PROVE-IT and REVERSAL - the concept of the lower the better for cholesterol therapy in patients with coronary heart disease
Last reviewed 01/2018
Two head-to-head randomised trials comparing intensive treatment with atorvastatin 80 mg/day with moderate treatment with pravastatin 40 mg/day
Atherosclerosis with Aggressive Lipid Lowering" (REVERSAL) trial (1,2)
502 patients with stable coronary disease
- 253 patients were randomized
to atorvastatin 80 mg/day (intensive lipid lowering) and 249 patients were randomized
to pravastatin 40 mg/day (moderate lipid lowering).
- low-density lipoprotein (LDL) cholesterol levels decreased from a baseline mean of 150 mg/dL (3.9 mmol/L) in both groups to 79 mg/dL (2.0 mmol/L) in the atorvastatin group and 110 mg/dL (2.9 mmol/L) in the pravastatin group
- high-sensitivity C-reactive protein (hs-CRP) levels decreased by 36.4% in the atorvastatin group versus 5.2% in the pravastatin group (P <0.001)
- for the primary end point of percent change in total atheroma volume, a significantly lower rate of progression from baseline was observed with atorvastatin (-0.4%) than with pravastatin (2.7%) (P = 0.02)
- results show that intensive lipid lowering with atorvastatin 80 mg/day for 18 months halted the progression of coronary atherosclerosis, whereas more moderate lipid lowering with pravastatin 40 mg/day was associated with progression (2)
- 253 patients were randomized to atorvastatin 80 mg/day (intensive lipid lowering) and 249 patients were randomized to pravastatin 40 mg/day (moderate lipid lowering).
- randomised 502 patients with stable coronary disease
"Pravastatin or Atorvastatin Evaluation and Infection Therapy" (PROVE-IT) trial
- 4162 patients with acute coronary syndromes were randomised to either
atorvastatin 80 mg or pravastatin 40 mg and followed for a mean of 24 months
- atorvastatin (mean LDL of 62 mg/dl) was superior to pravastatin (mean LDL of 95 mg/dl), resulting in a 16% percent lower relative risk (22.4% versus 26.3%) of the primary end point (primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke) (p = 0.005)
- there was no significant difference in CRP in comparison between the two treatment groups
- the study authors concluded that among patients who have recently had an acute coronary syndrome, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen
- 4162 patients with acute coronary syndromes were randomised to either atorvastatin 80 mg or pravastatin 40 mg and followed for a mean of 24 months
Thus, both REVERSAL and PROVE-IT support the concept "the lower, the better". However, they do not allow to disentangle the independent and interdependent effects of statins on LDL cholesterol and the process of arterial inflammation.
- British Journal of Cardiology (2004), 11 (2), 99.
- Nicholls SJ et al. Effect of atorvastatin (80 mg/day) versus pravastatin (40 mg/day) on arterial remodeling at coronary branch points (from the REVERSAL study). Am J Cardiol. 2005 Dec 15;96(12):1636-9. Epub 2005 Oct 28.
- Cannon CP et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495-504
trials of cholesterol reduction
intensive statin therapy in acute coronary syndromes and stable coronary heart disease: a meta-analysis (Afilalo J et al, 2007)