulative probability than other statins. In terms of reducing all-cause mortality, atorvastatin (78.6%), fluvastatin (77.1%) and pitavastatin (74.1%) had higher cumulative probability than other statins. Compared with placebo, statins increased the incidence risk of muscle disease (OR 1.05) and kidney disease (OR 1.11). Conclusions: Statins significantly reduced levels of blood lipids, with a high dose of atorvastatin being the most effective in blood-lipid level modification. Statins reduced the risk of CHD mortality and all-cause mortality, with atorvastatin and fluvastatin being the most effective in reducing the risk of CHD mortality and all-cause mortality. Statins increased the risk of muscle disease and kidney damage.
https://pubmed.ncbi.nlm.nih.gov/27764723/
Statins reduce risk of cardiovascular events by 26%; atorvastatin and rosuvastatin among most effective (meta-analysis)
We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. Results: In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal myocardial infarction (risk ratio 0.62), cardiovascular disease mortality (risk ratio 0.80), all-cause mortality (risk ratio 0.89), non-fatal stroke (risk ratio 0.83), unstable angina (risk ratio 0.75), and composite major cardiovascular events (risk ratio 0.74). Statins increased statistically significantly relative and absolute risks of myopathy (risk ratio 1.08); renal dysfunction (risk ratio 1.12); and hepatic dysfunction (risk ratio 1.16). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing cardiovascular disease events while atorvastatin appeared to have the best safety profile. Conclusions: All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type.
https://pubmed.ncbi.nlm.nih.gov/30716508/
Statins reduce overall mortality risk by 11%, different statins yield similar effects (nine trials)
A total of nine clinical trials were selected for further study, and in each of them patients had defined cardiovascular risk factors. Meta-analysis of the overall mortality results of the nine trials showed a significant reduction associated to statin therapy (odds ratio 0.886), when compared to the control situation. At least one trial showed a numerical reduction of overall mortality with pravastatin, with atorvastatin and with rosuvastatin. Separate meta-analyses were carried out with clinical trials with each of these three drugs, yielding similar effects: pravastatin – odds ratio 0.852; atorvastatin – odds ratio 0.853; rosuvastatin – odds ratio 0.870. Conclusions: Statins used in primary prevention lead to a significant decrease in overall mortality.
https://pubmed.ncbi.nlm.nih.gov/28249380/
Among adults with no previous cardiovascular events, statins reduce all-cause mortality risk by 14%, cardiovascular mortality by 31%, and cardiovascular events by 30% (n=71,344)
Nineteen trials (n = 71,344 participants; mean age, 51-66 years) compared statins vs placebo or no statin. Statin therapy was associated with decreased risk of all-cause mortality (risk ratio, 0.86), cardiovascular mortality (risk ratio, 0.69), stroke (risk ratio, 0.71), myocardial infarction (risk ratio, 0.64), and composite cardiovascular outcomes (risk ratio, 0.70). Relative benefits appeared consistent in demographic and clinical subgroups, including populations without marked hyperlipidemia (total cholesterol level <200 mg/dL); absolute benefits were higher in subgroups at higher baseline risk. Statins were not associated with increased risk of serious adverse events, myalgias, or liver-related harms. Conclusions and relevance: In adults at increased CVD risk but without prior CVD events, statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and CVD events, with greater absolute benefits in patients at greater baseline risk.
https://pubmed.ncbi.nlm.nih.gov/27838722/
Among low risk individuals, statins reduce risk of death from any cause by 9% (n=134,537)
This meta-analysis included individual participant data from 22 trials of statin versus control (n=134,537; mean LDL cholesterol difference 1·08 mmol/L (42 mg/dL); median follow-up 4·8 years) and five trials of more versus less statin. Findings: Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (risk ratio 0·79 per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (risk ratio per 1·0 mmol/L reduction from lowest to highest risk: 0·62, 0·69, 0·79, 0·81, and 0·79), which reflected significant reductions in these two lowest risk categories in major coronary events (risk ratio 0·57, and 0·61) and in coronary revascularisations (risk ratio 0·52, and 0·63). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (risk ratio per 1·0 mmol/L LDL cholesterol reduction 0·76) was also similar to that seen in higher risk categories. In participants without a history of vascular disease, statins reduced the risks of vascular (risk ratio per 1·0 mmol/L LDL cholesterol reduction 0·85) and all-cause mortality (risk ratio 0·91), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence, cancer mortality, or other non-vascular mortality. Interpretation: In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437972/
For higher risk individuals, there is higher certainty that statins improve health outcomes; risk of all-cause mortality reduced by 20% and cardiovascular mortality by 32% (n=60,194)
We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up. We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease (relative risk: 0.79) and myocardial infarction (relative risk: 0.45) but not all-cause or cardiovascular mortality or stroke. For secondary prevention, statins reduced all-cause mortality (relative risk: 0.80), cardiovascular mortality (relative risk: 0.68), coronary artery disease (relative risk: 0.68), myocardial infarction (relative risk: 0.68), and revascularization (relative risk: 0.68). Intensive (vs less-intensive) statin therapy reduced the risk of coronary artery disease and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. Conclusion: High-certainty evidence supports statin use for secondary prevention in older individuals.
https://pubmed.ncbi.nlm.nih.gov/30903687/
Previously participating in a statin drug trial reduces post-trial mortality by 10% (n=55,732)
We included eight trials, with mean post-trial follow-up ranging from 1.6 to 15.1 years, and including 13,781 post-trial deaths (6685 CVD). Direct effects of statins within trials were greater than legacy effects post-trials. Pooled post-trial hazard ratios for the three primary prevention studies demonstrated possible post-trial legacy effects on CVD mortality (hazard ratio=0.87) and on all-cause mortality (hazard ratio=0.90). Conclusions: Possible post-trial statin legacy effects on all-cause mortality appear to be driven by the primary prevention studies. Although these relative benefits were smaller than those observed within the trial, the absolute benefits may be similar for the two time periods.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173243/
Statins also reduce the risk of Alzheimer’s, dementia, and cognitive impairment
Statins reduce risk of Alzheimer’s by 19% and dementia by 19% (n=3,332,706)
Thirty-one eligible studies involving a total of 3,332,706 participants with 184,666 incident cases were included in this meta-analysis. Statins use was associated with dementia risk decrement (relevant risk: 0.85). Subgroup analysis showed statins use was associated with Alzheimer’s disease (relevant risk: 0.81) and non-Alzheimer disease dementia (relevant risk: 0.81) risk decrement. Furthermore, statins use was associated with dementia risk decrement in female (relevant risk: 0.89) and male (relevant risk: 0.88). In addition, a dose-response showed per 1 year of duration of statins use incremental increase was associated with 20% dementia risk decrement (relevant risk: 0.80), and per 5-mg mean daily dose incremental increase in statins use was associated with 11% dementia risk decrement (relevant risk: 0.89). Statins use was associated with dementia risk decrement. The potency and the cumulative duration of statin utilized played critical roles.
https://pubmed.ncbi.nlm.nih.gov/30045255/
Statins reduce risk of Alzheimer’s by 29%, mild cognitive impairment by 27%, and dementia by 15% (n=2,745,149)
Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (adjusted risk ratio = 0.849), Alzheimer’s disease (adjusted risk ratio = 0.719), and mild cognitive impairment (adjusted risk ratio = 0.737). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (adjusted risk ratio = 0.877) and possibly lower Alzheimer’s disease risk (adjusted risk ratio = 0.619). Lipophilic statins were associated with reduced risk of Alzheimer’s disease (adjusted risk ratio = 0.639). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, Alzheimer’s disease, and mild cognitive impairment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895617/
Statins may have added cardiovascular and cancer benefits, depending on circumstance
Among atrial fibrillation patients, statins reduce risk of recurrence after electrical cardioversion by 24% (n=524)
A total of 5 trials with 524 patients were available for analysis. The pooling analysis showed that statin agents significantly reduced the recurrence of atrial fibrillation after electrical cardioversion compared with no statin treatment (risk ratio=0.76). The beneficial effect was shown both in atrial fibrillation subjects receiving atorvastatin or rosuvastatin treatment (atorvastatin 80 mg: risk ratio=0.82; atorvastatin 10 mg: risk ratio=0.27; rosuvastatin: risk ratio=0.38). Furthermore, the benefit of statin agents on preventing atrial fibrillation recurrence after electrical fibrillation was demonstrated within 3-month follow-up, and the clinical benefit seemed likely to remain until no less than 12 months after electrical cardioversion.
https://pubmed.ncbi.nlm.nih.gov/25529758/
Statins reduce aortic aneurysm rupture by 33% and all-cause mortality by 33% (n=150,134)
A total of 32 observational studies involving 150,134 participants were enrolled into this meta-analysis. The risk ratios of statin therapy for abdominal aortic aneurysm rupture, postrepair mortality, all-cause mortality, and adverse events were 0.67, 0.60, 0.66, and 0.58, respectively. Our findings suggested that statin therapy could reduce the risks of abdominal aortic aneurysm rupture, postrepair mortality, all-cause mortality, and adverse events, without inducing the risk of abdominal aortic aneurysm incidence or cerebral aneurysm rupture.
https://pubmed.ncbi.nlm.nih.gov/30688798/
Among transcatheter aortic valve implantation patients, statins reduce midterm all-cause mortality risk by 20% (n=5,170)
Eight eligible studies with a total of 5,170 transcatheter aortic valve implantation patients were identified and included in the present meta-analysis. The primary meta-analysis demonstrated that statin treatment was associated with significantly lower midterm (≥1 year) all-cause mortality (hazard ratio, 0.74). The secondary meta-analysis also indicated an association of statin therapy with significantly lower midterm mortality (hazard ratio, 0.80). In conclusion, statin therapy is associated with better midterm survival after transcatheter aortic valve implantation.
https://pubmed.ncbi.nlm.nih.gov/31326076/
Among heart failure patients, statins reduce all-cause mortality risk by 23%, regardless of severity (n=88,100)
We included 17 studies (n = 88,100) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (hazard ratio 0.77), cardiovascular mortality (hazard ratio 0.82), and cardiovascular hospitalization (hazard ratio 0.78). All-cause mortality was reduced on statin therapy in heart failure with both ejection fraction < 40% and ≥ 40% (hazard ratio: 0.77, and hazard ratio 0.75, respectively). Similarly, cardiovascular mortality (hazard ratio 0.86, and hazard ratio 0.83, respectively), and cardiovascular hospitalizations (hazard ratio 0.80 and hazard ratio 0.76, respectively) were reduced in these ejection fraction subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. Conclusions: In conclusion, statins may have a beneficial effect on cardiovascular outcomes irrespective of heart failure etiology and left ventricular ejection fraction level.
https://pubmed.ncbi.nlm.nih.gov/31672151/
Among colon cancer patients, statins reduce all-cause mortality by 14% and cancer specific mortality by 18% (n=130,994)
Total fourteen studies involving 130,994 patients were included in this meta-analysis. For pre-diagnosis statin uses, the pooled hazard ratio of all-cause mortality was 0.85 and the pooled hazard ratio of cancer-specific mortality was 0.82. In terms of post-diagnosis statin uses, the pooled hazard ratio of all-cause mortality was 0.86, and the pooled hazard ratio of cancer-specific mortality was 0.79. For post-diagnosis statin uses, there is no difference in all-cause mortality when stratified by KRAS gene mutation status.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558478/
Among those with obstructive pulmonary disease, statins reduce all-cause mortality risk by 19% (n=16,269)
The pooled hazard ratio of statins to all-cause mortality involving 16,269 patients was 0.81 with moderate heterogeneity. After three possibly unpublished cohorts were imputed, the pooled hazard ratio of 0.83 still suggested a favorable prognosis in statin-treated patients. The pooled hazard ratio of statins to respiratory-related mortality were 0.55, although these results were not conclusive as we could not find a sufficient number of original studies dealing with those forms of mortality. Conclusions: The use of statins for patients suffering from chronic obstructive pulmonary disease may reduce all-cause mortality.
https://pubmed.ncbi.nlm.nih.gov/25029928/
Among cancer patients, statin use reduces all-cause mortality by 19% and cancer-specific mortality by 23% (n=990,649)
Thirty-nine cohort studies and two case-control studies involving 990,649 participants were included. The results showed that patients who used statins after diagnosis had a hazard ratio of 0.81 for all-cause mortality compared to non-users. Those who used statin after diagnosis (vs. non-users) had a hazard ratio of 0.77 for cancer-specific mortality. Prediagnostic exposure to statin was associated with both all-cause mortality (hazard ratio=0.79) and cancer-specific mortality (hazard ratio=0.69). Stratifying by cancer type, the three largest cancer-type subgroups were colorectal, prostate and breast cancer and all showed a benefit from statin use. Conclusions: In conclusion, the average effect of statin use, both postdiagnosis and prediagnosis, is beneficial for overall survival and cancer-specific survival.
https://pubmed.ncbi.nlm.nih.gov/25890842/
Among those with chronic kidney disease, statins reduce risk of all-cause mortality by 21% and cardiovascular mortality by 23% (n=37,274)
We were able to meta-analyse 38 studies (37,274 participants). Compared with placebo, statin therapy consistently prevented major cardiovascular events (risk ratio 0.72), all-cause mortality (risk ratio 0.79), cardiovascular death (risk ratio 0.77) and myocardial infarction (risk ratio 0.55). Statins had uncertain effects on stroke. Statins had uncertain effects on progression of chronic kidney disease. Statins clearly reduced risks of death, major cardiovascular events, and myocardial infarction in people with chronic kidney disease who did not have cardiovascular disease at baseline (primary prevention). Authors’ conclusions: Statins consistently lower death and major cardiovascular events by 20% in people with chronic kidney disease not requiring dialysis.
https://pubmed.ncbi.nlm.nih.gov/24880031/
Certain statins may have increased side effects, CoQ10 and vitamin D may prevent muscle symptoms
Intensive statin therapy, when compared to moderate therapy, is associate with 14% less cardiovascular related death, but 44% more adverse events (n=27,548)
Four trials were included in the analysis. Together, they included 27,548 patients. Intensive-dose therapy with atorvastatin or simvastatin 80 mg was associated with a significant increase in the risk for any adverse event (odds ratio = 1.44) and adverse events requiring discontinuation of therapy (odds ratio = 1.28). Intensive-dose therapy also was associated with an increased risk for abnormalities on liver function testing (odds ratio = 4.48) and elevations in creatine kinase (odds ratio = 9.97). The benefits of intensive-dose statin therapy included reductions in cardiovascular disease death (odds ratio = 0.86), myocardial infarction (odds ratio = 0.84), and stroke (odds ratio = 0.82). Conclusions: Although intensive-dose statin therapy was associated with a reduced risk for important cardiovascular events, it was also associated with an increased risk for statin-induced adverse events. Therefore, moderate-dose statin therapy may be the most appropriate choice for achieving CV risk reduction in the majority of individuals, whereas intensive-dose statin therapy may be reserved for those at highest risk.
https://pubmed.ncbi.nlm.nih.gov/17472818/
Atorvastatin associated with highest risk of adverse events and fluvastatin with the lowest (n=71,108)
Eighteen trials including 71,108 persons, and 301,374 person-years of follow-up were represented in this analysis. Statin therapy increased the risk of any adverse events by 39% compared with placebo. Statins were associated with a 26% reduction in the risk of a clinical cardiovascular event. Treating 1000 patients with a statin would prevent 37 cardiovascular events, and 5 adverse events would be observed. Atorvastatin was associated with the greatest risk of adverse events and fluvastatin with the least risk. Simvastatin, pravastatin, and lovastatin had similar odds of adverse events. Nonurgent adverse events such as myalgia and liver function elevations were responsible for approximately two thirds of adverse events reported in trials.
https://pubmed.ncbi.nlm.nih.gov/16490577/
CoQ10 improves statin-associated muscle symptoms (n=575)
Twelve randomized controlled trials with a total of 575 patients were enrolled; of them, 294 patients were in the CoQ10 supplementation group and 281 were in the placebo group. Compared with placebo, CoQ10 supplementation ameliorated statin-associated muscle symptoms, such as muscle pain (weighted mean difference , -1.60), muscle weakness (weighted mean difference , -2.28), muscle cramp (weighted mean difference, -1.78), and muscle tiredness (weighted mean difference, -1.75), whereas no reduction in the plasma creatine kinase level was observed after CoQ10 supplementation. Conclusions CoQ10 supplementation ameliorated statin-associated muscle symptoms, implying that CoQ10 supplementation may be a complementary approach to manage statin-induced myopathy.
https://pubmed.ncbi.nlm.nih.gov/30371340/
Low vitamin D levels associated with muscle pain among statin users (n=2420)
The final analysis included 7 studies with 2420 statin-treated patients divided into subgroups of patients with (n=666 [27.5%]) or without (n=1754) myalgia. Plasma vit D concentrations in the symptomatic and asymptomatic subgroups were 28.4±13.80ng/mL and 34.86±11.63ng/mL, respectively. The combination of data from individual observational studies showed that vit D plasma concentrations were significantly lower in patients with statin-associated myalgia compared with patients not manifesting this side effect (weighted mean difference -9.41ng/mL). Conclusions: This meta-analysis provides evidence that low vit D levels are associated with myalgia in patients on statin therapy.
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