| Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 trial (PROVE-IT TIMI 22) | |
|---|---|
| Study type | randomized controlled trial |
| Dates | November 2000 to December 2001 |
| Locations | Australia, Europe, and North America |
| Published | 2004 |
| Article | Cannon, Christopher P.; Braunwald, Eugene; McCabe, Carolyn H.; et al. (8 April 2004). "Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes". New England Journal of Medicine. 350 (15): 1495–1504. doi:10.1056/NEJMoa040583. |
PROVE-IT TIMI 22 Trial (Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis In Myocardial Infarction 22)
The Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis In Myocardial Infarction 22 (also known as PROVE-IT TIMI 22) trial was a significant clinical study designed to compare the effects of intensive versus standard lipid-lowering therapy with statins on cardiovascular outcomes in patients who had recently experienced an acute coronary syndrome (ACS). The trial aimed to determine whether high-dose atorvastatin could provide greater cardiovascular protection compared to standard-dose pravastatin.[1]
Background
editPatients who have experienced an ACS, including myocardial infarction or unstable angina, are at high risk for recurrent cardiovascular events. Statins, which lower low-density lipoprotein (LDL) cholesterol, are a cornerstone of therapy for these patients. The optimal intensity of statin therapy to maximize cardiovascular protection had not been definitively established prior to the PROVE-IT TIMI 22 trial. This study sought to fill this gap by comparing high-intensity statin therapy with standard therapy.[1]
Study Design
editThe PROVE-IT TIMI 22 trial was a multicenter, randomized, double-blind study that enrolled 4,162 patients who had been hospitalized for an ACS within the previous 10 days. Participants were randomized to receive either high-dose atorvastatin (80 mg daily) or standard-dose pravastatin (40 mg daily).
The primary endpoint was a composite of death from any cause, myocardial infarction, unstable angina requiring hospitalization, revascularization (performed at least 30 days after randomization), and stroke. Secondary endpoints included changes in lipid levels, individual components of the primary endpoint, and safety outcomes.[1]
Key Findings
editThe results of the PROVE-IT TIMI 22 trial, published in 2004, demonstrated several significant outcomes:[1]
- Reduction in Primary Endpoint: Patients receiving high-dose atorvastatin had a 16% relative reduction in the risk of the primary composite endpoint compared to those receiving standard-dose pravastatin.
- LDL Cholesterol Levels: The atorvastatin group achieved a significantly lower mean LDL cholesterol level (62 mg/dL) compared to the pravastatin group (95 mg/dL).
- Secondary Endpoints: High-dose atorvastatin also led to significant reductions in the rates of death from coronary heart disease, nonfatal myocardial infarction, and revascularization.
- Safety: Both treatment regimens were well-tolerated, with similar rates of serious adverse events, although there was a slightly higher incidence of elevated liver enzymes in the atorvastatin group.
Clinical Implications
editThe findings of the PROVE-IT TIMI 22 trial had significant implications for the management of patients following an acute coronary syndrome:[1]
- Intensive Lipid-Lowering Therapy: The trial provided strong evidence supporting the use of intensive statin therapy to achieve lower LDL cholesterol levels and improve cardiovascular outcomes in high-risk patients.
- Guideline Updates: The results influenced clinical guidelines, which began to recommend high-intensity statin therapy for patients with ACS to maximize cardiovascular protection.
Long-Term Impact
editThe PROVE-IT TIMI 22 trial was instrumental in shaping contemporary lipid management strategies for patients with recent ACS. Its findings reinforced the principle that "lower is better" when it comes to LDL cholesterol levels and highlighted the benefits of intensive lipid-lowering therapy in reducing the risk of recurrent cardiovascular events.[1]
References
edit- ^ a b c d e f Cannon, Christopher P.; Braunwald, Eugene; McCabe, Carolyn H.; Rader, Daniel J.; Rouleau, Jean L.; Belder, Rene; Joyal, Steven V.; Hill, Karen A.; Pfeffer, Marc A.; Skene, Allan M. (8 April 2004). "Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes". New England Journal of Medicine. 350 (15): 1495–1504. doi:10.1056/NEJMoa040583.
Cannon, C. P., et al. (2004). "Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes." New England Journal of Medicine, 350(15), 1495-1504. Grundy, S. M., et al. (2018). "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol." Journal of the American College of Cardiology, 73(24), e285-e350. Nissen, S. E., & Wolski, K. (2007). "Effect of rosuvastatin on progression of coronary artery atherosclerosis." New England Journal of Medicine, 352(1), 29-38.