What is the evidence for using statins (HMG-CoA reductase inhibitors) for secondary prevention of cardiovascular events?

Statin Therapy for Secondary Prevention of Cardiovascular Events

High-intensity statin therapy is strongly recommended for all patients with established atherosclerotic cardiovascular disease (ASCVD) for secondary prevention, as it significantly reduces cardiovascular events, including coronary heart disease death, recurrent myocardial infarction, cerebrovascular events, coronary revascularization, and all-cause mortality. 1

Evidence Supporting Statins for Secondary Prevention

• Statins inhibit the HMG-CoA reductase enzyme, the rate-limiting step in cholesterol biosynthesis, and are powerful drugs for lowering LDL-C, with reductions ≥50% observed with high-intensity statin regimens 1
• Multiple secondary prevention trials have demonstrated that statins reduce cardiovascular events, including coronary heart disease death, recurrent MI, cerebrovascular events, coronary revascularization, and all-cause mortality 1
• Statins have been shown to delay coronary atherosclerosis progression and possibly induce plaque regression, as demonstrated in serial angiographic and intravascular ultrasonographic studies 1
• Each 1-mmol/L (38.7-mg/dL) reduction in LDL-C results in approximately 21% reduction in the risk for cardiovascular disease events in patients with coronary heart disease 1
• In patients with cardiovascular disease other than coronary heart disease (including stroke, TIA, or peripheral arterial disease), statin therapy reduced the risk for CVD events by approximately 19% per 1-mmol/L LDL-C reduction 1

Intensity of Statin Therapy

• High-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) is recommended for patients ≤75 years of age with established ASCVD 1, 2
• More intensive statin regimens produced a highly significant 15% further reduction in major vascular events compared to less intensive therapy, driven by reductions in coronary death or non-fatal MI, coronary revascularization, and ischemic stroke 1
• In adults with coronary heart disease, fixed high-intensity statin treatment (atorvastatin 80 mg) that achieved a mean LDL-C of 77 mg/dL reduced cardiovascular events more than fixed lower-dose statin treatment that achieved a mean LDL-C of 101 mg/dL 1
• Moderate-intensity statins are recommended for patients >75 years of age and in those who have contraindications or intolerance to high-intensity regimens 1

Special Populations

• In adults with diabetes and coronary heart disease or other cardiovascular disease, moderate-dose statin therapy reduced cardiovascular events by approximately 20% per 1-mmol/L LDL-C reduction 1
• In adults ≥65 years of age with coronary heart disease, high-intensity statin treatment (atorvastatin 80 mg) reduced cardiovascular events more than fixed lower-intensity statin treatment 1
• In patients with chronic kidney disease (excluding hemodialysis) and coronary heart disease, high-intensity statin therapy significantly reduced cardiovascular events compared to lower-dose statin treatment 1
• For Asian patients, initiation at lower doses (5 mg) is recommended with careful titration up to 20 mg daily as needed, considering risks and benefits 3

Implementation and Adherence Considerations

• Statin therapy should be initiated before discharge in patients hospitalized with acute myocardial infarction to improve compliance with therapy 1
• Despite strong evidence supporting statin use in secondary prevention, adherence remains suboptimal, with only 50-60% of patients remaining adherent within 1 year of initiation, declining to 30-40% at 2 years 1
• In large, real-world registries of patients with coronary heart disease, adherence to statin therapy is even lower than in clinical trials and can reach 50% at 1 year 1
• Increasing levels of statin adherence are inversely associated with LDL-C levels and mortality after acute coronary syndrome 1

Safety Considerations

• Common side effects include myopathy and rhabdomyolysis, with risk factors including age ≥65 years, uncontrolled hypothyroidism, renal impairment, and concomitant use with certain other drugs 3
• There is an increased risk of incident diabetes with statin use, which may be limited to those with diabetes risk factors 1
• Despite the small increased risk of diabetes, the cardiovascular event rate reduction with statins far outweighs this risk, even for patients at highest risk for diabetes 1
• Treatment of 255 patients with statins for 4 years resulted in one additional case of diabetes while simultaneously preventing 5.4 vascular events among those same patients 1

Conclusion

The evidence strongly supports the use of high-intensity statin therapy for secondary prevention of cardiovascular events in patients with established ASCVD. The benefits of statin therapy in reducing cardiovascular morbidity and mortality significantly outweigh the potential risks, making statins a cornerstone of secondary prevention strategies.