What is the absolute risk reduction for statins (HMG-CoA reductase inhibitors) in secondary prevention?

From the Guidelines

The absolute risk reduction for statins in secondary prevention is approximately 15% over a period of time, as demonstrated by the Cholesterol Treatment Trialists' meta-analyses of individual participant data from randomized trials of more versus less intensive statin regimens 1. Statins, such as atorvastatin, rosuvastatin, or simvastatin, are strongly recommended for secondary prevention in patients with established cardiovascular disease. For optimal benefit, high-intensity statin therapy should be used, such as atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily. This means that for every 100 patients with existing cardiovascular disease treated with statins, about 15 fewer patients will experience a major cardiovascular event compared to those not taking statins or taking less intensive statin therapy. The mechanism behind this risk reduction is primarily through lowering LDL cholesterol, which reduces atherosclerotic plaque formation and stabilizes existing plaques. Statins also have pleiotropic effects, including anti-inflammatory properties, which may contribute to their benefits in secondary prevention. Key points to consider when prescribing statins for secondary prevention include:

• High-intensity statin therapy is recommended for patients ≤75 years of age with clinical atherosclerotic cardiovascular disease 1
• Moderate-intensity statins are recommended for patients >75 years of age or those with contraindications/intolerance to high-intensity regimens 1
• Statin therapy should be individualized in persons >75 years of age according to the potential for ASCVD risk-reduction benefits, adverse effects, drug-drug interactions, and patient preferences 1 It's essential to note that the absolute risk reduction can vary based on individual patient factors, including baseline risk and adherence to therapy. Regular monitoring of lipid levels and potential side effects is necessary to ensure optimal treatment.

From the FDA Drug Label

In Study 4S, patients were treated with standard care, including lipid-lowering diet, and randomized to either simvastatin 20-40 mg/day (n=2,221) or placebo (n=2,223) for a median duration of 5.4 years. Simvastatin significantly reduced the risk of mortality by 30% (p=0. 0003,182 deaths in the simvastatin group vs 256 deaths in the placebo group). The risk of CHD mortality was significantly reduced by 42% (p=0. 00001,111 deaths in the simvastatin group vs 189 deaths in the placebo group). Table 5: CHD Mortality and Cardiovascular Events in Adult Patients with High Risk of Developing a Major Coronary Event in Study HPS

• n = number of patients with indicated event Endpoint Simvastatin (N=10,269) n (%)* Placebo (N=10,267) n (%)* Risk Reduction (%) (95% CI) p-Value Primary Mortality 1,328 (12.9%) 1,507 (14.7%) 13 (6 to 19%) p=0.0003 CHD mortality 587 (5.7%) 707 (6. 9%) 18 (8 to 26%) p=0.0005 Table 7: LIPID - Primary and Secondary Endpoints Number (%) of Subjects Event Pravastatin 40 mg (N=4,512) Placebo (N=4,502) Risk Reduction p-value Primary Endpoint CHD mortality 287 (6.4) 373 (8.3) 24% 0.0004 Secondary Endpoints Total mortality 498 (11.0) 633 (14.1) 23% <0.0001 CHD mortality or nonfatal MI 557 (12.3) 715 (15.9) 24% <0. 0001 Table 8: CARE - Primary and Secondary Endpoints Number (%) of Subjects Event Pravastatin 40 mg (N=2,081) Placebo (N=2,078) Risk Reduction p-value Primary Endpoint CHD mortality or nonfatal MIa 212 (10.2) 274 (13.2) 24% 0.003

The absolute risk reduction (ARR) for statins (HMG-CoA reductase inhibitors) in secondary prevention can be calculated as follows:

• For simvastatin in Study 4S:
  • Mortality: ARR = 30% of the control group event rate = 0.3 * (256/2223) = 0.0346 or 3.46%
  • CHD mortality: ARR = 42% of the control group event rate = 0.42 * (189/2223) = 0.0338 or 3.38%
• For simvastatin in Study HPS:
  • Primary Mortality: ARR = 13% of the control group event rate = 0.13 * (1507/10267) = 0.019 or 1.9%
  • CHD mortality: ARR = 18% of the control group event rate = 0.18 * (707/10267) = 0.0123 or 1.23%
• For pravastatin in the LIPID study:
  • CHD mortality: ARR = 24% of the control group event rate = 0.24 * (373/4502) = 0.0199 or 1.99%
  • Total mortality: ARR = 23% of the control group event rate = 0.23 * (633/4502) = 0.0306 or 3.06%
• For pravastatin in the CARE study:
  • CHD mortality or nonfatal MI: ARR = 24% of the control group event rate = 0.24 * (274/2078) = 0.0314 or 3.14%

Key points:

• The absolute risk reduction for statins in secondary prevention varies depending on the specific statin, study, and outcome.
• The ARR for simvastatin in Study 4S was 3.46% for mortality and 3.38% for CHD mortality.
• The ARR for simvastatin in Study HPS was 1.9% for primary mortality and 1.23% for CHD mortality.
• The ARR for pravastatin in the LIPID study was 1.99% for CHD mortality and 3.06% for total mortality.
• The ARR for pravastatin in the CARE study was 3.14% for CHD mortality or nonfatal MI. 2, 3

From the Research

Absolute Risk Reduction for Statins in Secondary Prevention

• The absolute risk reduction (ARR) for statins in secondary prevention is estimated to be around 5.1% to 7.8% over 5 to 10 years, respectively, in elderly patients with vascular disease 4.
• A study found that 98% of patients with vascular disease had a 5-year ARR of ≥2.0%, compared to 31% of patients without vascular disease 4.
• The number needed to treat (NNT) with statins to prevent first cardiovascular events and death is estimated to be around 20 to 50, depending on the population and endpoint 5.
• The 2013 ACC/AHA Cholesterol Guideline estimates that treating all statin-eligible adults could prevent an estimated 243,589 ASCVD events annually, with an ARR of 5.4% and a 10-year NNT of 18 6.

Subgroup Analysis

• Subgroup analysis revealed that the protective effects of statins against ischemic cardiovascular and cerebrovascular events were more obvious in certain subgroups, such as patients who were 75-79 years old, statin-adherent, without diabetes mellitus at baseline, and non-adherent to aspirin or antiplatelet drugs 7.
• The ARR and NNT may vary depending on the specific population, such as men and women, whites and nonwhites, and those with or without metabolic syndrome 5.

Clinical Implications

• The use of statins in secondary prevention is warranted as a first-line agent in all patients, as well as those in primary prevention at high or very high risk for ASCVD events 8.
• The potency and dose of statins should be tailored to the individual's cardiovascular risk and tolerance to potential adverse effects to achieve guidelines-directed LDL goals 8.