In the Journals

More intensive LDL lowering decreases risk for CV, total mortality

Eliano Pio Navarese, MD, PhD
Eliano P. Navarese

Patients with higher baseline LDL levels who underwent more intensive LDL lowering had a greater risk reduction of total and CV mortality compared with those with less intensive treatment, according to a meta-analysis published in JAMA.

Analysis of randomized trials

Eliano P. Navarese, MD, PhD, director of international research at Inova Heart and Vascular Institute in Falls Church, Virginia, and colleagues conducted a meta-analysis of 270,288 patients from 34 randomized trials that received LDL lowering treatment for at least 48 weeks. Trials that included patients with end-stage renal disease or HF were excluded. Data included CV and mortality outcomes.

Patients were treated with a statin, a nonstatin therapy (ezetimibe or a PCSK9 inhibitor) or a combination of a statin with nonstatin therapy. Those treated with more intensive therapy (n = 136,299) received a more potent pharmacology strategy, whereas those with less intensive strategy (n = 133,989) were typically in the control group of a trial.

Coprimary endpoints were CV mortality and total mortality. Secondary endpoints were cerebrovascular events, MI, major adverse cardiac events and revascularizations.

All-cause mortality occurred in more patients who received less intensive therapy compared with more intensive therapy (7.08% vs. 7.7%; RR = 0.92; 95% CI, 0.88-0.96).

With each 40-mg/dL increase in baseline LDL, greater reductions in all-cause mortality were seen in patients who were assigned more intensive LDL lowering (change in RR per 40 mg/dL increase = 0.91; 95% CI, 0.86-0.96; P = .001). This was associated with an absolute risk difference of –1.05 incident cases per 1,000 person-years (95% CI, –1.59 to –0.51), although it was only seen in patients with a baseline LDL greater than 100 mg/dL (P for interaction < .001).

More patients who received less intensive therapy died from CV-related causes compared with those who received more intensive therapy (3.48% vs. 4.07%; RR = 0.84; 95% CI, 0.79-0.89).

For each 40-mg/dL increase in baseline LDL, there was a greater decrease in CV mortality in the more intensive therapy group vs. the less intensive therapy group (change in RR per 40 mg/dL increase = 0.86; 95% CI, 0.8-0.94; P < .001). This resulted in an absolute risk difference of –1 incident cases per 1,000 person-years (95% CI, –1.51 to –0.45) and was only seen in patients with baseline LDL levels greater than 100 mg/dL (P for interaction < .001).

Ann Marie Navar, MD, PhD
Ann Marie Navar

Greatest risk reduction

The greatest reduction in all-cause mortality was in patients with baseline LDL levels greater than 160 mg/dL (RR = 0.72; 95% CI, 0.62-0.84; P < .001), with 4.3 fewer deaths per 1,000 person-years.

Patients with higher baseline LDL levels who were assigned more intensive therapies also had greater risk reductions for revascularization, MI and major adverse cardiac events.

“If additional LDL-lowering therapies are considered in statin-treated patients, nonstatin LDL lowering therapies shown to reduce cardiovascular disease events are recommended,” Navarese and colleagues wrote. “This analysis further supports individualizing estimates of the potential for a cardiovascular risk reduction benefit from LDL-lowering therapy based on consideration of not only a patient’s absolute risk and current LDL level, but also an individualized estimate of the risk reduction based on current LDL level and the outcomes desired.”

Eric D. Peterson

In a related editorial, Ann Marie Navar, MD, PhD, assistant professor of medicine at Duke University School of Medicine, member of the Duke Clinical Research Institute and Cardiology Today’s Next Gen Innovator, and Eric D. Peterson, MD, MPH, Fred Cobb, MD Professor of Medicine at Duke University School of Medicine and director of the Duke Clinical Research Institute, wrote: “Clinicians ... need to consider the patient’s entire CVD risk profile when making therapeutic decisions. The potential benefits of therapy are dependent on a patient’s overall CVD risk, multiplied by the relative risk reduction conferred by therapy. Multiple factors beyond LDL affect risk of downstream events including age, blood pressure, diabetes and extent of vascular disease. Thus, patients with high overall CVD risk may achieve large absolute risk reductions, even if their potential relative risk reduction with therapy is blunted by lower starting LDL levels.” – by Darlene Dobkowski

Disclosures: Navarese reports he received research grants from Amgen and personal fees from Amgen and Sanofi. Navar reports she received grants and personal fees from Amgen, Regeneron and Sanofi. Peterson reports he received grants and personal fees from Amgen, AstraZeneca, Merck and Sanofi and a grant from Regeneron. Please see the study for all other authors’ relevant financial disclosures.

Eliano Pio Navarese, MD, PhD
Eliano P. Navarese

Patients with higher baseline LDL levels who underwent more intensive LDL lowering had a greater risk reduction of total and CV mortality compared with those with less intensive treatment, according to a meta-analysis published in JAMA.

Analysis of randomized trials

Eliano P. Navarese, MD, PhD, director of international research at Inova Heart and Vascular Institute in Falls Church, Virginia, and colleagues conducted a meta-analysis of 270,288 patients from 34 randomized trials that received LDL lowering treatment for at least 48 weeks. Trials that included patients with end-stage renal disease or HF were excluded. Data included CV and mortality outcomes.

Patients were treated with a statin, a nonstatin therapy (ezetimibe or a PCSK9 inhibitor) or a combination of a statin with nonstatin therapy. Those treated with more intensive therapy (n = 136,299) received a more potent pharmacology strategy, whereas those with less intensive strategy (n = 133,989) were typically in the control group of a trial.

Coprimary endpoints were CV mortality and total mortality. Secondary endpoints were cerebrovascular events, MI, major adverse cardiac events and revascularizations.

All-cause mortality occurred in more patients who received less intensive therapy compared with more intensive therapy (7.08% vs. 7.7%; RR = 0.92; 95% CI, 0.88-0.96).

With each 40-mg/dL increase in baseline LDL, greater reductions in all-cause mortality were seen in patients who were assigned more intensive LDL lowering (change in RR per 40 mg/dL increase = 0.91; 95% CI, 0.86-0.96; P = .001). This was associated with an absolute risk difference of –1.05 incident cases per 1,000 person-years (95% CI, –1.59 to –0.51), although it was only seen in patients with a baseline LDL greater than 100 mg/dL (P for interaction < .001).

More patients who received less intensive therapy died from CV-related causes compared with those who received more intensive therapy (3.48% vs. 4.07%; RR = 0.84; 95% CI, 0.79-0.89).

For each 40-mg/dL increase in baseline LDL, there was a greater decrease in CV mortality in the more intensive therapy group vs. the less intensive therapy group (change in RR per 40 mg/dL increase = 0.86; 95% CI, 0.8-0.94; P < .001). This resulted in an absolute risk difference of –1 incident cases per 1,000 person-years (95% CI, –1.51 to –0.45) and was only seen in patients with baseline LDL levels greater than 100 mg/dL (P for interaction < .001).

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Ann Marie Navar, MD, PhD
Ann Marie Navar

Greatest risk reduction

The greatest reduction in all-cause mortality was in patients with baseline LDL levels greater than 160 mg/dL (RR = 0.72; 95% CI, 0.62-0.84; P < .001), with 4.3 fewer deaths per 1,000 person-years.

Patients with higher baseline LDL levels who were assigned more intensive therapies also had greater risk reductions for revascularization, MI and major adverse cardiac events.

“If additional LDL-lowering therapies are considered in statin-treated patients, nonstatin LDL lowering therapies shown to reduce cardiovascular disease events are recommended,” Navarese and colleagues wrote. “This analysis further supports individualizing estimates of the potential for a cardiovascular risk reduction benefit from LDL-lowering therapy based on consideration of not only a patient’s absolute risk and current LDL level, but also an individualized estimate of the risk reduction based on current LDL level and the outcomes desired.”

Eric D. Peterson

In a related editorial, Ann Marie Navar, MD, PhD, assistant professor of medicine at Duke University School of Medicine, member of the Duke Clinical Research Institute and Cardiology Today’s Next Gen Innovator, and Eric D. Peterson, MD, MPH, Fred Cobb, MD Professor of Medicine at Duke University School of Medicine and director of the Duke Clinical Research Institute, wrote: “Clinicians ... need to consider the patient’s entire CVD risk profile when making therapeutic decisions. The potential benefits of therapy are dependent on a patient’s overall CVD risk, multiplied by the relative risk reduction conferred by therapy. Multiple factors beyond LDL affect risk of downstream events including age, blood pressure, diabetes and extent of vascular disease. Thus, patients with high overall CVD risk may achieve large absolute risk reductions, even if their potential relative risk reduction with therapy is blunted by lower starting LDL levels.” – by Darlene Dobkowski

Disclosures: Navarese reports he received research grants from Amgen and personal fees from Amgen and Sanofi. Navar reports she received grants and personal fees from Amgen, Regeneron and Sanofi. Peterson reports he received grants and personal fees from Amgen, AstraZeneca, Merck and Sanofi and a grant from Regeneron. Please see the study for all other authors’ relevant financial disclosures.

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