Halving cardiovascular risk with combined blood pressure and cholesterol lowering - Why are we not there yet?

Area of Science:

• Cardiovascular Medicine
• Clinical Trials
• Pharmacology

Background:

• Previous trials showed modest reductions in major adverse cardiovascular events (MACE) with combined blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) lowering therapies.
• The reasons for these modest reductions were unclear, potentially due to limited risk factor control or negative interactions between therapies.

Purpose of the Study:

• To evaluate whether modest MACE reductions in combined BP and LDL-C lowering trials were attributable to the degree of risk factor reduction.
• To investigate potential negative interactions between combined BP and LDL-C lowering therapies.

Main Methods:

• Systematic review of randomized controlled trials comparing combination BP and cholesterol-lowering treatment versus placebo.
• Calculation of expected relative risk reduction (RRR) in MACE based on observed systolic BP and LDL-C reductions, compared to previous meta-analyses of individual therapies.

Main Results:

• Included trials demonstrated small systolic BP reductions (1-6 mmHg) and small-to-moderate LDL-C reductions (0.5-1.1 mmol/L), generally less than anticipated.
• The three largest trials showed significant MACE reductions, with observed versus expected RRRs closely aligned (e.g., ASCOT: 32% vs. 24%, HOPE-3: 28% vs. 28%, TIPS-3: 20% vs. 21%).

Conclusions:

• MACE reductions achieved with combined BP and LDL-C lowering therapies directly correlate with the extent of risk factor reduction.
• Substantial cardiovascular risk reduction (halving risk) necessitates significant and sustained reductions in both BP (≥15 mmHg) and LDL-C (≥1.5 mmol/L).
• Long-term adherence to intensive LDL-C lowering and combination BP therapy is crucial for achieving significant cardiovascular risk reduction.