【正文】 = 19,257 Amlodipine 5–10 mg 177。f B et al. Lancet. 2023。 Fatal/nonfatal vascular events ASCOTLLA: Rationale ? Premise – High prevalence of dyslipidemia in hypertensive patients – Most CV disease events occur in patients with BP and lipid concentrations deemed normal ? Hypothesis – Lipid lowering will benefit hypertensive patients not conventionally deemed dyslipidemic Sever PS et al. Lancet. 2023。 N = 90,056 Cause of death Vascular causes: Stroke Other vascular Any vascular Any nonCHD vascular Nonvascular causes: Cancer Respiratory Trauma Other/unknown Any nonvascular Any death Events (%) Treatment better Control better CHD Relative risk Treatment (n = 45,054) Control (n = 45,002) Metaanalysis of 14 trials HPS: Assessing statin benefit in highrisk patients HPS Collaborative Group. Lancet. 2023。27:21547. Consider ACEIs in all patients with vascular disease – Assess risk/benefits and tolerability – Use doses proven in clinical trials Integrating Statins in CV Risk Reduction Statins reduce allcause death CTT Collaborators. Lancet. 2023。 21 randomized clinical trials ACEI ARB Stroke 1% (9% to 10%) HF 10% (10% to 0%) CHD 9% (14% to 3%) Stroke 2% (33% to 3%) HF 16% (36% to 5%) CHD 7% (7% to 24%) 30% 0 30% Decrease Increase Stroke P = HF P = CHD P = Risk RRR ACEIs in vascular disease: Conclusions ? ACEIs reduce mortality, MI, HF, and stroke in patients with vascular disease with/without LVSD or HF ? Benefit in addition to antiplatelet agents, βblockers, and lipidlowering agents – Combining ACEIs with these agents provides greatest benefit ? Benefit in patients across a broad range of risk for CV events – Annual rate in placebo groups of %–% Dagenais GR et al. Lancet. 2023。368:5818. Trial Patients (n) Annual rates in placebo groups OR (95% CI) P 5 20 40 5 30 15 35 Odds reduction (%) 25 10 0 PEACE 8290 7 (8 to 19) HOPE total 9297 25 (16 to 32) HOPE lower risk 3083 18 (4 to 35) HOPE med risk 3100 20 (3 to 33) HOPE high risk 3114 24 (12 to 34) EUROPA total 12,218 19 (8 to 28) EUROPA lower risk 3976 19 (5 to 38) EUROPA med risk 3975 28 (11 to 41) EUROPA high risk 3975 10 (4 to 22) AIRE 1986 24 (7 to 38) TRACE 1749 25 (9 to 33) SOLVDP 4228 15 (2 to 27) SOLVDT 2569 23 (10 to 33) SAVE 2231 20 (4 to 33) CV death,* nonfatal MI or stroke ACEI worse ACEI better *Or total mortality in AIRE, TRACE, SOLVD, SAVE trials ACEIs vs ARBs: Comparative effect on stroke, HF, and CHD Turnbull F. 15th European Meeting on Hypertension. 2023. Adapted by Strauss MH, Hall AS. Circulation. 2023。368:5818. HOPE, EUROPA: Benefit consistent across ancillary therapy Adapted from Dagenais GR et al. Lancet. 2023。 bendroflumethiazide, despite similar brachial systolic BP effects ? Central aortic systolic BP and pulse pressure differences may explain ASCOTBPLA outes ? Central aortic pulse pressure may be a determinant of CV outes CAFE Investigators. Circulation. 2023。113:121325. Similar effects on brachial BP CAFE: Summary ? Substantial and consistent differences in central aortic BP and hemodynamics with amlodipine 177。 bendroflumethiazide Amlodipine 177。f B et al. Lancet. 2023。f B et al. Lancet. 2023。 bendroflumethiazide – mg/potassium Amlodipine 5–10 mg 177。f B et al. Lancet. 2023。 bendroflumethiazide – mg/potassium Amlodipine 5–10 mg 177。19:113947. Sever PS et al. Lancet. 2023。f B et al. Lancet. 2023。 perindopril 4–8 mg Atenolol 50–100 mg 177。f B et al. Lancet. 2023。 N=162,341 Relative risk Favors more intensive Favors less intensive ASCOTBPLA: Rationale ? Premise – Multiple risk factors markedly increase CV disease severity – Standard BPlowering therapies (diuretics and βblockers) have not been proven to prevent CHD events – ASCOTBPLA pared newer vs older antihypertensive regimens in patients with ≥3 risk factors ? Hypothesis – Newer, aggressive bination BPlowering agents will prevent more CV events BPLTTC. Arch Intern Med. 2023。362:152735. Metaanalysis of 4 trials。 N = 958,074 Prospective Studies Collaboration. Lancet. 2023。 de P et al. N Engl J Med. 2023。348:38393. *CV death, MI, stroke, revascularization, amputation, PAD surgery。348:38393. Conventional therapy (n = 80) Intensive therapy (n = 80) Followup (years) Followup (years) 0 1 2 3 4 5 6 7 8 50 150 250 350 0 0 1 2 3 4 5 6 7 8 110 130 150 170 0 SBP (mm Hg) P TotalC (mg/dL) P 0 1 2 3 4 5 6 7 8 50 150 250 350 0 AlC (%) P TG (mg/dL) P = 0 1 2 3 4 5 6 7 8 5 7 9 11 0 Steno2: Multifactorial intervention improves macrovascular outes G230。348:38393. Steno2 results: Better control with intensive therapy G230。8(suppl 1):4082. Lifestyle intervention ? Diet ? Physical activity ? Smoking cessation ? Weight control Aggressive management of orbid conditions* ? Lipid modifying ? BP lowering ? ASA for prevention of vascular events *Dyslipidemia, hypertension, early renal disease Intensive glycemic control ? A1C ≤% ? Glucose (mg/dL) –Preprandial ≤110 –Postprandial ≤140 Steno2: Rationale for TargetDriven Behavior Modification and Polypharmacy Steno2: Goals of intensive pharmacologic strategy Therapy Goal ACE inhibitors All patients (ARBs, if contraindicated) Aspirin All patients (150 mg/d) BP control 130/80 mm Hg Lipid control TotalC 175 mg/dL Triglycerides 150 mg/dL Glucose control A1C % G230。113:29436. Gelfand EV, Cannon CP. J Am Coll Cardiol. 2023。 moderate physical activity vs little or no physical activity (–) (–) (–) Allcause death