Drugs to lower LDL cholesterol (LDL-C)
- General principles:
- HMGCoAreductase inhibitors
- Sponsored trials, mostly with statins, but also with ezetimibe and PCSK9i proved continuos reduction of ASCVD along LDL reductions.
- According to risk category, LDL goal goes from 130 to 55 mg/dL
- Nonfatal MI or CV death ↓29-37% every 38 mg/dL LDL reduction, depending on LDL level.
- Revascularization and stroke also ↓ but less
- Other metaanalysis show the lowest CV death for LDL <50.
- Initiate moderate-high intensity statin unless contraindicated.
- For residual risk reduction, adding ezetimibe (improve-it) or pcsk9i (fourier, oddisey) further ↓ composites about 15-20%. Colesevelam and bempedoic trials are ongoing.
- Cholesterol absorption inhibitors: ezetimibe: ↓C 10-25%, in improve-it ↓CVD with simvastatin
- Monoclonal Ab PCSK9 inhibitors: alirocumab and evolocumab. Very potent, SC every 2-4 weeks.
- Bile acid sequestrant: ↓LDL 15-25%, contraindicated if Tg>500, colesevelam also indicated for DM
- Bempedoic acid ↓LDL 15-25%, no proved CV reduction, ↑uric acid and gout, tendon rupture.
- Niacin ↓LDL 20% ↑HDL. No demonstrated CV benefit. ↑glycemia, flushing, hepatotoxicity.
- Other: lopitamide: microsomal triglyceride transfer protein (MTP) inhibitor, for HoFH, hepatotoxic.
- When to start statin
- Low risk patients unable to maintain LDL-C <130 mg/dL
- Moderate, high, very high or extreme risk patient regardless LDL level.
- Dose titration
- Measure LDL every 3 months , if >goal stepwise:
- Check adherence
- Increase statin dose-intensity
- Add 2nd drug: ezetimibe, PCSK9i, colesevelam, bempedioc acid depending needed↓
- Add 3rd drug
- Statin adverse effects:
- Myopathy: 5-20% in clinical practice
- Always warn
- Muscle pain, weakness, crumps
- ♀ >65, lean, frail
- CK not necessary, confirms if >x4, rhabdomyolisis >x10
- If not severe, try another or same statin lower dose
- Hyperglycemia, 10% ↑DM risk
- Contraindicated in active hepatic disease, the do not harm liver themselves.
Drugs to lower triglycerides.
- General principles:
- 150 mg/dL cut-off is somehow arbitrary.
- Trial of lowering Tg on ASCVD have failed until REDUCE-IT (IPE, icosapent ethyl) ↓CVD probably by TG-independent mechanism (only 18% TG↓). Beware adverse effects.
- Below mentioned measures are aimed to ↓TG and its consequences rather than CVD
- Non drug therapy:
- Weight loss:
- diet: ↓CH, fat, alcohol
- Exercise
- Investigate and treat secondary causes (see post 1)
- Drugs:
- Fibrates, the most potent, PPAR alpha agosnists, ↑beta oxidation, ↓TG 45-55%, may ↓CVD in TG>200+HDL<40
- Omega 3, EPA +-DHE, ↓TG 20-45%
- Niacin ↓TG 20-30% by ↓lipolysis
- Statins and PCSK9-a (moderate) and ezetimibe (mild).
- Algorithm:
- TG>=500 = pancreatitis risk, treat with fibrates, niacin or omega-3. Consider combination
- Tg <500:
- No ASCVD or DN +>=2 RF: if Tg >150 on statin, consider add fib, o-3 or niacin
- ASCVD: if Tg 135-500 on statin: add IPE (reduce-it ↓25% CV events). If TG>=150 on statin + IPE, consider add fibrates etc.
Drugs to lower Lp(a). No drug is aproved by FDA.
- AACE recommends measuring it in:
- ASCVD
- Family history (FH) of premature CVD or elevated Lp(a)
- Blacks and asians
- FH or antecedents of aortic stenosis
- LDL irresponsiveness to drugs
- 10y risk score >10%
- PCSK9i, estrogens, aspirin and niacin ↓Lp(a), antisense oligonucleotide trial are under way, and apheresis in extreme cases is possible.
