STUDIES OF CLINICAL IMPACT OF TREATMENT OF DYSLIPIDEMIAS


I. Meta-analyses of studies involving both primary and secondary prevention
  1. In a meta-analysis of 14 randomized trials of statins for prevention (both primary and secondary prevention) of coronary events, there was a significant 12% risk reduction in all-cause mortality per 39mg/dL reduction in LDL level over 2-6y f/u; similar results seen in various subgroups, e.g. by age, sex, baseline lipid levels, h/o HTN, DM, etc. (Lancet 366:1267, 2005--JW)
  2. In a meta-analysis of 26 controlled trials (either statins vs. placebo or high-dose vs. low-dose statins), with mean 5y f/u (Lancet 376:1670, 2010-JW):

  1. In a meta-analysis of 18 randomized studies involving over 45,000 pts, (most not on statins), fibrates vs. placebo were associated with a sig. but small reduction in incidence of cardiovascular events (RR 0.9) but no sig. reduction in incidence of cardiac death or all-cause mortality (Lancet 375:1875, 2010-JW)
  2. In a meta-analysis of 76 randomized studies comparing statins vs. (placebo or other non-drug control) involving 170,255 pts, statin therapy was associated with sig. reduction in all-cause mortality (RR 0.9), cardiovascular mortality (RR 0.8), and CVA (RR 0.86).  Among studies that reported new onset of diabetes, statins were associated with a significantly increased risk (OR 1.09) (QMJ 104:109, 2011-abst)

II. Primary prevention of coronary events

  1. Lipid Research Clinics Coronary Primary Prevention trial--3,806 men 35-59yo with tot. chol. > 265 and LDL > 190 randomized to cholestyramine vs. placebo; all had cholesterol-lowering diet; over avg. 7.4y f/u, cholestyramine group had RR 0.81 (sig.) for coronary death or MI (7% vs. 8.6%); all-cause mortality nonsig. reduced in cholestyramine group (RR 0.93) (JAMA 251:351, 1984--abst)
  2. Helsinki Heart Study--4,081 men 40-55yo with LDL > 199 and w/o CHD randomized to gemfibrozil vs. placebo x 5y; gemfibrozil group had sig. lower risk of fatal or nonfatal MI; all-cause mortality nonsig. higher in gemfibrozil group (2.19 vs. 2.07) (NEJM 317:1237, 1987; Circ. 85:37, 1992)
  3. West of Scotland Coronary Prevention Study--6595 men 45-65yo with mean tot chol 272; LDL > 154 (mean 192) but no heart disease randomized to pravastatin 40mg/d vs. placebo; over avg. 4.9y f/u, mortality was 3.2% in pravastatin vs. 4.1% in placebo group (p = 0.054) (NEJM 333:1301, 1995)
  4. AFCAPS/TexCAPS Trial (JAMA 279:1615, 1998)
    1. 6600 men 45-73yo and women 55-73yo with no known atherosclerotic disease and tot. chol. 180-264 (mean 221), LDL 130-190 (mean 150), and HDL < 46 for men or < 48 for women (mean 36 for men, 40 for women). Mean TG was 158.
    2. Randomized to lovastatin 20-40 mg/d vs. placebo; all were also counseled on a low-saturated fat, low-cholesterol diet.
    3. After avg. 5.2y f/u, RR 0.63 (sig.) for first coronary event (sudden cardiac death, MI, or unstable angina) (JAMA 279:1615, 1998--abst)
    4. BUT mortality was no different (sl. higher in lovastatin group); there was less death from cardiovascular causes and sl. more death from noncardiovascular causes in lovastatin group
  5. MRC/BHF [Medical Research Council/British Heart Foundation] Heart Protection Study (Sources: http://www.ctsu.ox.ac.uk/~hps/, European Heart Journal 20:725, 1999; personal communication with Dr Louise Bowman; also Lancet 360:7, 2002--JW)
    1. 20,536 pts 40-80yo with one of the following risk factors for CAD AND baseline total cholesterol of 135 mg/dL or greater:
      1. Past MI or other CAD
      2. Other occlusive arterial disease
      3. DM (5963 pts, 3985 of whom had no CAD)
      4. Treated HTN if male and > 64yo (only 237 had HTN but no CAD or other occlusive arterial disease)
    2. Baseline tot. chol. was < 5.5 mmol/L (212 mg/dL) in 7882 pts; LDL < 3.0 mmol/L (116 mg/dL) in 6888 pts
    3. Randomized into 4 groups: 40mg/d Simvastatin, Antioxidant blend (vit. E 600mg, vit. C 250mg, beta-carotene 20mg) QD, one or the other, or double-placebo
    4. Over 6y f/u, simvastatin group vs. placebo had sig. less all-cause mortality (12.9% vs. 14.6%, RR = 0.88) over the study f/u period; also sig. less stroke and vascular events in general.
    5. The reduction in risk for vascular events was significant in various subgroups including those with vascular disease but no CAD (e.g. PVD or cerebrovascular disease) as well as in diabetics; also sig. for all subgroups of LDL level including those with LDL < 3.0 mmol/L (116 mg/dL) and those with tot. chol. < 5.0 (193 mg/dL); also sig. for all age subgroups and for men & women as subgroups
    6. No sig. diff. in risk of vascular events between antioxidant groups and placebo\
  6. The Cardiovascular Health Study (Arch. Int. Med. 162:1395, 2002)
    1.  1914 pts > 65 yo w/o known cardiovascular disease and lipid levels meeting the 1993 NCEP guidelines for tx with meds; followed for avg. 7.3y (nonrandomized)
    2. Those on statins had sig. lower risk of cardiocascular events (hazard ratio 0.44) and all-cause mortality (hazard ratio 0.56); This effect was also seen in the subgroup of pts > 74yo at baseline.
  7. The ALLHAT Study (JAMA 288:2998, 2002--JW)
    1. This was a randomized trial comparing different antihypertensive regimens, but had a nonblinded randomized arm comparing Pravastatin 40mg QD vs. "usual care" in about 10,000 pts > 55yo with HTN, at least 1 other coronary risk factor, and either (LDL 120-189 and no known h/o CAD) or (LDL 100-189 and known h/o CAD)
    2. Over avg. 5y f/u, incidence of all-cause mortality or (coronary death or nonfatal MI) were not sig. diff. in the two groups
  8. The ASCOT-LLA study (Lancet 361:1149, 2003--abst)
    1. 19,342 pts 40-79yo with hypertension and 3 or more other CV risk factors as follows but no known h/o CAD.  Subjects had mean tot. chol. 214, mean LDL 132 mg/dL, and mean HDL 50 mg/dL.
    2. Risk factors used as inclusion criteria were:
      1. ECG findings of LVH, ST depression, TWI, BB block, or significant Q's
      2. Type 2 DM
      3. Peripheral vascular disease
      4. Prior CVA or TIA
      5. Male sex
      6. Age > 55yo
      7. Microalbuminuria or proteinuria
      8. Smoking
      9. Tot. chol./HDL ratio 6 or higher
      10. Family h/o premature CAD
    3. Randomized to atorvastatin 10mg/d vs. placebo
    4. After median 3.3y f/u, RR of (nonfatal MI or coronary death) was 0.64 (sig.); RR for overall mortality was 0.87 (nonsig.).
    5. The effects of atorvastatin on the primary endpoint was statistically significant in various subgroups including: nondiabetics, nonsmokers, non-obese, and no prior vascular disease. The effect was NOT statistically significant among the female patients!  For some reason, the authors did not do a subgroup analysis for baseline lipid levels!!!

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  1. In a meta-analysis of c & d above, active tx ass'd with sig. risk reduction in major coronary events (RR 0.66) and cardiovascular mortality (OR 0.68), but nonsig. reduction in all-cause mortality (OR 0.87); however, no diff. in incidence of noncardiovascular mortality between tx & placebo groups (OR 1.04 for active tx groups) (JAMA 282:2340, 1999)
  2. In a meta-analysis of 4 primary prevention trials, drug tx sig. reduced risk for CAD events (RR 0.7) but total mortality was not sig. reduced (OR 0.94); ditto for total mortality in just the studies using statins (0.89, nonsig.) (BMJ 321:983, 2000--JW)
  3. In a meta-analysis of 10 randomized trials involving > 70,000 pts with cardiovascular risk factor but no known CV disease (mean age 63yo, 34% women) randomized to statins vs. placebo x mean 4.1y, statin recipients had sig. lower incidence of mortality (5.1. vs. 57%), major coronary events (4.1 vs. 5.4%), or major cerebrovascular events (1.9% vs. 2.3%).  There was no association between statin use and cancer incidence.  For all-cause mortality, none of the specified subgroups had sig. reduction with statin use; for "major coronary events"; sig. reduction occurred for men (OR .72) but not women and < 65yo (OR 0.62) but not over ( (BMJ 338:b2376, 2009)
  4. In a meta-analysis of 26 controlled trials (either statins vs. placebo or high-dose vs. low-dise statins), with mean 5y f/u:
    Annual incidence of first major vascular event was sig. reduced in both placebo-controlled (2.8% vs. 3.6%) and high-dose vs. low-dose trials (4.5% vs. 5.3%).  An analysis of the reduction in 1y incidence of major vascular events per 1.0 mmol/L reduction in LDL showed sig. reductions in the following subgroups (Lancet 376:1670, 2010-JW):
  1. Pts with no h/o vascular disease (RR 0.75)
  2. Pts with no h/o diabetes (RR 0.78)
  3. Female pts (RR 0.83)
  4. Pts < 65yo (RR 0.78)
  5. Pts without hypertension (RR 0.76)
  6. Pts with normal BMI (RR 0.79)
  7. Pts with HDL > 1.3 (RR 0.80)
  8. Non-smokers (RR 0.78)
  1. Primary prevention in Diabetics:
  1. AFCAPS/TexCAPS had 394 pts with DM (out of 6605)--in their analysis they only looked at the 155 pts not on insulin and not surprisingly, did not find a significant effect of lipid-lowering tx.
  2. 2. WOSCOPS had 76 pts with DM (out of 4595) and did not include diabetics in their subgroup analysis
  3. The Helsinki Heart Study had 135 pts with DM (out of 4081) and showed a substantial (RR 0.68), though statistically insignificant (p = 0.19) reduction in incidence of the principal endpoint of fatal or nonfatal MI with treatment.
  4. The Lipid Research Clinics Coronary Primary Prevention trial excluded diabetics from enrollment.
  5. 5963 diabetic adults (40-80yo) with nonfasting tot. chol. > 135mg/dL randomized to Simvastatin 40mg QD vs. placebo. Over 5y f/u, simvastatin recipients had sig. lower incidence of first "major vascular event" (MI, CVA, or revascularization procedure) (RR 0.78); this was true of the subgroup of 2912 pts who had no occlusive arterial disease diagnosed before randomization (RR 0.67) and the subgroup of 2426 pts whose pretreatment LDL was < 116 mg/dL (RR 0.73) ("MRC/BHF Heart Protection Study"; Lancet 361:2005, 2003)
  6. In a study of 2,838 type 2 diabetic patients 40-75yo, all with LDL < 160mg/dL and TG < 616 mg/dL, all w/o known h/o cardiovascular disease, and all with one of (retinopathy, albuminuria, HTN, or tobacco use) randomized to atorvastatin 10mg/d vs. placebo, over median 4y f/u, incidence of (acute coronary event, coronary revascularization, or CVA) was sig. lower in atorvastatin group (5.8% vs. 9.0%) (Collaborative Atorvastatin Diabetes Study ("CARD")--Lancet 364:685, 2004--JW)
  7. In a study in 1,255 pts with type 2 DM on maintenance hemodialysis randomized to atorvastatin 20mg/d vs. placebo, over median 4y f/u, incidence of (cardiac death, MI, or CVA) was not sig. lower among atorvastatin recipients.  The risks various secondary endpoints were not sig. diff. either except that the risk of fatal CVA was sig. higher with atorvastatin (RR 2.03)  (NEJM 353:238, 2005--abst)
  8. In a study in 2,410 pts with type 2 DM + either ((LDL > 140 AND h/o CAD) OR (LDL > 160)) randomized to atorvastatin 10mg/d vs. placebo, over median 4y f/u, there was no sig. diff. in incidence of a composite primary endpoint (several cardiovascular events), or overall MI incidence in subgroups of pts with and without h/oc CAD ("Atorvastatin Study for Prevention of Coronary Heard Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus" ("ASPEN") Trial; Diab. Care 29:1478, 2006--JW)
  9. In a study in 9,795 pts with DM, tot. chol. 116-250 mg/dL, and (triglycerides 90-440 mg/dl or total-to-HDL radio > 4) randomized to fenofibrate 200mg/d vs. placebo.  Over median 5y f/u, there was no sig. diff. in incidence of (first MI or coronary death) ("FIELD" Trial; 366:1849, 2005--JW)
    1. In a report on a secondary outcome of the "FIELD" trial (nontraumatic lower-limb amputations), fenofibrate was associated with sig. less than placebo (0.9% vs. 1.4%; sig. diff. also seen for below-ankle amputations without large-vessel disease (0.4% vs. 0.7) but not in amputations with large-vessel disease.  No association seen between the fenofibrate effect and degree of dyslipidemia or glycemic control (Lancet 373:1780, 2009-JW)
  10. In a study in 5,518 pts with type 2 DM, HbA1c > 7.4%, LDL 60-180mg/dL, HDL < 55mg/dL, and triglycerides < 750mg/dL, all on simvastatin up to 40mg/d, randomized to addition of fenofibrate 160mg/d (adjusted for renal function) vs. placebo, over mean 4.7y f/u, there was no sig. diff. in incidence of the primary endpoint of (MI, CVA, or cardiovascular death) or overall mortality.  In subgroup of pts with TG > 203mg/dL and HDL < 35 mg/dL, there was a sig. reduction in the primary endpoint (RR .71) and in men ( 11.2% vs. 13.3%; RR 0.84); in women, th eprimary endpoint was sig. higher in fenofibrate recipients (9.1% vs. 6.6%) ("ACCORD" Trial group; NEJM 362:1563, 2010)
  1. Primary prevention in patients with Renal Failure
  1. In a study in 9,270 pts with chronic kidney disease (serum Cr at least 1.7 mg/dL in men or 1.5 in women; about 1/3 on dialysis) and no h/o MI or coronary revascularization, randomized to (simvastatin + ezetimibe) vs. placebo, over median 4.9y f/u, incidence of first major atherosclerotic event was sig. lower in active-tx group (11.3% vs. 13.4%).  The study did not have sufficient power to determine the effect of the study treatment on the subgroup of pts who were on dialysis ("SHARP" trial; Lancet 6/9/2011; e-pub ahead of printing; http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960739-3/abstract).
III. Secondary prevention of coronary events
  1. Niacin
    1. One placebo-controlled trial in men with h/o MI showed decreased 9y mortality (J. Am. Coll. Cardiol. 8:1245, 1986--Med. Letter)
    2. See under ezetimibe for information on "ARBITER-6 HALTS" trial which compared niacin to ezetimibe
  1. Gemfibrozil for pts with low HDL as the primary lipid abnormality
    1. 2,531 men (mean age 64y) with CHD, LDL < 140 (mean 111), TG < 300, and HDL < 40 (mean 32), randomized to gemfibrozil 1.2g/d vs. placebo; over mean 5.1y f/u, risk of (fatal or nonfatal MI) was sig. lower in gemfibrozil group (17% vs. 22%; sig.); RR of death from any cause was 0.89 (nonsig.) (VA-HIT Intervention Trial, NEJM 341:410, 1999--JW)
  1. HMG CoA-reductase inhibitors
  1. Scandinavian Simvastatin Survival Study ("4S")-4,444 pts (men & women) with tot. chol. 213-309 mg/dl and TG < 221 mg/dl and h/o angina or MI randomized to simvastatin (20 or 40mg/d) vs. placebo; after 4.9-6.3y f/u, simvastatin group had RR 0.66 for death (Lancet 344:1383, 1994--Med. Letter)
  2. Cholesterol and Recurrent events Trial ("CARE")--4,159 pts (men & women) with h/o MI, chol. < 240mg/dl, and LDL 116-174, and TG < 354 randomized to pravastatin 40mg/d vs. placebo. Risk of fatal or nonfatal MI over 5y f/u was 10.2% in pravastatin group vs. 13.2% in placebo group; need for revascularization 14.1% vs. 18.8% (NEJM 335:1001, 1996--Med. Letter & JW)
  3. 9,014 pts with MI or unstable angina in previous 3y, mean total chol. 218, TG < 445, randomized to pravastatin 40mg QD vs. placebo. Over mean 6y f/u, sig. reductions in repeat MI (7.4 vs. 10.3%), coronary death (6.4 vs. 8.3%), and overall mortality (11.0 vs. 14.1%) (NEJM 339:1349, 1998--JW)
  4. 1,283 pts 65-75yo (baseline tot. chol. 208, LDL 138, HDL 40) s/p MI randomized to pravastatin 40mg QD vs. placebo; placebo group had sig. lower (20% vs. 28%) 5y risk of major coronary events (coronary death, nonfatal MI, PTCA, or CABG) (Ann. Int. Med. 129:681, 1998--JW)--In a subsequently published subgroup analysis from this trial, the total mortality incidence over 6y f/u was sig. lower both for older pts (65-75yo; 16.5% vs. 20.6% w/placebo) and pts < 65yo (7.6% vs. 9.8% w/placebo) (Ann. Int. Med 134:931, 2001--JW)
  5. Long-Term Intervention with Pravastatin in Ischaemic Disease ("LIPID") trial randomized 9,014 pts (men & women) 31-75yo with h/o MI or unstable angina, tot. chol. 155-271, and triglycerides < 445 to pravastatin 40mg/d vs. placebo. All pts also received dietary counseling. RR of death from CHD in pravastatin group was 0.76; over 6y, RR for total mortality was 0.78 (NEJM 339:1349, 1998--AFP)
  6. Pravastatin in Elderly Individuals at Risk of Vascular Disease ("PROSPER") trial randomized 6000 pts 70-82yo with vasculr disease to pravastatin 40mg/d vs. placebo; mean LDL at enrollment was 147 mg/dLp over avg. 3y f/u, incidence of (coronary death, nonfatal MI, or CVA) was sig. lower in placebo group (14.1% vs. 16.2%); also had sig. reductions in coronary death and nonfatal MI; new cancers sig. more common in pravastatin group (8.5% vs. 6.8%) (Lancet 360:1623, 2002--JW)
  7. Incremental Decrease in End Points Through Aggressive Lipid Lowering ("IDEAL") trial randomized 8,888 pts < 80yo with h/o prior MI to atorvastatin 80mg/d vs. simvastatin 20mg/d; over mean 4.8y f/u, incidence of (coronary death, nonfatal MI, or cardiac arrest) was not sig. diff., but there was a sig. reduction in nonfatal MI incidence (6.0% vs. 7.2%) (JAMA 294:2437, 2005--abst)
  8. Treating to New Targets ("TNT") trial randomized 10,001 pts with stable CAD and LDL below 130 mg/dL to atorvastatin 80mg/d vs. 10mg/d; over 5y f/u, incidence of major cardiovascular events was sig. lower in high-dose group (8.7% vs. 10.9%); no sig. diff. in all-cause mortality (NEJM 352:1425, 2005--JW)
  9. In a separately-published subgroup analysis of data from the TNT trial, those pts with metabolic syndrome (BMI > 28, TG > 150, HDL < 40 in men or < 50 in women, BP > 130/85, and fasting glucose > 100 mg/dL) had sig. reduction in incidence of major cardiovascular events with high-dose atorvastatin (9.5% vs. 13%) but there was no sig. diff. in those without metabolic syndrome (Lancet 368:919, 2006--JW)
  10. In a meta-analysis of i, ii, and v, , active tx ass'd with sig. risk reduction in major coronary events (RR 0.70), cardiovascular mortality (OR 0.73), but and all-cause mortality (OR 0.70) (JAMA 282:2340, 1999)
  11. In a study in 8,888 pts with h/o MI randomized to atorvastatin 80mg/d vs. simvastatin 20mg/d, over median 4.8y f/u, there was no sig. diff. in incidence of primary endpoint (coronary death, nonfatal MI, or cardiac 
    arrest with resuscitation) or overall mortality ("Incremental Disease in Endpoints through Aggressive Lipid Lowering" ("IDEAL") Trial; JAMA 294:2437, 2005--JW)
  12. Initiation shortly after acute MI/unstable Angina
    1. In a nonrandomized retrospective study of 20,809 pts with unstable angina or acute MI, those prescribed lipid-lowering agents on discharge had sig. lower 6mo mortality (1.7% vs. 3.5%, persistent after adjusting for confounding variables )(Used data from "GUSTO IIb" and"PURSUIT" studies, Lancet 357:1063, 2001--JW)
    2. In a randomized trial of 3086 pts with unstable angina or non-Q-wave MI to atorvastatin 80mg/d vs. placebo starting 1-4d after hospital admission. At 16wks, atorvastatin group had si. lower risk for composite endpoint of (death, nonfatal MI, cardiac arrest, or recurrent ischemie) (14.8 vs. 17.4%, sig.). Mean pre-tx LDL in this group was 124mg/dL; risk reduction was similar for those with baseline LDL < 124 as for the study group as a whole (JAMA 285:1711, 2001--JW)
    3. In a randomized trial in 4,162 pts hospitalized for an acute coronary syndrome in the previous 10d to pravastatin 40mg/d vs. atorvastatin 80mg/d; over 24mos, incidence of (death, MI, unstable angina requiring hospitalization, revascularization, or CVA) was sig. lower in atorvastatin group (26.3% vs. 22.4%) ("PROVE-IT" trial; NEJM 350:1495, 2004--JW)
    4. 4,497 pts with acute coronary syndrome (mean LDL 112) randomized within days after the event to simvastatin 40mg/d x 1mo then 80mg/d vs. placebo x 4mos then simvastatin 20mg/d. At 2y, incidence of (MI, ACS readmission, CVA, or cardiovascular death) was not sig.different in the two groups though LDL reductions were sig. greater in the high-intensity group ("A to Z" Trial; JAMA 292:1307, 2004--JW)
    5. In a meta-analysis of 12 randomized trials of statin therapy started within 14d after an acute coronary syndrome vs. placebo in total 13,024 pts, there was no sig. diff. at 4mos in risk of (death, MI, or CVA), or all-cause mortality.  (JAMA 295:2046, 2006--JW)
  1. Medications for low HDL
    1. 160 pts with angiography-confirmed CAD, HDL < 36 (if male) or < 41 (if female), and LDL < 146 randomized to simvastain + niacin, antioxidant vitamins, combination of all 3, or placebo.  Over 3y f/u, incidence of combined endpoint of (coronary death, nonfatal MI, CVA, or revascularization) was lowest in pts in the simvastatin + niacin group (3% vs. 24% w/placebo, 21% with antioxidants alone, and 14% with combination therapy (NEJM 345:1583, 2001--JW)
    2. In a study in 15,000 pts with cardiovascular disease (82%) or diabetes (18%), all on atorvastatin with LDL < 100, randomized to torcetrapib (a drug that raises HDL by inhibiting cholesteryl ester transfer protein) vs. placebo, at 18mos the trial was terminated b/c, despite sig. higher HDL levels in torcetrapib recipients (mean increase 72%), the torcetrapib recipients had sig. higher incidence of cardiovascular events and all-cause mortality (also had higher BP). (NEJM 357:2109, 2007--JW)  
    3. In a study in 3,414 pts with cardiovascular disease, low HDL, and high TG, all of whom received simvastatin, randomized to extended-release niacin (Niaspan) vs. placebo, the trial was halted after mean 3y f/u due to absence of evidene of benefit and potential evidence of harm (nonsig. higher incidence of CVA in niacin group) ("AIM-HIGH" trial; JW 6/2011)
IV. Secondary prevention of cardiac events in patients with CAD and Heart Failure
  1. In a study in 5,011 pts > 60yo with symptomatic heart failure attributed to CAD and LVEF < 31% randomized to rosuvastatin 10mg/d vs. placebo, over median 33mo f/u, the rosuvastatin recipients had no sig. diff. in primary endpoint of (cardiovascular death, nonfatal MI, or nonfatal CVA), though there was a slight but statistically significant decrease (HR 0.92) for hospitalization for cardiovascular causes (NEJM 357:2248, 2007--JW)  
V. Primary prevention of CVA
  1. In a meta-analysis of 16 tirals involving > 29,000 pts (mean LDL 128-215, mean HDL 36-58) randomized to a "statin" med vs. placebo, statins ass'd with RR 0.71 for CVA and RR 0.78 for total mortality (JAMA 278:313, 1997--UW Pharm Letter)
  2. 9014 pts with recent MI or unstable angina and tot. chol. 155-271 randomized to pravastatin 40mg/d vs. placebo. Over avg. 6y f/u, RR for CVA lower in pravastatin group but barely reached statistcal significance (3.7% vs. 4.5%, p = 0.05); no diff. in rate of hemorrhagic CVA ("LIPID" trial; see also below; NEJM 343:317, 2000--JW)
  3. In the MRC/BHF study (see above), over 5y, simvastatin group had sig. lower incidence of CVA (4.3% vs. 5.7%); sig. reduction was seen also in subgroup of pts without prior h/o cerebrovascular disease (3.2% vs. 4.8%). (Lancet 363:757, 2004--JW)
VI. Secondary prevention of CVA
  1. In a study in 4,731 pts with CVA or TIA in prior 6mos and baseline LDL 100-190 mg/dL but no h/o coronary artery disease randomized to atorvastatin 80mg/d vs. placebo, over median 5y f/u, atorvastatin group had sig. lower incidence of CVA (11.2% vs. 13.1%); no sig. diff. in overall mortality ("SPARCL" Trial, NEJM 355:549, 2006--JW)