p.42 抽出テキスト

May 3, 2022 Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 e936

CLINICAL STATEMENTS AND GUIDELINES

Recommendation-Specific Supportive Text

1.	 Second-generation dihydropyridine calcium channel blockers, including amlodipine and felodipine, have greater selectivity for calcium channels in vascular smooth muscle cells and less myocardial depressant activity. By reducing peripheral vasoconstriction and LV afterload, calcium channel blockers were thought to have a potential role in the management of chronic HF. The PRAISE-1 (Prospective Randomized Amlodipine Survival Evaluation-1) study showed a reduction in mortality in the subgroup of patients with nonischemic cardiomyopathy who received amlodipine.1 However, in the PRAISE-2 (Prospective Randomized Amlodipine Survival Evaluation 2) trial, which enrolled only patients with nonischemic cardiomyopathy, no survival benefit was observed, indicating the limitations of conclusions derived from subgroup analyses.29 However, dihydropyridine calcium channel blockers may be used for treatment of hypertension in patients who have elevated blood pressure despite optimization of GDMT. 2.	 Many nutritional supplements and hormonal therapies have been proposed for the treatment of HF.3–9,30,31 Ultimately, most studies are limited by small sample sizes, surrogate endpoints, or nonrandomized design.32,33 In addition, adverse effects and drug-nutraceutical interactions remain unresolved. There is a lack of evidence of benefit from vitamin D,3–5 thiamine,34–36 carnitine,37 and taurine38,39 and potential harm from vitamin E.6,7 The largest RCT of coenzyme Q10—Q-SYMBIO (Coenzyme Q10 as adjunctive treatment of chronic heart failure with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide], and long-term Outcome [hospitalisations/mortality])—showed no changes in NYHA functional classification at 16 weeks, although the incidence of major adverse cardiovascular events at 2 years was significantly reduced (hazard ratio, 0.50; 95% CI, 0.32-0.80; P=0.003).8 Despite these findings, concerns about slow recruitment in this trial have tempered enthusiasm for coenzyme Q10 supplementation in clinical practice.9,31 Hormonal therapies have been proposed for the treatment of HF, but trials have shown a neutral effect of testosterone,40,41 growth hormone,30,42 and thyroid hormone43–45 in HF outcomes. 3.	 Nondihydropyridine calcium channel blockers—diltiazem and verapamil—are myocardial depressants and generally not well tolerated in HF. Verapamil had no impact of survival or major cardiac events post-MI, including in those patients with HFrEF after acute MI.10 In patients with nonischemic

Table 13.  Selected Prescription Medications That May Cause or Exacerbate HF

Drug or Therapeutic Class Associated With HF Magnitude of HF Induction or Precipitation LOE for HF Induction or Precipitation Possible Mechanism(s) Onset

Causes Direct Myocardial Toxicity Exacerbates Underlying Myocardial Dysfunction

COX, nonselective inhibitors (NSAIDs) X Major B Prostaglandin inhibition leading to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics Immediate

COX, selective inhibitors (COX-2 inhibitors) X Major B Thiazolidinediones X Major A Possible calcium channel blockade Intermediate Saxagliptin X Major A Unknown Intermediate to delayed Alogliptin X Major A Flecainide X Major A Negative inotrope, proarrhythmic effects Immediate to intermediate Disopyramide X Major B Sotalol X Major A Proarrhythmic properties, beta blockade Immediate to intermediate Dronedarone X Major A Negative inotrope Alpha-1 blockers Doxazosin X Moderate B Beta-1-receptor stimulation with increases in renin and aldosterone Intermediate to delayed Diltiazem X Major B Negative inotrope Immediate to intermediate Verapamil X Major B Nifedipine X Moderate C COX indicates cyclo-oxygenase; HF, heart failure; LOE, Level of Evidence; and NSAID, nonsteroidal anti-inflammatory drug. Adapted from Page RL 2nd et al.57 Copyright 2016 American Heart Association Inc.

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