Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance. We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P=0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P=0.16) was not associated with a significant reduction in incident AF/AFL. Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Dewland TA ，Soliman EZ ，Yamal JM ，Davis BR ，Alonso A ，Albert CM ，Simpson LM ，Haywood LJ ，Marcus GM ... -  《-》

Atrial fibrillation at baseline and during follow-up in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

Haywood LJ ，Ford CE ，Crow RS ，Davis BR ，Massie BM ，Einhorn PT ，Williard A ，ALLHAT Collaborative Research Group ... -  《-》

Influence of Prevalent and Incident Atrial Fibrillation on Post-Trial Major Events in ALLHAT.

Limited information is available on long-term antihypertensive and lipid-lowering therapy effects on hypertensive patients with atrial fibrillation/flutter (AF/AFL) compared to those without. AF/AFL at baseline or during the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (mean follow-up 4.9 years) markedly increased risk of stroke, heart failure, CHD, and all-cause mortality. We aimed to determine if AF/AFL continued to impact outcomes during post-trial follow-up (mean 3.8 years). Patients were randomized to chlorthalidone, amlodipine, or lisinopril, and to pravastatin vs. usual care in the lipid-lowering trial (LLT). Of 31,473 available subjects, AF/AFL occurred in 854; 383/14,371 chlorthalidone (2.7%), 247/8565 amlodipine (2.9%), and 224/8537 lisinopril (2.6%). Post-hoc analyses utilized administrative databases for post-trial data. Individuals with AF/AFL were compared to those without during post-trial. Outcomes were analyzed by treatment groups for the antihypertensive and LLT trials. Among 854 AF/AFL participants, 491 (57.5%) died: 220 in-trial, 271 post-trial. Ten-year all-cause mortality rates for those with in-trial AF/AFL were similar for chlorthalidone and lisinopril, but lower for amlodipine (68, 66, and 49 per 100 persons, respectively); adjusted HR for amlodipine vs. chlorthalidone was 0.68 (95% CI, 0.54-0.87). Ten-year all-cause mortality rates were 57 vs. 65 per 100 persons (pravastatin vs. usual care); non-CVD mortality rates, 18 vs. 39 per 100 persons (pravastatin vs. usual care) (adjusted HR = 0.46, 95% CI, 0.24-0.86). Post-trial follow-up revealed continued deleterious AF/AFL effects. The amlodipine (ALLHAT) and pravastatin (ALLHAT-LLT) treatment groups showed lower all-cause and non-CVD mortality compared to the chlorthalidone and usual-care groups, respectively.

Haywood LJ ，Davis BR ，Piller LB ，Cushman WC ，Cutler JA ，Ford CE ，Simpson LM ，Ghosh A ，Soliman EZ ，Wright JT Jr ，ALLHAT Collaborative Research Group ... -  《-》

Risk Factors Influencing Outcomes of Atrial Fibrillation in ALLHAT.

ALLHAT, a randomized, double-blind, active-controlled, multicenter clinical trial of high risk hypertensive participants, compared treatment with an ACE-inhibitor (lisinopril) or calcium channel blocker (amlodipine) with a diuretic (chlorthalidone). Primary outcome was the occurrence of fatal coronary heart disease or nonfatal myocardial infarction. For this report, post-hoc analyses were conducted to determine the contribution of baseline characteristics of participants with or without baseline or incident atrial fibrillation (AF) and atrial flutter (AFL) to stroke, heart failure (HF), coronary heart disease (CHD), and mortality outcomes. Minnesota Coding of baseline and biennial in-trial ECGs was used to determine the 334 baseline and 537 incident AF/AFL cases, respectively participants with AF/AFL: Cox regression was used to estimate hazard ratios of presence versus absence of either baseline or incident AF/AFL (as time-dependent covariate) for occurrence of stroke, CHD, HF, or mortality, while adjusting for selected baseline characteristics. Adjusted Cox regression was used to obtain hazard ratios (HRs) for presence versus absence of selected baseline characteristics among those with and without either baseline or incident AF/AFL. After adjusting for baseline characteristics, baseline AF/AFL was associated with stroke, HF, and mortality (HRs [95% CIs] 3.18, [2.34-4.33]; 2.65 [2.02-3.49]; and 2.10 [CI, 1.73-2.55], respectively, P < 0.05). Incident AF/AFL was a significant risk factor for HF and mortality (HRs 2.80 and 2.06, respectively, P < 0.05). Risk factor profiles for clinical outcomes for those with and without baseline or incident AF/AFL were largely similar. AF/AFL is a significant risk factor for stroke, HF, and mortality. Additional risk factors for these outcomes were generally similar for participants with and without baseline or incident AF/AFL.

Haywood LJ ，Davis BR ，Piller LB ，Simpson LM ，Ghosh A ，Einhorn PT ，Ford CE ，Probstfield JL ，Soliman EZ ，Wright JT Jr ，ALLHAT Collaborative Research Group ... -  《-》

Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHA

Barzilay JI ，Davis BR ，Cutler JA ，Pressel SL ，Whelton PK ，Basile J ，Margolis KL ，Ong ST ，Sadler LS ，Summerson J ，ALLHAT Collaborative Research Group ... -  《ARCHIVES OF INTERNAL MEDICINE》