Heart and Blood Pressure Medicines

TL;DR. These are the drugs most people end up taking, usually for conditions that cause no symptoms at all, which makes adherence the central problem: roughly half of people stop within a year. Statins are the most argued-about drugs in medicine and the evidence that they reduce heart attacks and strokes is about as strong as evidence gets; most reported muscle symptoms turn out in blinded trials to occur equally on placebo. Blood pressure targets have come down. And several of these drugs must never be stopped abruptly.

1. The blood pressure drugs

Why treat it. Hypertension causes no symptoms until it causes a stroke, heart attack, heart failure, kidney failure, or dementia. It is the single largest contributor to death worldwide. Treatment is entirely preventive, which is exactly why people stop taking it.

Targets have fallen. Most guidelines now aim for under 140/90 mmHg in the clinic, and under 130/80 for many people, following the SPRINT trial which found intensive lowering (systolic under 120) reduced cardiovascular events and death, at the cost of more hypotension and kidney effects. Home readings run about 5 mmHg lower than clinic ones.

The four main classes, and combining two at low dose usually beats maximising one:

ACE inhibitors (-pril)

Ramipril, lisinopril, enalapril, perindopril

Mechanism: block the conversion of angiotensin I to angiotensin II, a powerful vasoconstrictor that also drives aldosterone release. Result: vessels relax, sodium and water are excreted.

Also protects the kidney in diabetes and proteinuric kidney disease by reducing pressure in the glomerulus, which is why they are first-line there even when blood pressure is normal.

Side effects:

  • Dry, persistent cough in 10 to 20 percent, more in women and in East Asian populations, caused by bradykinin accumulation. It is not dangerous, it is intensely annoying, it can start months after beginning the drug, and it resolves on switching to an ARB.
  • Hyperkalaemia, particularly with kidney impairment, potassium supplements, potassium-based salt substitutes, or spironolactone.
  • First-dose hypotension.
  • Angioedema: rare (under 1 percent, more common in Black patients), potentially life-threatening swelling of lips, tongue, or airway. Absolute contraindication to ever taking an ACE inhibitor again.
  • Contraindicated in pregnancy: fetal kidney damage and death.

Angiotensin receptor blockers (-sartan)

Losartan, candesartan, valsartan, irbesartan

Block the receptor rather than the enzyme. Equally effective, no cough, much less angioedema. Same potassium and pregnancy cautions. Increasingly used first-line for that reason.

Never combine an ACE inhibitor and an ARB: trials found more harm and no benefit.

Calcium channel blockers (-dipine, plus verapamil and diltiazem)

Amlodipine, felodipine, nifedipine

Mechanism: block calcium entry into vascular smooth muscle, causing relaxation and dilation.

Two families that behave differently:

  • Dihydropyridines (amlodipine): mainly vascular. Cause ankle swelling (very common, dose-related, not fluid overload and not helped by diuretics), flushing, headache.
  • Non-dihydropyridines (verapamil, diltiazem): also slow the heart. Do not combine with beta blockers without specialist advice, because the combination can cause profound bradycardia and heart block. Verapamil causes constipation.

Grapefruit interacts with several (Chapter 22).

Often first-line in people over 55 and in those of African or Caribbean descent, in whom renin-based drugs work less well.

Diuretics

Thiazide-like (indapamide, chlortalidone; more effective than bendroflumethiazide) act on the distal tubule. First-line in many guidelines.

  • Side effects: low potassium, low sodium, raised uric acid (can precipitate gout), raised glucose, erectile dysfunction, and increased urination.

Loop diuretics (furosemide, bumetanide) are much more powerful, used mainly for fluid overload in heart failure rather than for blood pressure.

Potassium-sparing (spironolactone, eplerenone, amiloride): spironolactone is the standard add-on for resistant hypertension and improves survival in heart failure. It causes hyperkalaemia and, being an anti-androgen, gynaecomastia in men.

The triple whammy again: ACE inhibitor or ARB + diuretic + NSAID substantially raises the risk of acute kidney injury, especially during a dehydrating illness (Chapter 66). If you take the first two, do not add ibuprofen without asking.

Beta blockers (-olol)

Bisoprolol, atenolol, propranolol, carvedilol, metoprolol

Mechanism: block beta-adrenergic receptors, reducing heart rate and contractility.

No longer first-line for uncomplicated hypertension in most guidelines, having performed less well than other classes for stroke prevention. They remain essential for: after a heart attack, heart failure (specific ones: bisoprolol, carvedilol, metoprolol succinate, nebivolol), atrial fibrillation rate control, angina, and off-label for migraine prophylaxis, essential tremor, and performance anxiety.

Side effects: fatigue, cold hands and feet, vivid dreams and nightmares (with lipophilic ones like propranolol), erectile dysfunction, bradycardia, and masking of hypoglycaemia symptoms in diabetes, which is a genuine safety issue.

Never stop a beta blocker abruptly. Receptor upregulation during treatment means sudden withdrawal causes rebound tachycardia, hypertension, angina, and, in people with coronary disease, myocardial infarction. Taper over 1 to 2 weeks.

Caution in asthma: non-selective beta blockers can cause bronchospasm. Cardioselective agents (bisoprolol) are usually tolerated and are used when the cardiac indication is strong.

2. Statins

The most prescribed drug class in the world and the most publicly contested.

Mechanism: inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. The liver responds by upregulating LDL receptors, pulling LDL out of the blood. They also have plaque-stabilising and anti-inflammatory effects independent of LDL lowering.

The evidence:

  • The Cholesterol Treatment Trialists' Collaboration meta-analyses of individual patient data from over 170,000 participants in randomised trials found that each 1 mmol/L reduction in LDL reduces major vascular events by roughly 22 percent per year, consistently across age, sex, and baseline risk.
  • Secondary prevention (after a heart attack or stroke): substantial and undisputed benefit.
  • Primary prevention: benefit proportional to baseline risk. This is where the argument lives, because in low-risk people the absolute benefit is small.

Absolute numbers matter here. For someone with a 10 percent ten-year cardiovascular risk, a statin might reduce it to around 7.5 percent: an absolute reduction of 2.5 percentage points, or about 40 people treated for 10 years to prevent one event. Whether that is worth a daily tablet is a legitimate personal judgement, and it is a different judgement from someone at 30 percent risk.

Side effects, honestly:

  • Muscle symptoms are the dominant complaint, reported by 10 to 25 percent in clinical practice. In blinded randomised trials, muscle symptoms occur at almost the same rate on placebo. The SAMSON trial (2020) gave patients months of statin, placebo, and no tablet in random order and found that 90 percent of the symptom burden reported during statin months also occurred during placebo months. The StatinWISE n-of-1 trials found the same. This is a nocebo effect, and saying so is not calling patients liars: the symptoms are genuinely experienced and are not caused by the drug in most cases (Chapter 85).
  • Rhabdomyolysis, severe muscle breakdown, is real and very rare: roughly 1 to 3 per 100,000 patient-years. Risk rises with high doses, with interacting drugs, and with hypothyroidism. Muscle pain with dark urine needs urgent assessment.
  • New-onset diabetes: a real effect, roughly 1 extra case per 250 people treated for 4 years, mostly in those already close to the threshold. Outweighed by cardiovascular benefit in people who need a statin.
  • Liver enzyme rises: common, usually transient, rarely significant.
  • Not associated with cancer, dementia (if anything, the association runs the other way), or cognitive impairment in trials.

Practical points:

  • Simvastatin should be taken at night (short half-life, and cholesterol synthesis peaks overnight). Atorvastatin and rosuvastatin have long half-lives and can be taken any time, which helps adherence.
  • Grapefruit interacts with simvastatin, atorvastatin, and lovastatin. It does not interact with pravastatin, rosuvastatin, or fluvastatin.
  • Clarithromycin plus simvastatin is a genuinely dangerous combination for rhabdomyolysis; the statin is usually held during the antibiotic course.
  • If you have muscle symptoms, do not just stop. Options include a drug holiday and rechallenge, a different statin, alternate-day dosing, or a lower dose plus ezetimibe.

Other lipid drugs: ezetimibe blocks intestinal cholesterol absorption and adds a further LDL reduction; PCSK9 inhibitors (injectable monoclonals) and inclisiran (a twice-yearly siRNA injection) produce large reductions for high-risk patients; bempedoic acid is an option for statin-intolerant people.

3. Anticoagulants and antiplatelets

Don't be confused: these are not the same thing. Antiplatelets (aspirin, clopidogrel, ticagrelor) stop platelets clumping, and are used for arterial clots: heart attacks, strokes, stents. Anticoagulants (warfarin, DOACs, heparin) interfere with the clotting cascade, and are used for venous clots and for stroke prevention in atrial fibrillation. Using the wrong one is a serious error.

Warfarin

Blocks vitamin K recycling, reducing production of clotting factors II, VII, IX, and X.

  • Requires INR monitoring, with a target usually 2 to 3.
  • Narrow therapeutic index (Chapter 62) and an enormous interaction list: antibiotics, antifungals, amiodarone, NSAIDs, and many others.
  • Vitamin K in food: the advice is consistency, not avoidance. Eating a similar amount of green vegetables daily keeps the INR stable; large swings destabilise it in both directions (Chapter 38).
  • Cranberry juice has case reports of raised INR; the trial evidence is weak. Tell the clinic.
  • Reversed by vitamin K and by prothrombin complex concentrate.
  • Still first choice for mechanical heart valves and severe antiphospholipid syndrome, where DOACs perform worse.

Direct oral anticoagulants (DOACs)

Apixaban, rivaroxaban, edoxaban (factor Xa inhibitors); dabigatran (thrombin inhibitor)

  • No routine monitoring, few food interactions, more predictable, and in trials, similar or better efficacy with less intracranial bleeding than warfarin.
  • Dose depends on kidney function, age, and weight, and getting this wrong is a common prescribing error.
  • Reversal agents exist: idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors.
  • Rivaroxaban must be taken with food at treatment doses for adequate absorption.

For anyone on any anticoagulant: carry an alert card, tell every dentist and surgeon, expect longer bleeding from cuts, and seek urgent assessment after any head injury, even if you feel fine, because intracranial bleeding can be delayed and is the main serious risk.

4. Heart failure

The evidence here has changed substantially, and modern treatment for heart failure with reduced ejection fraction uses four drug classes together ("the four pillars"), which together reduce mortality substantially more than any one alone:

  1. ACE inhibitor / ARB, or sacubitril-valsartan (an ARNI, superior in the PARADIGM-HF trial)
  2. Beta blocker (bisoprolol, carvedilol, metoprolol succinate, nebivolol only)
  3. Mineralocorticoid receptor antagonist (spironolactone, eplerenone)
  4. SGLT2 inhibitor (dapagliflozin, empagliflozin), which turned out to benefit heart failure regardless of whether the person has diabetes, one of the more surprising findings of the last decade (Chapter 76)

Plus loop diuretics for symptom relief, which improve breathlessness and do not improve survival.

Digoxin is now a second-line rate-control and symptom drug: narrow therapeutic index, toxicity worsened by low potassium, and classic signs of toxicity include nausea, confusion, and visual disturbance with yellow-green haloes.

5. Angina and antiarrhythmics

GTN spray or tablets under the tongue for acute angina: it works within minutes by dilating veins and coronary arteries. Bypasses first-pass metabolism, which is why it must not be swallowed. Causes headache and flushing.

GTN and erectile dysfunction drugs (sildenafil, tadalafil) together can cause catastrophic hypotension. This is an absolute contraindication and it is a common and dangerous combination because both are often taken by the same demographic. Leave at least 24 hours after sildenafil and 48 after tadalafil.

Amiodarone is highly effective for arrhythmias and remarkably toxic in the long term: thyroid dysfunction (both directions), pulmonary fibrosis, liver injury, corneal deposits, photosensitivity, and skin discolouration, with a half-life of around 58 days.

6. Adherence: the actual problem

Roughly 50 percent of people stop cardiovascular medicines within a year. Because these drugs prevent events rather than relieve symptoms, there is no felt reward for taking them and no felt penalty for stopping until something happens.

What helps:

  • Combination pills reducing tablet burden; the "polypill" has trial evidence for improving adherence and outcomes.
  • Once-daily dosing where possible.
  • Taking them at a fixed anchor point in the day.
  • Understanding the absolute benefit, which is why asking for the NNT is worthwhile.
  • Home blood pressure monitoring, which gives feedback where there are no symptoms.
  • Discussing side effects rather than silently stopping. Most are manageable by switching within or between classes.

7. The bottom line

  • Blood pressure and cholesterol drugs treat conditions with no symptoms, which makes stopping easy and consequential. Roughly half of people stop within a year.
  • Four blood pressure classes: ACE inhibitors (cough, potassium, never in pregnancy), ARBs (same without the cough), calcium channel blockers (ankle swelling), and diuretics (potassium, gout, glucose). Low doses of two beat a high dose of one.
  • Statins reduce vascular events by around 22 percent per 1 mmol/L of LDL lowering. Most reported muscle symptoms occur equally on placebo in blinded trials, and rhabdomyolysis is real and very rare.
  • Antiplatelets are for arterial clots, anticoagulants for venous clots and atrial fibrillation. They are not interchangeable. On warfarin, keep green vegetables consistent rather than avoiding them.
  • Never stop a beta blocker abruptly. Never combine GTN with erectile dysfunction drugs. Never add an NSAID to an ACE inhibitor plus diuretic without asking.
  • Anyone on an anticoagulant who hits their head needs assessment, even feeling fine.

Sources and notes

Doses, cautions, and interactions follow the British National Formulary and the electronic Medicines Compendium; US figures follow FDA labelling. Blood pressure targets follow NICE NG136 and the ACC/AHA and ESC guidelines; the intensive lowering evidence is SPRINT, NEJM, 2015. Class comparisons and first-line choices follow the ALLHAT trial and NICE's ACD algorithm. ACE inhibitor cough and angioedema rates follow pharmacovigilance reviews. Spironolactone for resistant hypertension is PATHWAY-2, Williams et al., The Lancet, 2015. The triple whammy acute kidney injury risk follows Lapi et al., BMJ, 2013. Beta blocker demotion from first-line follows the ASCOT-BPLA and LIFE trials. Statin efficacy per 1 mmol/L LDL reduction follows the Cholesterol Treatment Trialists' Collaboration meta-analyses, The Lancet, 2010 and 2012. The nocebo demonstration is SAMSON, Wood et al., NEJM, 2020, and StatinWISE, Herrett et al., BMJ, 2021. Statin-associated diabetes follows Sattar et al., The Lancet, 2010. Warfarin versus DOAC evidence follows RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48. Heart failure four-pillar therapy follows PARADIGM-HF, DAPA-HF, EMPEROR-Reduced, RALES, and the ESC 2021 guideline. Digoxin toxicity signs follow standard cardiology. The GTN and PDE5 inhibitor contraindication follows product labelling. Adherence figures follow Chowdhury et al., European Heart Journal, 2013, and the polypill trials (TIPS, SECURE).

Open questions. Whether blood pressure targets below 130 systolic benefit older and frailer patients as much as SPRINT's population is contested. Why statin adherence is so poor despite the evidence is a behavioural question that trials have not solved.

👉 Next: diabetes and weight medicines.