Use of blood pressure lowering drugs in the. prevention of cardiovascular disease

Transcription

1 Use of blood pressure lowering drugs in the prevention of cardiovascular disease Law, Morris, Wald APPENDIX TABLES Appendix tables 1(i), 1(ii), 1(iii) Appendix table 2 Appendix table 3

2 Appendix table 1(i) Randomised controlled trials of blood pressure lowering drugs in persons generally having no clinical history of vascular disease on entry Average No of disease events: all events No of disease events: year 1 Average blood in Stopped No of Mean Mean pressure (mmhg) blood pressure study Lost to coronary heart heart coronary heart Trial Main participants age duration in controls (tr minus con) drug follow-up disease stroke failure disease stroke Single drug therapy drug Blind± tr con (y) (y) systolic diastolic systolic diastolic (%) (%) tr con tr con tr con tr con tr con HDFP: w1-w6 T N * 92 * SHEP w5-w7 T D SHEP pilot w8 T D EWPHE w5,w6,w9 T D Australian TTMH w10 T D * Oslo w11 T N VANHLBI w12 T P * 88 * MRC-1 w6,w13 T S B S MRC-2 w6,w14 T S B S HYVET pilot w15 T N A N UKPDS w16,w17 B N A N DREAM w18 A D PREVENDIT w19 A D FEVER w20 C D Syst-Eur w21 C D Syst-China w22 C D Hunan province w23 C N ADVANCE w24 any D HOT w25 any N ABCD-2 w26 AorC D BBB w27 any N # TOMHS w28 any D Combination drug therapy STOP w5,w29 T+B D HEP w5,w6,w30 T+B N USPHS w31 T+W D VA-2 w32 T+W+H D VA-1 w33 T+W+H D The expansion of acronyms is given in the references T thiazide, B beta-blocker, A ACE inhibitor, C calcium-channel blocker, W rauwolfia, H hydralazine, M methyldopa ± D = double blind, S = single blind, N = not blind All participants diabetic P placebo used, N no placebo * Systolic blood pressure not reported #The total number of participants was reported but not their allocation into the two groups; this was taken to be exactly equal Classified a single drug trial despite allocation of 2 drugs to treated group because add-on therapy amounted to 1.0 drugs per participant more in the placebo than the treated group

3 Appendix table 1(ii) Results of randomised controlled trials of blood pressure lowering drugs in persons with a clinical history of coronary heart disease (CHD) on entry Average blood pressure (mmhg) Stopped in controls study drug (%) No of disease events: all events coronary heart disease stroke heart failure No of CHD events: year 1 (%) tr con tr con tr con tr con Clinical Mean Mean history on No of participants age duration Trial Drug entry Blind± tr con (y) (y) sys dias Norwegian-1 w34,w35 B AMI D BHAT w36,w37 B AMI D MultiCentre Int w38 B AMI D EIS w39 B AMI D Capricorn w40 B AMI D ISDPG, low risk w41 B AMI D ISDPG, high risk w41 B AMI D Norwegian- 2 w42 B AMI D Olsson w43 B AMI D Pindolol Study w44 B AMI D Julian w45 B AMI D Wilhelmsson w46 B AMI D Baber w47 B AMI D Barber w48 B AMI D Amsterdam w49 B AMI D Copenhagen w50,w51 B AMI D LIT w52 B AMI D Ahlmark w53 B AMI N Mazur w54 B AMI N Salathia w55 B AMI D BEAT w56 B AMI D APSI w57 B AMI D Basu w58 B AMI D SSSD w59 B AMI N Reynolds w60 B AMI D Kaul w61 B AMI D Taylor w62 B AMI D Taylor w62 B CAD D MACB w63 B CAD D TIBET w64 B CAD D DECREASE w65 B CAD N ASIST w66 B CAD D MERIT-HF w67 B HF D BEST w68 B HF D COPERNICUS w69 B HF D CIBIS-2 w70 B HF D ANZHFRCG w71 B HF D Aronow w72 B HF N SAVE w73 A AMI D TRACE w74 A AMI D AIRE w75,w76 A AMI D JAMP w77 A AMI N CATS w78 A AMI D HOPE w79 A CAD D EUROPA w80 A CAD D PEACE w81 A CAD D QUIET w82 A CAD D PART-2 w83 A CAD D CAMELOT w84 A CAD D MARCATOR w85 A CAD D SCAT w86 A CAD D MERCATOR w87 A CAD D APRES w88 A CAD D SOLVD w89-w91 A HF D Kondo w92 R CAD N CHARM-1 w93 R HF D CHARM-2 w94 R HF D CHARM-3 w95 R HF D DAVIT 2 w96 C AMI D c MDPIT w97 C AMI D DAVIT-1 w98 C AMI D c SPRINT-1 w99 C AMI D CRIS w100 C AMI D SPRINT-2 w101 C AMI D INTERCEPT w102 C AMI D DEFIANT-2 w103 C AMI D ACTION w104 C CAD D PREVENT w105 C CAD D CAMELOT w84 C CAD D NICOLE w106 C CAD D TIBET w64 C CAD D INTACT w107,w108 C CAD D CAPARES w109 C CAD D VESPA w110 C CAD D MACH-1 w111 C HF D PRAISE w112 C HF D Lost to followup Listed as a name or acronym if there is one, otherwise first author; the expansion of acronyms is given in the references B beta-blocker, A ACE inhibitor, R angiotensin receptor blocker, C calcium-channel blocker ± D= double blind, N = not blind AMI = acute myocardial infarction (within previouis 4 months), CAD = coronary artery disease without recent infarction, HF = heart failure

4 Appendix table 1(iii) Randomised controlled trials of blood pressure lowering drugs in persons with a clinical history of stroke or other cerebrovascular disease on entry Main No of participants Mean age Mean duration Average blood pressure (mmhg) in controls Average in blood pressure (tr minus con) Trial drug Blind± rr Con (y) (y) systolic diastolic systolic diastolic No of disease events: all events No of disease events: year 1 Stopped study Lost to coronary heart coronary heart drugfollow-up heart disease stroke failure disease stroke (%) (%) tr con tr con tr con tr con tr con Single drug therapy PATS w113 T D HDFP w1,w5 T N * 92 * SHEP w5,w7 T D TEST w114 B D Dutch TIA w115 B D BCAPS w116 B D * SMIDT w117 C D EWPHE w5,w9 C D Progress: w118,w119 1 drug A D Combination drug therapy Progress: w118,w119 2 drugs T+A D HSCS w4,w120 T+W D Carter w121 T+M N * STOP w5,w29 T+B D HEP w5,w30 T+B N Listed as a name or acronym if there is one, otherwise first author; the expansion of acronyms is given in the references T thiazide, B beta-blocker, A ACE inhibitor, C calcium-channel blocker, M methyldopa, W rauwolfia ± D = double blind, N = not blind Participants had carotid artery disease, identified on ultrasound scanning *Systolic blood pressure not reported -

5 Appendix table 2 Randomised trials comparing blood pressure lowering drugs of different classes (drug comparison trials) Trial Mean age (y) Mean duration (y) Clinical history on entry Blind± Thiazides Beta-blockers ACE inhibitors no of participants CHD stroke HAPPHYφ w122,w N N MRC-1 w N S MRC-2 w N S USSR w N N VA Coop w N D Angiotensin-II receptor antagonists Calcium channel blockers Any alternative drug, at discretion of physician no of disease events: no of no of disease events: no of no of disease events no of no of disease events: no of no of disease events: no of no of disease events: heart participants heart partic- heart partici- heart partici- heart partic- failure CHD stroke failure ipants CHD stroke failure pants CHD stroke failure pants CHD stroke failure ipants CHD stroke ANBPS w N N HYVET pilot w N N NESTOR w N D PHYLLIS w CVA D ALLHAT w N D INSIGHT w N D SHELL w N N VHAS w N D MIDAS w N D NICS-EH w N D UKPDS w16,w N N LIFE w N D ASCOT w N S INVEST w CAD N APSIS w CAD D ELSA w N D TIBET w CAD D JBCMI w CAD N IPPSH w N D OPTIMAAL w AMI D VALIANT w AMI D ELITE-2 w HF D DETAIL w N D ELITE-1 w HF D STOP-2 w N N * JMIC-B w CAD N ABCD-2 w N D ABCD-1 w N D PATE w N N CAMELOT w CAD D FACET w N N GLANT w N N J MIND w N N CAPPP w N N * VALUE w N D IDNT w N D MOSES w CVA N SCOPE w N N E-COST w159,w N N NORDIL w N N * CONVINCE w N D * The expansion of acronyms is given in the references φ Incorporates data from the MAPHY trial w123 * Treatment either a thiazide or beta-blocker (at discretion of physician) ± D = double blind, S = single blind, N = not blind All participants diabetic N = no vascular disease, AMI = acute myocardial infarction, CAD = coronary artery disease without recent infarction, HF = heart failure, CVA = stroke heart failure

6 Web-table A Summary relative risk estimates (95% CI) and results of tests of heterogeneity in the subset analyses in the web-figures (see footnote* for a summary of the heterogeneity results) Effect Heterogeneity Web-figure Relative risk (95%CI) p value χ 2 degrees of freedom p value* 1a 0.69 (0.62,0.76) < difference trials of beta-blockers in persons with a recent infarct 1b 0.87 (0.71,1.06) difference trials of beta-blockers in persons with a history of CHD but no recent infarct 1c 0.89 (0.78,1.02) difference trials of beta-blockers in persons with no history of CHD 1d 0.85 (0.79,0.91) < difference trials of drugs other than beta-blockers in persons with a history of CHD 1e 0.85 (0.79,0.91) < difference trials of drugs other than beta-blockers in persons with no history of CHD 2a no history of vascular disease on entry 0.84 (0.79,0.90) < (0.75,0.88) 2b clinical history of CHD on entry (excluding trials of beta-blockers ) 0.85 (0.79,0.91) < (0.68,0.85) 2c clinical history of stroke on entry 0.85 (0.72,1.00) (0.64,1.00) 2d Strokes in blood pressure difference trials in persons with no history of vascular disease on entry 0.63 (0.55,0.73) < < (0.49,0.68) 2e Strokes in blood pressure difference trials in persons with clinical history of CHD on entry 0.77 (0.68,0.87) < (0.53,0.80) 2f Strokes in blood pressure difference trials in persons with clinical history of stroke on entry 0.76 (0.67,0.85) < (0.58,0.80)

7 Web-table A Summary relative risk estimates (95% CI) and results of tests of heterogeneity in the subset analyses in the web-figures (see footnote* for a summary of the heterogeneity results) Effect Heterogeneity Web-figure Relative risk (95%CI) p value χ 2 degrees of freedom p value* 3a 3b 3c 3d 3e 3f 3g 3h 3i 4a 4b 4c 4d 4e 4f 4g 4h 4i 4j 5a 5b 5c difference trials of thiazides difference trials of beta-blockers difference trials of ACE inhibitors difference trials of angiotensin receptor blockers difference trials of calcium-channel blockers Strokes in blood pressure difference trials of thiazides Strokes in blood pressure difference trials of beta-blockers Strokes in blood pressure difference trials of ACE inhibitors Strokes in blood pressure difference trials of calcium-channel blockers CHD events in drug comparison trials of thiazides versus any other drug CHD events in drug comparison trials of beta-blockers versus any other drug CHD events in drug comparison trials of ACE inhibitors versus any other drug CHD events in drug comparison trials of angiotensin receptor blockers versus any other drug CHD events in drug comparison trials of calcium-channel blockers versus any other drug Strokes in drug comparison trials of thiazides versus any other drug Strokes in drug comparison trials of beta-blockers versus any other drug Strokes in drug comparison trials of ACE inhibitors versus any other drug Strokes in drug comparison trials of angiotensin receptor blockers versus any other drug Strokes in drug comparison trials of calcium-channel blockers versus any other drug diastolic blood pressure on entry 70-74mmHg diastolic blood pressure on entry 75-79mmHg diastolic blood pressure on entry 80-84mmHg 0.86 (0.75,0.98) (0.78,1.02) (0.78,0.89) < (0.53,1.40) (0.78,0.92) < (0.53,0.72) < (0.70,0.99) (0.66,0.92) < (0.58,0.75) < (0.91,1.08) (0.92,1.17) (0.90,1.03) (0.94,1.16) (0.91,1.10) (0.82,1.09) (1.03,1.36) (0.94,1.20) (0.71,1.13) < (0.84,0.98) (0.65,0.88) < (0.76,0.94) (0.73,1.01)

8 Web-table A Summary relative risk estimates (95% CI) and results of tests of heterogeneity in the subset analyses in the web-figures (see footnote* for a summary of the heterogeneity results) Effect Heterogeneity Web-figure Relative risk (95%CI) p value χ 2 degrees of freedom p value* 5d 0.84 (0.76,0.93) diastolic blood pressure on entry 85-89mmHg 5e 0.88 (0.79,0.97) diastolic blood pressure on entry 90-94mmHg 5f 0.74 (0.58,0.94) diastolic blood pressure on entry 95+mmHg 5g Strokes in blood pressure difference 0.64 (0.50,0.80) < pressure on entry 70-74mmHg 5h Strokes in blood pressure difference 0.75 (0.62,0.91) pressure on entry 75-79mmHg 5i Strokes in blood pressure difference 0.76 (0.66,0.88) < pressure on entry 80-84mmHg 5j Strokes in blood pressure difference 0.78 (0.66,0.92) pressure on entry 85-89mmHg 5k Strokes in blood pressure difference 0.63 (0.56,0.72) < pressure on entry 90-94mmHg 5l Strokes in blood pressure difference pressure on entry 95+mmHg 0.54 (0.42,0.69) < a 6b 6c 6d 6e 6f 6g systolic blood pressure on entry mmHg systolic blood pressure on entry mmHg systolic blood pressure on entry mmHg systolic blood pressure on entry mmHg systolic blood pressure on entry mmHg systolic blood pressure on entry mmHg systolic blood pressure on entry 170+mmHg 0.78 (0.63,0.96) (0.66,0.90) (0.80,0.99) (0.76,0.94) (0.77,0.96) (0.66,0.95) (0.68,1.09)

9 Web-table A Summary relative risk estimates (95% CI) and results of tests of heterogeneity in the subset analyses in the web-figures (see footnote* for a summary of the heterogeneity results) Effect Heterogeneity Web-figure Relative risk (95%CI) p value χ 2 degrees of freedom p value* 6h Strokes in blood pressure difference 0.56 (0.29,1.06) pressure on entry mmHg 6i Strokes in blood pressure difference 0.75 (0.63,0.89) < pressure on entry mmHg 6j Strokes in blood pressure difference 0.77 (0.62,0.95) pressure on entry mmHg 6k Strokes in blood pressure difference 0.69 (0.60,0.80) < pressure on entry mmHg 6l Strokes in blood pressure difference 0.66 (0.50,0.87) pressure on entry mmHg 6m Strokes in blood pressure difference pressure on entry 170+mmHg 0.58 (0.46,0.74) < * Statistically significant heterogeneity was present in ten of the 54 sub-group analyses. In seven of these ten the heterogeneity was attributable to the effects of two large blood pressure difference trials, one unexpectedly showing an increase in CHD events, w94 the other an increase in stroke, w25 which each introduced heterogeneity into all the analyses in which they appeared. In one analysis the heterogeneity was attributable to the greater protective effect of calcium-channel blockers on stroke. The heterogeneity could not be explained in the remaining two analyses (web-figures 4e, 5h), but two statistically significant results out of 46 might be expected through the effects of chance alone

10 Appendix table 3 Relative risk estimates of CHD events and stroke (95% CI) according to age for a 20 mmhg lower systolic blood pressure and a 10 mmhg lower diastolic blood pressure (these are the regression slopes, S). Data from the Prospective Studies Collaboration 25 Age (years) Stroke systolic ( ) ( ) ( ) ( ) ( ) diastolic ( ) ( ) ( ) ( ) ( ) CHD systolic ( ) ( ) ( ) ( ) ( ) diastolic ( ) ( ) ( ) ( ) ( )