Evidence Table 4Post-revascularization and miscellaneous trials

Author
Year
Study Name
Study CharacteristicsPatient CharacteristicsInterventionStudy Duration (mean)Mean Baseline
LDL-c
Percent LDL-c ReductionPrimary EndpointPrimary Endpoint Results (provided only if it is a clinical health outcome)Other Clinical Outcomes MeasuredOther Clinical Outcome ResultsComments/Conclusions
Bertrand ME. et al., 1997
Prevention of Restenosis by Elisor after Transluminal Coronary Angioplasty (PREDICT)
Randomized, double-blind, placebo-controlled, intent to treat analysis for clinical events.695 men or women 25–75 years and TC 200–310 mg/dl who had undergone successful PTCA.Pravastatin 40 mg qpm or placebo qpm6 months155 mg/dl (4 mmol/L)23%Minimum lumen diameter as assessed by coronary angiography.N/ASecondary endpoints: restenosis rate and clinical events (death, MI, target vessel revascularization).There were no differences in clinical restenosis or events between groups (80 events in placebo vs. 74 events in pravastatin).There were no differences in the rate of clinical events or clinical restenosis in the pravastatin (74 events) vs. placebo (80 events) groups (death, MI, CABG, re- PTCA of target lesion). Fair in quality to assess differences in clinical events between groups (Relatively short follow up period).
Flaker GC. et al., 1999
Subgroup of CARE
Randomized, double-blind, placebo-controlled, intent to treat analysis. (Subgroup analysis of revascularized patients in CARE).2245 men or women with history of MI and <240 mg/dl and revascularization.Pravastatin 40 mg qpm or placebo qpm5 years138.4 mg/dl (3.6 mmol/L)28%Reduction in clinical cardiovascular events (CHD death or nonfatal MI, fatal and nonfatal MI, revascularizations and stroke).Pravastatin reduced the incidence of CHD death or nonfatal MI (RRR=36%, 95% CI 17–51%, p<0.001), fatal or nonfatal MI (RRR=39%, 95% CI 16–55%, p<0.002), and stroke (RRR=39%, 95% CI 3–62, p=0.037). There was a trend towards benefit with pravastatin in reducing repeat revascularization (RRR=18%, 95% CI 1–33%, p=0.068).Subgroup analysis of CARE of revascularized patients.See primary endpoint results.Pravastatin significantly reduced clinical events (CHD death, nonfatal MI and stroke) in previously revascularized patients. There was a trend to reduced revascularizations in the pravastatin vs. placebo groups. Good in quality to assess differences in clinical events between groups.
Kleeman A. et al.,
1999
The Cholesterol Lowering Atherosclerosis Trial (CLAPT)
Randomized, unblended treatment, blinded angiographic endpoint, intent to treat for clinical events.226 men 18–70 years scheduled for PTCA with a second vessel stenosis of >20% and LDL-c >135 mg/dl.Lovastatin 20 mg qpm or usual care. Lovastatin was titrated up to 80 mg qpm for LDL-c >120 mg/dl.2 years181 mg/dl (4.7 mmol/L)29%Angiographic progression and restenosis. Change in mean segment diameter (diffuse coronary atherosclerosis) of nondilated and dilated segments and MLD (focal coronary atherosclerosis) of dilated lesions at 2 years as assessed by angiography.N/APre-specified or defined clinical events: MI, re- PTCA, PTCA of another lesion, or death.There were 62 serious clinical events in lovastatin vs. 75 in usual care (NS). The only significant difference was a reduction in the 2nd or 3rd re-PTCA favoring lovastatin (p=0.02).There were no differences in the rate of clinical events in the lovastatin vs. placebo groups with the exception of 2nd or 3rd re-PTCA (p=0.02). Fair in quality to assess differences in clinical events between groups. (small sample size, unblinded).
Marz W. et al. 1999
The Target Tangible Trial (TT)*
Randomized, unblinded, intent to treat analysis for clinical events.2856 men or women 35– 70 years with CHD and an LDL-c ≥ 130 mg/dlAtorvastatin 10 to 40 mg qpm or simvastatin 10–40 mg qpm14 weeks188 mg/dl (4.9 mmol/LAtorvastatin 10 mg=37.6% vs simvastatin 10 mg=31.9%Safety (adverse events and laboratory events) and efficacy (LDL-c reduction).Serious adverse events were not different between groups. Serious cardiovascular adverse events occurred in 19 atorvastatin vs. 21 simvastatin patients (p<0.05 if 1-sided test applied).N/AN/ASerious cardiovascular adverse events were significantly higher in the simvastatin vs. atorvastatin group, p<0.05 if the 1-sided test is used.
Pitt B. et al. 1999
The Atorvastatin vs. Revascularization Treatment (AVERT)*
Randomized, unblinded, intent to treat analysis for clinical events.341 men or women 18–80 years with 50% stenosis of 1 or > coronary arteries and an LDL-c ≥115 mg/dl.Atorvastatin 80 mg qpm or PTCA18 monthsApproximately 140–148 mg/dl (3.6–3.8 mmol/L)46% (22% of all patients were on lipid-lowering drugs prior to randomization with no washout).Reduction in ischemic events: death from cardiac causes, resuscitation after cardiac arrest, nonfatal MI, CVA, CABG, PTCA, or hospitalization for angina.22 (13%) of the atorvastatin vs. 37 (21%) of the angioplasty group experienced ischemic events (p=0.048) NS as adjusted for interim analysis. Events making up the majority of the trend in favor of atorvastatin: CABG and hospitalization for angina.Time to first ischemic event.Time to first ischemic event was longer in the atorvastatin vs. angioplasty group (p=0.03 95% CI 5–67 RRR=36%)Unequal baseline characteristics between groups (sex, antiplatelets/anticoagulants, and location of target lesion). Approximately 70% of patients in the angioplasty group received a statin. Mean LDL-c 119 mg/dl in angioplasty group vs. 77 mg/dl in atorvastatin group. There was a trend in reduction in clinical events with atorvastatin vs. angioplasty, however CABG and hospitalization for angina accounted primarily for this difference. Angioplasty was the main variable in this study. Poor in quality for assessment of differences in clinical events between groups.
Pravastatin Multinational Study Group
1993*
Randomized, double-blind, placebo-controlled, intent to treat analysis for clinical events.1062 men or women 20– 69 years with 2 or > risk factors and a TC of 200– 300 mg/dl (5.2–7.8 mmol/L)Pravastatin 20 mg qpm or placebo. After 13 weeks, pravastatin could be doubled to 40 mg qpm26 weeks181 mg/dl (4.69 mmol/L)26.01%Change in serum lipids (TC, LDL-c, HDL-c, triglycerides)N/AReported clinical events as part of safety analysis, although cardiovascular events were predefined as fatal or requiring prolonged hospitalization.Significantly more serious cardiovascular events were reported in the placebo (13) vs. pravastatin (1) groups (p<0.001 ARR 2.2/100 persons NNT=44)There was a significant reduction in serious cardiovascular events in the pravastatin vs. placebo groups. Fair in quality to assess differences in clinical events between groups (relatively short follow up period).
Serruys PW. et al, 1999
Fluvastatin Angiographic Restenosis Trial (FLARE)
Randomized, double-blind, placebo-controlled, intent to treat analysis for clinical events.1054 men or women with symptomatic or ischemia producing coronary lesions amenable to angioplasty and an LDL-c <230 mg/dl (6 mmol/L).Fluvastatin 40 mg bid or placebo bid40 weeks153 mg/dl (3.96 mmol/L)33%Angiographic restenosis as assessed by quantitative coronary angiography as the loss of MLD during followup.N/APrespecified clinical endpoints: Death, MI, CABG or re-intervention.Major cardiac events occurred in 92 fluvastatin vs. 99 placebo recipients (p=0.74). When death and MI were combined, there was a significant reduction in the fluvastatin vs. placebo groups (p=0.03 ARR=2.5/100 persons NNT=39)Although not sufficiently powered to determine differences in clinical events, the combined endpoint of death/MI was significantly reduced in the fluvastatin vs. placebo groups s/p successful balloon angioplasty. The composite of major clinical events which included death/MI/CABG/re-intervention was not different between groups (p=0.74). Fair-poor in quality for assessment of differences in clinical events between groups (relatively short follow up period, insufficiently powered).
Serruys PW. et al., 2002
Lescol Intervention Prevention Study (LIPS)
Randomized, double-blind, intention-to-treat analysis for all randomized.1677 Men or women 18- 80 years status post successful percutaneous coronary intervention (PCI) and TC between 135 and 270 mg/dl (calculated 3.5–7.0 mmol/L).Fluvastatin 40 mg bid or placebo bid3.9 years131 mg/dl (3.4 mmol/L)27% (median)Survival time free of major coronary events (any death, nonfatal MI, repeat revascularization). Divergence seen at 1.5 years.Time to major coronary events was 1558 days in the fluvastatin vs. 1227 days in the placebo group (p=0.01). 181 (21.4%) of fluvastatin vs. 222 (26.7%) of placebo recipients (p=0.01, 95% CI 0.64–0.95, ARR 5.2/100 persons, NNT=19).Major coronary events excluding repeat revascularizations occurring within the first 6 months.Rate of major coronary events (excluding repeat revascularizations) diverged at 6 months and showed an extended event-free survival time in the fluvastatin vs. placebo groups (p<0.001, 95% CI 0.54–0.84)Time to major coronary events was significantly prolonged in the fluvastatin vs. placebo group. Adverse effects were not statistically different between groups. Fair-good in quality for assessment of differences in clinical events between groups (Number of diabetics was not equal between groups).
The Post Coronary Artery Bypass Graft Trial
1997
Post Coronary Artery Bypass Graft Trial (PCABG)
Randomized, intent to treat analysis for clinical events.1351 men or women 21–74 years with history of CABG 1–11 years prior and a baseline LDL-c of 130–175 mg/dl and at least 1 patent graft as seen on angiography.Aggressive LDL-c lowering with lovastatin 40 mg qpm titrated to 80 mg qpm (goal LDL-c < 85) or moderate LDL-c lowering with lovastatin 2.5 mg qpm titrated to 5 mg qpm (goal LDL-c <140 mg/dl). Warfarin 1 mg qd or placebo qd (titrated to 4 mg qd or INR of 2 or >) (2X2 design).4.3 years154 mg/dl (4 mmol/L)37–40% yearly in the aggressive group. 13–15% yearly in the moderate groupMean percentage per patient of grafts with a decrease of 0.6 mm or > in lumen diameter of initially patent grafts as assessed by angiographyN/APrespecified clinical endpoints as a composite and individually: Death from cardiovascular or unknown causes, nonfatal MI, stroke, CABG or PTCA .There were no differences in the composite or individual clinical outcomes between treatments. There was a 29% reduction of revascularization in the aggressive lovastatin group vs. the moderate lovastatin group but did not reach statistical significance criteria in this study (p=0.03).There was a significant difference in the rate of atherosclerotic progression favoring aggressive LDL-c lowering with lovastatin. There were no differences in composite or individual clinical outcomes between groups. There was a trend toward the aggressive lovastatin group in reducing revascularization. Fair in quality to assess differences in degree of LDL-c lowering and its effect on clinical outcomes, although no difference was noted.
Weintraub WS. et al., 1994
The Lovastatin Restenosis Trial
Randomized, double-blind, placebo-controlled, intent to treat analysis for clinical events.404 men or women in whom angioplasty of a native vessel with a stenosis of 50–99% was successful.Lovastatin 40 mg bid or placebo bid.6 months130 mg/dl (3.4 mmol/L)42%Extent of restenosis of the index lesion as assessed by angiography.N/AClinical events were spontaneously reported.There were no differences in the rate of death, stroke, CABG, re-intervention (angioplasty) between groups. There was a trend towards more MI in the lovastatin vs. placebo groups (p=0.058).There was no difference in the rate of restenosis between groups. There was also no difference in the rate of major clinical cardiac events in the lovastatin vs. placebo groups. There was a trend towards more MI in the lovastatin vs. placebo groups. Fair-poor in quality for assessment of differences in clinical events between groups (relatively short followup period, small sample size).
*

Studies included in the miscellaneous category. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty

From: Evidence Tables

Cover of Drug Class Review: HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin
Drug Class Review: HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin: Final Report Update 5 [Internet].
Smith MEB, Lee NJ, Haney E, et al.
Portland (OR): Oregon Health & Science University; 2009 Nov.
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